WO2024094607A1

WO2024094607A1 - Isotope labeled and non-labeled gentamicin c congeners

Info

Publication number: WO2024094607A1
Application number: PCT/EP2023/080207
Authority: WO
Inventors: Florian Mauritius Erasmus HUBER; Richard R. Schmidt; Joanna SIEBENHAAR; Edgar Voss
Original assignee: Roche Diagnostics Gmbh; F. Hoffmann-La Roche Ag; Roche Diagnostics Operations, Inc.
Priority date: 2022-10-31
Filing date: 2023-10-30
Publication date: 2024-05-10

Abstract

The present invention generally relates to the field of isotope labeled and non-labeled gentamicin congeners and synthetic methods for the preparation of such congeners. In particular, the present invention relates to isotope labeled gentamicin C or a salt or solvate or derivative thereof, the gentamicin C comprising at least one 13C, D and/or 15N atom and methods for the preparation of gentamicin C or salt or solvate or derivate thereof, in particular of gentamicin C comprising at least one 13C, D and/or 15N atom or salt or solvate or derivate thereof.

Description

Roche Diagnostics GmbH RD14252PC F. Hoffmann-La Roche AG Roche Diagnostics Operations, Inc. __________________________________________________________________________________ Isotope labeled and non-labeled Gentamicin C congeners Field of the invention The present invention generally relates to the field of isotope labeled and non-labeled gentamicin congeners and synthetic methods for the preparation of such congeners. In particular, the present invention relates to isotope labeled gentamicin C or a salt or solvate or derivative thereof, the gentamicin C comprising at least one 13C, D and/or 15N atom and methods for the preparation of gentamicin C or a salt or solvate or derivate thereof, in particular of gentamicin C comprising at least one 13C, D and/or 15N atom or a salt or solvate or derivate thereof. Related art Gentamicin C is a strong and the most commonly prescribed aminoglycoside antibiotic with broad antibiotic activity but very narrow therapeutic margin. Gentamicin C is not a homogenous compound but is composed and used as a mixture of five congeners (C1, C1a, C2, C2a and C2b) which have varying degrees of antimicrobial potency. Gentamicin C has the structure

with R1, R2 and R3 being, independently of each other -CH₃ or -H, wherein Fig.6 shows the respective residues R1, R2 and R3 of the respective naturally occurring congeners. As shown in structure (1), gentamicin C contains a 2-deoxystraptamine (ring A) and two aminosugar moieties, that is garosamine (ring C) and purpurosamine (ring B). The garosamine is glycosidically linked to the hydroxyl group at C-6 of 2-deoxystraptamine, thereby forming the pseudodisaccharide garamine (ring A + C). The purpurosamine (ring B) is glycosidically linked to the C-4 of garamine. The main drawbacks of the therapy with gentamicin C are nephrotoxic and ototoxic side effects, whereby each of those congeners differs in its ability to cause the nephrotoxicity. (A Non- Nephrotoxic Gentamicin Congener That Retains Antimicrobial Efficacy, JASN October 2006, 17 (10) 2697-2705; DOI: https://doi.org/10.1681/ASN.2005101124 ). For example, gentamicin congener C2 was isolated from native gentamicin and shown to induce no cellular injury and no nephrotoxicity in a rat model of gentamicin toxicity while retaining normal bactericidal properties. Because of limited access to pure gentamicin congeners, there are still not many studies focused on the different toxic effects of each of those compounds. Further, to reduce the side effects a method for the preparation of pure congeners in high yields and with high purity would be advantageous, in particular on an industrial scale. Bulman et al. (American Society for Microbiology, Antimicrobial Agents and Chemotherapy, Volume 64, Issue 9, 20 August 2020) have shown that there is substantial variation in the amounts of the gentamicin congeners within clinical formulations of gentamicin and commercially available gentamicin disks used to test antimicrobial susceptibility. In this study, the relative abundances of the four major congeners contained on commercial antibiotic susceptibility test (AST) disks were measured and it was found that the commercial AST disks varied up to 4.1-fold. Further, the potency of the congeners against strains harboring a common aminoglycoside-modifying enzyme (AME) differed up to 128-fold and the nephrotoxicity of the individual gentamicin congeners also differed significantly in cell-based and repeat-dose rat nephrotoxicity studies. The authors concluded that unexpected gentamicin treatment failure may occur if the ratios of gentamicin congeners present in the susceptibility testing product and the clinical dosing formulation are not the same, since microbiological activities of the congeners can differ. Thus, there remains a need for advantageous approaches to provide gentamicin congeners with a predefined and reliable purity. Further, there is a need for the determination of the amount of each gentamicin congener in a sample, such as in a sample derived from a patient as well as reliable methods to determine the composition of clinical formulations with respect to the ratio of congeners present therein. Some of the derivatives of aminoglycoside antibiotics are published and can be obtained by modification of already existing final compounds. Furthermore, recently a synthesis of some gentamicin derivatives and other aminoglycosides was published: WO2019/079706. Further, Rajasekaran and Crich (Org. Lett.2020, 22, 3850−3854) recently published a synthetic approach towards the synthesis of gentamicin B1 and gentamicin X2, both starting from sisomicin. In the synthesis of gentamicin B1 a protected glycosyl acceptor is reacted with a protected garamine-based 6-azido-6,7-dideoxy-D-glycero-D-glucoheptopyranosyl acceptor. However, the respectively obtained intermediate product is not suitable for the synthesis of gentamicin C analogues. Further, no synthesis of isotope labeled compounds is described therein. Thus, there is still the need for advantageous synthetic approaches to obtain pure gentamicin C congeners. There also remains a need for a synthetic approach to creating new gentamicin derivatives in the search for new antibiotics to combat microbial resistance and/or decrease the side effects of known aminoglycoside antibiotics. Further, up to date no source or synthetic pathway of specific isotope labelled gentamicin congeners is known. Such pure isotope labeled congeners would be highly advantageous, e.g. as calibration standard or internal standard for determining the amount of at least one gentamicin C congener present in a given sample for example via means of mass spectroscopy. Summary of the invention The solution of said object is achieved by providing the embodiments characterized in the claims. Surprisingly, it has been found that each gentamicin C congener, in particular C1, C1a, C2, C2a and C2b, can be advantageously prepared in a high purity by chemical synthesis, preferably each without any significant amount of the respective other congeners as contaminants. In particular, this approach also allows the synthesis of isotope labelled gentamicin C congeners which may e.g. be advantageously used as calibration standard for determining the amount of at least one gentamicin C congener present in a given sample. Specifically, this involves the use of mass spectroscopical methods. The inventive synthetic approach and the gentamicin C congeners according to the invention are described in more detail below. According to a preferred embodiment, the present invention relates to isotope labeled gentamicin C or a salt or solvate or derivative thereof, the gentamicin C comprising at least one 13C, D and/or 15N atom. Further, the present invention relates to a compound of formula (I*) OPG₂ OPG₅ 6 91 R 1 R Me N₃ R01 O 01 OPG₆ PG ⁷ O 8 R 1 Me ^N ₃O R _R PG G ₃O O O OPG₄ P¹ N₃ N_{3 (I*),} preferably of formula (I), OPG₂ OPG₅ 6 91 R 1 R Me N PGO ₃ R01 O 7 OPG O 8 ₆ Me ^N ₃ R _R PGO O OPG₄ P^G ₃ O 1 N₃ N_{3 (I),} wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting -CH-, -CD-, -13CD- and -13CH-, R011 is selected from the group consisting –CH 13 13 13 2-, -CD2-, -CHD-, - CD2-, - CH2-, - CHD-, and –R11(R1R2)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH, -13CH, -13 13 13 3 3 CDH2, - CD2H, - CD3, -CD2H, -CDH2, and -CD3, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, and wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6. The term “orthogonal protecting group” refers to a protective group that is attached to and cleaved from a molecular structure without affecting other protective groups present therein. Further, the present invention relates to a compound of formula (I-1*)

preferably of formula (I-1), OPG₂ OPG₅ 6 91 R 101 R Me O N PG O ₃ R 7 OPG O ₆ _R8 Me ^N ₃ R PG P^G ₃O O O OH 1 N₃ N_{3 (I-1),} wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting -CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, -13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, and wherein PG1, PG2, PG3, PG5 and PG6 are suitable protecting groups. Further, the present invention relates to the use of a compound of formula (I*), preferably of formula (I), for the preparation of gentamicin C, preferably of an isotope labeled gentamicin C

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting - CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH 13 13 13 2-, -CD2-, -CHD-, - CD2-, - CH2-, - CHD-, and –R11(R1R2)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH3, -13CH3, -13CDH2, -13CD2H, -13CD3, -CD2H, -CDH2, and -CD3, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, and wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, and wherein the method preferably further comprises the removal of the protecting group PG4 to give the compound of formula (I-1*)

preferably of formula (I)

Further, the present invention relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, the method comprising reacting an glycosylation acceptor (A) of formula

with a donor building block (B*) of formula

preferably with a donor building block (B) of formula OPG₅ 6 91 R 101 R ClC N₃ R 7 OPG O ₆ _R8 R O OPG₄ H^N _(B), to give a compound having the structure

R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of -CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, -13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, and wherein the method preferably further comprises the removal of the protecting group PG4 to give the compound of formula (I-1*)

preferably of formula (I-1)

Further, the present invention relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, as described above, wherein the gentamicin C or a salt or solvate or derivate thereof is an isotope labeled gentamicin C having the structure

wherein R1, R2 and R3 are, independently of each other, selected from the group consisting of - H, -D, -CH3, -13CH3, -13CDH2, -13CD2H, -13CD3, -CDH2, -CD2H and -CD3, wherein at least one of R1 or R2 is -H or -D, R4 is selected from the group consisting –NH-, -ND-, -15ND- and -15NH- , R5 is selected from the group consisting of –NH , -ND 15 15 15 6 7 2 2, - ND2, - NDH and - NH2, R , R and R8 are, independently of each other, selected from the group consisting –CH-, -CD-, 13CD- or -13CH-, R9 and R10, are, independently of each other, selected from the group consisting of - CH -, -CDH-, -CD -, -13CDH- 13 13 11 13 2 2 , - CD2- and - CH2- , and wherein R is C or C, more preferably wherein the isotope labeled gentamicin C has the structure (3)

more preferably the structure

, wherein R1, R2 and R3 are, independently of each other, selected from the group consisting of - H, -D, -CH 13 1 3, - CH3, - 3CDH2, -13CD2H, -13CD3, -CD2H, -CDH2, and -CD3, wherein at least one of R1 or R2 is -H or -D, R4 is selected from the group consisting -NH-, -ND-, -15ND- and - 15NH-, and wherein R11 is C or 13C. Further, the present invention relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, as described above, wherein the gentamicin C or a salt or solvate or derivate thereof is an isotope labeled gentamicin C having the structure according having the structure R 10 R 1 O 5 R R R 2 O 8 R 3 H N H O R⁷ R 11 R R H O 4 O R O H₂ N NH₂ , more preferably a structure according to formula (3)

wherein R1, R2 and R3 are, independently of each other, selected from the group consisting of - H, -D, -CH 13 13 3, - CH3, - CDH2, -13CD2H, -13CD3, -CD2H, -CDH2, and -CD3, wherein at least one of R9 and R10 is -C(DH)- or wherein the isotope labeled gentamicin C has more preferably the structure

Further, the present invention relates to a gentamicin C or a salt or solvate thereof obtained or obtainable by the method described above, preferably an isotope labeled gentamicin C or a salt or solvate thereof comprising at least one 13C, D and/or 15N atom. Further, the present invention relates to a pharmaceutical composition comprising a gentamicin C, as described above, and a pharmaceutically acceptable excipient. Further, the present invention relates to kit comprising an isotope labeled gentamicin C or a salt or solvate thereof, as described above, or a gentamicin C obtained or obtainable by the above described method, and a container. Further, the present invention relates to a method of treating a bacterial infection in a subject in need thereof, comprising administering to the subject an isotope labeled gentamicin C or a salt or solvate thereof, as described above, or a gentamicin C obtained or obtainable by the above- described method, or a pharmaceutical composition as described above. Further, the present invention relates to the use of at least one isotope labeled gentamicin C, as described above, or a salt or solvate or derivative thereof as calibration standard or as internal standard for determining the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample. Further, the present invention relates to a diagnostic composition comprising a gentamicin C, as described above, and a suitable excipient. Such can be a preservative as sodium azide, a stabilizing agent for example on protein basis, pH buffer salts as sodium citrate, sodium phosphate or sodium bicarbonate, or organic solvents as acetonitrile or ethanol, which modify the solubility of the gentamicin C. The term "diagnostic composition" as used herein refers to a composition for identifying the presence or absence of at least one gentamicin C congener, said composition comprising at least isotope labeled gentamicin C. Further, the present invention relates to at least one isotope labeled gentamicin C, as described above, or a salt or solvate or derivative thereof, for use as calibration standard or as internal standard for determining the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample. It is to be understood that one isotope labeled gentamicin C may be used as calibration standard or as internal standard or alternatively, a mixture of at least two isotope labeled gentamicin C congeners may be used. Further, the present invention relates to a method of determining the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample said method comprising (a) mixing the sample with a known amount of at least one isotope labeled gentamicin C, as described above, or a salt or solvate or derivative thereof (b) analyzing the sample via a mass spectrometry (c) comparing the peak area of at least one analyte of interest to a standard curve, wherein said standard curve has been created using the at least one isotope labeled gentamicin C or a salt or solvate or derivative, as described above and standards containing at least one analyte of interest, thereby determining the amount of the at least analyte of interest in the sample. Further, the present invention also relates to a computer-implemented method for assessing a sample comprising at least one gentamicin congener, the method comprising the steps of: (aa) mixing the sample with a known amount of at least one isotope labeled gentamicin C, as described above, or a salt or solvate or derivative thereof, or mixing the sample with a known amount of diagnostic composition that contains a known amount of said at least one isotope labeled gentamicin C, or a salt or solvate or derivative thereof, and receiving the value for the peak area of said isotope labeled gentamicin C in a sample (bb) receiving a value for the peak area of at the least one gentamicin C congeners present in the sample, (cc) comparing the values for the peak area of the at least one isotope labeled gentamicin C and the at the least one gentamicin C congeners and receiving a value for the amount of at least one gentamicin C congener; and (dd) assessing the sample on the comparison and/or the calculation made in step (cc). Further, the present invention relates to a diagnostic system, preferably a clinical diagnostic system, suitable to perform a method of determining the presence and/or the amount of at least one analyte of interest, preferably of the at least one gentamicin C congener, present in a sample, said method comprising the steps (a), (b) and (c), as described above. Further, the present invention relates use of the diagnostic system, described above, for determining the presence or absence or the amount of the at least one analyte of interest in the sample. The isotope labeled gentamicin C The term “isotope labeled gentamicin C” as used within the present invention is denoted to mean that the gentamicin C comprises at least one 13C, D and/or 15N. According to a preferred embodiment, the present relates to isotope labeled gentamicin C or a salt or solvate or derivative thereof, the gentamicin C comprising at least one 13C, D and/or 15N atom. Preferably, the present invention relates to isotope labeled gentamicin C or a salt thereof, the gentamicin C comprising at least one 13C, D and/or 15N atom. Preferably, the gentamicin is an isotope labeled gentamicin selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a. Preferred salts include in particular those salts prepared by reaction of gentamicin C with a mineral or organic acid. In case the pharmaceutical composition comprising a gentamicin C, as described above, comprises a salt of the gentamicin C, a pharmaceutically acceptable salt is employed. Such salts are known to the skilled person. Acids commonly employed to form acid addition salts are inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, and the like, and organic acids such as p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, p- bromophenylsulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, trifluoroacetic acid, acetic acid, and the like. Examples of such pharmaceutically acceptable salts are the sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, bromide, iodide, trifluoroacetate, acetate, propionate, decanoate, caprylate, acrylate, formate, hydrochloride, isobutyrate, caproate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexyne-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, hydroxybenzoate, methoxybenzoate, phthalate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, gamma-hydroxybutyrate, glycolate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, napththalene-2-sulfonate, mandelate and the like. Preferred acid addition salts are those formed with mineral acids such as hydrochloric acid and hydrobromic acid, and those formed with organic acids such as maleic acid and methanesulfonic acid. Salts of amine groups may also comprise quaternary ammonium salts in which the amino nitrogen carries a suitable organic group such as an alkyl, alkenyl, alkynyl, or aralkyl moiety. It should be recognized that the particular counter ion forming a part of any salt of this invention is usually not of a critical nature, as long as the counter ion does not contribute undesired qualities or properties, such as in pharmaceutical compositions or when used in the analytical methods according to the invention, for example that is e.g. calibration standard, in methods including mass spectrometry to the salt as a whole. Preferred salts are salts formed via reaction with e.g. sulfuric acid or trifluoroacetic acid, thus sulfate or trifluoroacetate salts. More preferably, the isotope labeled gentamicin C is present as trifluoroacetic acid salt. Further preferably, the isotope labeled gentamicin C obtained or obtainable by the method described above is present as trifluoroacetic acid salt. The term “pharmaceutically acceptable solvate” encompasses also suitable solvates of the gentamicin C of the invention, wherein the gentamicin C combines with a solvent such as water, methanol, ethanol, DMSO, acetonitrile or a mixture thereof to form a suitable solvate such as the corresponding hydrate, methanolate, ethanolate, DMSO solvate or acetonitrilate. Preferably, the isotope labeled gentamicin C according to the invention, or the isotope labeled gentamicin C obtained or obtainable by the above-described method, is at least, preferably only, labeled in the purpurosamine part (ring B), in other words the purpurosamine part (ring B) comprises preferably at least one 13C, D and/or 15N atom in the ring or in the substituents of the ring. In other words, in the purpurosamine part of structure (1) at least one C is replaced with 13C and/or at least one H is replaced with D and/or at least one N is replaced with 15N. More preferably only the purpurosamine part is labeled. Preferably, the isotope labeled gentamicin C, as described above, or the isotope labeled gentamicin C obtained or obtainable by the above-described method, is substantially free of other congeners. The term “substantially free of other congeners” within the meaning of the present invention is denoted to mean that respective gentamicin C comprises less than 1 % by weight, preferably less than 0.5 % by weight, more preferably less than 0.1 % by weight, more preferably less than 0.05 % by weight, more preferably less than 0.01 % by weight, more preferably essentially no, more preferably no impurities of respective other gentamicin C congeners, based on the total weight of the substantially free of other congeners gentamicin C congener, as determined via HPLC and HPLC-MS methods and LCMS. Typically, the amount of other congeners present or the absence of other congeners is determined via a spiking assay on LCMS apparatuses. Such spiking assays are known to the skilled person. Typically, if the amount (or absence) of an analyte is to be determined with a spiking assay, a known amount (a spike) of said analyte is added to the sample and the spiked sample is then analyzed. The amount of the analyte corresponds to the total amount of the analyte (analyte comprised in the sample plus added spike) minus the added spike of said analyte. The term “other gentamicin C congeners” in this context is denoted to comprise also unlabeled or differently isotope labeled gentamicin congeners, including the congener possessing the same molecular structure but being isotopically labeled at different or no atomic positions. Preferably, the isotope labeled gentamicin C, as described above, or the isotope labeled gentamicin C obtained or obtainable by the above-described method, is substantially pure. The term “substantially pure” within the meaning of the present invention is denoted to mean that the respective gentamicin C or the salt or solvate thereof comprises less than 5 % by weight, preferably less than 4%, more preferably less than 3 % by weight, more preferably less 2 % by weight, more preferably less than 1% by weight, more preferably less than 0.5 % by weight, more preferably less than 0.1 % by weight, more preferably less than 0.05 % by weight, more preferably less than 0.01 % by weight, more preferably essentially no, impurities, as determined via HPLC and HPLC-MS methods such as LCMS, wherein the term impurities includes all additional components, such as additional solvent and the like, other than (other) gentamicin C congeners. According to a preferred embodiment, the isotope labeled gentamicin C which has the general structure (1) is an isotope labeled version of gentamicin C1, thus, with R1 being –CH₃, R2 – H and R3 – CH₃, wherein the isotope labeled gentamicin C1 is preferably at least, more preferably only, labeled in the purpurosamine part. Thus, in the purpurosamine part of structure (1), including residues R1, R2 and R3, at least one C is replaced with 13C and/or at least one H is replaced with D and/or at least one N is replaced with 15N. Preferably, the isotope labeled gentamicin C1 is substantially free of other congeners. Further, the isotope labeled gentamicin C1 is preferably substantially pure. More preferably, the gentamicin C1 is substantially free of other congeners and substantially pure. According to a further preferred embodiment, the isotope labeled gentamicin C which has the general structure (1) is an isotope labeled version of gentamicin C2, thus, with R1 being –CH₃, R2 – H and R3 –H, wherein the isotope labeled gentamicin C2 is preferably at least, more preferably only, labeled in the purpurosamine part. Thus, in the purpurosamine part of structure (1), including residues R1, R2 and R3, at least one C is replaced with 13C and/or at least one H is replaced with D and/or at least one N is replaced with 15N. Preferably, the isotope labeled gentamicin C2 is substantially free of other congeners. Further, the isotope labeled gentamicin C2 is preferably substantially pure. More preferably, the gentamicin C2 is substantially free of other congeners and substantially pure. According to a further preferred embodiment, the isotope labeled gentamicin C which has the general structure (1) is an isotope labeled version of gentamicin C1a, thus, with R1 being –H, R2 – H and R3 –H, wherein the isotope labeled gentamicin C1a is preferably at least, more preferably only, labeled in the purpurosamine part. Thus, preferably, in the purpurosamine part of structure (1), including residues R1, R2 and R3, at least one C is replaced with 13C and/or at least one H is replaced with D and/or at least one N is replaced with 15N. Preferably, the isotope labeled gentamicin C1a is substantially free of other congeners. Further, the isotope labeled gentamicin C1a is preferably substantially pure. More preferably, the gentamicin C1a is substantially free of other congeners and substantially pure. According to a further preferred embodiment, the isotope labeled gentamicin C which has the general structure (1) is an isotope labeled version gentamicin C2a, thus, with R1 being -H, R2 – CH₃ and R3 –H, wherein the isotope labeled gentamicin C2a is preferably at least, more preferably only, labeled in the purpurosamine part. Thus, in the purpurosamine part of structure (1), including residues R1, R2 and R3, at least one C is replaced with 13C and/or at least one H is replaced with D and/or at least one N is replaced with 15N. Preferably, the isotope labeled gentamicin C2a is substantially free of other congeners. Further, the isotope labeled gentamicin C2a is preferably substantially pure. More preferably, the gentamicin C2a is substantially free of other congeners and substantially pure. According to a further preferred embodiment, the isotope labeled gentamicin C which has the general structure (1) is an isotope labeled version gentamicin C2b, thus, with R1 being –H, R2 – H and R3 -CH₃, wherein the isotope labeled gentamicin C2b is preferably at least, more preferably only, labeled in the purpurosamine part. Thus, in the purpurosamine part of structure (1), including residues R1, R2 and R3, at least one C is replaced with 13C and/or at least one H is replaced with D and/or at least one N is replaced with 15N. Preferably, the isotope labeled gentamicin C2b is substantially free of other congeners. Further, the isotope labeled gentamicin C2b is preferably substantially pure. More preferably, the gentamicin C2b is substantially free of other congeners and substantially pure. Preferably, the isotope labeled gentamicin C has the structure (2) OH 6 9 10 1 O 5 R R R R R 2 7 O 8 R 11 3 H N H O R R R R H O 4 O R O H₂ N NH₂ (2) including salts or solvates thereof, wherein R1, R2 and R3 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CDH₂, -CD₂H and -CD₃, wherein at least one of R1 or R2 is -H or -D, R4 is selected from the group consisting –NH-, -ND-, -15ND- and -15NH-, R5 is selected from the group consisting of –NH₂, -ND₂, -15ND_2, -15NDH and -15NH₂, R6, R7 and R8 are, independently of each other, selected from the group consisting –CH-, -CD-, -13CD- or -13CH-, R9 and R10, are, independently of each other, selected from the group consisting –CH₂-, -CDH-, -CD₂-, -13CDH-, -13CD₂- and -13CH₂- , and wherein R11 is C or 13C. More preferably, in these cases, R5 is –NH₂, R6, R7 and R8 are –CH- and the isotope labeled gentamicin C in particular has the structure (3)

According to one preferred embodiment, the isotope labeled gentamicin C has the structure according to formula (3), wherein at least one of R9 and R10 is –C(DH)-, more preferably the structure

Preferably, the isotope labeled gentamicin C has thus a structure selected from the group consisting of

and mixtures thereof, more preferably, the isotope labeled gentamicin has the structure (4a). According to a further preferred embodiment, R9 and R10 are both –C(H₂)-, the labeled gentamicin having the structure (5)

According to a preferred embodiment, the isotope labeled gentamicin C has the general structure (2), preferably the structure (3), more preferably the structure (4) or (5), and is an isotope labeled gentamicin C2, with R1 being selected from the group consisting of -CH₃, - 13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CDH₂, -CD₂H and -CD₃, preferably wherein R1 is –CD₃, and wherein R2 and R3 are, independently of each other, -H or –D. According to a further preferred embodiment, the isotope labeled gentamicin C has the general structure (2), preferably the structure (3), more preferably the structure (4) or (5), and is an isotope labeled gentamicin C1, with R1 being selected from the group consisting of -CH₃, - 13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CDH₂, -CD₂H and -CD₃, preferably wherein R1 is –CD₃, and wherein R2 is -H or –D and R3 selected from the group consisting of -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CDH₂, -CD₂H and -CD₃, preferably wherein R3 is –CD₃. According to a further preferred embodiment, the isotope labeled gentamicin C has the general structure (2), preferably the structure (3), more preferably the structure (4) (such as a structure selected from the group consisting of (4a), (4b), (4c) and (4d) or the structure (5), and is an isotope labeled gentamicin C1a, with R1 being –H or –D and wherein R2 and R3 are also -H or –D and wherein R4 is selected from the group consisting –NH-, -ND-, -15ND- and -15NH-. According to a further preferred embodiment, the isotope labeled gentamicin C has the general structure (2), preferably the structure (3), more preferably the structure (4) or (5), and is an isotope labeled gentamicin C2a, with R1 being –H or –D and wherein R3 is -H or –D and R2 is selected from the group consisting of -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CDH₂, -CD₂H and -CD₃, preferably wherein R2 is –CD₃. According to a further preferred embodiment, the isotope labeled gentamicin C has the general structure (2), preferably the structure (3), more preferably the structure (4) or (5), and is an isotope labeled gentamicin C2b, with R1 being –H or –D and wherein R2 is -H or –D and R3 is selected from the group consisting of -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CDH₂, -CD₂H and -CD₃, preferably wherein R3 is –CD₃. Preferably in the structure (4) and in the structure (5), R11 is C. The following isotope labeled compounds or salts or solvates thereof, are particularly preferred

