IT202000029195A1 - DIAGNOSTIC PROBES TO HIGHLIGHT INFRARED CELLS AND TISSUES AFFECTED BY PATHOLOGICAL OR METABOLIC CONDITIONS - Google Patents

Description

DESCRIPTION

Attached to a patent application for INDUSTRIAL INVENTION having the title

?Diagnostic probes to highlight cells and tissues affected by pathological or metabolic conditions in infrared?

TECHNICAL FIELD

The present invention belongs to the field of IR imaging and relates to a compound having general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof and a pharmaceutical composition comprising it. The present invention also relates to an in vitro diagnostic method for the detection, by infrared spectroscopy (IR), of cells and/or tissues affected by a pathological or metabolic condition in isolated biological samples.

STATE OF ART

The development of infrared probes (IR probes) represents an emerging field especially in the field of medical diagnostics which is instead currently based mainly on radioactive/radioopaque, luminescent markers, etc., while diagnostic techniques using infrared spectroscopy are not yet particularly widespread. How ? Known, cells and tissues have an IR transparency zone generally between 1800 and 2200 cm<-1>. This area of frequencies pu? therefore be exploited for diagnostic and chemical-physical characterization purposes using suitable probes characterized by strong absorptions in such an interval, conjugated with biomolecules to allow the establishment of interactions with the specific biological target. Chemical compounds showing high absorptions in such a frequency window are mainly represented by metal carbonyl complexes which show levels of sensitivity? more high compared to other functional groups generally used in the sector (such as, for example, nitriles) thanks to their high extinction coefficient, often higher than the value of 4000 M<-1>cm<-1>. For these reasons, in recent years, the metal-carbonyl complexes have been increasingly? studied and investigated as potential IR probes. Among these, the (cyclopentadienyl)rhenium(I) tricarbonyl complexes appear to be particularly attractive as they not only possess a strong IR absorption in the frequency range between 1900 and 2100 cm<-1>, but also exhibit chemical characteristics and ideal structures for their use as IR diagnostic probes. These complexes are in fact generally stable from a chemical point of view: they are not subject to hydrolysis reactions in aqueous media nor? to enzymatic degradation reactions in biological systems. Furthermore, these complexes are characterized by having limited dimensions and by essentially hydrophobic characteristics, thus allowing to minimize possible interferences with the interactions that must take place between the complexes themselves (when conjugated with biomolecules) and the specific biological target. As described by I. Peran et al. ?General Strategy for the Bioorthogonal Incorporation of Strongly Absorbing, Solvation-Sensitive Infrared Probes into Proteins?, J. Phys. chem. B 2014, 118 (28), 7946-7953, portions of (cyclopentadienyl)rhenium(I) tricarbonyl are already? been conjugated to large proteins, in order to label them and make them visible to IR in aqueous solutions. However, IR probes comprising portions of (cyclopentadienyl)rhenium(I) tricarbonyl linked to small bioactive molecules such as for example carbohydrates or oligopeptides/aminoacids do not appear to be known in the current state of the art. In the context of diagnostic probes containing carbohydrates, currently, the diagnosis and characterization of tumor pathologies are mainly based on the use of radioactive markers, such as, for example, fluorodeoxyglucose (FDG) used in Positron Emission Tomography (PET). The FDG ? a radioactive analogue of glucose which allows tumors to be made visible by exploiting the peculiar metabolism found in most tumors which tend to rapidly absorb large quantities of glucose. Such a technique, although widely used in in vivo imaging, is however less suitable for more advanced applications. routines that instead require, for example, the identification of tumor cells in ex vivo samples deriving from solid or liquid biopsies. This limitation mainly derives from the fact that FDG contains a fluorine radionuclide (F-18) which has a relatively short half-life (approximately 2 hours) and, therefore, must be produced by special generators which are not always present in the vicinity? of diagnostic facilities. Also, one more downside? represented by the fact that radiopharmaceuticals such as the FDG necessarily need caution in their production and handling significantly increasing cos? the costs related to their use in terms of laboratory and/or healthcare personnel. As regards instead diagnostic probes containing portions of the amino acid or oligopeptide type, as described by Y. Zou et al ?Cyclic RGD-Functionalized and Disulfide-Crosslinked Iodine-Rich Polymersomes as a Robust and Smart Theranostic Agent for Targeted CT Imaging and Chemotherapy of Tumor?, Theranostics 2019, 9, 8061, diagnostic probes incorporating cyclic tripeptides containing arginine-glycine-aspartate (c-RDG) are known, for example, used as contrast agents in computed tomography (CT) for the visualization of some tumor forms, thanks to the high affinity? and specificity? of this oligopeptide for integrins, transmembrane proteins that are often over-expressed in neoplastic tissues. However, even in this case, it is a diagnostic technique that involves the use of ionizing radiation. The present invention solves the problems of the known art, in particular related to the use of diagnostic technologies based on ionizing radiations, providing an efficient IR diagnostic probe. In particular, with the present invention, the Applicant provides a compound containing a moiety capable of being recognized by diseased cells or tissues and a ?probe? able to absorb in the IR transparency window of said cells or tissues thus allowing? effective characterization and visualization using infrared spectroscopy. The present invention also makes available an imaging method which allows cells and tissues affected by pathologies or metabolic conditions to be effectively highlighted in a rapid, non-invasive and non-radioactive manner.

SUMMARY OF THE INVENTION

The present invention relates to a compound of general formula (I):

Formula (I)

or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof,

in which:

Y ? selected from the group consisting of: carbohydrates of natural or synthetic origin, mimics of carbohydrates of synthetic origin, amino acids of natural or synthetic origin and derivatives thereof, or a combination thereof;

X ? selected from the group consisting of: C1-C20 linear alkyl or C3-C20 branched alkyl; said C1-C20 linear alkyl or C3-C20 branched alkyl optionally presenting one or more? groups selected from: aryl, heteroaryl, alkene, alkyne, amine, amide, ether, ester, ketone, thioether, sulfide, sulphone, sulfoxide, or a combination thereof.

The present invention also relates to a pharmaceutical composition, preferably formulated as an aqueous solution, comprising said compound of general formula (I) or a related pharmaceutically acceptable salt, stereoisomer, solvate or tautomer and one or more pharmaceutically acceptable excipients, diluents and/or carriers.

A further object of the present invention is a compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof or a pharmaceutical composition as described above, for use in the diagnosis of a pathological or metabolic condition by infrared spectroscopy (IR ), preferably said pathological or metabolic condition being selected from the group consisting of: a tumor, an infection, preferably bacterial or viral, an inflammation, a metabolic disorder, preferably metabolic syndrome, a MAGL-mediated condition, an autoimmune pathology, and a combination of them.

The present invention also relates to a method for the detection, by means of infrared spectroscopy (IR), of cells and/or tissues affected by a pathological or metabolic condition in isolated biological samples, in which said pathological condition ? preferably a tumor and said cells and/or tissues are preferably tumor cells and/or tissues. Preferably, said detection comprises the detection of alterations of protein components of said cells and/or tissues.

DESCRIPTION OF THE FIGURES

Figure 1 shows the FT-IR spectrum of untreated PDAC cells as described in Example 2.

Figure 2 shows FT-IR microscope images of untreated PDAC cells as described in Example 2.

Figure 3 shows the FT-IR spectrum of PDAC cells treated with compound F3 obtained with the synthesis described in Example 1.1, as described in Example 2.

Figure 4 shows FT-IR microscope images of PDAC cells treated with compound F3 obtained with the synthesis described in Example 1.1, as described in Example 2.

Figure 5 shows the FT-IR spectrum of PDAC cells treated with compound F1 obtained with the synthesis described in Example 1.1, as described in Example 2.

Figure 6 shows FT-IR microscope images of PDAC cells treated with compound F1 obtained with the synthesis described in Example 1.1, as described in Example 2.

Figure 7 shows the intensity display? of uptake in 3D of PDAC cells treated with compound F1 obtained with the synthesis described in Example 1.1, as described in Example 2.

Figure 8 shows the FT-IR spectrum of healthy pancreatic tissue treated with compound F3 obtained with the synthesis described in Example 1.1, as described in Example 2, with evaluation of the relationship between the intensity of the probe band compared to the amide I band (figure insert: band ratio at 2100 cm<-1>/amide I band = 0.284).

Figure 9 shows the FT-IR spectrum with the peak set on the amide I band, of PDAC tissue treated with compound F3 obtained with the synthesis described in Example 1.1, as described in Example 2, with evaluation of the relationship between the intensity ? of the probe band compared to the amide band (figure insert: band ratio at 2100 cm<-1>/amide band I = 0.536).

DETAILED DESCRIPTION OF THE INVENTION

For the purposes of the present invention, for ?ambient temperature (ta)? it means a range of temperatures between 20 and 25 ?C.