Thus, the present invention also relates to an isotope labeled gentamicin C2 having a structure according to formula (5), wherein R1 is –CD 2 4 3 3 and R is H, and wherein the group –R-R is – NH, and wh 11 2 erein R is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1 having a structure according to formula (5), wherein R1 is –CD 2 4 15 3 3 and R is H, and wherein –R is - NH- and –R is -13CH, an 11 3 d wherein R is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1 having a structure according to formula (5), wherein R1 is –CD₃ and R2 is H, and wherein R4 is -NH- and R3 is - CH₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2a having a structure according to formula (5), wherein R1 is H and R2 is –CD₃ and, and wherein R4 is -NH- and R3 is -H, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2b having a structure according to formula (5), wherein R1 is H and R2 is -H and, and wherein R4 is -NH- and R3 is –CD₃, and wherein R11 is preferably C. Thus, the present invention also relates to an isotope labeled gentamicin C2 having a structure according to formula (4), preferably according to formula (4a), wherein R1 is –CD₃ and R2 is H, and wherein the group –R4-R3 is –NH₂, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2 having a structure according to formula (4), preferably according to formula (4a), wherein R1 is –CD₃ and R2 is H, and wherein the group –R4-R3 is –15NH₂, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1 having a structure according to formula (4), preferably according to formula (4a), wherein R1 is –CD₃ and R2 is H, and wherein –R4 is -15NH- and –R3 is -13CH₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1 having a structure according to formula (4), preferably according to formula (4a), wherein R1 is –CD₃ and R2 is H, and wherein R4 is -NH- and R3 is -CH₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2a having a structure according to formula (4), preferably according to formula (4a),wherein R1 is H and R2 is –CD₃ and wherein R4 is -NH- and R3 is -H. , and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2b having a structure according to formula (4), preferably according to formula (4a),wherein R1 is H and R2 is -H and, and wherein R4 is -NH- and R3 is –CD₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1a having a structure according to formula (4), preferably according to formula (4a),wherein R1 is H and R2 is -H and, and wherein R4 is -15NH- and R3 is –H, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1 having a structure according to formula (4), preferably according to formula (4a), wherein R1 is –CD₃ and R2 is H, and wherein –R4 is -NH- and –R3 is -CD₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1 having a structure according to formula (4), preferably according to formula (4a), wherein R1 is –CD₃ and R2 is H, and wherein –R4 is -15NH- and –R3 is -CD₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1 having a structure according to formula (5), wherein R1 is –CD₃ and R2 is H, and wherein –R4 is -NH- and –R3 is -CD₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C1 having a structure according to formula (5), wherein R1 is –CD₃ and R2 is H, and wherein –R4 is -15NH- and –R3 is -CD₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2a having a structure according to formula (5), wherein R1 is H and R2 is –CH₃ and, and wherein R4 is - 15NH- and R3 is -H, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2a having a structure according to formula (5), wherein R1 is H and R2 is –CD₃ and, and wherein R4 is - 15NH- and R3 is -H, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2a having a structure according to formula (4), preferably according to formula (4a), wherein R1 is H and R2 is –CD₃ and, and wherein R4 is -15NH- and R3 is -H, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2b having a structure according to formula (5), wherein R1 is H and R2 is -H and, and wherein R4 is -15NH- and R3 is –CH₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2b having a structure according to formula (5), wherein R1 is H and R2 is -H and, and wherein R4 is -15NH- and R3 is –CD₃, and wherein R11 is preferably C. Further, the present invention also relates to an isotope labeled gentamicin C2b having a structure according to formula (4), preferably according to formula (4a), wherein R1 is H and R2 is -H and, and wherein R4 is -15NH- and R3 is –CD₃, and wherein R11 is preferably C. Thus, the present invention also relates to an isotope labeled gentamicin C2 having a structure according to formula (5), wherein R1 is –CD₃ and R2 is H, and wherein the group –R4-R3 is – 15NH₂, and wherein R11 is preferably C. Preferably, the isotope labeled gentamicin C congeners described above and below are present as trifluoroacetic acid salt. The method according to the invention: As outlined above, the present invention further relates to a method for preparing gentamicin C or a salt or solvate or derivate thereof, preferably for preparing an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above. Preferably, the gentamicin C or salt or solvate or derivate thereof, which is prepared by the method according to the present invention, is an isotope labeled gentamicin C comprising at least one 13C, D and/or 15N atom. In the inventive method a precursor of the garamine building block A-C is reacted with a precursor of the purpurosamine building block B*, preferably B, thereby linking the precursor of the purpurosamine building block B*, preferably B, to the carbon C-4 of garamine precursor A-C, in particular via a glycosidic linkage. Further, the present invention also relates to a gentamicin C congener obtained or obtainable by said method. Preferably, the isotope labeled gentamicin C, described above, is obtained or obtainable by the inventive method. With the inventive method, the respective gentamicin may be synthesized substantially free of other congeners. Thus, preferably, the gentamicin C or the isotope labeled gentamicin C obtained or obtainable by the above-described method, is substantially free of other congeners. Further, the gentamicin C or the isotope labeled gentamicin C obtained or obtainable by the above-described method, is substantially pure and substantially free of other congeners. Reference is made to the definition of the term “substantially free of other congeners” and “substantially pure” made above. The term “precursor” within the meaning of the invention is denoted to mean a suitable modified and/or protected building block which may be transformed in further reaction steps to the respective final building block present in the respective gentamicin C or in the respective isotope labeled gentamicin C according to the invention. With this advantageous method an access to all gentamicin C congeners by chemical synthesis is provided, so that each congener is accessible without a significant amount of other congeners as contaminants. Thus, the respective synthesized gentamicin C congener is preferably substantially free of other congeners. Further, the inventive approach advantageously allows for the synthesis of isotope labelled gentamicin C congeners using D, 13C and 15N isotope substitution, preferably in the purporosamine part. Further, the method allows introducing the modifications in the compound structure in the specific positions. In case of preparing an isotope labeled gentamicin C, the at least one isotope label may already have been present in either one of building blocks or may be introduced in a further method reaction step. In case, the at least one isotope label has already been present in one of the building blocks, the label is preferably present in the precursor of the purpurosamine building block B*, preferably B. Preferably, the garamine precursor building block A-C is a glycosylation acceptor (A) having the structure

wherein PG1, PG2 and PG3 are suitable protecting groups. Preferably, the purpurosamine building block is a glycosylation donor (B*) of formula (B*)

more preferably of formula (B)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, and wherein PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, and wherein R011 is selected from the group consisting –CH -, -CD -, -CH 13 13 2 2 D-, - CD2-, - CH2-, - 13CHD-, and –R11(R1R2)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH 13 13 13 13 3, - CH3, - CDH2, - CD2H, - CD3, -CD2H, -CDH2, and -CD , wherein at least one of R1 or R2 is -H or -D, and wh 11 13 3 erein R is C or C, The term “orthogonal” is denoted to mean that PG4 may be attached and cleaved without affecting the protecting groups PG1, PG2, PG3, PG5 and PG6. Thus, PG4 may be removed without removing PG1, PG2, PG3, PG5 and PG6. The term “suitable protecting group” refers to any organic moiety which is readily attached to the group to be protected, such as an amino group or a hydroxyl group, and which, when bound to the respective group, renders the resulting protected group inert to the reaction conditions to be conducted on other portions of the compound and which, at the appropriate time, can be removed to regenerate the respective functional group. PG1 is preferably a suitable amine protecting group, whereas PG2, PG3, PG4, PG5 and PG6 are suitable hydroxyl protecting groups. Such protecting groups are known to the person skilled and are in particular selected as follows: Preferably, PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5- DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, more preferably, wherein PG3 is Bn. Preferably, PG2 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5- DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1. Preferably PG2 and PG3 are the same. According to a preferred embodiment PG2 is Bn. Preferably, PG1 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2. According to one preferred embodiment, PG1 is para-trifluoromethyl-benzoyl. Preferably, PG4 is a protecting group selected from the group consisting of silyl protecting groups, the pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6- trimethylbenzoyl, para-phenyl-benzoyl, para-bromobenzoyl, trifluoromethyl-benzoyl or 2- (trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS). More preferably, PG4 is benzoyl (Bz). Preferably, PG5 and PG6 form together a cyclic group, more preferably PG5 and PG6 form together a diacetal protecting group. Such protecting groups are known to the skilled person and are e.g. described in Synlett 1996, 8, 793-795 and J. Chem. Soc., Perkin Trans. 1, 1997, 2023-2032. Preferably PG5 and PG6 form together the group

. In particular, the invention relates to a method, as described above, the method comprising reacting the glycosylation acceptor (A) of formula

with the glycosylation donor (B*) of formula

more preferably of formula (B)

to give a compound having the structure

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting –CH-, -CD-, -13CD- or -13CH-, wherein R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, - 13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, more preferably wherein PG4 is a protecting group selected from the group consisting of silyl protecting groups, the pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz, 2,4,6-trimethylbenzoyl, para-phenyl- benzoyl, para-bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), more preferably, PG4 is benzoyl (Bz), and wherein PG5 and PG6 form together a cyclic group, more preferably PG5 and PG6 form together a diacetal protecting group, in particular the group

. Further, the present invention also relates to a gentamicin C congener obtained or obtainable by said method. Preferably, the isotope labeled gentamicin C, described above, is obtained or obtainable by the inventive method. The compound of formula (I): In addition, the present invention relates to the compound of formula (I*) as such

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, wherein R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, -13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, - 13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, and wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups. Preferably the compound has the structure (Ia)

wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, more preferably wherein PG4 is a protecting group selected from the group consisting of silyl protecting groups, the pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para-bromobenzoyl, trifluoromethyl-benzoyl or 2- (trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), more preferably, PG4 is benzoyl (Bz), and wherein PG5 and PG6 form together a cyclic group, more preferably PG5 and PG6 form together a diacetal protecting group, in particular her the group

. In particular, the present invention also relates to the compound of formula (I*), more preferably of formula (I), more preferably, the compound of formula (Ia), wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, and wherein PG1 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups preferably 2- (trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4- (3,4-dimethoxyphenyl)benzyl, PG4 is a protecting group selected from the group consisting of silyl protecting groups, the pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para-bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 preferably form together a cyclic group, more preferably form together a diacetal protecting group, in particular the group

. In some preferred embodiments, the invention relates to a compound of formula (I*)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH -, -CD -, -CHD-, -13CD -, -13CH -, -13 2 2 2 2 CHD-, and –R11(R1R2)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH3, -13CH3, -13CDH2, -13CD2H, -13CD3, -CD2H, -CDH2, and -CD3, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, and wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein PG1 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5- DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5- DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, PG4 is a silyl protecting group, a pivaloyl group (Piv)or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para-bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group, preferably wherein the compound has the structure (Ia)

the compound of formula (I*), the compound of formula (I) and the compound of formula (Ia) each comprising at least one 13C, D and/or 15N atom. More preferably, the present invention also relates to the compound of formula (Ib), more preferably, the compound of formula (Ic) as shown below: (Ib), preferably the structure

According to an alternative preferred embodiment, in the compound of formula (I*), more preferably the compound of formula (I), more preferably in the compound of formula (Ia), PG1 forms a cyclic protecting group together with PG2, in particular a cyclic urethane protecting group. More preferably, the compound has the structure (Id)

more preferably the structure (Ie)

in particular the structure (If) (If). The present invention also relates to the use of a compound of formula (I*) as described above, preferably of formula (I), preferably of formula (Ia), for the preparation of gentamicin C or salt or solvate thereof, wherein the gentamicin C is preferably selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a and wherein the gentamicin is more preferably an isotope labeled gentamicin. According to one particular preferred embodiment, the present invention relates to the use of a compound of formula (Ib) as described above, preferably of formula (Ic) for the preparation of gentamicin C or salt or solvate thereof, wherein the gentamicin C is preferably selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a and wherein the gentamicin is more preferably an isotope labeled gentamicin. According to another particular preferred embodiment, the present invention relates to the use of a compound of formula (Id) as described above, preferably of formula (Ie), more preferably (If), for the preparation of gentamicin C or salt or solvate thereof, wherein the gentamicin C is preferably selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a and wherein the gentamicin is more preferably an isotope labeled gentamicin. Providing the glycosylation acceptor (A) The garamine precursor building block A-C is hereunder and above referred to as glycosylation acceptor (A). The glycosylation acceptor (A) described above and employed in the method according to the invention, preferably has the structure

wherein PG1, PG2 and PG3 are suitable protecting groups, as described above. According to one preferred embodiment, the glycosylation acceptor (A) has the structure (A1):

According to another preferred embodiment, the glycosylation acceptor A has the structure (A2):

Preferably, the method according to the invention further comprises the provision of the glycosylation acceptor (A). The provision of building block (A) is not particularly restricted and includes e.g. any possible synthesis of building block (A). Preferably, the provision is carried out by a semi-synthetic approach starting from sisomicin. Sisomicin is an aminoglycoside antibiotic, e.g. isolated from the fermentation broth of a new species of the genus Micromonospora inositola (see M J Weinstein et al. , J Antibiot (Tokyo)) Antibiot (Tokyo) 1970 Nov;23(11):551-4) having the structure

It may e.g. be obtained as a sulfate salt e.g. from Merck. Preferably, the method of the present invention further comprises the step of (a) providing the glycosylation acceptor (A), the glycosylation acceptor (A) preferably has the structure

Preferably the provision comprises the conversion of the primary amines functionalities of Sisomicin into azide groups, the suitable protection of the hydroxyl groups and the suitable of the amine to a of formula (a3)

which is transformed to give the compound of formula (A). More preferably step (a) comprises at least the steps: (a1) providing a compound of formula (a1) or a salt thereof

(a2) transforming the primary amine groups of the compound of formula (a1) to azide groups and suitably protecting the hydroxyl groups to give a compound of

wherein PG2 and PG3 are suitable protecting groups, as described above, preferably wherein PG2 and PG3 are the same, (a3) suitably protecting the Me-NH- group with a protecting group PG1 to give a compound of formula (a3)

wherein PG1 is a suitable protecting group, as described above, (a4) and transforming the compound of formula (a3) to compound (A), wherein the glycosylation acceptor of formula (A) preferably has the structure (A1) or (A2). It is to be understood that the providing in step (a1) includes obtaining the compound as a salt, such as a sulfate salt e.g. from Merck KGaA, and optionally transforming the salt into the free base. According to a first preferred embodiment, the glycosylation acceptor of formula (A) has the structure (A1). According to a second preferred embodiment, the glycosylation acceptor of formula (A) has the structure (A2). Preferably step (a4) is carried out under acidic conditions, wherein, e.g., H₂SO₄ in MeOH is employed. By way of example, the synthesis of the glycosylation acceptor may be carried out as shown in Fig.8 and as demonstrated in the working example A2. The donor building block The purpurosamine precursor building block is hereunder and above referred to as donor building block (B*) or according to a preferred embodiment as donor building block (B). The donor building block described above and employed in the method according to the invention, preferably has the structure (B*)

more preferably the donor building block has the structure (B)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting –CH-, -CD-, -13CD- or -13CH-, and wherein PG4, PG5 and PG6 are suitable protecting groups, and wherein R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD- , -13CD₂-, -13CH₂-, -13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, - CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C. As described above, PG5 and PG6 preferably form together a cyclic group, more preferably PG5 and PG6 form together a diacetal protecting group. According to a preferred embodiment, the donor building block described above and employed in the method according to the invention has the structure (B1)

with PG4 being more preferably Bz. In case the donor building block is not isotope labeled, the donor building block (B) has preferably the structure (B2)

with PG4 being even more preferably Bz. Preferably, the method according to the invention further comprises the provision of the glycosylation donor (B). Thus, preferably, the method of the present invention further comprises the step of (a) providing glycosylation donor (B*), preferably (B), the glycosylation donor preferably has the structure

more preferably the structure (B) OPG₅ 6 91 R 101 R N₃ R OPG₆ Cl₃C ⁷ O 8 O R _R OPG₄ H^N _(B). The provision of the glycosylation donor (B*), preferably (B), is not particular restricted and includes e.g. any possible synthesis of the glycosylation donor. By way of example, the provision of the glycosylation donor (B*) and (B), respectively, may be carried out as shown in Fig.7 and as demonstrated in the working example A1. As outlined above, the donor building block has preferably the structure (B), whereas the glycosylation acceptor of formula (A) preferably has the structure (A1) or (A2). Thus, the present invention also relates to a method, as described above, wherein the donor building block has preferably the structure (B), and wherein the glycosylation acceptor formula (A) preferably has the structure (A1) or (A2). Preferably, the method according to the invention further comprises the removal of the protecting group PG 4 to give a compound of formula (I-1*)

preferably of formula (I-1)

preferably of formula (Ia-1) OPG₂ OPG₅ Me O N OPG₆ PG O ₃ O Me N ₃ OH PG O O O PG ₃ ₁ N₃ N₃ (Ia-1). Thus, the present invention also relates to a method as described above, and to a gentamicin C obtained or obtainable by said method, the method comprising the steps (i) reacting an glycosylation acceptor A of formula

with a donor building block (B*) of formula

preferably with a donor building block (B*) of formula

to give a compound having the structure

preferably (I)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting –CH-, -CD-, -13CD- or -13CH-, wherein R011 is selected from the group consisting –CH -, -CD -, -CHD-, -13CD 13 13 11 2 2 2-, - CH2-, - CHD-, and –R (R1R2)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH3, -13CH3, -13CDH2, -13CD2H, -13CD3, -CD2H, -CDH2, and -CD3, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, (ii) removing the protecting group PG 4 to give a compound of formula (I-1*)

(I-1). In some preferred embodiments, the method for the preparation of gentamicin C or a salt or solvate or derivate thereof, wherein the gentamicin C or a salt or solvate or derivate thereof is an isotope labeled gentamicin C comprising at least one 13C, D and/or 15N atom, comprises (i) an (A) of formula

with a glycosylation donor (B*) of formula

to give a compound having the structure (I*)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, -13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein PG1 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5- DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5- DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para-bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group, preferably wherein the donor building block has the structure

and wherein reacting the glycosylation donor (B) with the glycosylation acceptor (A) gives a compound having the structure (Ia) OPG₂ OPG₅ OPG Me O N_{3 6} Me N PG₃O O OPG₄ PG₃O O O PG₁ N₃ N₃ (Ia); wherein at least the compound of formula (I*), the compound of formula (I) and the compound of formula (Ia) each comprise at least one 13C, D and/or 15N atom. In some preferred embodiments, the method further comprises (ii) removing the protecting group PG 4 to give a compound of formula (I-1*)

more preferably of formula (Ia-1)

_(Ia-1). The way of removing the protecting group PG4 depends on the protecting group used. Suitable methods are known to those skilled in the art. Preferably, in case the protecting group PG4 is a Bz protecting group, the removal of PG4 is carried out under basic hydrolysis conditions, e.g. with NaOMe, KOH or K₂CO₃, preferably with NaOMe. The removal of group PG4 may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent, e.g. in a solvent selected from the group consisting of methanol, ethanol, iPrOH or nPrOH, preferably in MeOH, and mixtures of two or more thereof. The compound is preferably allowed to react for a time in the range of from 2 min to 24 h, such as overnight. Preferably, the removal gives a compound of formula (I-1*), more preferably of formula (I-1), more preferably of formula (Ia-1)

_(Ia-1). Further, the present invention also relates to a compound of formula (I-1*), or a compound obtained or obtainable by the inventive method, the compound having the structure

preferably of the structure (I-1)

more preferably of formula (Ia-1)

_(Ia-1). Depending on the congeners desired, compound (I-1*), preferably (I-1), more preferably (Ia- 1), is then further modified to give the final gentamicin C congener, preferably the isotope labeled gentamicin C congener, as described above and below. Advantageously, starting from compound (I*) or compound (I) or compound (Ia) respectively, the skilled person can prepare any desired gentamicin C congeners by suitably modifying the primary hydroxyl group (or the group –OPG4). Thus, with this chemical pathway all of the gentamicin C congeners may be obtained, e.g. as shown in Fig.1-5. In the following particular preferred methods are described. Method A – e.g. preferred for gentamicin C2, C2a or C1 According to a first preferred embodiment A, the primary hydroxyl group of compound (I-1), preferably of compound (Ia-1) is subjected to oxidizing conditions such that the hydroxyl group is transformed into an aldehyde group. This step is in particular carried out in case optionally isotope labeled gentamicin C2, C2a or C1 or derivatives thereof shall be prepared. Thus, the method according to the invention, preferably further comprises the step (iii)(A) reacting the compound of formula (I-1), preferably (Ia-1) with an oxidizing agent to give a compound of formula (I-2A)

Thus, the present invention also relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above, wherein the gentamicin C is preferably gentamicin C2, C2a or C1, the method additionally comprising the step (iii)(A). Suitable oxidizing methods of primary hydroxyl groups are known to those skilled in the art. Suitably oxidizing methods include, but are not limited to, Swern oxidation (DMSO, oxalyl chloride and TEA), Pfitzner-Moffatt oxidation (DCC/DMSO), Dess-Martin Periodinane oxidation, oxidation using TEMPO and a cooxidant or a hypervalent iodide reagent like 2- iodoxybenzoic acid (IBX), TPAP/NMO (tetrapropylammonium perruthenate / N- methylmorpholine N-oxide) or modifications thereof. In a preferred embodiment, the oxidation reaction is a Dess-Martin oxidation. Preferably, the reaction of step (iii)(A) is carried out in a water free solvent or mixture of solvents , such as dichloromethane (DCM), acetone, tetrahydrofuran (THF) or mixtures thereof; and more preferably the reaction solvent is DCM. The reaction of step (iii)(A) is preferably carried out at a temperature of -80° C to the reflux temperature of the solvent used, preferably at a temperature in the range from -20°C to rt. In case that an, optionally isotope labeled, gentamicin C2, C2a or C1 or derivative thereof is prepared, the compound of formula (I-2A), preferably of (Ia-2A), is further modified at the (electrophilic) carbon atom of the aldehyde group with a nucleophile via an addition reaction, thereby introducing a group R12, preferably a methyl group or an isotope labeled methyl group, in particular –CH₃ or –CD₃. Preferably this reaction is carried out in the presence of a basic organometallic reagent, preferably an alkyllithium compound, alkylmagnesium compound, alkylcopper compound, alkylaluminum compound or alkylzinc compound, such as e.g. a Grignard reagent, more preferably a Grignard reagent, in particular in the presence of CD₃MgI or CH₃MgI. Thus, the method according to the invention, preferably further comprises the step (iv)(A) modifying the carbon atom of the aldehyde group with a nucleophilic group, thereby attaching a group R12 to the carbon atom, preferably a methyl group or an isotope labeled methyl group, in particular –CH₃ or –CD₃, thereby forming a compound of formula (I-3A)

preferably (Ia-3A) OPG₂ OPG₅ OPG Me O N ₆ PG ₃ ₃O O 12 Me N R PG O O P_{G 3} O 1 N₃ N₃ ^OH ….(Ia-3A), wherein R12 is –CH₃ or –CD₃, preferably –CD₃. Thus, the present invention also relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above, as well as to a gentamicin obtained or obtainable by said method, wherein the gentamicin C is preferably gentamicin C2, C2a or C1, the method additionally comprising the step (vi)(A) and (iv)(A). Depending on the further steps, R12 corresponds either to R1 or to R2 in the final gentamicin C (see e.g. Fig.6) obtained or obtainable by the present invention. In case of gentamicins C1 and C2, e.g. R12 corresponds to R1 and in case of gentamicin C2a, R12 corresponds to R2, and wherein preferably this reaction is carried out in the presence of a basic organometallic reagent, preferably an alkyllithium compound, alkylmagnesium compound, alkylcopper compound, alkylaluminum compound or alkylzinc compound, such as e.g. a Grignard reagent, more preferably a Grignard reagent, in particular in the presence of CD₃MgI or CH₃MgI. Method A1 – preferred for gentamicin C2 In case that an, optionally isotope labeled, gentamicin C2, or derivative thereof is prepared, the method further comprises transforming the primary hydroxyl group of compound (I-3A), preferably of compound (Ia-3A), into a leaving group, and preferably reacting thus obtained compound with a nucleophile comprising a nitrogen or 15N atom, such as an optionally isotope labeled amine, optionally isotope labeled ammonia, an optionally isotope labeled hydrazine, an optionally isotope labeled hydrazide or an optionally isotope labeled azide. The term “leaving group” as used in this context of the present invention is denoted to mean a molecular fragment that departs the reacting substrate with a pair of electrons in heterolytic bond cleavage upon reaction of the attached center of the substrate with a nucleophile, such as with an amine group, ammonia, hydrazine, a hydrazide, 15NH₃, or the azide ion. Examples of leaving groups are, inter alia, halogens, sulfonic esters (such as, inter alia, the mesyl and tosyl group or triflate groups) or the like. Thus, the method according to the invention, preferably further comprises the step (v)(A1) transforming the primary hydroxyl group into a leaving group –L to give a compound of formula (I-4A1) OPG₂ OPG₅ 6 91 R R R101 Me O N₃ OPG₆ Me ^N PG₃O R⁷ O _R8 12 R PG₃O O O PG₁ N₃ N₃ ^L (I-4A1), preferably (Ia-4A1) OPG₂ OPG₅ e O N OPG M ₆ PG ₃ ₃O O 12 Me N R PG O O O P_{G 3} ₁ N₃ N₃ ^L ….(Ia-4A1), wherein the leaving group is preferably a sulfonic ester and wherein step (v)(A1) preferably comprises the reaction with a sulfonic acid halide, preferably chloride. More preferably, L is –O-tosyl or –O-mesyl. Thus, the present invention also relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above, wherein the gentamicin C is preferably gentamicin C2, the method additionally comprising the step (v)(A1). Preferably, the reaction is carried out in pyridine. The compound of formula (I)(A1) is preferably reacted with the nucleophile in the presence of a suitable base. Thus, the method according to the invention, preferably further comprises the step (vi)(A1) reacting the compound of formula (I-4A1), preferably (Ia-4A1), with a nucleophile, such as with an optionally isotope labeled amine, optionally isotope labeled ammonia, an optionally isotope labeled hydrazine, an optionally isotope labeled hydrazide or an optionally isotope labeled azide to give a compound of formula (I-5A1)

(I-5A1), preferably (Ia-5A1) OPG₂ OPG₅ Me O N₃ OPG₆ O 12 Me ^N PG₃O R PG O O O PG ₃ ₁ N₃ N₃ Nu … (Ia-5A1), wherein Nu is the attached nucleophile, preferably Nu is selected from the group consisting of -N , -NH , -NH-NH , –N H H 15 15 15 15 15 H 3 2 2 H-N(R )2, –NH-NH(R ), - NH-NH2, - NH- NH2, – NH- N(R )2, –15NH-15NH(RH), –15NH-N(RH) –15NH-NH(RH), 15N-labeled -N , -NH-Me 13 2, 3, , -NH CH3, - 15NH13CH3, -15NH-Me, and -15NH2, with RH being aryl or alkyl, preferably alkyl, wherein the reaction is preferably carried in the presence of a suitable base. The suitable base is preferably an amino group comprising base, most preferably a non- or little nucleophilic base selected from the group consisting of diisopropyethyllamine (DIPEA), triethylamine (TEA), N-methylmorpholine, N-methylimidazole, 1,4-diazabicyclo[2.2.2]octane (DABCO), N-methylpiperidine, N-methylpyrrolidine, 2,6-lutidine, collidine, pyridine, 4- dimethylaminopyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5- diazabicyclo(4.3.0)non-5-en (DBN). Preferably the reaction is carried out in an organic solvent, such as methanol or DMF. The temperature of the reaction is preferably in the range of from 0 to 120 °C, more preferably in the range of from 20 to 85 °C, the temperature may be varied, preferably in the above given ranges, or held essentially constant. Thus, the present invention also relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above, as well as to a gentamicin C obtained or obtainable by said method, wherein the gentamicin C is preferably gentamicin C2, the method additionally comprising the step (v)(A1) and (vi)(A1). Preferably, the method thus further comprises a step (v)(A1). In this step, the protecting groups PG5 and PG6 of compound of formula (I-5A1), preferably (Ia-5A1), are preferably removed, and the resulting diol is preferably transformed into an alkene group, thereby forming a compound of formula (I-6A1)

preferably (Ia-6A1) OPG₂ Me O N P ₃ O 12 Me ^N G₃O R PG PG ₃O O O 1 N₃ N₃ Nu ….(Ia-6A1). Methods to remove the protecting groups PG5 and PG6 and methods to transform the resulting diol to an alkene are known to the skilled person and are not particularly restricted. These methods include, but are not restricted to methods known as Corey–Winter olefin synthesis using e.g. thiocarbonyldiimidazole or thiophosgene and trimethyl phosphite, or conditions as disclosed in Org. Lett. 2000, 2, 25, 4029–4031. Further, the diol may be transformed to the corresponding epoxide, which may then be deoxygenated (see e.g. Org. Synth.1981, 60, 29). The way of removing the protecting group PG5 and PG6 depends on the protecting group used. Suitable methods are known to those skilled in the art. In the preferred case that PG5 and PG6 form together a cyclic group, more preferably a diacetal protecting group, more preferably the