For the purposes of the present invention, the following chemical words/compounds and relative abbreviations are to be understood as reported: hours (h), minutes (min), days (dd), aqueous solution (aq.), ethyl ether (Et2O) dichloromethane ( DCM), chloroform (CHCl3), methanol (MeOH), ethyl acetate (EtOAc), dimethyl sulfoxide (DMSO), ethanol (EtOH), tetrahydrofuran (THF), diethylamine (Et2NH), triethylamine (Et3N), acetonitrile (CH3CN), N ,N-dimethylformamide (DMF), molar concentration (M), volume/volume ratio (v/v), millimoles (mmol), milliliters (mL), thin layer chromatography (TLC), nuclear magnetic resonance (NMR), triphenylphosphine (PPh3).

For the purposes of the present invention, with the expression ?possibly replaced? it means that the indicated group pu? be unsubstituted, or substituted at one or two or three positions.

For purposes of the present invention, ?C1-C20 linear alkyl? indicates a straight chain alkyl group containing from a minimum of one to a maximum of twenty carbon atoms. Similarly, with ?C3-C20 branched alkyl? means a branched chain alkyl group which contains from a minimum of three up to a maximum of twenty carbon atoms.

For the purposes of the present invention, ?aryl? denotes a ring carbocyclic system having 6 to 15 carbon atoms. This system can be a monocyclic, bicyclic or tricyclic system.

For purposes of the present invention, ?heteroaryl? indicates a ring carbocyclic system having from 6 to 15 carbon atoms comprising at least one heteroatom (that is any atom other than carbon, preferably selected from among sulphur, phosphorus, oxygen or nitrogen). This system can be a monocyclic, bicyclic or tricyclic system

For purposes of the present invention, the term "pharmaceutically acceptable salt, stereoisomer, solvate or tautomer" refers to a salt, stereoisomer, solvate or tautomer which maintains the efficacy and properties of a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer. biological compounds of the compound of general formula (I) according to embodiments of the present invention and which typically are not? biologically or otherwise undesirable.

For the purposes of the present invention, the term ?fabric? refers both to the fabric in its entirety and to a portion of said fabric.

The present invention relates to a compound of general formula (I):

Formula (I)

or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof,

in which:

Y ? selected from the group consisting of: carbohydrates of natural or synthetic origin, mimics of carbohydrates of synthetic origin, amino acids of natural or synthetic origin and their derivatives, or a combination thereof, wherein said carbohydrates of natural or synthetic origin and said mimics of carbohydrates of synthetic origin are chosen from the group consisting of:

- glucose and its derivatives, preferably alpha- and beta-O-glycosides comprising units? of D-glucose;

- fructose and its derivatives, preferably fructopyranose nuclei;

- 2,5-anhydrous D-mannitol and its derivatives;

and wherein said amino acids of natural or synthetic origin and their derivatives are selected from the group consisting of: arginine-glycine-aspartate (RGD) tripeptides, glycine, alanine, norvaline, or a combination thereof.

X ? selected from the group consisting of: C1-C20 linear alkyl or C3-C20 branched alkyl, preferably C2-C10.

According to an embodiment of the invention, said C1-C20 linear alkyl or C3-C20 branched alkyl, preferably C2-C10, has one or more? groups selected from: aryl, heteroaryl, alkene, alkyne, amine, amide, ether, ester, ketone, thioether, sulfide, sulphone, sulfoxide, or a combination thereof.

Preferably said C1-C20 linear alkyl or C3-C20 branched alkyl, preferably C2-C10, has one or more? groups selected from the group consisting of: benzene, 1,2,3-triazole, ethylene, ethyne or a combination thereof.

According to a preferred embodiment, Y ? a cycle with 5 or 6 carbon atoms.

According to a preferred embodiment, Y ? chosen from the group consisting of: alpha- and beta-O-glycosides comprising units? of D-glucose; fructopyranose nuclei, 2,5-anhydrous D-mannitol, arginine-glycineaspartate (RGD) tripeptides, glycine, alanine, norvaline, and a combination thereof. According to one embodiment of the present invention, X ? chosen from one of the groups having one of the following general formulas:

in which

p ? an integer between 0 and 18, preferably between 0 and 6;

q ? an integer between 0 and 18, preferably between 1 and 4;

r ? an integer between 0 and 1.

According to a particularly preferred embodiment of the present invention, the compound of general formula (I) or a related pharmaceutically acceptable salt, stereoisomer, solvate or tautomer as previously described? chosen between:

Without wanting to be bound to a specific theory, the Applicant has nevertheless found that said compound of general formula (I) is particularly stable from a chemical point of view, not being subject to hydrolysis reactions in aqueous media nor? to enzymatic degradation reactions in biological systems. Furthermore, said compound of general formula (I) has essentially hydrophobic characteristics which advantageously allow minimizing possible interferences with the interactions which must take place between the compound of general formula (I) itself and the specific biological target.

The present invention also relates to a pharmaceutical composition comprising the compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof as previously described and one or more? pharmaceutically acceptable excipients, diluents and/or carriers.

According to an embodiment of the invention, said pharmaceutical composition comprises at least one compound of general formula (I) or a related pharmaceutically acceptable salt, stereoisomer, solvate or tautomer as previously described and one or more? pharmaceutically acceptable excipients, diluents and/or carriers.

Preferably, said pharmaceutical composition ? formulated as an aqueous solution.

Preferably said pharmaceutical composition is stable for a prolonged time, ie for a time between 6 and 18, preferably between 10 and 14 months.

What? as for the compound of general formula (I), also in the case of the pharmaceutical composition comprising it, this is particularly stable from a chemical point of view since no hydrolysis reactions are observed in aqueous media nor? enzymatic degradation reactions in biological systems.

The present invention also relates to the use of the compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof or of the pharmaceutical composition as previously described, in the diagnosis of a pathological or metabolic condition, by infrared spectroscopy (IR ).

According to one embodiment, the present invention also relates to the use of the compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof or of the pharmaceutical composition as described above, in the prevention and/or prophylaxis and / or in the treatment of a pathological or metabolic condition that can? be prevented, cured, improved and/or eradicated by the evidence by IR spectroscopy of alterations of protein components of cells and/or tissues.

Preferably said pathological or metabolic condition? selected from the group consisting of: a tumor, an infection, preferably bacterial or viral, an inflammation, a metabolic disorder, preferably metabolic syndrome, a MAGL-mediated condition, an autoimmune disease, and a combination thereof.

Preferably, said pathological condition ? a tumor, preferably selected from the group consisting of: pancreatic cancer, lung cancer, colorectal cancer, breast cancer, ovarian cancer, liver cancer, and a combination thereof, plus preferably a carcinoma or an adenocarcinoma, even more? preferably said tumor being primary or metastatic.

Without wanting to be bound to a specific theory, the Applicant has found that said compound having general formula (I) is particularly advantageous in the diagnostic and ?imaging? field. as it contains a portion capable of being recognized by diseased cells and/or tissues (group Y) and, at the same time, a ?probe? able to absorb in the IR transparency window of said cells and/or tissues thus allowing? an effective characterization and visualization by infrared spectroscopy of cells and/or tissues affected by a pathological or metabolic condition as described above.

As also demonstrated in the Examples section, thanks to the presence of the bio-relevant portion (Y group), conjugated to the ?probe? active at IR within the compound of general formula (I) according to the present invention, said cells and/or tissues affected by a pathological or metabolic condition as described above tend to efficiently accumulate said compound.

The present invention also relates to a method for the detection, by infrared spectroscopy (IR), of cells and/or tissues affected by a pathological or metabolic condition in isolated biological samples comprising said cells and/or tissues.

Preferably said pathological or metabolic condition? as previously described.

Preferably, said detection comprises the detection of alterations of protein components of said cells and/or tissues.

Said method includes the steps of:

i) making available an isolated biological sample, preferably deposited on a support suitable for being analyzed by IR spectroscopy, said support preferably being a slide; ii) contacting the compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof or the pharmaceutical composition as previously described, with said isolated biological sample;

iii) analyzing the sample obtained in step ii) by means of an IR microscope, preferably an FTIR microscope, obtaining at least one spectrum of said sample;

iv) analyzing said at least one spectrum obtained in step iii) and possibly comparing it with a control model.

Preferably, said isolated biological sample ? a sample from a solid or liquid biopsy.

According to an embodiment of the invention, said pathological condition ? a tumor and said cells and/or tissues are tumor cells and/or tissues.

According to an embodiment of the invention, said pathological condition ? a bacterial or viral infection and said detection includes the detection of antigenic components resulting from infections caused by viruses or bacteria.

Without wanting to be bound to a specific theory, the Applicant has found that advantageously, the method according to the present invention, thanks to the use of the compound of general formula (I) or of the pharmaceutical composition as previously described, allows to highlight effectively, rapidly , non-invasive and non-radioactive cells and/or tissues affected by pathologies or metabolic conditions.

EXAMPLES

Example 0 ? Synthesis of intermediate compounds

For the synthesis of the compounds of general formula (I), the following compounds (S), hereinafter referred to as ?probe? compounds, were initially synthesized:

Example 0.1 ? Synthesis of compound S1

The reaction, exemplified in Scheme 1 below, is carried out in an inert environment under a flow of Ar.