, the deprotection is preferably carried out under acidic conditions, such as with a strong mineral or organic acids, such as with HCl or TFA. The removal of these protecting groups may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent optionally mixed with water, more preferably in a solvent selected from the group consisting of methanol, ethanol, trifluoroethanol (TFE), dichloromethane, 1,2-dichloroethane, DMF, DMSO, NMP, methanol, ethanol, propanol, isopropanol, butanol, s-butanol, t-butanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof, optionally mixed with water, most preferably in dichloromethane and water. Preferably, the removal is carried out at a temperature in the range of from 0 to 40 °C, more preferably in the range of from 10 to 30°C, more preferably at room temperature. During the reaction, the temperature may be varied or held essentially constant. Suitable methods to convert the diol to the alkene group are known to those skilled in the art, and have been described above. Preferably the free hydroxyl groups are transformed into leaving groups (L), such, a sulfonic esters, such as, inter alia, mesyl groups, tosyl groups or triflate group, preferably triflate groups, which are then removed in a further step. Such removal is preferably been carried out using Na₂S₂O₃ in combination with NaI, The removal may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent selected from the group consisting of acetone, acetonitrile, γ-butyrolactone, DMSO, dichloromethane, DMF, DMSO, NMP, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof, preferably in acetone. Preferably, the method according to this preferred embodiment further comprises the step (vii)(A1) converting the azide groups present in the formula (I-6A1), preferably of (Ia-6A1), including group Nu which is selected from the group consisting of is selected from the group consisting of is selected from the group consisting of -N₃, -NH₂, -NH-NH₂, –NH-

15NH-N(RH)_2, –15NH-NH(RH), 15N labeled -N_3, and -15NH₂, with RH being aryl or alkyl, preferably alkyl, to primary amine groups thereby obtaining a compound of formula (I- 7A1)

…. 7A1), with R12 being –CH₃ or –CD₃, preferably –CD₃ and wherein Nu* is –NH₂ or -15NH_2. Preferably, this step is carried out in the presence of a phosphine, such as an alkylphosphine or an arylphosphine, in particular in the presence of PPh₃, TCEP, or PMe₃, preferably PMe₃. Preferably in a further step, the double bond is reduced. Preferably, in this step, conditions are applied in which in the same step PG3 and PG2 are removed. Alternatively, the method comprises a step of reducing the alkene group and at least one step to remove PG3 and PG2. Reduction of the alkene group and optionally removal of PG2 and PG3 gives the optionally isotope labeled PG1 protected gentamicin C2. The reduction is preferably carried out the presence of hydrogen or deuterium employing a suitable catalyst. Thereby, also protecting groups which may be removed under such reductive conditions, may advantageously be removed, such as PG3 and PG2. Thus, preferably, the method according to this second preferred embodiment B further comprises the step (viii)(A1) reducing the compound of formula (I-7A1), preferably of (Ia-7A1), preferably in the presence of hydrogen or deuterium employing a suitable catalyst, thereby preferably also removing PG2 and PG3. PG2 and PG3 are in particular removed in case they are both Bn groups. The reduction is preferably carried out in the presence of hydrogen employing a suitable catalyst. If deuteration is desired, D₂ may be used. The catalyst may be a homogenous or heterogeneous catalyst. In case, a heterogeneous catalyst is used, the catalyst is preferably selected from the group consisting of Pd, Pd/C, Pt or Pt/C, Rh/Al₂O₃, Pd/Al₂O₃, Pt/Al₂O₃, Pd(OH)₂, PtO₂, PdO * (H₂O)_x, Pd/CaCO₃, Pd/BaSO₄, Rh/Al₂O₃ and Ru/Al₂O₃, more preferably the catalyst is a palladium comprising catalyst, more preferably Pd/C. In this case, the reduction of the double bond may be carried out at a temperature of about 0 °C to about 100 °C for about 1 h to about 48 h, such as overnight. The amount of the catalyst used for this reaction to the total amount of the compound of formula (I-7A1) is preferably in the range of from 0.1 mol-% to 100 mol-% preferably 5 mol-% to 10 mol-%, based on the total amount of the compound of formula (I-7A1) in [mol]. As to the solvent used in step (vi)(B), any suitable organic solvent known to those skilled in the art may be used. Preferably, the solvent is selected from the group consisting of acetic acid and water. After having finished the reduction and the removal of PG2 and PG3, preferably PG1 is removed to give the final isotope labeled gentamicin C2. This removal is preferably carried out under basic conditions such as e.g. with KOH, NaOMe, NaOH or Ba(OH)₂ at a temperature of about rt to about 100 °C for about 1 h to about 48 h, such as overnight. It is conceivable that the respective gentamicin C or gentamicin C derivative obtained may be subjected to a suitable work-up. Such work-up may comprise one or more stages wherein preferably at least one stage comprises a purification, such as an extraction and/or a precipitation and/or filtration and/or chromatography. Method A2 – preferred e.g. for gentamicin C1 In case that an, optionally isotope labeled, gentamicin C1, or derivative thereof is prepared, the method A further comprises transforming the primary azide groups of compound (I-3A), preferably of compound (Ia-3A), into primary amine groups. Thus, the method further comprises the step (v)(A2) transforming the primary azide groups of compound (I-3A), preferably of compound (Ia-3A), into primary amine groups to give a compound of formula (I-4A2)

Preferably, this step is carried out in the presence of a phosphine, such as an alkylphosphine or an arylphosphine, in particular in the presence of PPh₃, TCEP, or PMe₃, preferably PMe₃. Thus, the present invention also relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above, wherein the gentamicin C is preferably gentamicin C1, the method additionally comprising the step (v)(A2). Preferably, in a further step, the primary amine groups are protected with a suitable protecting group PG7 to give a compound of formula (I-5A2), such as a compound of formula (Ia-5A2). Preferred protecting groups are known to the skilled person. In particular, PG7 is a Cbz group. Thus, the method according to the invention, preferably further comprises the step (vi)(A2) protecting the primary amine groups to give a compound of formula (I-5A2) OPG₂ OPG₅ PG₇NH 6 91 R 101 R M_e ^O R OPG₆ PG O ⁷ O 8 Me N ₃ R _R 12 R PG₃O O O PG₁ PG ^OH 7NH NHPG₇ (I-5A2), preferably (Ia-5A2) OPG₂ OPG₅ OP Me O PG₇NH G₆ e ^N P O 12 M G₃O R PG P_{G 3}O O O 1 PG₇NH NHPG₇ ^OH ….(Ia-5A2). Preferably in a subsequent step, the method comprises: transforming the secondary hydroxyl group of compound (I-5A2), preferably of compound (Ia-5A2), into a leaving group, and preferably reacting the thus obtained compound with a nucleophile comprising a nitrogen or 15N atom, such as an optionally isotope labeled amine, optionally isotope labeled ammonia, an optionally isotope labeled hydrazine, an optionally isotope labeled hydrazide or an optionally isotope labeled azide. The term “leaving group” as used in this context of the present invention is denoted to mean a molecular fragment that departs the reacting substrate with a pair of electrons in heterolytic bond cleavage upon reaction of the attached center of the substrate with a nucleophile, such as with an amine group, ammonia, hydrazine, a hydrazide, 15NH3, or the azide ion. Examples of leaving groups are, inter alia, halogens, sulfonic esters (such as, inter alia, the mesyl and tosyl group or triflate groups) or the like. Thus, the method according to the invention, preferably further comprises the step (vii)(A2) transforming the primary hydroxyl group into a leaving group –L to give a compound of formula (I-6A2)

(I-6A2), preferably (Ia-6A2) OPG₂ OPG₅ O Me O PG NH PG₆ Me P ₇ O 12 N G₃O R PG G₃O O P O 1 PG₇NH NHPG₇ ^L ….(Ia-6A2), wherein the leaving group is preferably a sulfonic ester and wherein the step preferably comprises the reaction with a sulfonic acid halide, preferably chloride. more preferably, L is –O-tosyl or –O-mesyl. The compound of formula (I-6A2), preferably (Ia-6A2), is preferably then reacted with the nucleophile in the presence of a suitable base. Thus, the method according to the invention, preferably further comprises the step (viii)(A2) reacting the compound of formula (I-6A2), preferably (Ia-6A2), with a nucleophile, such as with an optionally isotope labeled amine, optionally isotope labeled ammonia, an optionally isotope labeled hydrazine, an optionally isotope labeled hydrazide or an optionally isotope labeled azide to give a compound of formula (I-7A2)

…. , wherein Nu is the attached nucleophile, preferably Nu is selected from the group consisting of -N₃, -NH₂, -NH-NH₂, –NH-N(RH)_2, –NH-NH(RH)_, -15NH-NH₂, -15NH-15NH₂, –15NH-15N(RH)_2, –15NH-15NH(RH), –15NH-N(RH)_2, –15NH-NH(RH), 15N labeled -N_3, -NH-Me, -NH13CH₃, - 15NH13CH₃, -15NH-Me and -15NH₂, with RH being aryl or alkyl, preferably alkyl, wherein the reaction is preferably carried in the presence of a suitable base. Preferably, Nu is an 15N labeled azide. The suitable base is preferably an amino group comprising base, most preferably a non- or little nucleophilic base selected from the group consisting of diisopropyethyllamine (DIPEA), triethylamine (TEA), N-methylmorpholine, N-methylimidazole, 1,4-diazabicyclo[2.2.2]octane (DABCO), N-methylpiperidine, N-methylpyrrolidine, 2,6-lutidine, collidine, pyridine, 4- dimethylaminopyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5- diazabicyclo(4.3.0)non-5-en (DBN). Preferably the reaction is carried out in an organic solvent, such as methanol or DMF. The temperature of the reaction is preferably in the range of from 0 to 120 °C, more preferably in the range of from 20 to 85 °C, the temperature may be varied, preferably in the above given ranges, or held essentially constant. Preferably, the method further comprises a step (ix)(A2). In this step, the protecting groups PG5 and PG6 of compound of formula (I-7A2), preferably (Ia-7A2), are preferably removed, and the resulting diol is preferably transformed into an alkene group, thereby forming a compound of formula (I-8A2)

Methods to remove the protecting groups PG5 and PG6 and methods to transform the resulting diol to an alkene are known to the skilled person and are not particularly restricted. These methods include, but are not restricted to methods known as Corey–Winter olefin synthesis using e.g. thiocarbonyldiimidazole or thiophosgene and trimethyl phosphite, or conditions as disclosed in Org. Lett. 2000, 2, 25, 4029–4031. Further, the diol may be transformed to the corresponding epoxide, which may then be deoxygenated (see e.g. Org. Synth.1981, 60, 29). The way of removing the protecting group PG5 and PG6 depends on the protecting group used. Suitable methods are known to those skilled in the art. In the preferred case that PG5 and PG6 form together a cyclic group, more preferably a diacetal protecting group, more preferably the group , the deprotection is preferably carried out under acidic conditions, such as with a strong mineral or organic acids, such as with HCl or TFA. The removal of these protecting groups may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent optionally mixed with water, more preferably in a solvent selected from the group consisting of methanol, ethanol, trifluoroethanol (TFE), dichloromethane, 1,2-dichloroethane, DMF, DMSO, NMP, methanol, ethanol, propanol, isopropanol, butanol, s-butanol, t-butanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof optionally mixed with water, most preferably in dichloromethane and water. Preferably, the removal is carried out at a temperature in the range of from 0 to 40 °C, more preferably in the range of from 10 to 30°C, more preferably at room temperature. During the reaction, the temperature may be varied or held essentially constant. Suitable methods to convert the diol to the alkene group are known to those skilled in the art, and are described above. Preferably the hydroxyl groups are transformed into leaving groups (L), such, a sulfonic ester, such as, inter alia, mesyl groups, tosyl groups or triflate group, preferably triflate groups, which are then removed in a further step. Such removal is preferably been carried out using Na2S2O3 in combination with NaI. The removal may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent selected from the group consisting of acetone, acetonitrile, γ-butyrolacton, DMSO, dichloromethane, DMF, DMSO, NMP, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof, preferably in acetone. In case Nu in the compound of formula I-8A2, preferably (Ia-8A2) is –N₃ or a 15N labeled -N_3, the method preferably further comprises a step (xA2), that is the reduction of the azide and the transformation of the primary amine to a tertiary amine, the compound having the structure (I- 9A2) OPG₂ 101 PG₇NH 6 R 91 R R M_e ^O 8 Me ^N PG₃O R⁷ O _R 12 R PG G ₃O O O P ₁ PG ^N 7NH NHPG₇ (I-9A2), preferably the structure (Ia-9A2)

Step (xA2) is preferably carried out in the presence of benzaldehyde and NaCNBH3 and further in the presence of paraformaldehyde and NaCNBH3. Further, the method preferably comprises the removal of PG2, PG3 and PG7. Reference is made to the respective conditions described in this context above and below. PG2 and PG3 and PG7 are particularly preferably Bn and/or Cbz groups. The removal is preferably carried out via reduction. In this case the additional Bn group on the secondary amine is preferably removed as well. The reduction is preferably carried out in the presence of hydrogen employing a suitable catalyst. If deuteration is desired, D2 may be used. The catalyst may be a homogenous or heterogeneous catalyst. In case, a heterogeneous catalyst is used, the catalyst is preferably selected from the group consisting of Pd, Pd/C, Pt or Pt/C, Rh/Al2O3, Pd/Al2O3, Pt/Al2O3, Pd(OH)2, PtO2, PdO * (H2O)x, Pd/CaCO3, Pd/BaSO4, Rh/Al2O3 and Ru/Al2O3, more preferably the catalyst is a palladium comprising catalyst, more preferably Pd/C. Suitable conditions are already discussed above. Preferably, PG1 is subsequently removed to give the final gentamicin C1 or isotope labeled gentamicin C1. This removal is preferably carried out under basic conditions such as e.g. with KOH, NaOMe, NaOH or Ba(OH)2 at a temperature of about RT to about 100 °C for about 1 h to about 48 h, such as overnight. It is conceivable that the respective gentamicin C or gentamicin C derivative obtained may be subjected to a suitable work-up. Such work-up may comprise one or more stages wherein preferably at least one stage comprises a purification, such as an extraction and/or a precipitation and/or filtration and/or chromatography. Method A3 – e.g. preferred for gentamicin C2a In case that an, optionally isotope labeled, gentamicin C2a, or derivative thereof is prepared, the method A further comprises transforming the primary azide groups of compound (I-3A), preferably of compound (Ia-3A), into primary amine groups. Thus, the method further comprises the step (v)(A3) transforming the primary azide groups of compound (I-3A3), preferably of compound (Ia-3A3), into primary amine groups to give a compound of formula (I- 4A3)

Preferably, this step is carried out in the presence of a phosphine, such as an alkylphosphine or an arylphosphine, in particular in the presence of PPh₃, TCEP, or PMe₃, preferably PMe₃. Thus, the present invention also relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above, wherein the gentamicin C is preferably gentamicin C2a, the method additionally comprising the step (v)(A3). Preferably, in a further step, the primary amine groups are protected with a suitable protecting group PG7 to give a compound of formula (I-5A3), such as a compound of formula (Ia-5A3). Preferred protecting groups are known to the skilled person. In particular, PG7 is a Cbz group. Thus, the method according to the invention, preferably further comprises the step (vi)(A3) protecting the primary amine groups to give a compound of formula (I-5A3) OPG₂ OPG₅ PG₇NH 6 91 R 101 R M_e ^O R OPG₆ PG O ⁷ O 8 Me N ₃ R _R 12 R PG O G ₃O O P ₁ PG NH ^OH 7 NHPG₇ (I-5A3), preferably (Ia-5A3) OPG₂ OPG₅ Me O PG N OPG₆ Me ^N PG ₇ H 3O O 12 R PG G₃O O P O 1 PG₇NH NHPG₇ ^OH ….(Ia-5A3). Preferably PG7 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl and trifluoroacetyl. According to one preferred embodiment, PG7 is Cbz. Preferably, in a further step, the primary alcohol is reacted via a Mitsunobu reaction to yield in a compound of formula (I-6A3)

Preferably, the reaction is carried out in the presence of triphenylphosphine and an azodicarboxylate such as diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD). Typically, the reaction is carried out initially at a temperature in the range of from - 30°C to 0°C, preferably at around −10 °C, typically in THF or toluene and is later heated to reflux. Preferably in a subsequent step, the method comprises: transforming the primary hydroxyl group of compound (I-6A3), preferably of compound (Ia-6A3), into a leaving group, and preferably reacting the thus obtained compound with a nucleophile comprising a nitrogen or 15N atom, such as an optionally isotope labeled amine, optionally isotope labeled ammonia, an optionally isotope labeled hydrazine, an optionally isotope labeled hydrazide or an optionally isotope labeled azide. The term “leaving group” as used in this context of the present invention is denoted to mean a molecular fragment that departs the reacting substrate with a pair of electrons in heterolytic bond cleavage upon reaction of the attached center of the substrate with a nucleophile, such as with an amine group, ammonia, hydrazine, a hydrazide, 15NH₃, or the azide ion. Examples of leaving groups are, inter alia, halogens, sulfonic esters (such as, inter alia, the mesyl and tosyl group or triflate groups) or the like. Thus, the method according to the invention, preferably further comprises the step (vii)(A3) transforming the primary hydroxyl group into a leaving group –L to give a compound of formula (I-7A3)

…. , wherein the leaving group is preferably a sulfonic esters and wherein step (v)(A1) preferably comprises the reaction with a sulfonic acid halide, preferably chloride. more preferably, L is –O-tosyl or –O-mesyl. The compound of formula (I-7A3), preferably (Ia-7A3), is preferably then reacted with the nucleophile in the presence of a suitable base. Thus, the method according to the invention, preferably further comprises the step (viii)(A3) reacting the compound of formula (I-7A3), preferably (Ia-7A3), with a nucleophile, such as with an optionally isotope labeled amine, optionally isotope labeled ammonia, an optionally isotope labeled hydrazine, an optionally isotope labeled hydrazide or an optionally isotope labeled azide to give a compound of formula (I-8A3)

…. , wherein Nu is the attached nucleophile, preferably Nu is selected from the group consisting of -N , -NH , -NH-NH , –NH-N(RH) –NH-NH(RH) 15 15 15 15 15 H 3 2 2 2, , - NH-NH2, - NH- NH2, – NH- N(R )2, –15NH-15NH(RH), –15NH-N(RH) –15NH-NH(RH), 15N labeled -N -NH-Me 13 2, 3, , -NH CH3, - 15NH13CH , -15NH-Me and -15NH , with RH 3 2 being aryl or alkyl, preferably alkyl, wherein the reaction is preferably carried in the presence of a suitable base. The suitable base is preferably an amino group comprising base, most preferably a non- or little nucleophilic base selected from the group consisting of diisopropylethylamine (DIPEA), triethylamine (TEA), N-methylmorpholine, N-methylimidazole, 1,4-diazabicyclo[2.2.2]octane (DABCO), N-methylpiperidine, N-methylpyrrolidine, 2,6-lutidine, collidine, pyridine, 4- dimethylaminopyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo- (4.3.0)non-5-en (DBN). Preferably the reaction is carried out in an organic solvent, such as methanol or DMF. The temperature of the reaction is preferably in the range of from 0 to 120 °C, more preferably in the range of from 20 to 85 °C, the temperature may be varied, preferably in the above given ranges, or held essentially constant. Preferably, the method thus further comprises a step (ix)(A3). In this step, the protecting groups PG5 and PG6 of compound of formula (I-8A3), preferably (Ia-8A3), are preferably removed, and the resulting diol is preferably transformed into an alkene group, thereby forming a compound of formula (I-9A3) OPG₂ 101 PG₇NH 6 R ₉₁ R R Me O 8 Me PG O ⁷ O N ₃ R _R 12 R PG₃O O O PG₁ PG ^Nu 7NH NHPG₇ (I-9A3), preferably (Ia-9A3) OPG₂ Me O PG N PG ₇ H 3O O 12 Me N R PG P_{G 3}O O O 1 PG₇NH NHPG₇ ^Nu ….(Ia-9A3). Methods to remove the protecting groups PG5 and PG6 and methods to transform the resulting diol to an alkene are known to the skilled person and are not particularly restricted. These methods include, but are not restricted to methods known as Corey–Winter olefin synthesis using e.g. thiocarbonyldiimidazole or thiophosgene and trimethyl phosphite, or conditions as disclosed in Org. Lett. 2000, 2, 25, 4029–4031. Further, the diol may be transformed to the corresponding epoxide, which may then be deoxygenated (see e.g. Org. Synth.1981, 60, 29). The way of removing the protecting group PG5 and PG6 depends on the protecting group used. Suitable methods are known to those skilled in the art. In the preferred case that PG5 and PG6 form together a cyclic group, more preferably a diacetal protecting group, more preferably the

, the deprotection is preferably carried out under acidic conditions, such as with a strong mineral or organic acids, such as with HCl or TFA. The removal of these protecting groups may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent optionally mixed with water, more preferably in a solvent selected from the group consisting of methanol, ethanol, trifluoroethanol (TFE), dichloromethane, 1,2-dichloroethane, DMF, DMSO, NMP, methanol, ethanol, propanol, isopropanol, butanol, s-butanol, t-butanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof optionally mixed with water, most preferably in dichloromethane and water. Preferably, the removal is carried out at a temperature in the range of from 0 to 40 °C, more preferably in the range of from 10 to 30°C, more preferably at room temperature. During the reaction, the temperature may be varied or held essentially constant. Preferably the hydroxyl groups are transformed into leaving groups (L), such, a sulfonic ester, such as, inter alia, mesyl groups, tosyl groups or triflate group, preferably triflate groups, which are then removed in a further step. Such removal is preferably been carried out using Na₂S₂O₃ in combination with NaI. The removal may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent selected from the group consisting of acetone, acetonitrile, γ-butyrolacton, DMSO, dichloromethane, DMF, DMSO, NMP, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof, preferably in acetone. Preferably, the method further comprises reduction of the double bond. Preferably, in this step, conditions are applied in which in the same step PG3 and PG2 and PG7 are removed. Alternatively, the method comprises a step of reducing the alkene group and at least one or more steps to remove PG3 and PG2 and PG7. Reduction of the alkene group and optional removal of PG2 and PG3 and PG7 gives the optionally isotope labeled and PG1 protected gentamicin C2a. The reduction is preferably carried out in the presence of hydrogen employing a suitable catalyst. Thereby, also protecting groups which may be removed under such reductive conditions, may advantageously be removed. Thus, preferably, the method according to this second preferred embodiment B further comprises the step (x)(A3) reducing the compound of formula (I-9A3), preferably of (Ia-9A3), preferably in the presence of hydrogen employing a suitable catalyst, thereby preferably also removing PG2 and PG3 and PG7. PG2 and PG3 and PG7 are in particular removed in case they are Bn and/or Cbz groups. The reduction is preferably carried out in the presence of hydrogen employing a suitable catalyst. If deuteration is desired, D₂ may be used. The catalyst may be a homogenous or heterogeneous catalyst. In case, a heterogeneous catalyst is used, the catalyst is preferably selected from the group consisting of Pd, Pd/C, Pt or Pt/C, Rh/Al₂O₃, Pd/Al₂O₃, Pt/Al₂O₃, Pd(OH)₂, PtO₂, PdO * (H₂O)_x, Pd/CaCO₃, Pd/BaSO₄, Rh/Al₂O₃ and Ru/Al₂O₃, more preferably the catalyst is a palladium comprising catalyst, more preferably Pd/C. Suitable conditions are already discussed above. After having finished the reduction and the removal of PG2 and PG3 and PG7, preferably PG1 is removed to give the final isotope labeled gentamicin C2a. This removal is preferably carried out under basic conditions such as e.g. with KOH, NaOMe, NaOH or Ba(OH)₂. It is conceivable that the respective gentamicin C or gentamicin C derivative obtained may be subjected to a suitable work-up. Such work-up may comprise one or more stages wherein preferably at least one stage comprises a purification, such as an extraction and/or a precipitation and/or filtration and/or chromatography. Method A4 – Alternative preferred synthesis of gentamicin C1 According to a further preferred embodiment A4, the primary hydroxyl group of compound (I-

(I-3A), preferably of compound (Ia-3A)

….(Ia-3A), is protected with a suitable protecting group PG4’, preferably followed by a removal of protecting groups PG5 and PG6. The protecting group PG4’ is orthogonal to the other protecting groups present in compound (I-3A), and in compound (Ia-3A), and is preferably selected from the group consisting of SEM, TBS, triethylsilyl (TES), TBDPS, TIPS and allyl. Method 4A is particularly preferable in case, optionally isotope labeled, gentamicin C1, or a derivative thereof shall be prepared. Thus, the method according to the invention, preferably further comprises the step (v)(A4) protecting the hydroxyl group of the compound of formula (I-3A), preferably of compound (Ia-3A), with a protecting group PG4’ selected from the group consisting of SEM, TBS, triethylsilyl (TES), TBDPS, TIPS and allyl, preferably wherein PG4’ is allyl and the protecting group is preferably introduced via reaction of compound (I-3A), preferably of compound (Ia-3A), with NaH and allylbromide to give a compound of formula (I-4A4)

Preferably, the method thus further comprises a step (vi)(A4). In this step, the protecting groups PG5 and PG6 of compound of formula (I-4A4), preferably (Ia-4A4), are preferably removed, and the resulting diol is preferably transformed into an alkene group, thereby forming a compound of formula (I-5A4)

…. . Methods to remove the protecting groups PG5 and PG6 and methods to transform the resulting diol to an alkene are known to the skilled person and are not particularly restricted. These methods include, but are not restricted to methods known as Corey–Winter olefin synthesis using e.g. thiocarbonyldiimidazole or thiophosgene and trimethyl phosphite, or conditions as disclosed in Org. Lett. 2000, 2, 25, 4029–4031. Further, the diol may be transformed to the corresponding epoxide, which may then be deoxygenated (see e.g. Org. Synth.1981, 60, 29). The way of removing the protecting group PG5 and PG6 depends on the protecting group used. Suitable methods are known to those skilled in the art. In the preferred case that PG5 and PG6 form together a cyclic group, more preferably a diacetal protecting group, more preferably the group