Step 1: 34.63 mg of Fe2(CO)9 (0.095 mmol, 2.5% mol) are introduced into a two-necked flask, equipped with a magnetic stirrer and coolant. Then 0.69 mL of pinacol borane (4.76 mmol,1.25 eq), 0.50 mL of 1,7-octadine (3.81 mmol,1.00 eq) and finally 3.89 mL of anhydrous toluene. What is the mixture? obtained ? heated to 100 ?C and left to stir for the whole night (about 16 hours). Upon heating, the reaction mixture takes on a brown colour. The progress of the reaction is monitored by TLC (hexane/ethyl ether 10:1 eluent mixture), Rf = 0.38. The mixture is dried under low pressure. The crude is purified by flash chromatography with n-hexane/Et2O 10:0.5 eluent mixture. 294.4 mg of intermediate 1 (yellow oil) are obtained with a yield of 33%.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.26 (s, 12H), 1.52-1.56 (m,4H), 1.93 (t, 1H, J = 2.7Hz), 2.15-2.21 ( m, 4H), 5.44 (dt, 1H, J = 18.0, 1.6 Hz), 6.62 (dt, 1H, J = 17.9, 6.4 Hz).]

Step 2a: In a flask, 191.2 mg of intermediate 1 (0.82 mmol, 1.00 eq) are dissolved in 8.90 mL of acetone; then sodium periodate NaIO4 (530.6 mg, 2.48 mmol, 3.02 eq), ammonium acetate NH4OAc (141 mg, 1.82 mmol, 2.23 eq) and finally 8.90 mL of distilled water H2O. The reaction is carried out at room temperature for 16 hours. The progress of the reaction is monitored by analytical TLC in a mixture of n-hexane/Et2O 1:1, Rf = 0.44. The acetone is then removed by low pressure evaporation. The remaining aqueous solution is extracted with EtOAc. The organic solution is then washed with 5 mL of saturated NaCl solution, dried with sodium sulphate, filtered and finally dried. 112.14 mg of intermediate 2 (yellow oil) are obtained with a yield equal to 90% yield.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.54-1.63 (m, 4H), 1.97 (t, 1H, J = 2.7Hz), 2.17-2.28 (m, 4H), 5.55 ( dt, 1H, J = 17.6, 1.5 Hz), 6.95 (dt, 1H, J = 17.6, 6.5 Hz).]

Step 3a: 316.2 mg of intermediate 2 (2.08 mmol, 2.00 eq) are dissolved in 20.8 mL of anhydrous CH3CN and added to the reaction flask, equipped with a magnetic stirrer, cooler and containing a solution of the complex [(CH3CN)3Re(CO)3]<+>TfO<- >(1.04 mmol, 1.00 eq) (Minutolo F. and Katzenellenbogen J. A., J. Am. Chem. Soc., 1998, 120, 4514 -4515). 0.58 mL of Et3N (4.16 mmol, 4.00 eq) and 650.0 mg of the functionalized supported PPh3N2Cp resin are added 3.0 mmolP?g<-1 >(1.95 mmol, 1.50 eq ) (Minutolo F. and Katzenellenbogen J. A., Angew. Chem. Int. Ed., 1999, 38(11), 1617-1620). The mixture is left for 16 hours at 80°C and during heating the reaction mixture takes on a brown colour. The progress of the reaction is monitored by analytical TLC n-hexane/Et2O 10:0.7. The mixture is filtered through a layer of celite, taken up in acetonitrile and dried at low pressure. The crude is purified by flash chromatography with n-hexane/Et2O (10:0.7) eluent mixture. The S1 compound? obtained in 14% yield (128.0 mg) as a yellow oil.

<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.54-1.56 (m, 4H), 1.95 (t, 1H, J = 2.6Hz), 2.11-2.23 (m, 4H), 5.27 ( pseudo t, 2H, J = 2.2 Hz), 5.41 (pseudo t, 2H, J = 2.2 Hz), 5.90-6.03 (m, 2H). <13>C-NMR (400 MHz, CDCl3) ? (ppm): 18.35, 27.91, 28.10, 32.05, 68.54, 80.92, 84.02, 84.45, 107.09, 120.58, 133.41, 194, 46. FTIR: ? ? 1911 (vs), 2011 (vs), 2857 (w), 2926 (w), 3303 (w) cm<-1>.

Scheme 1

Example 0.2 ? Synthesis of compound S2

Step 2b: the reaction, exemplified in Scheme 2 below, is carried out in a 250 mL flask in which 1.0 g (4.40 mmol, 1.00 eq) of 4-acid pinacolic ester has been solubilized commercially available ethinylphenylboronic acid in 45.3 mL of acetone. NaIO 42.86 g (13.4 mmol, 3.03 eq), NH4OAc 759.3 mg (9.85 mmol, 2.23 eq), and 45.3 mL of H2O were then added. The solution ? was stirred at room temperature. After 16 hours, the TLC analysis (n-hexane/EtOAc 1:1) showed the disappearance of the starting substrate. Once the mixture was concentrated under reduced pressure, 45.3 mL (90.6 mmol of NaOH) of a 2M NaOH solution were added; the solution ? been extracted with a portion of CH2Cl2 and following the separation of the phases, the aqueous phase? been acidified to pH ? 3 and left for 2 hours at 0 ?C. After filtration and washing of the solid with H2O, the crude ? was purified by silica gel flash chromatography eluting with nexane/EtOAc (1:1). ? pure intermediate 3 (510.3 mg, 3.59 mmol, 79% yield) was isolated by <1>H-NMR analysis. The derivative? a white solid having Rf = 0.3 (n-hexane/EtOAc 1:1)

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 3.16 (s, 1H), 7.52 (d, 2H, J = 8.2Hz), 7.70 (d, 2H, J = 8.1Hz).]

Step 3b: 314.9 mg (0.410 mmol, 1.00 eq) of (Et4N)2[ReBr3(CO)3] were then solubilized (Alberto R., J. Chem. Soc., Dalton Trans., 1994, 2815-2820) in 12.0 mL of anhydrous CH3CN, the solution ? was treated with 347.0 mg (1.35 mmol, 3.30 eq) of AgOTf. The precipitate of AgBr formed? was removed by filtration and to the obtained supernatant solution were added 8.20 mL of anhydrous CH3CN, 119.3 mg (0.820 mmol, 2.00 eq) of intermediate 3, 0.22 mL (1.63 mmol, 4.00 eq) of Et3N, 28.0 ?L (1.55 mmol, 4.00 eq) of H2O, and 348.3 mg (0.760 mmol, 1.50 eq) of PPh3N2Cp resin (2.2 mmolP?g<-1 >) (Minutolo F. and Katzenellenbogen J. A., Angew. Chem. Int. Ed., 1999, 38(11), 1617-1620). The mixture ? been left under stirring at 80?C. After 16 hours the TLC analysis (n-hexane/Et2O 9:1) showed the formation of the desired product having Rf = 0.23. The mixture diluted with CH3CN ? been filtered through a layer of celite. After elimination of the solvent under reduced pressure, the crude ? was purified by silica gel flash chromatography eluting with n-Hexane/Et2O 9:1. Compound S2 (Rf = 0.23, 39.2 mg) ? was obtained with a yield of 22%.

<1>H-NMR (400 MHz, CDCl3) ? (ppm): 3.13 (s, 1H), 5.42 (pseudo t, 2H, J = 2.2Hz), 5.77 (pseudo t, 2H, J = 2.2Hz), 7.34 (AA?XX?, 2H, JAX = 8.6 Hz, JAA?XX? = 1.8 Hz), 7.46 (AA?XX?, 2H, JAX = 8.6 Hz, JAA?XX? = 1 .8 Hz).<13>C-NMR (400 MHz, CDCl3) ? (ppm): 78.47, 82.27, 83.13, 84.64, 106.99, 122.36, 126.27, 132.54, 132.69, 193.80. FTIR:?? 1915 (vs), 2016 (vs), 2924 (m), 3117 (m), 3294 (m) cm<-1>.

Scheme 2

Example 0.3 ? Synthesis of compounds S4, S5 and S6

Step 1a: the reaction, exemplified in Scheme 3 below, is carried out in a flamed flask under a flow of Ar, equipped with a magnetic stirrer and coolant. In said flask, 210.0 mg of the complex (Et4N)2[ReBr3(CO)3] (0.273 mmol, 1.00 eq) solubilized in 4.1 mL of anhydrous CH3CN are introduced. 231.5 mg of AgOTf (0.901 mmol, 3.3 eq) are added; the formation of a yellow precipitate of silver bromide AgBr is immediately noted. The suspension is left under stirring for 45 min at 80°C. At the end of the reaction, the AgBr precipitate is eliminated by pipette filtration with the aid of cotton. The supernatant is used in the next reaction.