, the deprotection is preferably carried out under acidic conditions, such as with a strong mineral or organic acids, such as with HCl or TFA, optionally including formic acid. The removal of these protecting groups may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent optionally mixed with water, more preferably in a solvent selected from the group consisting of methanol, ethanol, trifluoroethanol (TFE), dichloromethane, 1,2-dichloroethane, DMF, DMSO, NMP, propanol, isopropanol, butanol, s-butanol, t-butanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof optionally mixed with water, most preferably in dichloromethane and water. Preferably, the removal is carried out at a temperature in the range of from 0 to 40 °C, more preferably in the range of from 10 to 30°C, more preferably at room temperature. During the reaction, the temperature may be varied or held essentially constant. Preferably the hydroxyl groups are transformed into leaving groups (L), such as sulfonic esters, such as, inter alia, mesyl groups, tosyl groups or triflate group, preferably triflate groups, which are then removed in a further step. Such removal is preferably been carried out using Na2S2O3 in combination with NaI. The removal may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent selected from the group consisting of acetone, acetonitrile, γ-butyrolacton, DMSO, dichloromethane, DMF, DMSO, NMP, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof, preferably in acetone. Preferably in a further step (vii)(A4), the protecting group PG4’ is removed to give the respective free hydroxyl group. Deprotection methods are known to those skilled in the art and are chosen depending on the respective protecting group to be removed. In case, PG4’ is an allyl group, the following deprotection methods are, e.g., conceivable, deprotection with trihaloboranes, deprotection with tert-butyllithium, transition metal-catalyzed, such as Pd- catalyzed, such as with PdCl₂. Preferably after that or in the same reaction step, the double bond is reduced. Preferably, in this step, conditions are applied in which the other protecting groups are not removed and the azide functionalities remains unmodified Advantageously, the reaction is carried out under dry and non-acidic conditions, preferably involving a reduction method that generates and/or operates with diimide as H₂ supplying hydrogenation reagent. Preferably any aryl- or heteroarylsulfonyl hydrazide is used in a dry solvent, preferably at a temperature range of 60-180 °C. More preferably benzenesulfonyl hyrazide is used, preferably at 100-130 °C, more preferably in dry xylenes. Thus, preferably, the method according to this second preferred embodiment B further comprises the step (vii)(A4) - removing the PG4’ and reducing the alkene group to give a compound of formula (I-6A4)

…. 6A4). It is to be understood that step (vii)(A4) may comprise multiple steps and optional work-up procedures. For example, preferably PG4’ is removed prior to the reduction of the double bond in the presence of PdCl2 in MeOH. Preferably in a further step, the hydroxyl group is transformed into a leaving group, which is then preferably reacted with a nucleophile comprising a nitrogen or 15N atom, such as with, optionally isotope labeled amine, preferably with MeNH 13 13 15 15 2, CH3NH2, CH3 NH2 or Me NH2. The term “leaving group” as used in this context of the present invention is denoted to mean a molecular fragment that departs the reacting substrate with a pair of electrons in heterolytic bond cleavage upon reaction of the attached center of the substrate with a nucleophile. Examples of leaving groups are, inter alia, halogens, sulfonic esters (such as, inter alia, the mesyl and tosyl group or triflate group) or the like. Thus, the method according to the invention, preferably further comprises the step (viii)(A4) transforming the primary hydroxyl group into a leaving group –L to give a compound of formula (I-7A4)

wherein the leaving group is preferably a sulfonic ester and wherein (viii)(A4) comprises the reaction with a sulfonic acid halide, preferably chloride. More preferably, L is –O-tosyl or –O-mesyl. The obtained compound is preferably reacted subsequently with the nucleophile in the presence of a suitable base. Thus, the method according to the invention, preferably further comprises the step (ix)(A4) reacting the compound of formula (I-7A4), preferably (Ia-7A4), with a nucleophile, more preferably with MeNH 13 13 15 15 2, CH3NH2, CH3 NH2 or Me NH2, to give a compound of formula (I-8A4)

8A4), wherein Nu is selected from the group consisting of MeNH₂, 13CH₃NH₂, 13CH₃15NH₂ or Me15NH₂, preferably MeNH₂. Preferably the reaction is carried out in a solvent selected from the group consisting of water, methanol, ethanol, trifluoroethanol (TFE), dichloromethane, DMF, DMSO, NMP, propanol, isopropanol, butanol, s-butanol, t-butanol, tetrahydrofuran, 2- methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures thereof. The temperature of the reaction is preferably in the range of from 0 to 120 °C, more preferably in the range of from 20 to 85 °C, the temperature may be varied, preferably in the above given ranges, or held essentially constant. Preferably, the method further comprises transforming the azide grous to amines. Reference is made to the respective conditions described in this context above. Further, the method preferably comprises the removal of PG2 and PG3. Reference is made to the respective conditions described in this context above. Preferably PG1 is subsequently removed to give the final isotope labeled gentamicin C1. This removal is preferably carried out under basic conditions such as e.g. with KOH, NaOMe, NaOH or Ba(OH)₂. Reference is made to the respective conditions described in this context above. It is conceivable that the respective gentamicin C or gentamicin C derivative obtained may be subjected to a suitable work-up. Such work-up may comprise one or more stages wherein preferably at least one stage comprises a purification, such as an extraction and/or a precipitation and/or filtration and/or chromatography. Method B - preferred synthesis of gentamicin C1a According to a second preferred embodiment B, the primary hydroxyl group of compound (I- 1), preferably of compound (Ia-1), is transformed into a leaving group, which is then preferably reacted with a nucleophile comprising a nitrogen or 15N atom, such as with, optionally isotope labeled amine, optionally isotope labeled ammonia, an optionally isotope labeled hydrazine, an optionally isotope labeled hydrazide or an optionally isotope labeled azide. Method B is particularly preferable in case, optionally isotope labeled, gentamicin C1a or derivatives thereof is prepared. The term “leaving group” as used in this context of the present invention is denoted to mean a molecular fragment that departs the reacting substrate with a pair of electrons in heterolytic bond cleavage upon reaction of the attached center of the substrate with a nucleophile, such as with an amine group, hydrazine, a hydrazide, ammonia, 15NH₃, or the azide anion. Examples of leaving groups are, inter alia, halogens, sulfonic esters (such as, inter alia, the mesyl and tosyl group or triflate grousp) or the like. Thus, the method according to the invention, preferably further comprises the step (iii)(B) transforming the primary hydroxyl group into a leaving group –L to give a compound of formula (I-2B)

…. , wherein the leaving group is preferably a sulfonic ester and wherein (iii)(B) comprises the reaction with a sulfonic acid halide, preferably chloride. More preferably, L is –O-tosyl or –O-mesyl. Thus, the present invention also relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above, wherein the gentamicin C is preferably gentamicin C1a, the method additionally comprising the step (iii)(B). Preferably, the reaction is carried out in pyridine. The compound of formula (I-2B) is preferably reacted with the nucleophile in the presence of a suitable base. Thus, the method according to the invention, preferably further comprises the step (iv)(B) reacting the compound of formula (I-2B), preferably (Ia-2B), with a nucleophile, such as with optionally isotope labeled amine, optionally isotope labeled ammonia, an optionally isotope labeled hydrazine, an optionally isotope labeled hydrazide or an optionally isotope labeled azide to give a compound of formula

(I-3B), preferably (Ia-3B)

….(Ia-3B), wherein Nu is the attached nucleophile, preferably Nu is selected from the group consisting of -N , -NH , -NH-NH H H 15 15 3 2 2, –NH-N(R )2, –NH-NH(R ), - NH-NH2, - NH- 15NH , –15NH-15 H 15 15 H 15 H 15 H 15 2 N(R )2, – NH- NH(R ), – NH-N(R )2, – NH-NH(R ), N labeled -N -NH-Me 13 15 13 15 15 H 3, , -NH CH3, - NH CH3, - NH-Me and - NH2, with R being aryl or alkyl, preferably alkyl, and wherein the reaction is preferably carried in the presence of a suitable base. The suitable base is preferably an amino group comprising base, most preferably a base selected from the group consisting of diisopropylethylamine (DIPEA), triethylamine (TEA), N- methylmorpholine, N-methylimidazole, 1,4-diazabicyclo[2.2.2]octane (DABCO), N- methylpiperidine, N-methylpyrrolidine, 2,6-lutidine, collidine, pyridine, 4- dimethylaminopyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5- diazabicyclo(4.3.0)non-5-en (DBN). Preferably the reaction is carried out in an organic solvent, such as methanol, ethanol, trifluoroethanol (TFE), dichloromethane, DMF, DMSO, NMP, propanol, isopropanol, butanol, s-butanol, t-butanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures thereof. The temperature of the reaction is preferably in the range of from 0 to 120 °C, more preferably in the range of from 20 to 85 °C, the temperature may be varied, preferably in the above given ranges, or held essentially constant. Thus, the present invention also relates to a method for the preparation of gentamicin C or a salt or solvate or derivate thereof, preferably of an isotope labeled gentamicin C or a salt or solvate or derivative thereof, as described above, as well as to a gentamicin C obtained or obtainable by said method, wherein the gentamicin C is preferably gentamicin C1a, the method additionally comprising the step (iii)(B) and (iii)(B1). In case Nu is an azide, the formula (I-3B), preferably (Ia-3B), is preferably directly further reacted in step (iv)(B1). In case, Nu is an amine, such as preferably -NH 15 2 or - NH2, the amine is preferably first converted to an azide. Such methods are known to the skilled person and preferably include e.g. the reaction with imidazole-1-sulfonyl azide hydrochloride , CuSO4, K2CO3 in methanol diazo transfer reaction as e.g. disclosed in Org. Lett. 2007, 9(19), 3797– 3800. Further, reactions with ZnCl₂, triethylamine, trifluoromethanesulphonyl chloride and NaN₃ are preferred. Such reactions are preferably carried out in water. Preferably, in this reaction NaN₃ and trifluoromethanesulphonyl chloride are reacted to five trifluoromethanesulphonyl azide, prior to adding this azide to the compound to be reacted with Nu. Preferably, the method thus further comprises a step (iv)(B1). In this step, the protecting groups PG5 and PG6 of compound of formula (I-3B), preferably (Ia-3B), in which Nu is -15N=N₂, - 15N=15N₂ or –N₃ are preferably removed, and the resulting diol is preferably transformed into an alkene group, thereby forming a compound of formula (I-4B)

Methods to remove the protecting groups PG5 and PG6 and methods to transform the resulting diol to an alkene are known to the skilled person and are not particularly restricted. These methods include, but are not restricted to methods known as Corey–Winter olefin synthesis using e.g. thiocarbonyldiimidazole or thiophosgene and trimethyl phosphite, or conditions as disclosed in Org. Lett. 2000, 2, 25, 4029–4031. Further, the diol may be transformed to the corresponding epoxide, which may then be deoxygenated (see e.g. Org. Synth.1981, 60, 29). The way of removing the protecting group PG5 and PG6 depends on the protecting group used. Suitable methods are known to those skilled in the art. In the preferred case that PG5 and PG6 form together a cyclic group, more preferably a diacetal protecting group, more preferably the group

, the deprotection is preferably carried out under acidic conditions, such as with a strong mineral or organic acids, such as with HCl or TFA.. The removal of these protecting groups may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent optionally mixed with water, more preferably in a solvent selected from the group consisting of methanol, ethanol, trifluoroethanol (TFE), dichloromethane, 1,2-dichloroethane, DMF, DMSO, NMP, propanol, isopropanol, butanol, s- butanol, t-butanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof optionally mixed with water, most preferably in dichloromethane and water. Preferably, the removal is carried out at a temperature in the range of from 0 to 40 °C, more preferably in the range of from 10 to 30°C, more preferably at room temperature. During the reaction, the temperature may be varied or held essentially constant. Suitable methods to convert the diol to the alkene group are known to those skilled in the art. Reference is made to the examples disclosed above and below.. Preferably the hydroxyl groups are transformed into leaving groups (L) such as sulfonic esters, such as, inter alia, mesyl groups, tosyl groups or triflate groups, preferably triflate groups, which are then removed in a further step. Such removal is preferably carried out using Na₂S₂O₃ in combination with NaI. Preferably, the reaction is carried out in an organic solvent selected from the group consisting of acetone, acetonitrile, γ-butyrolacton, DMSO, dichloromethane, DMF, DMSO, NMP, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof, preferably in acetone. Preferably, the method according to this second preferred embodiment B further comprises the step (v)(B) converting the azide groups present in the formula (I-4B), preferably of (Ia-4B), including group Nu which is selected from the group consisting of –15N=N₂, –15N=15N₂ or –N₃ to primary amine groups thereby obtaining a compound of formula (I-5B)

(I-5B), preferably of (Ia-5B) OPG₂ Me O H N PG ₂ O Me N ₃O 3 PG O ⁴ O O R R 3 PG₁ H₂ N NH₂ ….(Ia-5B), with R3 being H and R4 being selected from -15NH- and –NH-. Preferably, this step is carried out in the presence of presence of a phosphine, such as an alkylphosphine or an arylphosphine, in particular in the presence of PPh₃, TCEP or PMe₃, preferably PMe_3. Preferably in a further step, the double bond is reduced. Preferably, in this step, conditions are applied in which in the same step PG3 and PG2 are removed. Alternatively, the method comprises a step of reducing the alkene group and at least one step to remove PG3 and PG2. Reduction of the alkene group and optionally removal of PG2 and PG3 gives the optionally isotope labeled PG1 protected gentamicin C1a. The reduction is preferably carried out in the presence of hydrogen employing a suitable catalyst. If deuteration is desired, D₂ may be used. Thereby, also protecting groups which may be removed under such reductive conditions, may advantageously be removed. Such as PG3 and PG2 Thus, preferably, the method according to this second preferred embodiment B further comprises the step (vi)(B) reducing the compound of formula (I-5B), preferably of (Ia-5B), preferably in the presence of hydrogen employing a suitable catalyst, thereby preferably also removing PG2 and PG3. If deuteration is desired, D₂ may be used. PG2 and PG3 are in particular removed in case they are both Bn groups. The reduction is preferably carried out in the presence of hydrogen employing a suitable catalyst. If deuteration is desired, D2 may be used. The catalyst may be a homogenous or heterogeneous catalyst. In case, a heterogeneous catalyst is used, the catalyst is preferably selected from the group consisting of Pd, Pd/C, Pt or Pt/C, Rh/Al2O3, Pd/Al2O3, Pt/Al2O3, Pd(OH)2, PtO2, PdO * (H2O)x, Pd/CaCO3, Pd/BaSO4, Rh/Al2O3 and Ru/Al2O3, more preferably the catalyst is a palladium comprising catalyst, more preferably Pd/C. In this case, the reduction of the double bond may be carried out at a temperature of about 0 °C to about 100 °C for about 1 h to about 48 h, such as overnight. The amount of the catalyst used for this reaction to the total amount of the compound of formula (I-5B) is preferably in the range of from 0.1 mol-% to 100 mol-% preferably 5 mol-% to 10 mol-%, based on the total amount of the compound of formula (I-5B) in [mol]. As to the solvent used in step (vi)(B), any suitable organic solvent known to those skilled in the art may be used. In particular, the solvent is selected from the group consisting of acetic acid and water. If deuteration is desired, acetic acid-D₄ and D₂O may be used. After having finished the reduction and the removal of PG2 and PG3, preferably PG1 is removed to give the final isotope labeled gentamicin C1a is obtained. This removal is preferably carried out under basic conditions such as with KOH, NaOMe, NaOH or Ba(OH)₂. Reference is made to the respective conditions described in this context above. It is conceivable that gentamicin C or the gentamicin derivative obtained may be subjected to a suitable work-up. Such work-up may comprise one or more stages wherein preferably at least one stage comprises a purification, such as an extraction and/or a precipitation and/or filtration and/or chromatography. Method C – e.g. preferred synthesis of gentamicin C2b According to a further preferred embodiment C, the primary hydroxyl group of compound (I- 1), preferably of compound (Ia-1), is protected with a suitable protecting group PG4’, preferably followed by a removal of protecting groups PG5 and PG6. The protecting group PG4’ is orthogonal to the other protecting groups present in compound (I-1), and in compound (Ia-1), and is preferably selected from the group consisting of SEM, TBS, triethylsilyl (TES), TBDPS, TIPS and allyl. Method C is particularly preferable in case, optionally isotope labeled, gentamicin C2b, or a derivative thereof shall be prepared. Thus, the method according to the invention, preferably further comprises the step (iii)(C) protecting the hydroxyl group of the compound of formula (I-1), preferably of compound (Ia-1), with a protecting group PG4’ selected from the group consisting of SEM, TBS, triethylsilyl (TES), TBDPS, TIPS and allyl, preferably wherein PG4’ is allyl and the protecting group is preferably introduced via reaction of compound (I-1) with NaH and allylbromide to give a compound of formula (I-C)

(I-C), preferably (Ia-C)

Preferably, the method thus further comprises a step (iv)(C). In this step, the protecting groups PG5 and PG6 of compound of formula (I-C), preferably (Ia-C), are preferably removed, and the resulting diol is preferably transformed into an alkene group, thereby forming a compound of formula (I-1C)

…. . Methods to remove the protecting groups PG5 and PG6 and methods to transform the resulting diol to an alkene are known to the skilled person and are not particularly restricted. These methods include, but are not restricted to methods known as Corey–Winter olefin synthesis using e.g. thiocarbonyldiimidazole or thiophosgene and trimethyl phosphite, or conditions as disclosed in Org. Lett. 2000, 2, 25, 4029–4031. Further, the diol may be transformed to the corresponding epoxide, which may then be deoxygenated (see e.g. Org. Synth.1981, 60, 29). The way of removing the protecting group PG5 and PG6 depends on the protecting group used. Suitable methods are known to those skilled in the art. In the preferred case that PG5 and PG6 form together a cyclic group, more preferably a diacetal protecting group, more preferably the group , the deprotection is preferably carried out under acidic conditions, such as with a strong mineral or organic acids, such as with HCl or TFA, optionally including formic acid. The removal of these protecting groups may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent optionally mixed with water, more preferably in a solvent selected from the group consisting of methanol, ethanol, trifluoroethanol (TFE), dichloromethane, 1,2-dichloroethane, DMF, DMSO, NMP, propanol, isopropanol, butanol, s-butanol, t-butanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof optionally mixed with water, most preferably in dichloromethane and water. Preferably, the removal is carried out at a temperature in the range of from 0 to 40 °C, more preferably in the range of from 10 to 30°C, more preferably at room temperature. During the reaction, the temperature may be varied or held essentially constant. Suitable methods to convert the diol to the alkene group are known to those skilled in the art. Reference is made to the examples disclosed above and below. Preferably the hydroxyl groups are transformed into leaving groups (L) such as sulfonic esters, such as, inter alia, mesyl groups, tosyl groups or triflate group, preferably triflate groups, which are then removed in a further step. Such removal is preferably been carried out using Na2S2O3 in combination with NaI. The removal may be carried out in any suitable solvent known to those skilled in the art. Preferably, the reaction is carried out in an organic solvent selected from the group consisting of acetone, acetonitrile, γ-butyrolacton, DMSO, dichloromethane, DMF, DMSO, NMP, tetrahydrofuran, 2-methyltetrahydrofuran, methyltertbutylether, diethylether, diisopropylether, toluene, acetonitrile and mixtures of two or more thereof, preferably in acetone. Preferably in a further step (v)(C), the protecting group PG4’ is removed to give the respective free hydroxyl group. Deprotection methods are known to those skilled in the art and are chosen depending on the respective protecting group to be removed. In case, PG4’ is an allyl group, the following deprotection methods are, e.g., conceivable, deprotection with trihaloboranes, deprotection with tert-butyllithium, transition metal-catalyzed, such as Pd-catalyzed, such as with PdCl₂. Preferably after that or in the same reaction step, the double bond is reduced. Preferably, in this step, conditions are applied in which the other protecting groups are not removed and the azide functionalities remain unmodified. Advantageously, the reaction is carried out under dry and non-acidic conditions, preferably involving a reduction method that generates and/or operates with diimide as H₂ supplying hydrogenation reagent. Preferably any aryl- or heteroarylsulfonyl hydrazide is used in a dry solvent, preferably at a temperature range of 60-180 °C. More preferably benzenesulfonyl hydrazide is used, preferably at 100-130 °C, more preferably in dry xylenes. Thus, preferably, the method according to this second preferred embodiment B further comprises the step (v)(C) - removing the PG4’ and reducing the alkene group to give a compound of formula (I-2C)

Preferably, the method further comprises a step (vi)(C) of transforming the group –CH₂-OH into the group –R11(R1R2)-R4-R3, with R11 being C, preferably with -R11(R1R2)- being –CH₂- and R3 and R4 being as described above. In this step the primary hydroxyl group of compound (I-2C), preferably of compound (Ia-2C), is transformed into a leaving group, and the thus obtained compound is preferably reacted with a nucleophile HR4-R3, preferably H-NH-R3 or H-15NH-R3, with R3 being more preferably –CH₃, –13CH₃, –13CD₃ or –CD₃. The term “leaving group” as used in this context of the present invention is denoted to mean a molecular fragment that departs the reacting substrate with a pair of electrons in heterolytic bond cleavage upon reaction of the attached center of the substrate with a nucleophile, such as with an amine group, ammonia, hydrazine, a hydrazide, 15NH₃, or the azide anion. Examples of leaving groups are, inter alia, halogens, sulfonic esters (such as, inter alia, the mesyl and tosyl group or triflate groups) or the like. In step (vi)(C) preferably the compound of formula (I-3C) OPG₂ 6 91 R 101 R R 1 Me O N₃ R 2 PG₃O ⁷ O 8 R Me ^N R R PG 4 3 3O O PG₁ R R N₃ O N3 (I-3C), more preferably (Ia-3C) OPG₂ 1 R 2 R Me O N e P ₃ O M N G₃O 4 3 R R PG O O G ₃ O P ₁ N₃ N₃ ….(Ia-C3), is obtained, with -C(R1R2)- being –CH₂-. In this step the primary hydroxyl group of compound (I-C2), preferably of compound (Ia-C2), is thus transformed into the -R4-R3, with –R4-R3 being preferably H-NH-R3 or H-15NH-R3, and with R3 being more preferably –CH₃, –13CH₃, –13CD₃ or –CD₃. Preferably, the method according to this third preferred embodiment C further comprises (vi)(C) converting the azide groups present in the formula (I-C3), preferably of (Ia-C3), to primary amine groups thereby obtaining a compound of formula (I-4C), preferably of (Ia- 4C) and removal of the remaining protecting groups to give the compound of formula (I-5C)