38.3 mg of 3-butyn-1-ol (0.546 mmol, 2.0 eq) are dissolved in 2.8 mL of anhydrous CH3CN and added to the reaction flask, equipped with magnetic stirrer, cooler and containing solution of the complex rhenium triflate. 0.15 mL of Et3N (1.09 mmol, 4.0 eq) and 171.0 mg of the supported PPh3N2Cp resin with functionalization 3.0 mmolP?g<-1>(0.513 mmol, 1.50 eq) are added. The mixture is left for 16 hours at 80°C and during heating the reaction mixture takes on a brown colour. The progress of the reaction is monitored by analytical TLC n-hexane/ethyl acetate 7:3. The mixture is filtered through a layer of celite, taken up in acetonitrile and dried at low pressure. The crude is purified by flash chromatography with a nexane/ethyl acetate eluent mixture (7:3).

The intermediate 5 ? obtained with a yield of 23%.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.74 (t, 1H, J = 6.4Hz), 2.60 (t, 2H, J = 6.2Hz), 3.76 (q, 2H, J = 6.2Hz ), 5.27 (pseudo t, 2H, J = 1.9 Hz), 5.55 (pseudo t, 2H, J = 2.2 Hz. <13>C-NMR (400 MHz, CDCl3) ? (ppm ): 23.72, 61.03, 73.20, 84.03 (2C), 87.22, 87.30 (2C), 87.49, 193.58 (3C).].

Step 1b: Intermediate 5 ? was also synthesized with a different synthetic procedure. 241.5 mg of (bromocyclopentadienyl)tricarbonyl rhenium (Herman W. A., Chem. Ber., 1978, 111, 2458-2460) (0.583 mmol, 1 .00 eq) solubilized in 38.0 mL of a 1:1 v/v tetrahydrofuran/triethylamine mixture. The reaction mixture is degassed under a stream of N2 for 10 minutes. After that? add: 40.9 mg of Pd(PPh3)2Cl2 (0.0583 mmol, 0.100 eq), 22.3 mg of CuI (0.117 mmol, 0.200 eq) and 0.09 mL of 3-butyn-1-ol ( 1.17 mmol, 2.00 eq). The mixture is left for 16 h at 95°C and during the heating the reaction mixture turns from a turbid yellowish color to a brown colour. The progress of the reaction is monitored by analytical TLC nexane/ethyl acetate 7:3. The mixture is filtered through a layer of celite and taken up again with dichloromethane. The organic phase is placed in a separating funnel, washed with NH4Cl saturated solution (twice), washed with NaCl saturated solution (once), dried over sodium sulphate, filtered and dried at low pressures. The crude is purified by flash chromatography with n-hexane/ethyl acetate eluent mixture (7:3). The intermediate 5 ? obtained with a yield of 44%. [Same NMR data as above in step 1b].

Step 2: 34.8 mg of intermediate 5 synthesized in the previous step (step 1a or 1b) (0.0863 mmol, 1.00 eq ) solubilized in 2.0 mL of MeOH for HPLC. 5.0 mg of 10% Pd/C was added. The reaction ? was left under stirring for 24 h at room temperature under a hydrogen atmosphere (1 atm). The solution ? was filtered through a layer of celite and the solvent removed by evaporation under reduced pressure. The S4 compound ? was obtained without further purification as a dark yellow oil (yield >99%).

Step 3: 95.3 mg of compound S4 (0.234 mmol, 1.00 eq) solubilized in 0.20 mL of anhydrous dichloromethane are introduced into a one-necked flask, equipped with a magnetic stirrer and a three-way stopcock. 0.04 mL of Et3N is then added. The reaction mixture is then cooled to 0°C with an ice bath and subsequently MsCl (0.04 mL, 0.468 mmol, 2.00 eq) is dropped. After capping the CaCl2, the reaction mixture is left under stirring for 16 h at room temperature. The solution ? diluted with saturated solution of ammonium chloride, extracted with dichloromethane (three times), the organic phase? washed with distilled H2O (twice), dried over sodium sulphate, filtered and concentrated under reduced pressure. The S5 compound ? was obtained without further purification as a brown oil (97% yield).

<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.59-1.69 (m, 2H), 1.77-1.86 (m, 2H), 2.44-2.50 (m, 2H), 3.02 (s, 3H ), 4.25 (t, 2H, J = 6.3Hz), 5.26 (s, 4H). <13>CNMR (400 MHz, CDCl3) ? (ppm): 27.66, 27.82, 28.90, 37.56, 69.36, 83.16 (4C), 83.85, 110.47, 194.50 (3C). FTIR:?? 595, 932, 1170, 1348, 1890, 2012, 2940, 3112cm<-1>.

Step 4: 106.0 mg of compound S5 (0.218 mmol, 1.00 eq) solubilized in 0.48 mL of anhydrous DMF are introduced into a two-necked flask flaming under a flow of Ar, equipped with a magnetic stirrer. 31.2 mg of sodium azide (0.480 mmol, 2.20 eq) are added. It is left under stirring at room temperature for 16 h. At the end of the reaction time, monitored by analytical n-hexane/ethyl acetate 95:5 TLC, the reaction mixture is diluted with distilled H2O, extracted with ethyl acetate (three times), the organic phase is washed with saturated with NaCl (six times), dried over sodium sulfate, filtered and evaporated. The crude is purified by flash chromatography with n-hexane/ethyl acetate eluent mixture (95:5). Compound S6, a pale yellow, opalescent oil, is obtained with a yield of 59%.

<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.55-1.70 (m, 4H), 2.41-2.50 (m, 2H), 3.31 (t, 2H, J = 6.5Hz), 5.25 ( s, 4H).<13>C-NMR (400 MHz, CDCl3) ? (ppm): 27.88, 28.68, 29.00, 51.23, 83.08 (2C), 83.79 (2C), 110.78, 194.47(3C). FTIR: ? ? 594, 1252, 1455, 1888, 2013, 2095, 2865, 2932, 3113cm<-1>.

Scheme 3

Example 0.4 ? Synthesis of compound S8

Step 1: the reaction, exemplified in Scheme 4 below, is carried out in a flamed flask under a flow of Ar and equipped with a magnetic stirrer in which 0.65 mL of commercial 1,7-octadine (5.0 mmol, 1.0 eq) in anhydrous THF (50 mL). The reaction mixture is cooled to -78°C. After that? 1.0 M LiHMDS (5.0 mL, 5.0 mmol) is dropped. The reaction mixture is then stirred for 15 minutes and subsequently 0.37 mL of acetone (5.0 mmol, 1.0 eq) is added. The reaction mixture? then left to stir further for about 2 hours at room temperature. The course of the reaction is monitored by analytical TLC nexane/ethyl ether 6:4. The mixture is cooled under argon flow and diluted with NH4Cl saturated solution. The organic phase is extracted with Et2O, dried over sodium sulphate, filtered and dried at low pressures. The crude is purified by flash chromatography with n-hexane/ethyl acetate eluent mixture (6:4). The intermediate 6 ? obtained with a yield of 26%.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.49 (s, 6H), 1.58-1.65 (m, 4H), 1.84-1.89 (m, 1H), 1.95 (t, 1H, J = 2 .7Hz), 2.18-2.24 (m, 4H).]

Step 2: 50.0 mg of (bromocyclopentadienyl)tricarbonyl rhenium (Herman W. A., Chem. Ber., 1978, 111, 2458-2460) (0.121 mmol, 1.00 eq) solubilized in a 1:1 v/v mixture of tetrahydrofuran/triethylamine 8.0 mL. The reaction mixture is degassed under argon flow for 10 minutes. After that? the following are added: 8.5 mg of Pd(PPh3)2Cl2 (0.012 mmol, 0.10 eq), 4.6 mg of CuI (0.0242 mmol, 0.200 eq) and 39.7 mg of intermediate 6 (0.242 mmol, 2.00 eq). The mixture is left for 4 hours at 95°C and during the heating the reaction mixture changes from a cloudy yellow to a brown colour. The progress of the reaction is monitored by analytical TLC nexane/ethyl acetate 7:3. The mixture is filtered through a layer of celite and taken up again with dichloromethane. The organic phase is placed in a separating funnel, washed with NH4Cl saturated solution (twice), washed with NaCl saturated solution (once), dried over sodium sulphate, filtered and dried at low pressures. The crude is purified by flash chromatography with n-hexane/ethyl acetate eluent mixture (7:3). The intermediate 8 ? obtained with a yield of 35%.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.50 (s, 6H), 1.58-1.64 (m, 4H), 1.86 (s, 1H), 2.22 (t, 2H, J = 6.7Hz) , 2.35 (t, 2H, J = 6.7 Hz), 5.25 (weight t, 2H, J = 2.2 Hz), 5.53 (weight t, 2H, J = 2.2 Hz) . <13>C-NMR (400 MHz, CDCl3) ? (ppm): 18.24, 18.83, 27.55, 27.79, 31.87 (2C), 65.45, 71.66, 82.04, 83.81 (2C), 85.67, 87.23 (2C), 87.96, 90.62, 193.69 (3C).] Step 3: Into a flamed flask under Ar flow, equipped with a magnetic stirrer and condenser, are introduced: 200.0 mg of intermediate 8 (0.402 mmol, 1.00 eq), 67.9 mg KOH (1.21 mmol, 3.00 eq), 256.9 mg K3PO4 (1.21 mmol, 3.00 eq) and solubilized in 16.0 mL of anhydrous toluene. The mixture is left for 18h at 115°C and during the heating the reaction mixture assumes a yellow and clear colour. The progress of the reaction is monitored by analytical TLC n-hexane/ethyl acetate 7:3. After the foreseen time, the reaction mixture has assumed a brown color and the formation of the desired product can be observed. The reaction mixture is cooled to room temperature under argon and subsequently filtered through a layer of celite and taken up again with toluene. The crude is concentrated under reduced pressure and purified by column chromatography (n-hexane/ethyl acetate 9:1). The S8 compound ? obtained as a light yellow oil and with a yield of 50%.