–R4-R3 being preferably H-NH-R3 or H-15NH-R3, and with R3 being more preferably –CH3, – 13CH 13 3, – CD3 or –CD3. Methods to convert azides to amine groups and deprotection methods are known to those skilled in the art and are not particular restricted. It is to be understood that (vi)(C) may be carried out in one step or in multiple steps. Preferably, first the azides are converted to amines, then PG1 and PG2 are removed and finally PG1 is removed. Preferred methods therefore are already described in the preferred embodiments A and B described above which may also be applied in step (vi)(C). Use of compositions comprising gentamicin C (a) Pharmaceutical composition The present invention also relates to a pharmaceutical composition comprising a gentamicin C according to the present invention and a pharmaceutically acceptable excipient. The term ”pharmaceutical composition” as used herein refers to a composition to be applied for medical uses. Said composition shall comprise a gentamicin C according to the present invention and a pharmaceutically acceptable excipient. The said composition, depending on the envisaged medical use, may also comprise further ingredients. The pharmaceutical composition of the invention shall provide upon administration to a subject a therapeutically effective dose of a gentamicin C according to the present invention. This may be achieved as a result of a bolus administration, i.e. administration one times, or as a result of separate or continuous administrations. The pharmaceutical composition is, preferably, for topical or systemic administration. Conventionally, the pharmaceutical composition may be administered orally, intra-muscular, into the blood or subcutaneous. However, depending on the nature and the desired therapeutic effect and the mode of action, the pharmaceutical composition may be administered by other routes as well. The pharmaceutical composition is, preferably, administered in conventional dosage forms prepared by combining the ingredients with standard pharmaceutically acceptable excipients according to conventional procedures. These procedures may involve mixing or dissolving the ingredients as appropriate to the desired preparation. Preferably, a solution is envisaged. It will be appreciated that the form and character of the pharmaceutical acceptable excipient is dictated by the amount of active ingredient with which it is to be combined, the route of administration and other well-known variables. An excipient must be acceptable in the sense of being compatible with the other ingredients of the formulation and being not deleterious to the recipient thereof. The pharmaceutically acceptable excipient employed may include a solid carrier, a gel, or a liquid carrier. Examples for solid carriers are lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, stearic acid and the like. Exemplary of liquid carriers are phosphate buffered saline solution, syrup, oil, water, emulsions, various types of wetting agents, distilled water, physiological saline, Ringer's solutions, dextrose solution, and Hank's solution, and the like. Similarly, the carrier may include time delay material well known to the art, such as glyceryl mono-stearate or glyceryl distearate alone or with a wax. Said suitable carriers comprise those mentioned above and others well known in the art, see, e.g., Remington´s Pharmaceutical Sciences, 23rd Edition - October 30, 2020, Mack Publishing Company, Easton, Pennsylvania. In addition, the pharmaceutical composition may also include other ingredients such as adjuvants or non-toxic, non-therapeutic, non-immunogenic stabilizers and the like. A therapeutically effective dosage refers to an amount of the gentamicin C to be used in pharmaceutical composition which elicits a desired therapeutic effect, e.g., which cures the bacterial infection in a subject. Therapeutic efficacy and toxicity of a compound can be determined by standard pharmaceutical procedures, e.g., ED50 (the dose therapeutically effective in 50 % of the population) and LD50 (the dose lethal to 50 % of the population). The dose ratio between therapeutic and toxic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED50. The dosage regimen will be determined by the attending physician and other clinical factors. As is well known in the medical arts, dosages for any one patient depend upon many factors, including the patient's size, body surface area, age, the particular compound to be administered, sex, time and route of administration, general health, and other drugs being administered concurrently. Progress can be monitored by periodic assessment. The pharmaceutical composition according to the present invention may also comprise drugs or other ingredients which are added to the medicament during its formulation. Finally, it is to be understood that the formulation of a pharmaceutical composition takes place under GMP standardized conditions or the like in order to ensure quality, pharmaceutical security, and effectiveness of the medicament. The pharmaceutical composition of the present invention may by therapeutically applied in various medical fields and, in particular, for treating bacterial infection. Typical medical use cases are described elsewhere herein in more detail. The invention further relates to a kit comprising a gentamicin C according to the invention, and a container. The term “kit” as used herein refers to a collection of the aforementioned component provided in a container. The container also typically comprises instructions for using the gentamicin C according to the invention. Moreover, the kit may, usually, comprise further components such as agents required for applying said gentamicin C in any use described herein. The present invention also relates to a method of treating a bacterial infection in a subject in need thereof, comprising administering to the subject a gentamicin C according to the invention, or a pharmaceutical composition of the invention. Moreover, it will be understood that the present invention also relates to isotope labeled gentamicin C or a salt or solvate or derivative thereof according to the invention, or pharmaceutical composition of the invention for use in treating a bacterial infection in a subject in need thereof. The term “bacterial infection” as used herein refers to a process where bacteria enter the body of a subject and subsequently increase in number and, typically, cause an inflammatory reaction in the body. Bacteria may enter into the body via different routes such as respiratory route, pharyngeal route, blood system, including wounds or gastrointestinal rout. Typically, a bacterial infection may be associated with various symptoms such as fatigue, fever, swollen lymph nodes, headache, respiratory problems, gastrointestinal problems, nausea and/or vomiting. Bacterial infection may be caused by pathogenic bacteria. Pathogenic bacteria are specially adapted and endowed with mechanisms for overcoming the normal body defense mechanisms and can invade parts of the body, such as the blood, where bacteria are normally not found. Pathogenic bacteria may also intrude the surface epithelium, skin or mucous membrane and many travel to other locations within the body. In rare cases, pathogenic bacteria can infect an entirely healthy person, but infection usually occurs only if the body's defense mechanisms are impaired. Such an impairment may be caused by trauma or an underlying debilitating disease, such as wounding, intoxication, chilling, fatigue, and malnutrition. Pathogenic bacteria can be typically grown in cultures and can be identified by using the gram staining technique. Bacteria are subdivided into gram-positive and gram-negative bacteria according to this technique. Preferably, said bacterial infection in accordance with the present invention is an infection with gram-negative bacteria. More preferably, said gram-negative bacteria are selected from the group consisting of: Haemophilus influenza, Shigella sp., Escherichia coli, Enterobacter, Klebsiella, Proteus, Pseudomonas aeruginosa, Citrobacter, Serratia, and Yersinia enterocolitica. The term “treating” as used herein refers to any improvement or amelioration of bacterial infection or symptom thereof as referred to herein. However, more preferably, treating means that bacterial infection is cured. It will be understood that treatment may not occur in 100 % of the subjects to which the composition has been administered. The term, however, requires that the treatment occurs in a statistically significant portion of subjects (e.g. a cohort in a cohort study). Whether a portion is statistically significant can be determined without further ado by a person skilled in the art using various well-known statistic evaluation tools, e.g., determination of confidence intervals, p-value determination, Student´s t-test, Mann-Whitney test etc. Details are found in Dowdy and Wearden, Statistics for Research, John Wiley & Sons, New York 1983. Preferred confidence intervals are at least 90 %, at least 95 %, at least 97 %, at least 98 % or at least 99 %. The p-values are, preferably, 0.05, 0.01, 0.005, 0.001, or 0.0001. The term “subject” as used herein refers to animals including laboratory animals such as rodents, pet, farming animals or primates. More typically, the subject referred to herein is a mammal and, preferably a human. Preferably, the subject suffers from renal failure. Renal failure as used herein refers to an impairment of renal function in a subject. Typically, renal failure is characterized by 15 % or less function of the kidney compared to a healthy control. Kidney function is typically investigated by measuring the glomerular filtration rate (GFR). Renal failure as meant herein typically has severe consequences for the subject suffering therefrom such as volume overload, uremia, high potassium levels in the blood. Renal failure may be acute or chronic renal failure. The term “administering” as used herein refers to applying the non- or isotope labeled gentamicin C or a salt or solvate or derivative thereof to the subject to be treated such that it can exert its therapeutic effects. To this end, the non- or isotope labeled gentamicin C or a salt or solvate or derivative thereof is, typically, introduced into the body either systemically or topically. Routes of administration are well known to the skilled person and include those mentioned elsewhere herein. Preferably, said non- or isotope labeled gentamicin C or a salt or solvate or derivative thereof is to be administered systemically. Also preferably, said non- or isotope labeled gentamicin C or a salt or solvate or derivative thereof is to be administered topically, preferably, for ophthalmic administration. (b) Diagnostic composition Yet, the present invention also relates to a diagnostic composition comprising an isotope labeled gentamicin C according to the present invention and a suitable excipient. The term "diagnostic composition" as used herein refers to a composition for identifying the presence or absence of at least one gentamicin C congener said composition comprising at least one isotope labeled gentamicin C. Yet, the present invention also provides for the use of at least one isotope labeled gentamicin C according to the invention or a salt or solvate or derivative as calibration standard for determining the amount or the presence of at least one analyte of interest, preferably of at least gentamicin C congener, present in a sample. The term “sample” as used in this context refers to any portion of material comprising or suspected to comprise at least one gentamicin C congener. Said sample may be typically a liquid sample from a solution comprising or suspected to comprise said at least one gentamicin C congener. Such solutions are typically made or occur as artificial samples, e.g., during manufacturing processes or as biological or as clinical samples which include but are not limited to fluid samples such as blood, serum, plasma, synovial fluid, spinal fluid, urine, saliva, and lymphatic fluid, or solid biological or clinical samples such as dried blood spots and tissue extracts. Further examples of biological or clinical samples are cell cultures or tissue cultures. Preferably, the sample is obtained from biological or clinical samples which include but are not limited to fluid samples such as blood, serum, plasma, synovial fluid, spinal fluid, urine, saliva, and lymphatic fluid, or solid biological or clinical samples such as dried blood spots and tissue extracts. The term “determining” as used in this context refers to determining the presence or absence and/or the of at least one gentamicin C congener. Further, this term refers to determining the amount of at least one present gentamicin C congener. Thus, determining as used herein encompasses qualitative as well as quantitative determinations. Quantitative determination includes determining the absolute amount as well as relative amounts. In principle any detection method may be used for determining the amount of at least one gentamicin C congener. Such detection techniques are well known in the art. Determining the amount in the method of the present invention may thus be carried out by any technique which allows for detecting the presence or absence or the amount of the respective congener(s). Preferably, the amount is determined via mass spectroscopy (MS), more preferably MRM- based MS. Further, the present invention relates to at least one isotope labeled gentamicin C, as described above, or a salt or solvate or derivative thereof, for use as calibration standard or as internal standard for determining the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample The at least one internal standard can be added to the sample. Typically, an “internal standard“ (ISTD) is a known amount of a substance which exhibits similar properties as the analyte of interest when subjected to the mass spectrometric detection workflow (i.e. including any pre- treatment, enrichment and actual detection step). Although the ISTD exhibits similar properties as the analyte of interest, it is still clearly distinguishable from the analyte of interest. Exemplified, during ion mobility separation, the ISTD has the same ion size but different m/z ratio than the analyte of interest. Preferably the internal standard is in its ion size not distinguishable from the analyte but different in the m/z ratio. Thus, both the analyte and the ISTD enter the mass spectrometer at the same time. The ISTD however, exhibits a different molecular mass than the analyte of interest from the sample. This allows a mass spectrometric distinction between ions from the ISTD and ions from the analyte by means of their different mass/charge (m/z) ratios. Both are subject to fragmentation and provide daughter ions. These daughter ions can be distinguished by means of their m/z ratios from each other and from the respective parent ions. Consequently, a separate determination and quantification of the signals from the ISTD and the analyte can be performed. Since the ISTD has been added in known amounts, the signal intensity of the analyte from the sample can be attributed to a specific quantitative amount of the analyte. Thus, the addition of an ISTD allows for a relative comparison of the amount of analyte detected, and enables unambiguous identification and quantification of the analyte(s) of interest present in the sample when the analyte(s) reach the mass spectrometer. Typically, but not necessarily, the ISTD as used within the meaning of the present invention is an at least via one isotope labeled gentamicin C which is added to the sample and which is determined (i.e. the amount of the internal standard compound is determined). Thus, the internal standard is preferably not naturally present in the sample to be tested. The internal standard can be dissolved in a suitable solvent. Further, the present invention relates to a method of determining the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample said method comprising (a) mixing the sample with a known amount of at least one isotope labeled gentamicin C, as described above, or a salt or solvate or derivative thereof (b) analyzing the sample via a mass spectrometry (c) comparing the peak area of at least one analyte of interest to a standard curve, wherein said standard curve has been created using the at least one isotope labeled gentamicin C or a salt or solvate or derivative, as described above and standards containing at least one analyte of interest, thereby determining the amount of the at least one analyte of interest in the sample. Preferably, the sample according to (a) is mixed with a predefined amount of the isotope labeled gentamicin C according to (b) prior to analyzing the sample via mass spectrometry. In a preferred embodiment, step (c) comprises (c1) analyzing the sample mixed with the ISTD via mass spectrometry, and (c2) comparing the peak area of at least one analyte of interest to a standard curve, wherein said standard curve has been created using the at least one isotope labeled gentamicin C or a salt or solvate or derivative, as described above and standards containing at least one analyte of interest, (c3) calculating the amount of the at least one analyte of interest in the sample. Preferably, the mass spectrometry is MRM-based (multi reaction monitoring) mass spectrometry. Further, the present invention also relates to a computer-implemented method for assessing a sample comprising at least one gentamicin congener, the method comprising the steps of: (aa) mixing the sample with a known amount of at least one isotope labeled gentamicin C, as described above, or a salt or solvate or derivative thereof, and receiving the value for the peak area of said isotope labeled gentamicin C in a sample (bb) receiving a value for the peak area of at the least one gentamicin C congeners present in the sample, (cc) comparing the values for the peak area of the at least one isotope labeled gentamicin C and the at the least one gentamicin C congeners and receiving a value for the amount of at least one gentamicin C congener; and (dd) assessing the sample on the comparison and/or the calculation made in step (cc). The term “computer-implemented” as used herein means that the method or individual steps thereof is/are carried out in an automated fashion on a data processing unit which is, typically, comprised in a data processing device such as a computer. The data processing unit shall receive values for the amount of the analyte of interest that is the gentamicin C congeners present in the sample. Such values can be the amounts, relative amounts or any other calculated value reflecting the amount as described elsewhere herein in detail. The term “comparing” as used herein encompasses comparing the determined amount of the at least one congeners as referred to herein with the isotope labeled gentamicin C as reference. It is to be understood that comparing as used herein refers to any kind of comparison made between the chosen value for the amount with the reference. The comparison may be carried out manually or computer assisted. The value of the amount and the reference can be, e.g., compared to each other and the said comparison can be automatically carried out by a computer program executing an algorithm for the comparison. The computer program carrying out the said evaluation will provide the desired assessment in a suitable output format. The present invention also, in principle, contemplates a computer program, computer program product or computer readable storage medium having tangibly embedded said computer program, wherein the computer program comprises instructions which, when run on a data processing device or computer, carry out the method of the present invention as specified above. Further, the present invention relates to a diagnostic system, preferably a clinical diagnostic system, suitable to perform a method of determining the presence or the amount of at least one analyte of interest, preferably of the at least one gentamicin C congener, present in a sample, said method comprising the steps (a), (b) and (c), as described above. Yet, the invention relates to the use of the diagnostic system, described above, for determining the presence or the amount of the at least one analyte of interest in the sample. Summarizing the findings of the present invention, the following embodiments are preferred: 1. An isotope labeled gentamicin C or a salt or solvate or derivative thereof, the gentamicin C comprising at least one 13C, D and/or 15N atom. 2. The isotope labeled gentamicin C according to embodiment 1, wherein the gentamicin C is an isotope labeled gentamicin C selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a. 3. The isotope labeled gentamicin C according to embodiment 1, having the structure

or a salt or solvate thereof, wherein R1, R2 and R3 are, independently of each other, selected from the group consisting of - H, -D, -CH3, -13CH3, -13CDH2, -13CD2H, -13CD3, -CDH2, -CD2H and -CD3, wherein at least one of R1 or R2 is -H or -D, R4 is selected from the group consisting –NH-, -ND-, -15ND- and -15NH-, R5 is selected from the group consisting of –NH 15 15 15 2, -ND2, - ND2, - NDH and - _NH2, R6, R7 and R8 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R9 and R10, are, independently of each other, selected from the group consisting of –CH -, -CDH-, -CD -, -13CDH-, -13CD 13 2 2 2- and - CH2- and wherein R11 is C or 13C. 4. The isotope labeled gentamicin C according to embodiment 3, wherein R1 is selected from the group consisting of -CH 13 13 13 13 3, - CH3, - CDH2, - CD2H, - CD3, -CDH2, -CD2H and -CD3, preferably wherein R1 is –CD3. 5. The isotope labeled gentamicin C according to embodiment 4, wherein R2 and R3 are, independently of each other, -H or –D. 6. The isotope labeled gentamicin C according to embodiment 4, wherein R2 is -H or –D and R3 selected from the group consisting of -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CDH₂, -CD₂H and -CD₃, preferably wherein R3 is –CD₃. 7. The isotope labeled gentamicin C according to embodiment 3, wherein R1 is –H or -D. 8. The isotope labeled gentamicin C according to embodiment 7, wherein R2 and R3 are, independently of each other, -H or –D. 9. The isotope labeled gentamicin C according to embodiment 7, wherein R2 is -H or –D and R3 is selected from the group consisting of -CH₃, -13CH₃, -13CDH₂, -13CD₂H, - 13CD₃, -CDH₂, -CD₂H and -CD₃, preferably wherein R3 is –CD₃. 10. The isotope labeled gentamicin C according to embodiment 7, wherein R3 is -H or –D and R2 is selected from the group consisting of -CH₃, -13CH₃, -13CDH₂, -13CD₂H, - 13CD₃, -CDH₂, -CD₂H and -CD₃, preferably wherein R2 is –CD₃. 11. The isotope labeled gentamicin C according to embodiment 3, having the structure

. 12. The isotope labeled gentamicin C according to embodiment 11, wherein R11 is C. 13. The isotope labeled gentamicin C according to embodiment 11 or 12, wherein one of R1 is –CD₃ and R2 is H, and wherein the group –R4-R3 is –NH₂ (in other words, R4 is –NH_ and R3 is H). 14. The isotope labeled gentamicin C according to embodiment 11 or 12, wherein one of R1 is –CD₃ and R2 is H, and wherein –R4 is -15NH- and –R3 is -13CH₃. 15. The isotope labeled gentamicin C according to embodiment 11 or 12, wherein one of R1 is –CD₃ and R2 is H, and wherein R4 is -NH- and R3 is -CH₃. 16. The isotope labeled gentamicin C according to embodiment 11 or 12, wherein one of R1 is H and R2 is –CD₃ and, and wherein R4 is -NH- and R3 is -H. 17. The isotope labeled gentamicin C according to embodiment 11 or 12, wherein one of R1 is -H and R2 is -H and, and wherein R4 is -NH- and R3 is –CD₃. 18. The isotope labeled gentamicin C according to embodiment 4, having the structure

19. The isotope labeled gentamicin C according to embodiment 18, wherein R11 is C. 20. The isotope labeled gentamicin C according to embodiment 18 or 19, wherein R10 is - CDH- and R9 is –CDH-. 21. The isotope labeled gentamicin C according to any one of embodiments 18 to 20 having

selected from the group consisting of

D OH D 1 R O 2 H₂ N R H N O R11 3 4 R H O H O R O O H₂ N NH₂ OH D D 1 R O 2 H₂ N R O 11 3 H N H O R 4 R H O R O O H₂ N NH₂ and mixtures thereof, preferably wherein the structure is

. 22. The isotope labeled gentamicin C according to any one of embodiments 18 to 21, wherein R1 and R2 are both -H, and wherein –R4 is -15NH- and -R3 is -H. 23. The isotope labeled gentamicin C according to any one of embodiments 1 to 22, wherein the gentamicin C is present as trifluoroacetic acid salt. 24. The isotope labeled gentamicin C according to any one of embodiments 1 to 23, is a substantially pure congener comprising less than 1.0 weight-% of other gentamicin C congeners. 25. A compound of formula (I*)

preferably of formula (I) OPG₂ OPG₅ 6 91 R 101 R Me O N₃ R OPG 8 ₆ Me ^N PG₃O R⁷ O _R PG₃O O O OPG₄ P^G1 N₃ N_{3 (I),} wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, - 13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, and wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein PG1 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, PG4 is a silyl protecting group, a pivaloyl group (Piv)or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert- butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group, preferably wherein the compound has the structure (Ia)

preferably of formula (I)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH 13 13 2-, -CD2-, -CHD-, - CD2-, - CH2-, - 13CHD-, and –R11(R1R2)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH, -13CH, -13CDH, -13 13 3 3 2 CD2H, - CD3, -CD2H, -CDH, and -CD, wherein at 1 2 11 2 3 least one of R or R is -H or -D, and wherein R is C or 13C, and wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein PG1 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, PG4 is a silyl protecting group, a pivaloyl group (Piv)or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert- butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group, preferably wherein the compound has the structure (Ia)

the compound of formula (I*), the compound of formula (I) and the compound of formula (Ia) each comprising at least one 13C, D and/or 15N atom. 27. The compound of embodiment 25 or 26, wherein PG4 is benzoyl (Bz). 28. The compound of any one of embodiments 25 to 27, wherein PG5 and PG6 form together the group

. 29. The compound of any one of embodiments 25 to 28, wherein PG3 is Bn. 30. The compound of any one of embodiments 25 to 29, wherein PG2 is Bn. 31. The compound of any one of embodiments 25 to 30, wherein PG1 is para- trifluoromethyl-benzoyl. 32. The compound of embodiment 25 or of embodiment 26 having the structure

preferably the structure (Ic). The compound of any one of embodiments 25 to 29, wherein PG1 and PG2 form together a cyclic urethane group, preferably wherein the compound has the structure ^Me O Me _Me

The compound of embodiment 33 having the structure (If)

Use of a compound according to any one of embodiments 25 to 34 for the preparation of gentamicin C or salt or solvate thereof, wherein the gentamicin C is preferably selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a, more preferably of a gentamicin C according to any one of embodiments 1 to 26. Method for the preparation of gentamicin C or a salt or solvate or derivate thereof, wherein the gentamicin C is preferably selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a, and wherein the gentamicin C is preferably isotope labeled, the method comprising an (A) of formula

with a glycosylation donor (B*) of formula

to give a compound having the structure (I*)

preferably of formula (I) OPG₂ OPG₅ 6 91 R 1 R R 01 Me O N₃ ⁷ OPG 8 ₆ Me ^N PG₃O R O _R PG₃O O O OPG₄ P^G1 N₃ N_{3 (I),} wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, - 13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein PG1 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert- butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group, preferably wherein the donor building block has the structure

and wherein reacting the glycosylation donor (B) with the glycosylation acceptor (A) gives a compound having the structure (Ia)

(Ia). Method for the preparation of gentamicin C or a salt or solvate or derivate thereof, wherein the gentamicin C is preferably selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a, and wherein the gentamicin C is isotope labeled and comprises at least one 13C, D and/or 15N atom, the method comprising (ii) an (A) of formula

with a glycosylation donor (B*) of formula

preferably of formula (B) OPG₅ 6 91 R 101 R ClC N₃ R 7 8 OPG₆ R O _R O OPG₄ H^N _(B), to give a compound having the structure (I*)

preferably of formula (I)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH -, -CD -, - 13 13 2 2 CHD-, - CD2-, - CH2-, - 13CHD-, and –R11(R1R2)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH 13 13 13 13 3, - CH3, - CDH2, - CD2H, - CD3, -CD2H, -CDH , and -CD , wherein at least one 1 2 11 2 3 of R or R is -H or -D, and wherein R is C or 13C, wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein PG1 is a protecting group selected from the group consisting of benzyloxycarbonyl (Cbz), benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert- butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group, preferably wherein the donor building block has the structure

(Ia). 38. The method of embodiment 36 or 37, wherein PG4 is benzoyl (Bz). 39. The method of any one of embodiments 36 to 38, wherein PG5 and PG6 form together the group . The method of any one of embodiments 36 to 39, wherein PG3 is Bn and PG2 is Bn. The method of any one of embodiments 36 to 40, wherein PG1 is para- trifluoromethylbenzoyl. The method of embodiment 36 or 37, the glycosylation acceptor (A) having the structure

and the glycosylation donor (B) having the structure (B1)

more preferably, the structure (B2)

with PG4 being even more preferably Bz. The method of embodiment 42, the glycosylation donor (B) having the structure (B2) and the compound of formula (I) having the structure

. The method of embodiment 36 or 37, the glycosylation acceptor (A) having the structure

_, the glycosylation donor (B) having the structure (B1)

more preferably, the structure (B2)

with PG4 being preferably Bz, and wherein glycosylation donor (B) preferably has the structure (B2) with PG4 being Bz and the compound of formula (I) having the structure . The method according to any one of embodiments 36 to 44, the method further comprising (ii) removing the protecting group PG 4 to give a compound of formula (I-1*)

more preferably of formula (Ia-1)

The method according to any one of embodiments 36 to 44, the method further comprising (iii) removing the protecting group PG 4 to give a compound of formula (I-1*) OPG₂ OPG₅ 6 91 R 1 R R01 Me O N PGO ₃ OPG 7 O _R8 ₆ 011 Me ^N ₃ R R PG₃O O O OH PG₁ N₃ N₃ (I-1*), preferably of formula (I-1) OPG₂ OPG₅ 6 91 R 101 R Me O N R OPG₆ PG ₃ ⁷ O 8 Me N ₃O R _R OH PG₃O O O PG₁ N₃ N₃ (I-1), more preferably of formula (Ia-1)

wherein formula (I-1*), formula (I-1) and formula (Ia-1) each have at least one 13C, D and/or 15N atom. The method according to embodiment 45 or 46, further comprising (iii)(A) reacting the compound of formula (I-1*), preferably of formula (I-1), preferably (Ia-1) with an oxidizing agent to give a compound of formula (I-2A)

_(I-2A), preferably (Ia-2A) OPG₂ OPG₅ Me O N OPG₆ Me PG ₃ O N ₃O O PG P^G ₃O O O 1 N₃ N_{3 ….(Ia-2A).} 48. The method according to embodiment 47, further comprising (iii)(A1) modifying the carbon atom of the aldehyde group of structure (I-2A) or more preferably of (Ia-2A) with a nucleophilic group, thereby attaching a group R12 to the carbon atom, preferably a methyl group or an isotope labeled methyl group, in particular –CH3 or –CD3, thereby forming a compound of formula (I-3A)

The method according to embodiment 45 or 46, further comprising (iii)(B) transforming the primary hydroxyl group into a leaving group –L to give a compound of formula (I-2B)

(I-2B), preferably (Ia-2B) OPG₂ OPG₅ Me O N₃ OPG₆ O Me N PG₃O L PG₃O O O PG₁ N₃ N₃ ….(Ia-2B), wherein the leaving group is preferably a halogen or sulfonic ester, and wherein (iii)(B) comprises the reaction with a sulfonic acid halide, preferably chloride. The method according to embodiment 49, further comprising (iii)(B1) reacting the compound of formula (I-2B), preferably (Ia-2B), with a nucleophile, such as with an amine, ammonia, 15NH3, a hydrazine, hydrazide or an azide, to give a compound of formula (I-3B)

…. , wherein Nu is the attached nucleophile, preferably Nu is selected from the group consisting of is selected from the group consisting of -N₃, -NH₂, -NH-NH₂, –NH-

15NH-N(RH)_2, –15NH-NH(RH), 15N labeled -N_3, -NH-Me, -NH13CH₃, -15NH13CH₃, - 15NH-Me and -15NH₂, with RH being aryl or alkyl, preferably alkyl, and wherein the reaction is preferably carried in the presence of a suitable base. 51. The method according to embodiment 45 or 46, further comprising (iii)(C) protecting the hydroxyl group of the compound of formula (I-1), preferably of compound (Ia-1), with a protecting group PG4’ selected from the group consisting of SEM, TBS, triethylsilyl (TES), TBDPS, TIPS and allyl, preferably wherein PG4’ is allyl and the protecting group is preferably introduced via reaction of compound (I-1) with NaH and allylbromide to give a compound of formula (I-2B)

…. . 2. A gentamicin C or a salt or solvate thereof, preferably an isotope labeled gentamicin C or a salt or solvate thereof comprising at least one 13C, D and/or 15N atom, the gentamicin C being obtained or obtainable by a method according to any one of embodiments 36 to 51. 3. A pharmaceutical composition comprising a gentamicin C according to any one of embodiments 1 to 24 and a pharmaceutically acceptable excipient. 4. A kit comprising a gentamicin C according to any one of embodiments 1 to 24, and a container. 5. A method of treating a bacterial infection in a subject in need thereof, comprising administering to the subject a gentamicin C according to any one of embodiments 1 to 24, or a pharmaceutical composition of embodiment 54. 6. The method of claim 55, wherein the subject suffers from renal failure. Isotope labeled gentamicin C or a salt or solvate or derivative thereof according to any one of embodiments 1 to 24, or pharmaceutical composition of embodiment 53 for use in treating a bacterial infection in a subject in need thereof. The isotope labeled gentamicin C or a salt or solvate or derivative thereof according to embodiment 57 wherein the subject suffers from renal failure. The isotope labeled gentamicin C or a salt or solvate or derivative thereof according to embodiment 57 or 58, wherein said isotope labeled gentamicin C or a salt or solvate or derivative thereof is to be administered systemically. The isotope labeled gentamicin C or a salt or solvate or derivative thereof according to embodiment 57 or 58, wherein said isotope labeled gentamicin C or a salt or solvate or derivative thereof is to be administered topically, preferably, for ophthalmic administration. The isotope labeled gentamicin C or a salt or solvate or derivative thereof according to any one of embodiments 57 to 60, wherein said bacterial infection is an infection with gram-negative bacteria. The isotope labeled gentamicin C or a salt or solvate or derivative thereof according to embodiment of embodiment 61, wherein said gram-negative bacteria are selected from the group consisting of: Haemophilus influenza, Shigella sp., Escherichia coli, Enterobacter, Klebsiella, Proteus, Pseudomonas aeruginosa, Citrobacter, Serratia, and Yersinia enterocolitica. A diagnostic composition comprising at least one isotope labeled gentamicin C according to any one of embodiments 1 to 24 or an isotope labeled gentamicin C or a salt or solvate, according to embodiment 52, and a suitable excipient. Use of at least one isotope labeled gentamicin C according to any one of embodiments 1 to 24 or a salt or solvate or derivative, or of an isotope labeled gentamicin C or a salt or solvate according to embodiment 52, as calibration standard for determining the amount of at least one gentamicin C congener present in a sample. The use according to embodiment 64, wherein the sample is obtained from biological or clinical samples which include but are not limited to fluid samples such as blood, serum, plasma, synovial fluid, spinal fluid, urine, saliva, and lymphatic fluid, or solid biological or clinical samples such as dried blood spots and tissue extracts. The use according to embodiment 64, wherein the sample is obtained from cell cultures or tissue cultures. 67. A method of determining the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample said method comprising (a) mixing the sample with a known amount of at least one isotope labeled gentamicin C, as described in any one of embodiments 1 to 24, or a salt or solvate or derivative thereof, or with an isotope labeled gentamicin C or a salt or solvate thereof according to embodiment 52 comprising at least one 13C, D and/or 15N atom, or mixing the sample with a known amount of diagnostic composition according to embodiment 63 that contains a known amount of said at least one isotope labeled gentamicin C, or a salt or solvate or derivative thereof (b) analyzing the sample via a mass spectrometry (c) comparing the peak area of at least one analyte of interest to a standard curve, wherein said standard curve has been created using the at least one isotope labeled gentamicin C or a salt or solvate or derivative, as described above and standards containing at least one analyte of interest, thereby determining the amount of the at least one analyte of interest in the sample. 68. The method according to embodiment 67, wherein the sample according to (a) is mixed with a predefined amount of the isotope labeled gentamicin C according to (b) prior to analyzing the sample via mass spectrometry. 69. The method according to embodiment 68, wherein step (c) comprises (c1) analyzing the sample mixed with the ISTD via mass spectrometry, and (c2) comparing the peak area of at least one analyte of interest to a standard curve, wherein said standard curve has been created using the at least one isotope labeled gentamicin C or a salt or solvate or derivative, as described above and standards containing at least one analyte of interest, (c3) calculating the amount of the at least one analyte of interest in the sample. 70. The method according to any one of embodiments 67 to 69, wherein the mass spectrometry is MRM-based mass spectrometry. 71. The method according to any one of embodiments 67 to 69, wherein the method is automated. 72. A kit for quantifying the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample, the kit comprising at least one isotope labeled gentamicin C or a salt or solvate or derivative according to any one of embodiments 1 to 24, or an isotope labeled gentamicin C or a salt or solvate thereof according to embodiment 52 comprising at least one 13C, D and/or 15N atom, such as one isotope labeled gentamicin C or a salt or solvate or derivative or a mixture of 2, 3, 4 or 5 isotope labeled gentamicin C congeners or salts or solvates or derivatives thereof, as calibration standard or internal standard. 73. Isotope labeled gentamicin C, according to any one of embodiments 1 to 24, or a salt or solvate or derivative thereof, or isotope labeled gentamicin C or a salt or solvate thereof according to embodiment 52 comprising at least one 13C, D and/or 15N atom, for use as calibration standard or as internal standard for determining the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample 74. Diagnostic system, preferably a clinical diagnostic system, suitable to perform the method of determining the amount of at least one analyte of interest, preferably of the at least one gentamicin C congener, present in a sample said method comprising (a) mixing the sample with a known amount of at least one isotope labeled gentamicin C, as described in any one of embodiments 1 to 24, or a salt or solvate or derivative thereof, or with an isotope labeled gentamicin C or a salt or solvate thereof according to embodiment 52 comprising at least one 13C, D and/or 15N atom, or mixing the sample with a known amount of diagnostic composition according to embodiment 63 that contains a known amount of said at least one isotope labeled gentamicin C, or a salt or solvate or derivative thereof, (b) analyzing the sample via a mass spectrometry (c) comparing the peak area of at least one analyte of interest to a standard curve, wherein said standard curve has been created using the at least one isotope labeled gentamicin C or a salt or solvate or derivative, as described above and standards containing at least one analyte of interest, thereby determining the amount of the at least one analyte of interest in the sample. 75. Use of the diagnostic system, according to embodiment 74, for determining the presence or the amount of the at least one analyte of interest in the sample. 76. Computer-implemented method for assessing a sample comprising at least one gentamicin congener, the method comprising the steps of: (aa) mixing the sample with a known amount of at least one isotope labeled gentamicin C, as described in any one of embodiments 1 to 24, or a salt or solvate or derivative thereof, or with an isotope labeled gentamicin C or a salt or solvate thereof according to embodiment 52 comprising at least one 13C, D and/or 15N atom, or mixing the sample with a known amount of diagnostic composition according to embodiment 63 that contains a known amount of said at least one isotope labeled gentamicin C, or a salt or solvate or derivative thereof, and receiving the value for the peak area of said isotope labeled gentamicin C in a sample (bb) receiving a value for the peak area of at the least one gentamicin C congeners present in the sample, (cc) comparing the values for the peak area of the at least one isotope labeled gentamicin C and the at the least one gentamicin C congeners and receiving a value for the amount of at least one gentamicin C congener; and (dd) assessing the sample on the comparison and/or the calculation made in step (cc). 77. The isotope labeled gentamicin C according to embodiment 11 or 12, wherein R1 is –CD₃ and R2 is H, and wherein the group –R4-R3 is –15NH₂, and wherein R11 is preferably C. SHORT DESCRIPTION OF THE FIGURES Fig.1 shows the synthesis of Gentamicin C2-D₃ from OBz-Sisomicin (1) as carried out in example 1. Fig.2 shows the synthesis of Gentamicin C1a-15N-D₂ from OBz-Sisomicin (1) as carried out in example 2. Fig.3 shows a synthesis of Gentamicin C1-D₃ from OBz-Sisomicin (1) as carried out in example 3. Fig.4 shows a synthesis of Gentamicin C2a-D₃ from OBz-Sisomicin (1). Fig.5 shows a synthesis of Gentamicin C2b-D₃ from OBz-Sisomicin (1). Fig.6 shows the structures of naturally occurring Gentamicin C congeners. Fig.7 shows the synthesis of a glycosylation donor (B) as carried out in reference examples A1. Fig.8 shows the synthesis of a glycosylation acceptor (A) starting from sisomicin as carried out in reference examples A2. Fig.9 shows the synthesis of Compound 1 OBz-Sisomicin as carried out in reference examples A. Fig.10 shows an alternative synthesis of Gentamicin C1-D₃ from OBz-Sisomicin (1) as carried out in example 4. Fig.11_B1 shows chromatograms for the samples Cal 1 and Cal 6 for the analyte Gentamicin C1 using Gentamicin C1-D₃ as isotopically labeled internal standard. Fig.11_B2 shows chromatograms for the samples Cal 1 and Cal 6 for the analyte Gentamicin C1a using Gentamicin C1a-15N-D₂ as isotopically labeled internal standard. Fig.11_B3 shows chromatograms for the samples Cal 1 and Cal 6 for the analytes Gentamicin C2, C2a and C2b using Gentamicin C2-D₃ as isotopically labeled internal standard.