Scheme 4

Example 1 ? Synthesis of the final compounds having formula (I)

The following final compounds of general formula (I) (hereinafter referred to, purely for classification purposes as compounds ?F?), were synthesized by the reactions reported in the following Schemes (Scheme 5-12 and using the compounds (S1-S8 ) synthesized as described in the group of Examples 0 (Examples 0.1-0.4)

Example 1.1 ? Synthesis of compounds F1, F2 and F3

Step 1: The reaction, exemplified in Scheme 5 below, is carried out in a 10 mL two-neck flask, under an inert atmosphere, in which 116.7 mg of the compound 2,3,4,6-tetra have been solubilized -O-acetyl-?-D-glucopyranosyl trichloroacetimidate (Cheng H., J. Med. Chem., 2005, 48, 645-652) (0.240 mmol, 1.00 eq) in 1.0 mL anhydrous toluene. The solution is dried and the residue left under vacuum for 2 hours in order to eliminate any traces of water. The residue is then solubilized in 5.0 mL of anhydrous DCM and activated molecular sieves, AW300, are added to the solution, also left to dry for 2 hours under vacuum. 0.55 mL (0.710 mmol, 3.00 eq) of 2-azido ethanol (Dong Y., Green Chem., 2008, 10(9), 990-994) 1.3 M solution in DCM is then added. The mixture ? then kept under stirring at -20 ?C under an inert atmosphere. After 30 minutes, 0.47 mL of a 0.1 M solution of TMSOTf in anhydrous DCM (0.0500 mmol of TMSOTf, 0.200 eq) are added; the solution is left under stirring at room temperature. After 24 hours, the TLC analysis (nesane/EtOAc 6:4) showed the disappearance of the starting product and the formation of two products having Rf 0.16 and 0.06. The reaction mixture, diluted with DCM, is was then neutralized with Et3N and filtered through a celite layer washing with a solution of DCM/MeOH (95:5). After elimination of the solvent under reduced pressure, the crude ? was purified by column chromatography on silica gel eluting with n-Hexane/EtOAc (6:4). ? Pure intermediate 9 (44.7 mg, 45% yield) was isolated by <1>H-NMR analysis. The derivative obtained ? a white crystalline solid having Rf = 0.16 (nesane/EtOAc 6:4).

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.98 (s, 3H), 2.01 (s, 3H), 2.03 (s, 3H), 2.07 (s, 3H), 3.23-3.29 (m, 1H), 3.45-3.51 (m, 1H), 3.64-3.71 (m, 2H), 3.99-4.04 (m, 1H), 4.16 (dd, 1H, J = 12.0, 2.4Hz), 4.25 (dd, 1H, J = 12.0, 4.4Hz), 4.58 (d, 1H, J = 8.0Hz), 5, 03 (dd, 1H, J = 9.6, 8.0Hz), 5.10 (t, 1H, J = 9.6Hz), 5.21 (t, 1H, J = 9.6Hz). <13>C-NMR (400 MHz, CDCl3) ? (ppm): 171.05, 170.33, 169.76, 169.55, 100.86, 72.97, 72.10, 71.22, 68.82, 68.46, 61.70, 50, 70, 40.28, 20.97, 20.92, 20.83.]

Step 2: In a 25 mL two-necked flask, 124.3 mg (0.290 mmol, 1.00 eq) of intermediate 9 was solubilized in 3.0 mL of MeOH and 2.0 mL of DCM. To the solution was added 2.2 mL (0.740 mmol, 2.50 eq) of a freshly prepared 0.33 M MeONa in MeOH solution. The reaction mixture? was stirred at room temperature. After 2 hours, the TLC analysis (EtOAc/MeOH 95:5) showed the disappearance of SM and the formation of a product having Rf = 0.11. The reaction mixture? been diluted with DCM and neutralized using Amberlite resin<? >IR-120 hydrogen form. After filtration, washing of the resin with MeOH and elimination of the solvent under reduced pressure ? Intermediate 10 was obtained. The desired product (7.2 mg, 97% yield) is so? obtained is pure <1>H-NMR analysis and ? a solid having Rf = 0.11 (EtOAc/MeOH 95:5).

[<1>H-NMR (400 MHz, MeOD) ? (ppm): 3.20 (dd, 1H, J = 904, 7.7Hz), 3.27-3.30 (m, 1H), 3.24-3.33(m, 2H), 3, 46 (t, 2H, J = 5.06), 3.61-3.70 (m, 1H), 3.71- 3.80 (m, 1H), 3.87 (dd, 1H, J = 11 .8, 2.2Hz), 3.96-4.05 (m, 1H), 4.31 (d, 1H, J = 7.7Hz).]

Step 3: 6.5 mg (0.0200 mmol, 1.00 eq) of intermediate 10 was solubilized in 0.41 mL of t-BuOH, to which 11.5 mg (0.0200 mmol, 1.00 eq) of compound S1 solubilized in 0.46 mL of 1,4-dioxane and a solution of Na ascorbate (5.2 mg, 0.0200 mmol, 1.00 eq) and CuSO4?5 H2O (3, 3 mg, 0.0100 mmol, 0.500 eq) in 0.86 mL of H2O. The mixture ? been left under stirring at 100?C. After 18 hours, the TLC analysis (CHCl3/MeOH 8:2) showed the disappearance of the starting glucosidic substrate and the formation of the final product F1 having Rf = 0.25. The reaction mixture? was filtered through a layer of celite and taken up with MeOH. The crude obtained? was purified by preparative TLC on silica gel (CHCl3/MeOH 9:1). ? The final compound F1 (9.1 mg, 51% yield) was isolated as a white waxy solid, pure by <1>H- and <13>C-NMR analysis.

<1>H-NMR (400 MHz, MeOD) ? (ppm): 1.48 (quint, 2H, J = 7.5Hz), 1.70 (quint, 2H, J = 7.7Hz), 2.14-2.23 (m, 2H), 2 .70 (t, 2H, J = 7.5Hz), 3.18 (dd, 1H, J = 9.0, 7.8Hz), 3.26-3.30 (m, 2H), 3, 33-3.37 (m, 1H), 3.66 (dd, 1H, J = 12.6, 4.6Hz), 3.87 (dd, 1H, J = 12.0, 0.9Hz) , 3.95-4.03 (m, 1H), 4.20-4.28 (m, 1H), 4.31 (d, 1H, J = 7.8Hz), 4.61 (t, 2H , J = 5.1 Hz), 5.44 (pseudo t, 2H, J = 2.2 Hz), 5.67 (pseudo t, 2H, J = 2.2 Hz), 5.99-6.15 (m, 2H), 7.86 (s, 1H). <13>C-NMR (MeOD) ? (ppm): 26.06, 29.62, 29.90, 33.16, 51.50, 62.73, 69.13, 71.56, 74.97, 77.97, 78.09, 82, 41, 85.32, 104.59, 108.57, 121.91, 124.27, 134.27, 148.89, 195.90. FTIR:?? 1896, 2007, 2851, 2919, 2955, 3386cm<-1>. HPLC: tR = 10.77 min, peak area: 96%. MS: m/z 692 (M<+>, <187>Re, 100%), 690 (M<+>, <185>Re, 62%).