EXAMPLES The following Examples shall merely illustrate the invention. Whatsoever, they shall not be construed as limiting the scope of the invention. Example A: OBz-Sisomicin (1)

A.1 Synthesis of the donor compound

Compound A1-a was obtained according to the literature: Chem. Commun., 2019, 55, 13291- 13294 and Angew. Chem.2003, 115, 4389-4292.

Compound A1-a (97,25 g, 0,26 mol) was dissolved in DMF (400 mL) at room temperature. Subsequently hydrazine acetate (24 g., 0,26 mol) was added. After 2 h at rt, an additional portion of hydrazine acetate (2g.) was added. After 1 h, the reaction mixture was concentrated, dissolved in isopropylacetate and washed with KHCO₃, H₂O and NaHCO₃. The organic layer was dried over Na₂SO_4, filtered and dried to obtain 88,3 g. product A1-b. 1H NMR confirmed that compound A1-b was obtained. 1H-NMR (400 MHz, 288 K, CDCl₃): δ = 5.22 (dd, J = 10.4, 10.5 Hz, 1 H), 5.39 (t, J = 3.5 Hz, 1H) 5.09-4.97 (m, 2H), 4.73 (dd, J = 7.9 Hz, 0.6 H), 4.31-4.19 (m, 2.6 H).4.16-4.08 (m, 2.2 H), 3.76-3.68 (m, 0.6 H), 3.64-3.60 (br m, 1 H), 3.52-3.45 (m, 0.6 H), 3.42 (ddd, 1 H), 2.09 (s, 3H), 2.08 (s, 3 H), 2.08 (s, 1.8 H), 2.04 (s, 3 H), 2.02 (s, 1.8 H), 2.01 (s, 1.8 H) ppm.

Compound A1-b (88,3 g, 0,26 mol) was dissolved in DCM (500 mL) at room temperature. Subsequently imidazole (21,78 g, 0,26 mol) was added. The reaction mixture was cooled with an ice bath and then TBDMS-Cl (44,19 g, 0,29 mol) was added. The reaction was left stirring as such overnight at rt. The organic layer was then washed with H2O, citric acid, dried over MgSO4, filtered and concentrated under vacuum to obtain 108 g of product A1-c (91 %). 1H NMR confirmed that A1-c was obtained. 1H-NMR (400 MHz, 288 K, CDCl3): δ = 4.98-4.91 (m, 2 H), 4.61 (d, 1 H), 4.17 (dd, 1 H), 4.09 (dd, 1 H), 3.70-3.61 (m, 1 H), 3.45-3.36 (m, 1 H), 2.06 (s, 3 H), 2.05 (s, 3H), 2.00 (s, 3 H), 0.92 (s, 9 H), 0.15 (d, 6 H) ppm.

Compound A1-c (108,58 g, 0,24 mol) was dissolved in MeOH (350 mL) at room temperature. Subsequently 7 M Ammonia in MeOH (350 mL) was added. The reaction was continued to stir at room temperature for 20 hours. Once the conversion was complete, the reaction was concentrated at 45 oC to give the crude compound A1-d, which was purified by flash column chromatography: Column: 330g silica with acetone in n-heptane 10% to give compound d in 72,69g. (93% yield). 1H NMR confirmed that compound A1-d was obtained. 1H-NMR (400 MHz, 288 K, CDCl₃): δ = 4.58 (d, 1 H), 4.29 (br d, 1 H), 4.12 (d, 1 H), 3.85 (br t, 2 H), 3.62 (td, 1 H), 3.36 (td, 1 H), 3.32-3.27 (m, 1 H), 3.24 (dd, 1 H), 2.81 (br t, 1 H), 0.94 (s, 9 H), 0.16 (d, 6 H) ppm.

Compound A1-d (72,19 g, 0,25 mol) was dissolved in DCM (1,3 L) at room temperature. Subsequently, tetramethoxybutane (45,68 g, 0,25 mol) was added. The reaction mixture was cooled with an water ice bath and then BF3Et2O (27,9 mL, 0,26 mol) was added. It was then continued to stir at room temperature. After the reaction was finished the reaction mixture was washed with saturated aqueous NaHCO3, the organic phase was dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by flash column chromatography to give 65,6 g of compound A1-e (67 %). Column: 750g Silica gel with EtOAc / DCM = 1 % to 6 %. LCMS confirmed that compound A1-e was obtained. M = 456 (M+Na)+ 1H-NMR (400 MHz, 288 K, CDCl3): δ = 4.57 (d, 1 H), 3.84 (ddd, 1 H), 3.75-3.67 (m, 2 H), 3.55 (t, 1 H), 3.47 (ddd, 1 H), 3.34 (dd, 1 H), 3.30 (s, 3 H), 3.25 (s, 3 H), 1.79 (dd, 1 H), 1.34 (s, 3 H), 1.28 (s, 3 H), 0.93 (s, 9 H), 0.15 (d, 6 H) ppm. Compound A1-e (66,05 g, 0,15 mol) was dissolved in ACN (350 mL) at room temperature. Subsequently DIPEA (33,90 mL, 0,198 mol) and DMAP (18,61 g, 0,15 mol) and benzoylchloride (21,20 mL, 25,59 mol) were added. It was continued to stir at room temperature. After the reaction was finished the reaction mixture was diluted with methyl tert- butyl ether, washed with H₂O, citric acid and NaHCO₃. The organic phase was then dried over Na₂SO₄, filtered and concentrated under vacuum. The crude product 82,19 g of compound A1- f (quant.) was purified by flash column chromatography before further reaction. LCMS confirmed that compound A1-f was obtained. M = 456 (M+Na)+

Chemical Formula: C₂₅H₃₉N₃O₈Si Chemical Formula: C₁₉H₂₅N₃O₈ Exact Mass: 537,25 Exact Mass: 423,16 Molecular Weight: 537,69 Molecular Weight: 423,42 Compound A1-f (35 g, 0,065 mol) was dissolved in THF (350 mL) at room temperature. The reaction mixture was cooled to -20 oC and then AcOH (3,72 mL, 0,065 mol) and TBAF (65,1 mL, 0,065 mol) were added. It was continued to stir -10 oC for about 25 min. After the reaction was finished, the reaction mixture was diluted with methyl tert-butyl ether, washed with citric acid and NaHCO3. The organic phase was dried over Na2SO4, filtered and concentrated under vacuum. The crude product A1-g 26,48 g. was obtained in 96,1 % yield. LCMS and 1H-NMR confirmed that compound A1-g was obtained. M = 446 (M+Na)+ Mixture of of α- and β-isomer: 1H-NMR (400 MHz, 288 K, CDCl3): δ 8.07-8.01 (m, 2 H), 7.53-7.59 (m, 1 H), 7.46-7.40 (m, 2 H), 5.33 ( br t, 0.8 H), 4.67 (d, 0.2 H), 4.62 (dd, 0.2 H), 4.59 (dd, 0.8 H), 4.49 (dd, 0.8 H), 4.46 (dd, 0.2 H), 4.38-4.29 (m, 1.6 H), 3.93-3.82 (m, 1 H), 3.83-3.77 (ddd, 0.2 H), 3.37-3.65 (dd, 0.4 H), 3.52-3.45 (m, 1 H), 3.38 (s, 2.4 H), 3.33 (0.6 H), 3.21 (br s, 0.8 H), 3.19 (s, 2.4 H), 3.17 (0.6 H), 1.37 (s, 2.4 H), 1.36 (s, 0.6 H), 1.31 (s, 2.4 H), 1.28 (s, 0.6 H) ppm .

Compound A1-g (26,45 g, 0,0625 mol) was dissolved in DCM (350 mL) at room temperature. The reaction mixture was cooled with ice bath and then DBU (2,80 mL, 0,019 mmol) and trichloroacetonitrile (56,4 mL, 0,562 mmol) were added. It was continued to stir for about 1 h. After the reaction was finished, the reaction mixture was concentrated under vacuum. The crude product A1-h (B) was purified by flash column chromatography to give 27,23 g. 1H-NMR confirmed that compound A1-h was obtained.1H-NMR (400 MHz, 288 K, CDCl3): δ 8.77-8.70 (m, 0.9 H), 8.05-7.97 (m, 2 H), 7.59-7.52 (m, 1 H), 7.46-7.38 (m, 2 H), 6.45 (d, 0.7 H), 5.70-5.66 (m, 2 H), 4.62-4.44 (m, 2 H), 4.40-4.25 (m, 1.6 H), 4.01-3.88 (m, 1.0 H), 3.75 (dd, 1.0 H), 3.37 (s, 2.4 H), 3.32 (s, 0.6 H), 3.16 (s, 2.4 H), 3.14 (s, 0.6 H) 1.37 (s, 2.4 H), 1.35 (s, 0.6 H), 1.32 (s, 2.4 H), 1.28 (s, 0.6 H)ppm. A.2 Providing the Acceptor Compound

Sisomycin-sulfate (4.60 g, 0,053 mol, 1 eq., obtained from Merck KGaA) was dissolved in H₂O (180 mL) at room temperature. Subsequently, ZnCl₂ (0.87 g., 0.006 mol) and NEt₃ (74 mL, 0,531 mol) were added. The mixture was cooled with an water ice bath. In a separate flask NaN₃ (17,27 g., 0,27 mol) in acetonitrile (160 mL) was suspended and at low temperature (2-8 °C). Then trifluoromethanesulphonyl chloride (44,76 g , 0,27 mol) was added to the azide solution. To the resulting suspension of TfN₃, slowly the beforehand prepared Sisomicin solution was added. The temperature was slowly elevated to rt. After the reaction was finished, methanol (10 mL) was added and the suspension was concentrated. To the concentrated mixture, H₂O was added and the resulting solution extracted with EtOAc. The organic phase was dried over MgSO₄, filtered and concentrated under vacuum. The crude product was purified by flash column chromatography to give 18,27 g sisomicin N₃ (62,4 %). Column: 330g Silica with MeOH in Ethylacetate 0% - 20%. LCMS confirmed that sisomicin N₃ was obtained. M = 552,2 (M+H)+ 1H-NMR (400 MHz, 288 K, CDCl₃): δ = 5.89 (d, 1 H), 4.99 (d, 1 H), 4.95 (dd, 1 H), 3.80-3.52 (m, 8 H), 3.45-3.35 (m, 2 H), 3.32-3.26 (m, 1 H), 2.61 (s, 3 H), 2.51-2.40 (m, 2 H), 2.36-2.25 (m, 2 H), 1.48 (q, 1 H), 1.18 (s, 3 H) ppm.

Sisomycin N₃ (16.05 g, 0.028 mol, 1 eq.) was dissolved in DCM (180 mL) at room temperature. The resulting mixture was cooled with an ice bath. Subsequently, H₂O (90 mL) and K₂CO₃ (7,86 g.) were added. To this mixture, 4-(trifluoromethyl)benzoyl chloride (7,26 g.) in DCM (60 mL) was added. It was then continued to stir at ice bath temperature for one hour and subsequently warmed to 15 oC. After the reaction was finished, it was extracted with DCM and washed with H₂O. The organic layer was dried over MgSO₄, filtered and concentrated to give a dry product, which was purified by flash chromatography to give 17,75 g. of pure sisomicin N₃ CF₃ (87 % yield) Column: 330g Büchi® Silica column (toluene/EtOAc = 6:4) LCMS confirmed that sisomicin N + 3 CF3 was obtained. M = 724,4 (M+H) 1H-NMR (400 MHz, 288 K, CDCl₃): δ = 7.75-7.65 (m, 2.2 H), 7.64-7.50 (m, 2.2 H), 7.28-7.13 (m, 1.8 H), 6.96 (br d, 0.2 H), 5.92-5.79 (m, 1 H), 5.25-5.19 (m, 0.8 H), 5.08 (d, 0.1 H), 5.01-4.93 (m, 1.2 H), 4.15-4.08 (0.9 H), 4.00 (br d, 0.1 H) 3.84-3.54 (m, 6 H), 3.54-3.28 (m, 4 H), 3.25 (s, 0.4 H), 3.22-3.15 (m, 0.3 H), 3.09 (s, 0.5 H), 3.08 (s, 2 H), 2.94 (d, 0.2 H), 2.80 (d, 0.2 H), 2.70 (d, 0.6 H), 2.54-2.42 (m, 1 H), 2.42-2.24 (m, 3 H).2.11-2.00 (m, 1 H), 1.60-1.46 (2x q, 1 H), 1.31 (s, 0.6 H), 1.28 (s, 2 H), 1.10 (s, 0.4 H) ppm.

Sisomicin N3 CF3 (17,68 g, 0.024 mol) was dissolved in DMF (170 mL) and cooled with an ice bath. Subsequently, TBAI (8,93 g, 0,024 mol), NaH (5,69 g, 60 wt-% dispersion in mineral oil, 0,142 mol) and BnBr (17,4 mL, 0,142 mol) were added. The reaction was stirred at room temperature for around 3 hours. Subsequently, the reaction mixture was poured into ice-cooled H2O and was extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated to dryness. Crude Sisomicin N3 Bn was purified by crystallization and subsequent column chromatography to obtain pure 20,82 g. Sisomicin N3 Bn (88,4 % yield) LCMS confirmed that Sisomicin N Bn was obtained. M + 3 = 1016 (M+Na) 1H-NMR (400 MHz, 288 K, CDCl3): δ = 7.75-7.67 (m, 2.3 H), 7.60 (d, 0.9 H), 7.44 (d, 0.9 H), 7.40- 7.14 (m, 14 H), 6.90 (d, 1.2 H), 6.04 (d, 0.4 H), 5.94 (d, 0.6 H), 5.67 (d, 0.4 H), 5.37 (d, 0.7 H), 5.33 (br s, 0.3 H), 5.15 (dd, 0.9 H), 4.94 (ddd, 1 H), 4.89 (d, 1 H), 4.54 (dd, 1.6 H), 4.35 (dd, 1 H), 4.28-4.18 (m, 2 H), 4.12 (q, 0.6 h), 4.00 (d, 0.6 H), 3.92 (t, 0.4 H), 3.87-3.75 (m, 2 H), 3.75-3.55 (m, 4 H), 3.52 (d, 0.5 H), 3.48-3.38 (m, 1.2 H), 3.35 (d, 0.9 H), 3.33-3.24 (m, 1 H), 3.22 (q, 0.9 H), 3.05 (s, 1.7 H), 2.70 (s, 1.3 H), 2.45-2.31 (m, 2 H), 2.25-2.10 (m, 1 H), 1.65-1.50 (m, 1.2 H), 0.58 (s, 1.3 H), 0.39 (s, 1.7 H) ppm.

Sisomicin N₃ Bn (21,3g., 0.021 mol) was dissolved in MeOH (160 mL) and cooled with an ice bath. Subsequently, H₂SO₄ (conc., 8,9 mL, 0,16 mol) was added. The reaction was stirred at room temperature After the reaction was finished, the mixture was cooled with an ice bath and diluted with EtOAc and MTBE. The organic layer was washed with NaHCO₃, dried over MgSO₄, filtered and concentrated. The crude acceptor (A) was purified flash column chromatography to obtain pure acceptor (A) 12,86g (75,8 % yield). Column: 330g Büchi® Silica column (toluene/EtOAc = 8:2). LCMS confirmed that the desired acceptor (A) was obtained. M = 838 (M+Na)+ 1H NMR confirmed that acceptor (A) was obtained. 1H-NMR (400 MHz, 288 K, CDCl₃): δ =7.73-7.64 (m, 2 H), 7.60 (d, 1 H), 7.40-7.13 (m, 14 H), 6.94 (d, 1 H), 6.02 (d, 0.5 H), 5.88 (d, 0.5 H), 5.29 (d, 0.5 H), 5.20 (d, 0.5 H), 4.97-4.86 (m, 1.5 H), 4-61- 4.50 (dd, 1 H), 4.46-4.34 (m, 1 H), 4.34-4.22 (m, 2.5 H), 4.07 (d, 0.5 H), 3.93 (d, 0.5 H), 3.76 (t, 0.5 H), 3.67-3.54 (m, 3 H), 3.52-3.38 (m, 3 H), 3.07 (s, 1.5 H), 3.00 (t, 0.5 H), 2.76 (t, 1.5 H), 2.53 (dd, 0.8 H), 2.36 (s, 1.5 H), 2.35-2.26 (m, 1 H), 1.63-1.48 (m, 1 H), 0.94 (s, 3 H), 0.63 (s, 1.5 H) ppm. A.3 Glycosylation of the acceptor and donor compounds

A suspension of acceptor (A) (500 mg, 0,613 mmol), donor A1-h(B) (497 mg, 1,4 eq., 0,858 mmol) and ground molecular sieves 4 Å (100 mg) in dry DCM (15 mL) was stirred for 30 min at room temperature under argon atmosphere. The reaction mixture was cooled to -60 oC and dilute TMSOTf (0,3 eq., 50 µL in 1.0 mL DCM) was added dropwise. Reaction was slowly allowed to warm to -10 oC. After 5 hours, the reaction was stopped by diluting it in DCM and subsequent filtration over Celite into a stirred solution of NaHCO₃ (sat., aq.). The organic layer was washed with sat. aq. NaHCO₃ solution, dried over NaSO₄, filtered and concentrated. The trisaccharide compound 1 was purified by flash column chromatography (DCM/MeOH = 150/1 to 100/1) to give 549 mg of pure compound 1 as an white solid (73 % yield). LCMS confirmed that compound 1 was obtained. M = 1243 (M+Na)+ 1H-NMR (400 MHz, 288 K, CDCl3): δ = ppm 0.02 - 0.08 (m, 3 H) 0.37 (s, 2 H) 0.51 - 0.57 (m, 2 H) 1.19 - 1.38 (m, 10 H) 1.60 - 1.77 (m, 1 H) 2.29 - 2.44 (m, 1 H) 2.67 - 2.71 (m, 2 H) 3.00 - 3.39 (m, 14 H) 3.42 - 3.83 (m, 11 H) 3.98 (d, J=11.04 Hz, 1 H) 4.14 - 4.37 (m, 6 H) 4.40 - 4.65 (m, 6 H) 4.88 (dd, J=11.55, 3.51 Hz, 2 H) 5.12 - 5.25 (m, 2 H) 5.29 (s, 4 H) 5.54 (d, J=4.02 Hz, 1 H) 5.66 - 5.87 (m, 2 H) 5.92 (d, J=3.51 Hz, 1 H) 6.03 (d, J=3.51 Hz, 1 H) 6.47 - 6.72 (m, 2 H) 6.83 - 6.93 (m, 2 H) 7.12 - 7.28 (m, 9 H) 7.30 - 7.47 (m, 14 H) 7.51 - 7.61 (m, 3 H) 7.63 - 7.85 (m, 4 H) 7.99 - 8.13 (m, 3 H) ppm. Example 1: Synthesis of Gentamicin C2-D3 from OBz-Sisomicin (1)

1.1 From OBz-Sisomicin (1) to OH-Sisomicin (2)

OBz-Sisomycin 1 (4.60 g, 3.77 mmol, 1 eq.) was dissolved in MeOH (65 mL) at room temperature. Subsequently, 25 mol-% NaOMe in MeOH (200 µL) were added dropwise until pH = 11 was reached. It was then continued to stir at room temperature for 6 hours (TLC n- Hex/EtOAc = 3/1). If the conversion was not complete, the pH was adjusted to 11 again and the reaction left stirring overnight. Once the conversion was complete, the reaction was neutralized with HCl (conc.) to pH = 5-6 (ca.250 µL) and concentrated under vacuum to give crude OH-sisomicin 2, which was purified by flash column chromatography: Column: PF-30SIHP-F0120 g. (n-Hex/EtOAcs, elution at 50%) to give OH-Sisomicin 2 in 4.10 g. (97% yield). LCMS confirmed that OH-Sisomicin 2 was obtained. M= 1117 (M+H)+ 1H-NMR (400 MHz, 288 K, CDCl₃): δ = 0.33 - 0.47 (m, 1 H) 0.57 (s, 1 H) 0.78 - 1.01 (m, 1 H) 1.21 - 1.38 (m, 5 H) 1.55 - 1.62 (m, 1 H) 1.65 - 1.81 (m, 1 H) 1.97 - 2.07 (m, 1 H) 2.31 - 2.48 (m, 1 H) 2.61 - 2.79 (m, 1 H) 2.98 - 3.13 (m, 1 H) 3.16 - 3.25 (m, 2 H) 3.28 - 3.51 (m, 4 H) 3.55 - 3.68 (m, 2 H) 3.69 - 3.90 (m, 2 H) 3.96 - 4.06 (m, 1 H) 4.08 - 4.27 (m, 2 H) 4.29 - 4.39 (m, 1 H) 4.44 - 4.66 (m, 1 H) 4.68 - 4.92 (m, 1 H) 5.11 - 5.25 (m, 1 H) 5.25 - 5.39 (m, 1 H) 6.04 (d, J=3.51 Hz, 1 H) 6.38 (s, 1 H) 6.85 (d, J=7.53 Hz, 1 H) 7.13 - 7.39 (m, 7 H) 7.63 - 7.76 (m, 1 H) ppm. 1.2 From OH-Sisomicin 2 to Aldehyde 3

OH-Sisomycin 2 (4.13 g, 3.70 mmol, 1 eq.) was dissolved in dry DCM (120 mL) at room temperature. To this suspension ground molecular sieves 4 Å (300 mg) and NaHCO3 (3.11 g, 37.02 mmol, 10 eq) were added. The reaction mixture was cooled with an ice bath and then Dess-Martin periodinane (2.36 g, 5.56 mmol, 1.5 eq) was added in two portions. After 5 minutes, the ice bath was removed and the reaction mixture was allowed to warm to room temperature. The reaction was continued to stir for 2 hours. n-Hexane (60 mL) was added and then continued to stir for 30 min, filtered over Celite, washed with DCM and dried over MgSO4. After filtration, the solution was concentrated to dryness. Aldehyde 3 was used for the next reaction without further purification. LCMS confirmed that aldehyde 3 was obtained. M= 1115 (M+H)+ 1.3 From Aldehyde 3 to Alcohol 4 Methylmagensium iodide D3 in diethyl ether (1 M, 3 eq., 11.03 mL) was added to dry diethyl ether (30 mL) and cooled to -50 °C. To this solution aldehyde 3 (4.10 g, 3.68 mmol, 1 eq.) dissolved in dry diethyl ether (100 mL) was added dropwise (white/yellow suspension). The reaction was continued to stir continued for 30 min at -50 °C, was then diluted with diethyl ether, quenched with saturated NH4Cl, dried over MgSO4, filtered and concentrated to dryness. Crude alcohol 4 was purified by flash column chromatography: Column: PF-30SIHP-F0330 g. (n-Hex/EtOAc, elution at 40%) to give alcohol 4 in 3.17 g (76% yield over 2 steps) LCMS confirmed that alcohol 4 was obtained. M= 1134 (M+H)+ 1.4 From Alcohol 4 to Mesylate 5

Alcohol 4 (1.00 g, 0.88 mmol) was dissolved in dry pyridine (20 mL) and then MsCl (2.64 mmol, 3 eq.) was added dropwise. The reaction was stirred at room temperature for around 16 hours. Subsequently, the reaction mixture was diluted with DCM, washed with NaHCO₃ and the organic layer was dried over MgSO₄, filtered and concentrated to dryness. Crude Mesylate 5 was purified by flash column chromatography: Column: PF-30SIHP-F0040 g. (n-Hex/EtOAc, elution at 60%) to give Mesylate 5 in 962 mg (90% yield). LCMS confirmed that Mesylate 5 was obtained. M= 1212 (M+H)+ 1.5 From Mesylate 5 to Azide 6