Step 4: 43.4 mg (0.104 mmol, 1.00 eq) of intermediate 9 and 55.0 mg (0.125 mmol, 1.20 eq) of compound S1 were solubilized in 1.8 mL of 1.4- dioxane and a solution of Na-ascorbate 20.6 mg (0.104 mmol, 1.00 eq) and CuSO4?5 H2O 13.0 mg (0.0520 mmol, 0.500 eq) in 3.5 mL of H2O. The mixture ? was left under stirring at 100°C for 3 hours. The TLC (n-hexane/ethyl acetate 4:6 eluent mixture) showed the disappearance of the starting glycosidic substrate and the formation of intermediate 11 having Rf = 0.11. The reaction mixture? was filtered through a layer of celite and taken up with ethyl acetate. The crude obtained? was purified by column chromatography (hexane/ethyl acetate eluent mixture 4:6). ? The desired intermediate compound 11 (71.7 mg, 80% yield) was isolated as an off-white, pure solid by NMR analysis.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.44-1.53 (m, 2H), 1.65-1.74 (m, 2H), 1.95 (s, 3H), 2.00 (s, 3H), 2, 03 (s, 3H), 2.09 (s, 3H), 2.14-2.20 (m, 2H), 2.66-2.75 (m, 2H), 3.66-3.73 ( m, 1H), 3.87-3.96 (m, 1H), 4.09-4.16 (m, 2H), 4.18-4.28 (m, 2H), 4.47 (d, 1H, J = 8.0Hz), 4.53-4.61 (m, 1H), 4.99 (dd, 1H, J = 9.6, 8.0Hz), 5.04-5.10 (m, 1H), 5.15-5.21 (m, 1H), 5.27 (pseudo t, 2H, J = 2.2 Hz), 5.42 (pseudo t, 2H, J = 2.2 Hz), 5.94-5.98 (m, 2H), 7.35 (s, 1H). <13>C-NMR (400 MHz, CDCl3) ? (ppm): 20.71 (4C), 20.77, 20.88, 28.71 (2C), 32.29 (2C), 61.90, 68.36, 71.12, 72.14, 72 ,63 (2C), 81.02, 84.03 (2C), 84.04 (2C), 100.70, 107.18, 120.58, 133.52, 169.41, 169.56, 170, 25, 170.72, 194.52 (3C).]

Step 5: Final Compound F1 ? was also synthesized with an alternative synthetic procedure. 50.0 mg of intermediate 11 (0.0582 mmol, 1.00 eq) solubilized in 2.0 mL of anhydrous MeOH are introduced into a two-necked flask, flamed under a flow of Ar, equipped with a magnetic stirrer and a cooler. The reaction mixture is cooled to 0°C and then 18.9 mg of solid MeONa (0.349 mmol, 6.00 eq) is added. The mixture is stirred at room temperature for a total of 51 h and, after adding a total of 12.00 eq of MeONa (s), the reaction mixture is diluted with MeOH and filtered through a layer of celite. The crude is purified by flash chromatography with CHCl3/MeOH 9:1 eluent mixture. The desired final compound F1 (Rf = 0.13, in CHCl3/MeOH 9:1) ? a white solid with caramel consistency (33.2 mg, 83% yield) pure by NMR analysis.

Step 6: 31.0 mg of the final compound F1 (0.0448 mmol, 1.00 eq) solubilized in 2.2 mL of MeOH for HPLC are introduced into a one-necked flask, equipped with a stirrer and a three-way stopcock . 12.5 mg of 10% Pd/C was added. The reaction ? was stirred for 16 h at room temperature. After the elapsed time, the reaction mixture ? been filtered on celite, taken up with MeOH and the solvent ? been removed by evaporation under reduced pressure. The final compound F3 ? a pure caramel white solid by NMR analysis (24.4 mg, 0.0352 mmol, 79% yield).

<1>H-NMR (400 MHz, MeOD) ? (ppm): 1.36-1.46 (m, 4H), 1.49-1.59 (m, 2H), 1.63-1.73 (m, 2H), 2.39-2.47 (m, 2H), 2.69 (t, 2H, J = 7.6Hz), 3.17 (dd, 1H, J = 9.0, 7.7Hz), 3.24-3.29 (m, 2H), 3.32-3.38 (m, 1H), 3.62-3.68 (m, 2H), 3.87 (dd, 1H, J = 11.8, 1.6Hz), 3 .94-4.02 (m, 1H), 4.23 (dt, 1H, J = 11.7, 5.1Hz), 4.30 (d, 1H, J = 7.8Hz), 4, 60 (t, 2H, J = 5.1 Hz), 5.39 (pseudo t, 2H, J = 2.1 Hz), 5.44 (pseudo t, 2H, J = 2.1 Hz), 7, 86 (s, 1H).

<13>C-NMR (400 MHz, MeOD) ? (ppm): 26.21, 29.10, 29.86, 30.04, 30.39, 32.78, 51.50, 62.72, 69.14, 71.57, 74.97, 77, 97, 78.09, 84.54 (2C), 84.90 (2C), 104.58, 113.27, 124.24, 149.01, 196.08(3C). FTIR: ? ? 1906.7, 2016.4, 2856.6, 2927.7, 3338.2cm<-1>. HPLC: tR = 10.98 min, peak area: 90%. MS: m/z 716 (M<+>, <187>Re, 100%), 694 (M<+>, <187>Re, 53%), 692 (M<+>, <185>Re, 24 %).

Step 7: ? Intermediate 10 (14.9 mg, 0.0590 mmol, 1.00 eq) was solubilized in 0.95 mL of t-BuOH. To the solution was added compound S2 (26.0 mg, 0.0590 mmol, 1.00 eq) solubilized in 1.0 mL of 1,4-dioxane and sodium ascorbate solution (11.8 mg, 0. 0590 mmol, 1.00 eq) and CuSO4?5H2O (7.5 mg, 0.0290 mmol, 0.500 eq) in 2.0 mL of H2O. The mixture ? was left under stirring at 100 ?C for 20 hours. After verifying the incomplete disappearance of the glucosidic substrate by analytical TLC (EtOAc/MeOH 95:5) and <1>H-NMR, the reaction mixture ? was filtered through a layer of celite eluting with MeOH. After elimination of the solvent under reduced pressure, the crude ? was solubilized in 0.6 mL of a THF/H2O 20:1 mixture and introduced into a 10 mL single-necked flask equipped with a magnetic stirrer. The solution ? was treated with polymer-supported PPh3 (13.7 mg, 0.0400 mmol, 1.70 eq) and stirred at room temperature. After 48 hours, the solution? filtered and the solvent removed under reduced pressure. The crude ? was solubilized in 0.4 mL of anhydrous THF and introduced into a 10 mL flask equipped with a magnetic stirrer. The solution ? was treated with an isocyanate-functionalized resin 54.0 mg (0.0700 mmol, 3.00 eq) and stirred at room temperature. After 5 hours, the solution? filtered and the solvent removed under reduced pressure. The crude obtained? was purified by preparative TLC on silica gel (CHCl3/MeOH 9:1, three developments). ? The final compound F2 (17.4 mg, 42% yield) was isolated as a white solid, pure by <1>H- and <13>C-NMR analysis.

<1>H-NMR (400 MHz, MeOD) ? (ppm): 3.22 (dd, 1H, J = 8.0Hz), 3.27-3.37 (m, 3H), 3.63-3.68 (m, 1H), 3.89 ( dd, 1H, J = 11.9, 1.5), 4.02-4.11 (m, 1H), 4.29-4.34 (m, 1H), 4.36 (d, 1H, J = 8.0 Hz), 4.67-4.71 (m, 2H), 5.61 (pseudo t, 2H, J = 2.2 Hz), 6.13 (pseudo t, 2H, J = 2, 2Hz), 7.58 (AA?XX?, 2H, JAX = 8.6Hz, JAA?XX? = 1.8Hz), 7.82 (AA?XX?, 2H, JAX = 8.6Hz , JAA?XX? = 1.8Hz), 8.50 (s, 1H). <13>C-NMR (400 MHz, MeOD) ? (ppm): 51.74, 62.71, 69.08, 71.56, 75.01, 78.02, 78.10, 83.35, 86.00, 86.02, 104.59, 108, 77, 123.65, 127.01, 127.72, 131.86, 133.34, 148.08, 195.52. FTIR:?? 1914, 1931, 2016, 2833, 2943, 3338cm<-1>. HPLC: tR= 10.43 min, peak area: 99%. MS: m/z 685 (M, <187>Re, 100%), 683 (M, <185>Re, 65%).

Scheme 5

Example 1.2 ? Synthesis of compounds F4 and F5

Step 1: The reaction, exemplified in Scheme 6 below, is carried out in a flask under an inert atmosphere in which 300.0 mg methyl-?-D-glucopyranoside, commercial derivative of glucose, (1.54 mmol, 1.00 eq) in 10.8 mL of a mixture

1:1 (v/v) of DCM/Py. The solution ? was brought to 0 ?C in an ice/water bath. Then 500.7 mg of p-TsCl (2.63 mmol, 1.70 eq.) are added, keeping the mixture at the same temperature, under stirring for 16 h. To eliminate the excess of p-TsCl, 1.0 mL of MeOH is added and the mixture is left under stirring for a few minutes. To remove the pyridine, toluene is added and then evaporation is carried out at low pressure. From the analytical TLC with the eluent mixture EtOAc/MeOH (95:5) we note the disappearance of the starting product and the appearance of the desired product which has Rf = 0.40. After having evaporated the solvent at low pressure, the crude is purified by flash chromatography on silica with eluent mixture first EtOAc/MeOH 99:1 and subsequently 95:5. 307.1 mg of intermediate 12 are obtained (yield 57%).

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 2.43 (s, 3H), 3.34 (s, 3H), 3.42-3.47 (m, 1H), 3.68-3.74 (m, 1H), 4, 23-4.32 (m,1H), 4.68 (s, 1H), 7.33 (d, 2H, J = 8Hz) 7.79 (d, 1H, J = 8Hz).]

Step 2: 307.1 mg of intermediate 12 (0.880 mmol, 1.00 eq) is dissolved in 31.4 mL of a H2O/acetone mixture (2:3) in a flask fitted with a magnetic stirrer and condenser. 171.6 mg of NaN3 (2.64 mmol, 3.00 eq) are added and the mixture is left under stirring at 85°C for 30 h. From the analytical TLC performed with CHCl3/MeOH 9:1 eluent mixture (2 developments), the disappearance of the starting product and the appearance of the desired product which has Rf = 0.30 can be noted. The solvent is evaporated at low pressures. After eliminating the solvent, a crude product is obtained which is purified by flash chromatography with a CHCl3/MeOH 9:1 eluent mixture. 100.0 mg of pure intermediate 13 are obtained by NMR analysis (yield 52%).

[<1>H-NMR (400 MHz, MeOD) ? (ppm): 3.37-3.42 (m,2H), 3.43 (s, 3H), 3.45-3.49 (m, 1H), 3.50 (dd, 1H, J = 13 ,2, 2.4Hz), 3.59 (t, 1H, J = 9.2Hz), 3.65-3.70 (m, 1H), 4.69 (d, 1H, J = 3, 6Hz).]

Step 3: 13.6 mg (0.0600 mmol, 1.00 eq) of intermediate 13 was solubilized in 0.5 mL of a 5:1 (v/v) 1,4-dioxane/H2O mixture, to solution 27.0 mg (0.0620 mmol, 1.00 eq) of probe 2 solubilized in 0.5 mL of 1,4-dioxane/H2O 5:1 (v/v), sodium ascorbate 5.0 was added mg (0.0200 mmol, 1.00 eq) and CuSO4?5H2O 2.9 mg (0.0100 mmol, 0.500 eq). The mixture ? was left under stirring at 100 ?C for 20 hours. After verifying the disappearance of the starting glucosidic substrate by analytical TLC, the reaction mixture ? was filtered through a layer of celite eluting with MeOH. After elimination of the solvent under reduced pressure, the crude ? was purified by preparative TLC (CHCl3/MeOH 9:1, two developments). ? The final compound F4 (16.8 mg, 42% yield) was isolated as a white semisolid, pure by NMR analysis.

<1>H-NMR (400 MHz, MeOD) ? (ppm): 3.13-3.18 (m, 1H), 3.16 (s, 3H), 3.37 (dd, 1H, J = 10, 3.6Hz), 3.58-3, 65 (m, 1H), 3.88-3.93 (m, 1H), 4.58 (dd, 1H, J = 14.2, 8.2Hz), 4.66 (d, 1H, J = 3.6 Hz), 4.87 (dd, 1H, J = 14.2, 3.6 Hz), 5.60 (pseudo t, 2H, J = 2.2 Hz), 6.13 (pseudo t, 2H, J = 2.2Hz), 7.60 (AA?XX?, 2H, JAX = 8.6Hz, JAA?XX? = 1.8Hz), 7.81 (AA?XX?, 2H, JAX = 8.6 Hz, JAA?XX? = 1.8 Hz), 8.37 (s, 1H).<13>C-NMR (400 MHz, MeOD) ? (ppm): 52.82, 55.74, 71.94, 73.22, 73.59, 75.18, 83.53, 86.27, 101.52, 108.93,124.08, 127.15, 127.93, 131.92, 133.61, 148.22, 195.75. FTIR:?? 1909, 1929, 2027, 2848, 2915, 3350cm<-1>. HPLC: tR = 10.90 min, peak area: 99 %. MS: m/z 656 (M+, <187>Re, 100%), 654 (M+, <185>Re, 56%).

Step 4: 17.5 mg of intermediate 13 (0.0800 mmol, 1.00 eq) and 35.5 mg of compound S1 (0.0800 mmol, 1 .00 eq) solubilized in 2.7 mL of 1,4-dioxane. 15.9 mg of Na-ascorbate (0.0800 mmol, 1.00 eq) and 9.0 mg of CuSO4?5H2O (0.0396 mmol, 0.500 eq) are added in 5.5 mL of H2O. The reaction mixture is left under stirring for 15 hours at 80°C. The analytical TLC (eluent mixture EtOAc/MeOH 95:5) showed the disappearance of the starting glycosidic substrate and the formation of the final product 5 having Rf = 0.22. The reaction mixture? was filtered through a layer of celite eluting with MeOH. The crude obtained? was purified by flash chromatography on silica gel (eluent mixture EtOAc/MeOH 95:5). ? The final compound F5 (22.0 mg, 42% yield) was isolated as a white waxy solid, pure by NMR analysis.

<1>H-NMR (400 MHz, MeOD) ? (ppm): 1.43-1.47 (m,2H), 1.64-1.70 (m, 2H), 2.14-2.19 (m,2H), 2.70 (t, 2H , J = 7.2), 3.11-3.10 (m, 1H), 3.13-3.13 (m, 3H), 3.37-3.36 (m,1H), 3.64 -3.58 (m, 1H), 3.84-3.8 (m 1H), 4.46 (q, 1H, J = 14.0, 8.0Hz), 4.62 (d, 1H, J = 3.6 Hz), 4.78 (dd, 1H, J = 14.4, 2.4 Hz) 5.44 (pseudo t, 2H, J = 2.0 Hz), 5.65 (pseudo t , 2H, J = 2.0Hz), 5.99-6.10 (m, 2H), 7.74( s, 1H). <13>C-NMR (400 MHz, MeOD) ? (ppm): 25.97, 29.49, 29.92, 33.10, 52.37, 55.49, 71.84, 73.00, 73.37, 74.93, 82.40, 85, 33, 101.24, 108.49, 121.94, 124.58, 134.20, 148.83, 195.87. FTIR:?? 1907, 2016, 2856, 2925, 3349cm<-1>. HPLC: tR = 12.02 min, peak area: 94%. MS: m/z 662 (M<+>, <187>Re, 100%), 660 (M<+>, <185>Re, 53%).

Scheme 6

Example 1.3 ? Synthesis of compounds F6 and F7

Step 1: The reaction, exemplified in Scheme 7 below, is carried out by dissolving the starting compound 1-deoxy-1-azide-2,3:4,5-di-O-diisopropylidene-?-D-fructopyranoside (Maryanoff B. E., J. Med. Chem., 2005, 48, 1941-1947) (200.0 mg, 0.700 mmol, 1.00 eq) in 2.0 mL of H2O and then added with CF3COOH (18.0 mL), under stirring for 10 min at rt. After trituration with Et2O and after having dried it under vacuum, the intermediate 14? was obtained pure in 70% yield (Rf = 0.10, EtOAc/MeOH 9:1).

[<1>H-NMR (300 MHz, D2O) ? (ppm): 3.50-3.57 (m, 1H), 3.70-3.81 (m, 2H), 3.88-3.95 (m, 1H), 4.00-4.07 (m, 2H), 4.09-4.17 (m, 1H). <13>C-NMR (62.5 MHz, D2O) ? (ppm): 15.16, 31.24, 36.24, 54.39, 54.56, 55.28, 56.51, 62.42, 63.20, 64.01, 65.36, 68, 78, 69.42, 70.00, 75.46, 77.49, 82.57, 82.61, 82.93, 98.78, 102.30, 104.96, 143.45.]

Step 2: 17.45 mg (0.0600 mmol, 1.00 eq) of 1-deoxy-1-azide-2,3:4,5-di-O-diisopropylidene-?-D-fructopiranoside (Maryanoff B. E. , J. Med. Chem., 2005, 48, 1941-1947) and 27.0 mg (0.0600 mmol, 1.00 eq) of compound S1 in 1.1 mL of 1,4-dioxane and a solution of sodium ascorbate (12.1 mg, 0.0600 mmol, 1.00 eq) and CuSO4?5H2O (7.4 mg, 0.0300 mmol, 0.500 eq) in 2.0 mL H2O. The mixture ? was left under stirring at 100°C for 15 hours. The TLC (n-hexane/ethyl acetate eluent mixture 1:1) showed the disappearance of the starting glycosidic substrate and the formation of the desired final product F6 having Rf = 0.38. The reaction mixture? was filtered through a layer of celite eluting with MeOH. The crude obtained? was purified by silica gel flash chromatography (n-Hexane/EtOAc 1:1). ? The final compound F6 (23.0 mg, 61% yield) was isolated as a white waxy solid, pure by NMR analysis.