Mesylate 5 (950 mg, 0.78 mmol) was dissolved in dry DMF (15 mL) and then NaN3 ( 509.6 mg, 7.84 mmol, 10 eq.) was added at room temperature. The resulting suspension was heated to 90 °C and stirred overnight. When the reaction was judged complete, the reaction mixture was cooled to room temperature, diluted with EtOAc and washed with H2O. The organic layer was dried over MgSO4, filtered and concentrated to dryness. Crude Azide 6 was used for the next step without further purification. LCMS confirmed that Azide 6 was obtained. M= 1159 (M+H)+ 1.6 From Azide 6 to Diol 7

Crude azide 6 from the previous reaction (0.78 mmol) was dissolved in 7 mL of DCM. Then, 0.5 mL of H₂O and 10 mL of TFA were added. The reaction mixture turned yellow. Stirring was continued at room temperature for 30 min. Subsequently, the reaction was diluted with DCM and 10 mL of saturated aq. NaHCO₃ was added dropwise. After extraction, the organic layer was dried over MgSO_4, filtered and concentrated to dryness. Crude diol 7 was purified by flash column chromatography: Column: PF-30SIHP-F0080 g. (interchim Column) (n-Hex/EtOAc, elution at 55%) to give diol 7 in 800 mg (98% yield, over 2 steps). 1.7 From Diol 7 to Triflate 8

Diol 7 (800 mg, 0.77 mml) was dissolved in dry DCM (12 mL) under argon atmosphere and then dry pyridine (30 eq, 1.85 mL) was added. The reaction mixture was cooled to 0 °C and triflic anhydride (3.83 mmol.5 eq) was added. The reaction mixture turned yellow. Stirring was continued at room temperature for 30 min. After another 1.5 h, the reaction was not complete and therefore more triflic anhydride (300 µL, 5 eq) was added. When the reaction was finished (IPK via LCMS), the reaction mixture was diluted with DCM, quenched with saturated aq. NaHCO₃ and washed with brine. The organic layer was dried over MgSO₄, filtered and concentrated to dryness. Crude triflate 8 was used for the next step without further purification. 1.8 From Triflate 8 to Alkene 9 Crude triflate 8 from the previous reaction (0.77 mmol) was dissolved in 10 mL of dry acetone. Subsequently, Na₂S₂O₃ (3.08 mmol, 4 eq) and NaI (2.31 mmol, 3 eq) were added at room temperature. Stirring was continued at room temperature overnight. The reaction was diluted with EtOAc and washed with 10% Na₂S₂O₃, sat. aq. NaHCO₃ and brine. The organic layer was dried over MgSO_4, filtered and concentrated to dryness. Crude alkene 9 was purified by flash column chromatography: Column: PF-30SIHP-F0080 g. (interchim column) (n-Hex/EtOAc, elution at 30%) to give alkene 9 in 640 mg (82 % yield, over 2 steps) LCMS confirmed that alkene 9 was obtained. M= 1011 (M+H)+ 1.9 From Alkene 9 to Amine 10

Alkene 9 (630 mg, 0.62 mmol) was dissolved in THF (10 mL) and then 2 mL of NaOH (0.1 M, aq.) solution was added. Subsequently, PMe3 (1 M in THF, 3.74 mmol, 6 eq.) was added. The reaction mixture was heated to 50 °C for 2 h. The reaction mixture then was transferred to a round bottom flask and concentrated to dryness. Crude amine 10 was purified by HPLC. Column: YMC Actus C18-S (ACN/H2O elution at 80%) to give amine 10 in 575 mg (as a TFA salt.68 % yield). LCMS confirmed that amine 10 was obtained. M= 907 (M+H)+ 1H NMR confirmed that amine 10 was obtained. 1H NMR (400 MHz, METHANOL-d₄): δ = 1.08 (s, 1 H) 1.20 - 1.42 (m, 3 H) 2.17 (br d, J=12.05 Hz, 1 H) 2.30 (q, J=12.59 Hz, 1 H) 2.47 - 2.64 (m, 3 H) 2.66 (br s, 1 H) 3.03 - 3.28 (m, 1 H) 3.31 - 3.42 (m, 1 H) 3.43 - 3.69 (m, 3 H) 3.78 - 3.95 (m, 2 H) 3.95 - 4.19 (m, 2 H) 4.31 - 4.53 (m, 4 H) 4.56 - 4.68 (m, 2 H) 4.69 - 4.82 (m, 2 H) 4.90 - 5.10 (m, 1 H) 5.27 (dd, J=14.87, 11.36 Hz, 2 H) 5.34 - 5.47 (m, 1 H) 5.52 (d, J=2.76 Hz, 1 H) 5.58 (br s, 1 H) 5.75 - 6.02 (m, 2 H) 6.03 - 6.17 (m, 1 H) 7.21 - 7.46 (m, 11 H) 7.55 (br d, J=8.28 Hz, 2 H) 7.66 - 7.89 (m, 2 H) ppm. From Amine 10 to Compound 11

Chemical Formula: C₄₉H₅₇D₃F₃N₅O₈ Chemical Formula: C₂₈H₃₉D₃F₃N₅O₈ Exact Mass: 906,46 Exact Mass: 636,32 Molecular Weight: 907,06 Molecular Weight: 636,68 Amine 10 (575 mg, 0.63 mmol) was dissolved in 5 mL acetic acid and 15 mL of H₂O. To this solution 10 wt-% Pd/C (20 mol-%) was added and the reaction pressurized under H₂ (1 atm). The reaction was left stirring overnight at room temperature and then filtered through Celite, washed with MeOH, H₂O and concentrated to dryness. Crude compound 11 was used for the next step without further purification. LCMS confirmed that compound 11 was obtained. M= 639 (M+H)+ 1.10 From compound 11 to Gentamicin C2-D₃ (12)

Crude compound 11 from the previous reaction was dissolved in 2 mL of H₂O and 2 mL of EtOH were added. Subsequently, KOH (aq.1.5 M, 10 mL) was added. Stirring was continued at 55 °C for 4 h. After the reaction was completed it was neutralized with TFA to pH = 8, concentrated and lyophilized. The obtained crude Gentamicin C2-D₃ (12) was purified by HPLC: Column: YMC Actus C18-S (H₂O + 0,1% TFA elution) to provide Gentamicin C2-D₃ in 72.5 mg (as a TFA salt). Subsequently, crude product 12 was further purified with chromatography on SepPak C18 (Elution with H₂O). to provide 64.8 mg of Gentamicin C2-D₃. 1H NMR confirmed that Gentamicin C2-D₃ was obtained. LCMS confirmed that Gentamicin C2-D₃ was obtained. M= 467 (M+H)+. 1H NMR (500 MHz, D₂O) δ= 1.33 (s, 3 H) 1.49 - 1.62 (m, 1 H) 1.76 - 2.07 (m, 4 H) 2.49 - 2.57 (m, 1 H) 2.91 (s, 3 H) 3.42 - 3.62 (m, 6 H) 3.75 - 3.88 (m, 2 H) 3.92 - 4.02 (m, 2 H) 4.05 - 4.12 (m, 1 H) 4.22 (dd, J=10.88, 3.63 Hz, 1 H) 5.08 (d, J=3.78 Hz, 1 H) 5.80 (d, J=3.47 Hz, 1 H) ppm Example 2: Synthesis of Gentamicin C1a-15N-D2 from OH-Sisomicin 2 2.1 From OH-Sisomicin 2 to Tosylate 3

OH-Sisomycin 2 (1.5 g, 1.34 mmol, 1 eq.) was dissolved in pyridine (25 mL) at room temperature. Subsequently, TsCl (640 mg, 2.5 eq.) was added. The reaction was continued to stir at room temperature for 20 hours. After the reaction was finished, it was concentrated to dryness. Tosylate 3 was purified by flash column chromatography: Column: Interchim: PF-30SIHP-F0120 g. (n-Hex/EtOAc, elution at 30%) to give Tosylate 3 in 1.35 g (80%). LCMS confirmed that tosylate 3 was obtained. M = 1271 (M+H)+. 2.2 From Tosylate 3 to 15N-Amine 4

Tosylate 3 (1.3 g, 1.02 mmol, 1 eq.) was dissolved in dry NMP (19 mL) under argon at room temperature in a suitable pressure tube. The mixture was cooled to -30 °C and 15NH₃ (g) was slowly bubbled into the mixture until the volume had increased by ca.2 mL. The pressure tube was sealed and left warming to room temperature. Then, it was heated to 85 °C and stirred at this temperature for 2 days. Then the reaction was concentrated to dryness. Thus obtained crude 15N-amine 4 was purified by flash column chromatography: Column: (n-Hex/EtOAc + 1% MeOH, elution with 1/1, 1/2, 1/3 ) to give 1.19 g 15N-amine 4 as an oil. LCMS confirmed that 15N-amine 4 was obtained. M= 1117 (M+H)+ 2.3 From 15N-Amine 4 to Azide 5

15N-Amine 4 (1.1g ,0.98 mmol) was dissolved in dry MeOH 50 mL, then K₂CO₃ (680 mg, 4.9 mmol 5 eq.) was added. The reaction mixture was cooled with a water ice bath and subsequently, imidazole-1-sulfonyl azide HCl salt (629 mg, 2.95 mmol, 3eq.) and CuSO₄*(H₂O)₅ (25 mg, 0.098 mmol, 0.1 eq.) were added. After 10 min. the ice bath was removed and stirring continued overnight at room temperature. After the reaction was finished it was concentrated to dryness, the residue redissolved in DCM and washed with sat. aq. NaHCO₃. The organic phase was dried over MgSO₄, filtered and concentrated. Crude azide 5 was used for the next step without further purification. LCMS confirmed that azide 5 was obtained. M= 1143 (M+H)+ 2.4 From Azide 5 to Diol 6

Exact Mass: 1142,46 Molecular Weight: 1029,01 Molecular Weight: 1143,16 Crude azide 5 from the previous reaction was dissolved in 7 mL of DCM. Then 0.5 mL of H2O and 10 ml of TFA were added. The resulting reaction mixture turned yellow. Stirring was continued at room temperature for 30 min. Subsequently, the reaction was diluted with DCM and 10 mL of saturated aq. NaHCO3 was added dropwise. After extraction, the organic layer was dried over MgSO4, filtered and concentrated to dryness. The crude diol 6 was purified by flash column chromatography: Column: PF-30SIHP-F0080 g. (n-Hex/EtOAc, elution at 50%) to give diol 6 in 613 mg (59%, over 2 steps). LCMS confirmed that diol 6 was obtained. M= 1029 (M+H)+ 2.5 From Diol 6 to Triflate 7 OBn OH O OBn O N O OH Tf OTf N O, py, DCM, 0 C BnO BnO N N O O N O OTf O O N N N BnO BnO N N O O N N diol 6 CF Chemical Formula: C H F N NO triflate 7 CF Chemical Formula: C H F N NO S Exact Mass: 1028,39 Exact Mass: 1292,29 Molecular Weight: 1029,01 Molecular Weight: 1293,13 Diol 6 (380 mg, 0.37 mml) was dissolved in dry DCM (3 mL) under argon atmosphere and then dry pyridine (15 eq, 450 µL) was added. The reaction mixture was cooled to 0 °C and triflic anhydride (1.85 mmol. 5 eq) was added. Reaction mixture turned yellow. Stirring was continued at room temperature for 30 min. After another 1.5 h, the reaction was not complete and therefore more triflic anhydride (30 µL) was added. When reaction was finished, the reaction mixture was diluted with DCM, quenched with sat. NaHCO3 and washed with brine. The organic layer was dried over MgSO4, filtered and concentrated to dryness. Crude triflate 7 was used for the next step without further purification. LCMS confirmed that triflate 7 was obtained. M= 1293 (M+H)+ 2.6 From Triflate 7 to Alkene 8

Crude triflate 7 from the previous reaction (0.36 mmol) was dissolved in 7 mL of dry acetone. Subsequently, Na₂S₂O₃ (1.45 mmol, 4 eq) and NaI (1.27 mmol, 3.5 eq) was added at room temperature. Stirring was continued at room temperature for overnight. The reaction was diluted with EtOAc and washed with 10 wt-% aq. Na₂S₂O₃, sat. aq. NaHCO₃ and brine. After extraction, the organic layer was dried over MgSO_4, filtered and concentrated to dryness. Crude alkene 8 was purified by flash column chromatography: Column interchim: PF-30SIHP-F0040 g. (n-Hex/EtOAc, elution at 40%) to give alkene 8 in 208 mg (57%, over 2 steps). LCMS confirmed that alkene 8 was obtained. M= 995 (M+H)+. 2.7 From Alkene 8 to Amine 9

Alkene 8 (208 mg, 0.21 mmol) was dissolved in THF (1 mL) and then 0.2 mL of NaOH (aq., 0.1 M) solution was added. Subsequently, PMe₃ (1.0 M in THF, 1.25 mmol, 6 eq.) was added. The reaction mixture was heated to 50 °C for 2 hours, then transferred to a suitable round bottom flask and concentrated to dryness. Crude amine 9 was purified by HPLC: Column: YMC Actus C18-S (MeCN+0,1 %TFA/H2O+0,1%TFA, elution at 80%) to give amine 9 in 211 mg (as a TFA salt., 75 %). LCMS confirmed that amine 9 was obtained. M= 891 (M+H)+ 2.8 From Amine 9 to D2-genta 10 Amine 9 (211 mg as a TFA salt) was dissolved in 2 mL acetic acid-D₄ and 1 mL of D₂O. In a separate flask, Pd/C (10 wt-% Pd, 1 spatula), 2 mL of acetic acid-D₄ and 1 mL of D₂O were placed and flushed with D₂ for 10 min. To this suspension add the prepared mixture of amine 9 and set under D₂ pressure (1 atm). The reaction was left overnight at room temperature and then filter through a Celite plug, washed with MeOH and H₂O and then the filtrate was concentrated to dryness. Crude D₂-genta 10 was used for the next step without further purification. LCMS confirmed that D₂-genta 10 was obtained. M = 625 (M+H)+ 2.9 From D₂-genta 10 to Gentamicin C1a-15N-D₂11

Crude D₂-genta 10 from the previous reaction was dissolved in 2 mL of H₂O. Subsequently, NaOH (aq., 1 M, 10 mL) was added. Stirring was continued at 60 °C for 4 hours. After the reaction was completed, it was neutralized with TFA to pH = 5 and lyophilized. The dry product was dissolved in 30 mL of H₂O and purified with Sep-Pak C18 (see e.g. www.flinnsci.com “Sep-Pak® C18 Cartridge for Column Chromatography”), Elution with H₂O and 50% ACN. The combined product containing H₂O fractions were lyophilized and further purified by HPLC: Column: YMC Actus C18-S (H₂O + 0.1% TFA elution ) to give 77.2 mg Gentamicin C1a- 15N-D₂11 as a TFA salt. LCMS confirmed that Gentamicin C1a-15N-D₂11 was obtained. M = 453 (M+H)+ , M = 475 (M+Na)+ 1H NMR confirmed that Gentamicin C1a-15N-D₂11 was obtained. 1H NMR (500 MHz, D₂O): δ = 1.36 (s, 3 H) 1.58 - 1.63 (m, 1 H) 1.88 - 2.07 (m, 4 H) 2.54 - 2.60 (m, 1 H) 2.93 (s, 3 H) 3.09 - 3.15 (m, 1 H) 3.24 - 3.27 (m, 1 H) 3.27 - 3.30 (m, 1 H) 3.49 - 3.55 (m, 2 H) 3.55 - 3.65 (m, 3 H) 3.77 - 3.88 (m, 2 H) 3.98 - 4.05 (m, 2 H) 4.16 - 4.20 (m, 1 H) 4.22 - 4.26 (m, 1 H) 5.11 (d, J=3.56 Hz, 1 H) 5.81 (d, J=3.56 Hz, 1 H) ppm. 3. Example 3: Experiments for Gentamicin C1-D₃ – According to the alternative preferred Synthesis of Gentamicin C1 (Method A4): 3.1 From Alcohol 4 to Allyl Ether C1-4

Sodium hydride (60 wt-% in mineral oil, 140 mg, 3.50 mmol, 1.80 eq.) was suspended in dry N,N-dimethylformamide (5.0 mL) under inert gas atmosphere at room temperature. The resulting mixture was cooled to 0 °C. To this, alcohol 4 (2.20 g, 1.94 mmol, 1.00 eq.) dissolved in dry N,N-dimethylformamide (5.0 mL) was slowly added and the reaction was stirred for 30 minutes. Subsequently, allyl bromide (0.67 mL, 7.77 mmol, 4.00 eq.) was added dropwise, the reaction mixture warmed to room temperature and left stirring overnight. Afterwards, the brownish reaction mixture was concentrated in vacuo. The crude product was purified via normal phase MPLC (silica, gradient n-hexane/EtOAc = 100:0 to 30:70). Drying in vacuo yielded allyl ether C1-4 (1.97 g, 1.68 mmol, 86%) as colorless solid. R_f(n-Hex:EtOAc = 3:1) = 0.50. ESI-LRMS for C₅₈H₆₇D₃F₃N₁₀O₁₃+ [MH+]: calculated 1174.5 found 1174.7. 3.2 From Allyl Ether C1-4 to Diol C1-5

Allyl ether C1-4 (1.97 g, 1.68 mmol) was dissolved in dichloromethane (10.0 mL) at room temperature. To this, dest. H₂O (2 drops) and trifluoroacetic acid (20.0 mL) were added. The reaction mixture then turned yellow and was stirred for 30 minutes until complete consumption of substance C1-4. Subsequently, the reaction was diluted with dichloromethane (40.0 mL) and neutralized via slow addition of sat. aq. bicarb solution. The organic layer was separated and the aqueous phase extracted with dichloromethane (2 × 50 mL). The combined organic layers were dried over MgSO₄, filtered and concentrated to dryness. The crude product was purified via normal phase MPLC (silica, gradient n-hexane/acetone = 75:25 to 0:100). Drying in vacuo yielded diol C1-5 (1.77 g, 1.49 mmol, 89%) as colorless solid. R_f(n-Hex:EtOAc = 3:1) = 0.10. ESI-LRMS for C₅₂H₅₇D₃F₃N₁₀O₁₁+ [MH+]: calculated 1060.5 found 1060.6. 3.3 From Diol C1-5 to Bistriflate C1-6

Diol C1-5 (900mg, 0.85 mmol, 1.00 eq.) was dissolved in dry dichloromethane (18.0 mL) under inert gas atmosphere at room temperature. Thereafter, dry pyridine (2.06 mL, 25.5 mmol, 30.0 eq.) was added under stirring and the reaction mixture was cooled to 0 °C. To this, triflic anhydride (1.08 mL, 6.79 mmol, 8.00 eq.) was added and stirring continued for two hours at room temperature. The reaction became first cloudy and then turned to a brownish solution. When diol C1-5 was consumed, the resulting solution was diluted with dichloromethane (50 mL), then quickly washed with aq. HCl (0.1 ^M, 2 × 50 mL) and sat. aq. bicarb solution (50 mL). The aqueous phases were re-extracted with dichloromethane (2 × 50 mL) and the combined organic layers dried over Na₂SO_4, filtered and concentrated in vacuo. The obtained crude orange solid (1.08 g) was employed for further reaction without additional purification. R_f(n-Hex:EtOAc = 3:1) = 0.55. ESI-LRMS for C₅₄H₅₅D₃F₉N₁₀O₁₅S₂+ [MH+]: calculated 1324.4 found 1324.5. 3.4 From Bistriflate C1-6 to Alkene C1-7

The crude bistriflate C1-6 (assumed 0.85 mmol, 1.00 eq.) from the transformation 3.3 was dissolved in dry acetone (13.5 mL) at room temperature under inert gas atmosphere. Subsequently, Na2S2O3 (537 mg, 3.40 mmol, 4.00 eq) and NaI (382 mg, 2.55 mmol, 3.00 eq) were added. Stirring was continued at room temperature for 27 hours until substance C1-6 was completely consumed. The reaction was then diluted with dichloromethane (150 mL) and washed with aq. Na2S2O3 solution (10 wt-%, 50 mL), sat. aq. bicarb solution (50 mL) and brine (50 mL). The aqueous phases were re-extracted with dichloromethane (2 × 50 mL) and the combined organic layers dried over Na2SO4, filtered and concentrated in vacuo. Thus obtained crude brown wax was redissolved in acetonitrile and purified via reversed-phase HPLC (C-18 reversed-phase silica, gradient MeCN/H2O = 20:80 to 95:5). The product containing fractions were collected and lyophilized, yielding alkene C1-7 (540 mg, 0.53 mmol, 62%, two steps) as colorless foam. R_f(n-Hex:EtOAc = 2:1) = 0.35. ESI-LRMS for C₅₂H₅₅D₃F₃N₁₀O₉+ [MH+]: calculated 1026.5 found 1026.5. 3.5 From Alkene C1-7 to Alcohol C1-8 Alkene C1-7 (540 mg, 0.53 mmol, 1.00 eq.) and PdCl2 (37.4 mg, 0.21 mmol, 0.40 eq.) were dissolved in dry methanol (16.2 mL) under inert gas atmosphere at room temperature. The resulting mixture was stirred for 40 hours until the starting material (C1-7) was completely consumed and subsequently filtered over a short Celite® plug (methanol washings). The obtained yellow wax was purified via reversed-phase HPLC (C-18 reversed-phase silica, gradient MeCN/H2O = 20:80 to 95:5). The product containing fractions were collected and lyophilized, yielding alcohol C1-8 (494 mg, 0.50 mmol, 95%) as colorless foam. R_f(n-Hex:EtOAc = 2:1) = 0.30. ESI-LRMS for C₄₉H₅₁D₃F₃N₁₀O₉+ [MH+]: calculated 986.4 found 986.6. 3.6 From Alcohol C1-8 to Triazide C1-9

Alcohol C1-8 (50.0 mg, 50.7 μmol, 1.00 eq.) and predried benzenesulfonyl hydrazide (51.7 mg, 0.30 mmol, 6.00 eq.) were suspended in dry p-xylene (2.80 mL) via sonication in a proper pressure vessel under inert gas atmosphere. The reaction mixture was heated to 145 °C for 30 minutes, upon which a new batch of predried benzenesulfonyl hydrazide (51.7 mg, 0.30 mmol, 6.00 eq.) was added. The reaction mixture was again heated to 145 °C and the described cycle was repeated every 30 minutes until two hours of reaction time had passed, about 24.0 eq. of benzenesulfonyl hydrazide had been added in total and substance C1-8 was consumed completely. The reaction mixture was then diluted with dichloromethane (50 mL) and washed with sat. aq. bicarb solution (40 mL). The aqueous phase was extracted with dichloromethane (2 × 30 mL) and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude orange product was redissolved in acetonitrile and purified via reversed- phase HPLC (C-18 reversed-phase silica, gradient MeCN/H2O = 20:80 to 95:5). The product containing fractions were collected and lyophilized, yielding triazide C1-9 (33.9 mg, 34.3 μmol, 67%) as colorless foam. R_f(n-Hex:EtOAc = 3:1) = 0.20. ESI-LRMS for C₄₉H₅₃D₃F₃N₁₀O₉+ [MH+]: calculated 988.4 found 988.4. 3.7 From Triazide C1-9 to Mesylate C1-10

Triazide C-19 (150 mg, 0.15 mmol, 1.00 eq.) was dissolved in dry pyridine (3.40 mL) at room temperature under inert gas atmosphere. The stirred mixture was cooled to 0 °C and mesyl chloride (94.1 μL, 1.20 mmol, 8.00 eq.) was added dropwise. After ten minutes the reaction was warmed to room temperature and stirred for three hours. Absolute ethanol (100 μL) was added at 0 °C to quench the reaction and stirring continued for another 10 minutes. Subsequently, the resulting solution was diluted with dichloromethane (50 mL), then quickly washed with aq. HCl (0.2 ^M, 2 × 50 mL) and aq. bicarb solution (7.0 wt-%, 50 mL). The aqueous phases were re-extracted with dichloromethane (2 × 50 mL) and the combined organic layers dried over Na2SO4, filtered and concentrated in vacuo. The crude product (C1-10) was obtained as colorless foam (211 mg) and used a such for further reaction without additional purification. Rf(n-Hex:EtOAc = 3:1) = 0.25. ESI-LRMS for C50H55D3F3N10O11S+ [MH+]: calculated 1066.4 found 1066.6. 3.8 From Mesylate C1-10 to Methylamine C1-11

The crude mesylate C1-10 (assumed 0.15 mmol) was suspended in aq. methylamine (44 wt-%, 6.00 mL) in a suitable pressure vessel under inert gas atmosphere at room temperature. The reaction mixture was heated to 105 °C under vigorous stirring and was reacted for 48 hours. Reaction control via LMCS indicated complete conversion at this point. Subsequently, the resulting solution was diluted with sat. aq. bicarb solution (50 mL) and extracted with dichloromethane (4 × 50 mL). The combined organic layers were dried over Na₂SO₄, filtered and concentrated in vacuo. The obtained yellowish foam (216 mg) was redissolved in acetonitrile and purified via reversed-phase HPLC (C-18 reversed-phase silica, gradient MeCN/H₂O/TFA = 20:80:0.05 to 95:5:0.05). The product containing fractions were collected and lyophilized, yielding methylamine C1-11 (141 mg, 126 μmol, 83%) as its TFA salt as colorless solid with a d.r. = 1:2, disfavoring the above shown stereochemistry at the introduced methylamine residue. ESI-LRMS for C₅₀H₅₆D₃F₃N₁₁O₈+ [MH+]: calculated 1001.5 found 1001.6. 3.9 From Methylamine C1-11 to Tetraamine C1-12

Methylamine C1-11 (141 mg, 126 μmol, 1.00 eq.) was dissolved in dry tetrahydrofuran (3.0 mL) under inert gas atmosphere at room temperature. Then, trimethylphosphine (1 M in THF, 0.76 mL, 0.76 mmol, 6.00 eq.) was added under stirring and the reaction heated to 50 °C for three hours. After cooling to room temperature, the resulting mixture was concentrated in vacuo and then redissolved in a mixture of water, TFA and methanol (v/v = 4:0.04:1, 1.0 mL) and purified via reversed-phase HPLC (Chromolith® C-18 reversed-phase silica, gradient MeCN/H2O/TFA = 10:90:0.1 to 98:2:0.1). The product containing fractions were collected and lyophilized, yielding tetraamine C1-12 (153 mg, 111 μmol, 88%) as its TFA salt as colorless solid with a d.r. = 1:2, disfavoring the above shown stereochemistry at the deuterium labeled methyl group. ESI-LRMS for C₅₀H₆₂D₃F₃N₅O₈+ [MH+]: calculated 922.5 found 922.5. 3.10 From Tetraamine C1-12 to Triol C1-13

The TFA salt of tetraamine C1-12 (153 mg, 111 μmol, 1.00 eq.) was dissolved in methanol (4.33 mL) and aq. HCl (0.1 M, 6.50 mL) at room temperature under inert gas atmosphere. Pearlman’s catalyst (20 wt-% Pd, 234 mg, 333 μmol, 3.00 eq.) was added and the reaction mixture vigorously stirred and flushed with H2 (1 atm, 3 times). The mixture was hydrogenated for 22 hours upon which it was filtered over a Celite® plug (methanol washings). The resulting solution was concentrated in vacuo yielding a colorless solid residue which was then redissolved in a mixture of water, TFA and methanol (v/v = 4:0.04:1, 1.0 mL). Purification via reversed-phase HPLC (C-18 reversed-phase silica, gradient MeCN/H2O/TFA = 5:95:0.05 to 90:10:0.05). The product containing fractions were collected and lyophilized, yielding triol C1- 13 (103 mg, 92.9 μmol, 84%) as its TFA salt as colorless solid with a d.r. = 1:2, disfavoring the above shown stereochemistry at the deuterium labeled methyl group. ESI-LRMS for C29H44D3F3N5O + 8 [MH+]: calculated 653.4 found 653.3. 3.11 From Triol C1-13 to Gentamicin C1-D3

The TFA salt of triol C1-13 (102 mg, 92.0 μmol, 1.00 eq.) was dissolved in aq. sodium hydroxide solution (1.5 M, 4.11 mmol, 67.0 eq.) under inert gas atmosphere at room temperature. The reaction was heated to 60 °C under stirring for 7 hours upon which C1-13 was completely consumed. The pH value was adjusted to ca.6.0 via addition of a mixture of H2O and TFA (v/v = 4:1) and the resulting mixture concentrated in vacuo. The obtained yellowish wax was redissolved a mixture of H2O and TFA (v/v = 98:2) and purified via reversed-phase HPLC-MS (C-18 reversed-phase silica, gradient MeCN/H2O/TFA = 0:100:0.2 to 10:90:0.2). The product containing fractions were collected and lyophilized, yielding Gentamicin C1-D3 (25.5 mg, 24.3 μmol, 26%) as its TFA salt, colorless solid and as single isomer. ESI-HRMS for C₂₁H₄₁D₃N₅O₇+ [MH+]: calculated 481.3424 found 481.3477. 1H NMR (D₂O, DCl, DDS, 500 MHz): δ = 5.86 (J = 3.51 Hz, 1H), 5.12 (d, J = 3.66 Hz, 1H), 4.24 (dd, J = 11.00, 4.00 Hz), 4.17 (dt, J = 12.28, 2.63 Hz, 1H), 4.07−3.97 (m, 2H), 3.87 (t, J = 8.85 Hz, 1H), 3.81 (t, J = 9.77 Hz, 1H), 3.67−3.55 (m, 3H), 3.53 (dd, J = 12.97, 6.71 Hz, 2H), 3.49 (d, J = 2.90 Hz, 1H), 2.94 (s, 3H), 2.76 (s, 3H), 2.57 (dt, J = 12.59, 4.16 Hz, 1H), 2.12−1.94 (m, 4H), 1.58 (dq, J = 13.40, 4.30 Hz, 1H), 1.37 (s, 3H) ppm. 13C NMR (D₂O, DCl, DDS, 125 MHz): δ = 104.0, 98.3, 86.5, 79.7, 72.6, 72.1, 70.6, 69.0, 66.0, 60.3, 52.3, 51.5, 51.1, 37.2, 34.0, 30.7, 25.0, 23.7, 23.3 ppm. 19F NMR (D₂O, DCl, DDS, 470 MHz): δ = 75.59 (s) ppm. 4. Example 4: Experiments for Gentamicin C1-D₃ – According to the preferred Synthesis of Gentamicin C1 (Method A2): 4.1 From Alcohol 4 to Triamine C1-14

Alcohol 4 was dissolved in THF (16 mL/mmol) and treated with 0.1 M NaOH and PMe₃ (1 M in THF, 4 equiv.). The mixture was stirred at room temperature until strong gas evolution had ceased and the mixture was subsequently heated to 50 °C for 30 min. The solvent was removed under reduced pressure and the crude product was purified via RP-MPLC (25^100 % MeCN) to give the desired product C1-14 as a yellow/beige solid. ESI-LRMS for C₅₅H₆₉D₃F₃N₄O₁₃+ [MH+]: calculated 1057.52 found 1057.60. 4.2 From Triamine C1-14 to Alcohol C1-15 Triamine C1-14 was dissolved in a mixture of THF / sat. NaHCO₃ (v:v = 1:1, 80 mL/mmol), CbzCl (4 equiv.) was added and the mixture was stirred thoroughly for one hour at room temperature. After analysis via UHPLC indicated full conversion to the desired product, the layers were separated, and the aqueous phase re-extracted twice with EtOAc. The combined organic fractions were dried over sodium sulfate, filtered and the solvent removed under reduced pressure. Purification via flash chromatography (25^75 % EtOAc in cyclohexane) gave the desired product C1-15 as a yellow foam. ESI-LRMS for C₇₉H₈₇D₃F₃N₄O₁₉+ [MH+]: calculated 1457.63 found 1457.61. 4.3 From Alcohol C1-15 to Mesylate C1-16

Alcohol C1-15 was dissolved in anhydrous pyridine (20 mL/mmol) and methanesulfonyl chloride (3 equiv.) was added. The mixture was stirred at room temperature for 16 h. After analysis via UHPLC indicated full conversion, the mixture was quenched by addition of saturated sodium bicarbonate solution and the mixture was extracted with dichloromethane. After phase separation, the aqueous phase was re-extracted twice with dichloromethane. The combined organic fractions were dried over sodium sulfate, filtered and the solvent removed under reduced pressure. Purification via flash chromatography (25^70 % EtOAc in cyclohexane) yielded mesylate C1-16 as a beige foam. ESI-LRMS for C₈₀H₈₉D₃F₃N₄O₂₁+ [MH+]: calculated 1536.60 found 1536.65. 4.4 From Mesylate C1-16 to Azide C1-17

Mesylate C1-16 was dissolved in anhydrous DMF (16 mL/mmol) and sodium azide (10 equiv.) was added. The mixture was heated to 80 °C and stirred at this temperature for 16 h. After analysis via UHPLC indicated full conversion, the mixture was quenched by addition of water and the mixture was extracted with EtOAc. After phase separation, the aqueous phase was re- extracted twice with EtOAc. The combined organic fractions were washed with sat. sodium bicarbonate solution, dried over sodium sulfate, filtered and the solvent removed under reduced pressure. The crude product C1-17 (brownish-beige foam) was directly used in the next step. ESI-LRMS for C₇₉H₈₆D₃F₃N₇O₁₈+ [MH+]: calculated 1483.63 found 1483.61. 4.5 From Azide C1-17 to Diol C1-18

Azide C1-17 Diol C1-18 C₇₉H₈₅D₃F₃N₇O₁₈ C₇₃H₇₅D₃F₃N₇O₁₆ M_w = 1483.61 g/mol M_w = 1369.47 g/mol Compound C1-17 was dissolved in dichloromethane / water (v:v = 15:1, 9 mL/mmol) and TFA (55 equiv.) was added. The mixture was stirred for two hours and then quenched carefully by addition of saturated sodium bicarbonate solution until termination of gas evolution. The layers were separated and the aqueous phase re-extracted twice with dichloromethane. The combined organic fractions were dried over Na₂SO₄ and the solvent removed under reduced pressure. Purification via RP-MPLC (60-100 % MeCN) gave the desired product C1-18 as a white foam. ESI-LRMS for C₇₃H₇₅D₃F₃N₇O₁₇+ [MH+]: calculated 1368.56 found 1368.56. 4.6 From Diol C1-18 to Bistriflate C1-19 Tf₂O OBn p OBn Cbz OH y Cbz OTf Me O N M_e ^N O OH Me O N OTf CD CH Cl O BnO BnO H _{3 2 2 Me} ^N BnO H CD₃ O O H N₃ 0 °C, Ar BnO O O H N₃ O HN N HN N C_bz ^Cbz O C_bz ^Cbz CF₃ CF₃ Diol C1-18 Bistriflate C1-19 C₇₃H₇₅D₃F₃N₇O₁₆ C₇₅H₇₃D₃F₉N₇O₂₀S₂ M_w = 1369.47 g/mol M_w = 1633.59 g/mol Diol C1-18 was dissolved in dichloromethane (5.5 mL/mmol) and anhydrous pyridine (30 equiv.) was added under argon. The solution was cooled to 0 °C and triflic anhydride (10 equiv.) was added. The mixture was stirred at 0 °C for 24 to 48 hours (until UHPLC analysis indicated completion of reaction). The reaction mixture was diluted with dichloromethane and carefully quenched with sat. NaHCO3 (aq.) solution. The aqueous phase was extracted with dichloromethane (2 times), washed with 10 wt-% citric acid (aq.), dried over sodium sulfate and the solvent removed under reduced pressure. Bistriflate C1-19 was used for further reaction without any additional purification. ESI-LRMS for C₇₅H₇₄D₃F₉N₇O₂₀S₂+ [MH+]: calculated 1633.46 found 1633.49. 4.7 From Bistriflate C1-19 to Alkene C1-20

Bistriflate C1-19 was dissolved in anhydrous acetone (20 mL/mmol) and sodium thiosulfate (6 equiv., dry) and sodium iodide (4.5 equiv., dry) were added. The mixture was stirred at room temperature for 72 hours. The orange brown reaction mixture was diluted with EtOAc and washed with 10 wt-%- sodium thiosulfate solution, sat. sodium bicarbonate solution and brine. The organic phase was dried over sodium sulfate, filtered and the solvent removed under reduced pressure. The crude product was purified via RP-MPLC (65-100 % MeCN) to yield olefin C1-20 as a yellow foam. ESI-LRMS for C H D F N + + 73 74 3 3 7O14 [MH ]: calculated 1335.56 found 1335.49. 4.8 From Alkene C1-20 to Amine C1-21

Alkene C1-20 Amine C1-21 C₇₃H₇₃D₃F₃N₇O₁₄ C₇₃H₇₅D₃F₃N₅O₁₄ M_w = 1335.46 g/mol M_w = 1309.46 g/mol Alkene C1-20 was dissolved in THF (25 mL/mmol) and treated with NaOH (aq., 0.1 M) and PMe₃ (1 M in THF, 1.5 equiv.). The mixture was stirred at room temperature for 16 hours. After completion of the reaction (indicated by UHPLC), acetic acid (20 equiv.) was added and the solvent was removed under reduced pressure. The crude product was purified via RP-MPLC (50^100 % MeCN) to give the desired product C1-21 as an orange solid. ESI-LRMS for C₇₃H₇₆D₃F₃N₅O₁₄+ [MH+]: calculated 1309.57 found 1309.60. 4.9 From Amine C1-21 to Methylbenzylamine C1-22

Amine C1-21 Methylbenzylamine C1-22 C₇₃H₇₅D₃F₃N₅O₁₄ C₈₁H₈₃D₃F₃N₅O₁₄ M_w = 1309.46 g/mol M_w = 1413.61 g/mol To free amine C1-21 in MeOH (6 mL/mmol) were added benzaldehyde (1.1 equiv.), sodium cyanoborohydride (1.15 equiv.) and acetic acid (1.0 equiv.). The mixture was stirred at room temperature until the starting material was consumed. Paraformaldehyde (5 equiv.), 3 Å molecular sieves and acetic acid (10 equiv.) were added and the mixture was stirred at room temperature for 4 hours. Subsequently, sodium cyanoborohydride (2.5 equiv.) was added and the mixture was stirred for additional 16 hours. The mixture was quenched by addition of sat. sodium bicarbonate solution and extracted with EtOAc (3 times). The combined organic layers were dried, filtered and the solvent removed under reduced pressure. The crude product was purified by RP-MPLC (50^100 % MeCN) to give the desired product C1-22 as a beige solid. ESI-LRMS for C₈₁H₈₄D₃F₃N₅O₁₄+ [MH+]: calculated 1413.62 found 1413.71. 4.10 From Methylbenzylamine C1-22 to Methylamine C1-23 Compound C1-22 was suspended in AcOH/H2O (v:v = 2:1, 30 mL/mmol) and Pd/C (10%,1 equiv.) was added. The atmosphere was exchanged for hydrogen (4 times) and the mixture stirred at room temperature until the starting material and all intermediates were converted to the desired product. The atmosphere was exchanged for argon and the mixture filtered over a pad of Celite, which was washed thoroughly with water. The combined fractions were freeze- dried or the solvent removed via azeotropic distillation with MeOH. The crude product was purified via RP-MPLC (0^50% MeCN) to give the desired product C1-23 as a TFA salt, being an off-white solid. ESI-LRMS for C29H44D3F3N5O + 8 [MH+]: calculated 653.35 found 653.36 4.11 From Methylamine C1-23 to Gentamicin C1-D3

Methylamine C1-23 was dissolved in a sat. solution of barium hydroxide (35 equiv.) and heated to 60 °C. After full consumption of the starting material, dry ice was added until a pH-value of 7 was reached. The mixture was filtered and the solid precipitate washed with water. TFA (20 equiv.) was added to the aqueous phase and the anew formed white precipitate filtered off. The filter cake was washed with water and the combined aqueous phases were frozen in a dry ice/iPrOH bath and freeze-dried. The crude product was purified via RP-HPLC to give Gentamicin C1-D₃ as a TFA-salt, being an off-white solid. The analytical data recorded for a compound obtained by the described reaction sequence proved identical to the data described already above in chapter 3.11 of the examples section. Example B: Use of Gentamicin C1-D₃, Gentamicin C1a-15N D₂, Gentamicin C2-D₃ as internal standards in MRM-based LCMS analytics of Gentamicin. Method: To quantify both the total amount of Gentamicin C as mixture of congeners and the content of the single congeners Gentamicin C1 and C1a, as well as the mixture of congeners being Gentamicin C2, C2a and C2b in a sample a LC-MS/MS method was devised including tuned MRM transitions for all compounds. A SeQuant Zic-cHILIC, 3 µm, 100 Å, 2.1 mm × 100 mm column (Merck KgaA; batch: FC098347; serial number: 913801) with solvent A: water with 1.0% HCOOH and 50 mM NH₄Ac and solvent B: CH₃CN with 1.0% HCOOH and a flow of 0.5 mL per minute on an Agilent Infinity II with PAL autosampler connected to an AB Sciex 6500+ MS, was used. For Gentamicin C1-D₃, Gentamicin C1a-15N D₂ and Gentamicin C2-D₃, two MRM transitions were used. Native Gentamicin C as mixture of congeners, included in the measurement, was analyzed regarding its composition of congeners in advance via quantitative 1H NMR spectroscopy (Gentamicin C128.5%, Gentamicin C1a 28.5%, Gentamicin C2, C2a and C2b 42.8%).

Table B1: Employed MRM transitions for Gentamicin C congeners and isotopically labeled internal standards. Additional MS parameters: Period summary (duration 6.000 min, delay time 0, cycles 2116, cycle 0.1701 sec), source gas (turbo spray IonDrive: curtain gas 40.0, collison gas 10, IonSpray voltage 3000.0, temperature 400.0, ion source gas 160.0 ion source gas 260.0). Calibration curve: Using the mixture of congeners of native Gentamicin C of known composition (see above) and the MRM transition settings described in table B1, a calibration curve was recorded by plotting the area ratio (area analyte / area internal standard) against the analyte concentration. The samples measured contained the internal standards Gentamicin C1- D₃ (2 µg/mL), Gentamicin C1a-15N-D₂ (2 µg/mL) and Gentamicin C2-D₃ (2 µg/mL), as well as the respective concentration of the congener mixture of native Gentamicin C given in table B2 (samples Cal1 to Cal6). The solvent mixture for all calibration and quality control (QC) samples was 100 mM formic acid in water. Three samples (QC1 to QC3) of unknown concentration of the mixture of congeners of native Gentamicin C were measured to access mean recovery (%) and the CV recovery (standard deviation/mean value * 100) of the established calibration curve. The results thereof are given in table B2 as well.

Table B2: Experimental details for the measurement of the calibration curve and the quality control samples thereof. The samples Cal 1-6 and QC 1-3 contained the internal standards Gentamicin C1-D₃ (2 µg/mL), Gentamicin C1a-15N-D₂ (2 µg/mL) and Gentamicin C2-D₃ (2 µg/mL) in 100 mM formic acid in water. MRMs for the internal standards are given in table B1. For the mean recovery every sample was measured 3 times and the shown value is the arithmetical mean. The figures 12_B1 to 12_B3 show the exemplified chromatograms for the samples Cal1 and Cal 6 for the determination of the content of Gentamicin C1, Gentamicin C2 and Gentamicin C1a, respectively. The above shown results exemplify the applicability of use of isotopically labeled Gentamicin C congeners in substantially pure form, substantially free from respective other congeners in mixture with other isotopically labeled Gentamicin C congeners of similar grade to determine the content of Gentamicin C congeners, and thus the whole Gentamicin C content, in an in vitro sample of unknown concentration via MRM-based mass spectrometry coupled to a LC system. Furthermore, the shown concentration range of analyte is suitable to quantify amounts of Gentamicin C typically found in human serum and plasma. Thus, the employed isotopically labeled Gentamicin C congeners can be employed for the development of diagnostic methods to analyze humane samples of known volume according to their Gentamicin C content or the content of distinct Gentamicin C congeners. LITERATURE CITED - Ruben M. Sandoval et al. A Non-Nephrotoxic Gentamicin Congener That Retains Antimicrobial Efficacy, JASN October 2006, 17 (10) 2697-2705. - WO2019/079706. - Berkov-Zrihen Y. et al., Tobramycin and Nebramine as Pseudo-oligosaccharide Scaffolds for the Development of Antimicrobial Cationic Amphiphiles, Chem. Eur. J. 2015, 21, 4340 – 4349. - Semisynthetic Aminoglycoside Antibacterials. Part I. Preparation of Selectively Protected Garamine Derivatives, J. Chem. Soc., Perkin Trans.1, 1976, 1088-1097. - Stephen Hanessian and Juan Pablo Maianti, Biomimetic synthesis and structural refinement of the macrocyclic dimer aminoglycoside 66-40C—the remarkably selective self-condensation of a putative aldehyde intermediate in the submerged culture medium producing sisomicin, Chem. Commun., 2010, 46, 2013-2015. - Xifu Liang, Richard Krieger and Horst Prinzbach, D- and L- Purpurosamine C Type Glycosyl Donors Starting from D- Glucosamine, Tetrahedron Letters, Vol.36, No.36, pp.6433-6436, 1995. - Jianjun Zhang, Anthony Litke, Katherine Keller, Ravi Rai, Cheng-Wei Tom Chang, Synthesis of novel aminoglycosides via allylic azide rearrangement for investigating the significance of 2′-amino group, Bioorganic & Medicinal Chemistry 18 (2010) 1396– 1405. - Synlett 1996, 8, 793-795. - J. Chem. Soc., Perkin Trans.1, 1997, 2023-2032. - Rajasejaran P. et al., Synthesis of Gentamicin Minor Components: Gentamicin B1 and Gentamicin X2, Org. Lett.2020, 3850-3854.

Claims

Roche Diagnostics GmbH RD14252PC F. Hoffmann-La Roche AG Roche Diagnostics Operations, Inc. CLAIMS 1. An isotope labeled gentamicin C or a salt or solvate thereof, the gentamicin C comprising at least one 13C, D and/or 15N atom; wherein the isotope labeled gentamincin C has the structure

wherein R1, R2 and R3 are, independently of each other, selected from the group consisting of - H, -D, -CH3, -13CH3, -13CDH2, -13CD2H, -13CD3, -CDH2, -CD2H and -CD3, wherein at least one of R1 or R2 is -H or -D, R4 is selected from the group consisting –NH-, -ND-, -15ND- and -15NH-, R5 is selected from the group consisting of –NH 15 15 15 2, -ND2, - ND2, - NDH and - NH2, R6, R7 and R8 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH- R9 and R10, are, independently of each other, selected from the group consisting of –CH2-, -CDH-, -CD2-, -13CDH-, -13CD2- and -13CH2- and wherein R11 is C or 13C. 2. The isotope labeled gentamicin C according to claim 1, wherein isotope labeled gentamicin C comprises less than 1 % by weight, of respective other gentamicin C congeners, based on the total amount of the isotope labeled gentamicin C. 3. A compound of formula (I*) OPG₂ OPG₅ 6 91 R 101 R Me O N PG O ₃ R 7 OPG O 8 011 ₆ R Me ^N ₃ R _R PG O OPG₄ P^G ₃O O 1 N₃ N_{3 (I*),} preferably of formula (I) OPG₂ OPG₅ 6 91 R 101 R Me O N e ^N P ₃ R 7 OPG O 8 ₆M G₃O R _R PG₃O O O OPG₄ P^G1 N₃ N_{3 (I),} wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH 13 13 2-, -CD2-, -CHD-, - CD2-, - CH2-, - 13CHD-, and –R11(R1R2)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH , -13 13 13 13 3 CH3, - CDH2, - CD2H, - CD3, -CD2H, -CDH , and -CD , wherei 1 2 11 2 3 n at least one of R or R is -H or -D, and wherein R is C or 13C, and wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein - PG1 is a protecting group selected from the group consisting of Cbz, benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, - PG2 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3- DMPM), and 4-(3,4-Dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, - PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3- DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, - PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), - and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group, preferably wherein the compound has the structure (Ia)

wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein - PG1 is a protecting group selected from the group consisting of Cbz, benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, - PG2 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3- DMPM), and 4-(3,4-Dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, - PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3- DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, - PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), - and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group. 4. A compound of formula (I*)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, - 13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, and wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein - PG1 is a protecting group selected from the group consisting of Cbz, benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, - PG2 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3- DMPM), and 4-(3,4-Dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, - PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3- DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, - PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), - and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group, preferably wherein the compound has the structure (Ia)

wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein - PG1 is a protecting group selected from the group consisting of Cbz, benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, - PG2 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3- DMPM), and 4-(3,4-Dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1, - PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4-DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3- DMPM), and 4-(3,4-dimethoxyphenyl)benzyl, - PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), - and wherein PG5 and PG6 form together a cyclic group, preferably a diacetal protecting group; the compound of formula (I*), the compound of formula (I) and the compound of formula (Ia) each comprising at least one 13C, D and/or 15N atom. 5. A method for the preparation of gentamicin C or salt or solvate or derivate thereof, wherein the gentamicin C is preferably selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a, and wherein the gentamicin C is preferably isotope labeled, the method comprising (i) reacting a glycosylation acceptor (A) of formula

with a glycosylation donor (B*) of formula

preferably of formula (B)

to give a compound having the structure (I*)

preferably having formula (I)

wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, - 13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein PG1 is a protecting group selected from the group consisting of Cbz, benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM,

2,6-DMPM, and 2,

3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1 , PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,

4- DMPM, 3,5-DMPM, 2,

5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert- butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 form together a cyclic protecting group, preferably a diacetal protecting group, and wherein the method preferably further comprises (ii) removing the protecting group PG 4 to give a compound of formula (I-1*)

6. A method for the preparation of gentamicin C or salt or solvate or derivate thereof, wherein the gentamicin C is preferably selected from the group consisting of gentamicin C2, gentamicin C2a, gentamicin C2b, gentamicin C1 and gentamicin C1a, and wherein the gentamicin C is isotope labeled and comprises at least one 13C, D and/or 15N atom, the method comprising (ii) reacting a glycosylation acceptor (A) of formula

with a glycosylation donor (B*) of formula

to give a compound having the structure (I*)

preferably having formula (I) OPG₂ OPG₅ 6 91 R 101 R Me O N₃ R 7 8 OPG₆ Me ^N PG₃O R O _R PG OPG₄ P^G ₃O O O 1 N₃ N_{3 (I),} wherein R6, R7, R8, R91 and R101 are, independently of each other, selected from the group consisting of –CH-, -CD-, -13CD- or -13CH-, R011 is selected from the group consisting –CH₂-, -CD₂-, -CHD-, -13CD₂-, -13CH₂-, - 13CHD-, and –R11(R₁R₂)-, wherein R1 and R2 are, independently of each other, selected from the group consisting of -H, -D, -CH₃, -13CH₃, -13CDH₂, -13CD₂H, -13CD₃, -CD₂H, -CDH₂, and -CD₃, wherein at least one of R1 or R2 is -H or -D, and wherein R11 is C or 13C, wherein PG1, PG2, PG3, PG4, PG5 and PG6 are suitable protecting groups, and wherein PG4 is orthogonal to PG1, PG2, PG3, PG5 and PG6, in particular wherein PG1 is a protecting group selected from the group consisting of Cbz, benzoyl (Bz), acetyl, trifluoromethyl-benzoyl, trifluoroacetyl, and cyclic protecting groups forming a cyclic group together with PG2, PG2 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, as well as cyclic protecting groups forming a cyclic group together with PG1 , PG3 is a protecting group selected from the group consisting of silyl protecting groups, preferably 2-(trimethylsilyl)ethoxymethyl (SEM), tert-butyldimethylsilyl (TBS), tert- butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), as well as benzyl protecting groups, preferably benzyl (Bn), para-methoxybenzyl (PMB), dimethoxybenzyl (3,4- DMPM, 3,5-DMPM, 2,5-DMPM, 2,6-DMPM, and 2,3-DMPM), and 4-(3,4- dimethoxyphenyl)benzyl, PG4 is a silyl protecting group, a pivaloyl group (Piv) or a benzoyl protecting group, preferably benzoyl (Bz), 2,4,6-trimethylbenzoyl, para-phenyl-benzoyl, para- bromobenzoyl, trifluoromethyl-benzoyl or 2-(trimethylsilyl)ethoxymethyl (SEM), tert- butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), and triisopropylsilyl (TIPS), and wherein PG5 and PG6 form together a cyclic protecting group, preferably a diacetal protecting group, and wherein the method preferably further comprises (iii)removing the protecting group PG 4 to give a compound of formula (I-1*)

7. The method of claim 5 or 6, the glycosylation acceptor (A) having the structure

and the glycosylation donor (B) having the structure

and the compound of formula (I) having the structure

. 8. The method of claim 5 or 6, the glycosylation acceptor (A) having the structure

and the glycosylation donor (B) having the structure

and the compound of formula (I) having the structure

. 9. A diagnostic composition comprising at least one isotope labeled gentamicin C according to any one of claims 1 to 4 or at least one isotope labeled gentamicin C or a salt or solvate thereof comprising at least one 13C, D and/or 15N atom, or the gentamicin C being obtained or obtainable by a method according to any one of claims 5 to 8, and a suitable excipient. 10. Use of at least one isotope labeled gentamicin C according to any one of claims 1 to 4 or at least one isotope labeled gentamicin C or a salt or solvate thereof comprising at least one 13C, D and/or 15N atom, or the gentamicin C being obtained or obtainable by a method according to any one of claims 5 to 8 as calibration standard for determining the amount of at least one gentamicin C congener present in a sample. 11. A method of determining the amount of at least one analyte of interest, preferably of at least one gentamicin C congener, present in a sample said method comprising (a) mixing the sample with a known amount of at least one isotope labeled gentamicin C according to any one of claims 1 to 4 or at least one isotope labeled gentamicin C or a salt or solvate thereof comprising at least one 13C, D and/or 15N atom, or the gentamicin C being obtained or obtainable by a method according to any one of claims 5 to 8 (b) analyzing the sample via a mass spectrometry (c) comparing the peak area of at least one analyte of interest to a standard curve, wherein said standard curve has been created using the at least one isotope labeled gentamicin C or a salt or solvate or derivative, as described above and standards containing at least one analyte of interest, thereby determining the amount of the at least analyte of interest in the sample. 12. A computer-implemented method for assessing a sample comprising at least one gentamicin congener, the method comprising the steps of: (aa) mixing the sample with a known amount of at least one isotope labeled gentamicin C according to any one of claims 1 to 4 or at least one isotope labeled gentamicin C or a salt or solvate thereof comprising at least one 13C, D and/or 15N atom, or the gentamicin C being obtained or obtainable by a method according to any one of claims 5 to 8, or mixing the sample with a known amount of the diagnostic composition of claim 9, and receiving the value for the peak area of said isotope labeled gentamicin C in a sample (bb) receiving a value for the peak area of at the least one gentamicin C congeners present in the sample, (cc) comparing the values for the peak area of the at least one isotope labeled gentamicin C and the at the least one gentamicin C congeners and receiving a value for the amount of at least one gentamicin C congener; and (dd) assessing the sample on the comparison and/or the calculation made in step (cc).