<1>H-NMR (400 MHz, CDCl3) ? (ppm): 0.73 (s, 3H), 1.36 (s, 3H), 1.46-1.49 (m, 5H), 1.51 (s, 3H), 1.62-1, 70 (m, 2H), 2.12-2.18 (m, 2H), 2.70 (t, 2H, J = 7.7Hz), 3.79 (dd, 1H, J = 12.9, 0.8Hz), 3.92 (dd, 1H, J = 12.9, 1.9Hz), 4.24 (dd, 1H, J = 7.8, 1.1Hz), 4.47 ( d, 1H, J = 14.4Hz), 4.51 (d, 1H, J = 2.8Hz), 4.65 (dd, 1H, J = 7.8, 2.8Hz), 4, 71 (d, 1H, J = 14.5 Hz), 5.26 (pseudo t, 2H, J = 2.2 Hz), 5.40 (pseudo t, 2H, J = 2.2 Hz), 5, 92-5.94 (m, 2H) 7.40 (s, 1H). <13>C-NMR (400 MHz, CDCl3) ? (ppm): 24.01, 24.25, 25.37, 26.01, 26.42, 28.54, 28.82, 32.13, 54.78, 61.87, 70.12, 70, 60, 70.64, 80.76, 83.88, 100.89, 107.02, 109.30, 109.45, 113.84, 120.37, 123.73, 133.42, 134.35, 147.62, 194.32. FTIR:?? 1904.6, 2015.2, 2857.4, 2934.6, 2990.3, 3107.3 cm<-1>. HPLC: tR = 14.75 min, peak area: 97%. MS: m/z 728 (M<+>, <187>Re, 100%), 726 (M<+>, <185>Re, 62%).

Step 3: 16.3 mg (0.0800 mmol, 1.00 eq) of intermediate 14 and 35.1 mg (0.0800 mmol, 1.00 eq) of compound S1 were solubilized in 2.6 mL of 1 ,4-dioxane and a solution of sodium ascorbate (15.7 mg, 0.0800 mmol, 1.00 eq) and CuSO4?5H2O (7.4 mg, 0.0400 mmol, 0.500 eq) in 5.6 mL of H2O. The mixture ? was left under stirring at 100°C for 15 h. The TLC (eluent mixture EtOAc/MeOH 95:5) showed the disappearance of the starting glycosidic substrate and the formation of the final product F7 having Rf = 0.14. The reaction mixture? was filtered through a layer of celite eluting with MeOH. The crude obtained? was purified by flash chromatography on silica gel (eluent mixture EtOAc/MeOH 95:5). ? The final product F7 (9.0 mg, 17% yield) was isolated as a white waxy solid, pure by NMR analysis.

<1>H-NMR (400 MHz, MeOD) ? (ppm): 1.44-1.53 (m, 2H), 1.65-1.76 (m, 2H), 2.18 (q, 2H, J = 6.8Hz), 2.71 ( m, 2H), 3.45 (d, 1H, J = 9.3Hz), 3.68-3.64 (m, 1H), 3.75 (d, 1H, J = 6.8Hz), 3.79 (dd, 1H, J = 9.4, 3.4Hz), 3.86 (d, 1H, J = 5.8Hz), 4.35-4.54 (m, 1H), 4 .68 (d, 1H, J = 13.9 Hz), 5.43 (pseudo t, 2H, J = 2.2 Hz), 5.65 (pseudo t, 2H, J = 2.2 Hz), 5 .96-6.12 (m, 2H), 7.77 (s, 1H). <13>C-NMR (400 MHz, MeOD) ? (ppm): 61.25, 63.93, 64.30, 65.01, 70.05, 70.79, 71.55, 72.07, 76.11, 78.53, 82.39, 83, 44, 85.30, 101.50, 98.05, 108.58, 121.89, 134.34, 195.87. FTIR: ? ? 1897.8, 2013.9, 2857.4, 2854.0, 2926.8, 3346.8 cm<-1>. HPLC: tR = 12.02 min, peak area: 95%, MS: m/z 648 (M<+>, <187>Re, 100%), 646 (M<+>, <185>Re, 53 %).

Scheme 7

Example 1.4 ? Synthesis of compound F8

Step 1: The reaction, exemplified in Scheme 8 below, is carried out by dissolving 2,5-anhydro-D-mannose (Horton D. and Philips K. D., Carbohydrate Research, 1973, 30, 367-374) (1.30 g , 8.00 mmol, 1.00 eq) in 10.0 mL of anhydrous DMF and imidazole (1.41 g, 20.8 mmol) ? was added to the reaction flask at a temperature of 0°C. After that, TBDPS-Cl (2.86 g, 10.4 mmol, 1.30 eq) is added. The reaction mixture is left under stirring at room temperature for 18h. After the expected time, Et2O and ice were added to the reaction mixture. The organic phase? was extracted with Et2O, washed with brine (2x10 mL), dried over Na2SO4, filtered and evaporated at low pressure. The raw reaction? was purified by column chromatography with n-hexane/EtOAc 1:1 eluent mixture (Rf = 0.50) and then EtOAc. Intermediate 15 (1.60 g, 50% yield) ? was obtained as a pure amber oil by NMR analysis.

[<1>H-NMR (300 MHz, CDCl3) ? (ppm): 9.72 (s, 1H) 7.68 (t, 4H, J = 8.1Hz), 7.50-7.33 (m, 6H), 4.44 (d, 2H, J = 42.0Hz), 4.23 (d, 2H, J = 17.7Hz), 3.93 (dd, 1H, J = 3.0Hz), 3.76 -3.69 (m, 1H), 1.06 (s, 9H).<13>C-NMR (62.5 MHz, CDCl3) ? (ppm): 203.06, 136.65, 136.57, 132.930, 132.59, 131.26, 131.19, 129.02, 129.00, 92.02, 88.37, 80.68, 79.64, 65.67, 27.70, 20.05.] Step 2: Intermediate 15 (1.42 g, 3.56 mmol, 1.00 eq) ? was dissolved in 20.0 mL of EtOH and treated with NaBH4 (202.0 mg, 5.33 mmol, 1.50 eq). After 2 h at room temperature, the reaction mixture ? was diluted with H2O and extracted with DCM. The organic phase? been dried on Na2SO4, filtered and concentrated at low pressures thus obtaining? intermediate 16 as a colorless oil without further purification (1.34 g, 94% yield).

[<1>H-NMR (300 MHz, CDCl3) ? (ppm): 7.67 (t, 4H, J = 7.1Hz), 7.38 (t, 6H, J = 6.3Hz), 4.21 (d, 1H, J = 3.7Hz ), 4.17-4.09 (m, 1H), 3.99 (d, 2H, J = 3.1Hz), 3.80-3.64 (m, 4H), 1.05 (s, 9H).<13>C-NMR (62.5 MHz, CDCl3) ? (ppm): 135.64, 135.59, 132.71, 132.58, 129.96, 129.91, 127.86, 127.83, 85.28, 85.07, 78.91, 78, 10, 64.93, 62.34, 60.47, 26.88, 26.82, 21.05, 19.14, 14.19.]

Step 3: Intermediate 16 (352.0 mg, 0.870 mmol, 1.00 eq) is was dissolved in 60 mL of anhydrous DCM and 1 mL of pyridine (4.35 mmol, 5.00 eq). p-TsCl (165.9 mg, 0.870 mmol, 1.00 eq) ? been added dropwise at 0?C and the reaction mixture ? was stirred at room temperature for 18 h. After the expected time, DCM, ice and H2O were added to the reaction mixture. The organic phase? been separated from the aqueous phase, with neutral/basic pH. The organic phase? dried over Na2SO4, filtered and evaporated at low pressure. The raw reaction? was purified by column chromatography (SiO2; eluent mixture n-hexane/EtOAc 8:2, 1:1 with Rf = 0.67, EtOAc). The intermediate tosylate 17 (240.0 mg, yield 50%) is was obtained as a sticky oil, pure by NMR analysis.

[<1>H-NMR (300 MHz, CDCl3) ? (ppm): 7.80 (d, 2H, J = 8.2Hz), 7.69-7.58 (m, 4H), 7.49-7.36 (m, 6H), 7.13 ( d, 2H, J = 9.8Hz), 4.29 (t, 1H, J = 3.7Hz), 4.22-4.03 (m, 4H), 3.91 (d, 1H, J = 3.1Hz), 3.78 (dd, 1H, J = 3.5Hz), 3.68 (dd, 1H, J = 2.7Hz), 2.42 (s, 3H), 1, 05 (s, 9H). <13>C-NMR (62.5 MHz, CDCl3) ? (ppm): 144.98, 135.61, 135.5, 132.44, 132.20, 130.07, 130.02, 129.87, 128.04, 127.92, 127.89, 84, 83, 82.75, 79.28, 69.05, 64.75, 60.40, 26.78, 21.04, 14.1973.]

Step 4: Intermediate 17 (240.0 mg, 0.430 mmol, 1.00 eq) is was dissolved in 7.0 mL of anhydrous DMF and treated with an excess of NaN3. The reaction mixture? was stirred at rt for 18 h. After the expected time, ? was extracted with DCM/H2O; the organic phase dried on Na2SO4, filtered and evaporated, thus obtaining? intermediate 18 without further purifications is pure by NMR analysis (166.0 mg, 90% yield).

[<1>H-NMR (300 MHz, CDCl3) ? (ppm): 7.67 (t, 4H, J = 7.7Hz), 7.49-7.35 (m, 6H), 4.30 (d, 1H, J = 3.4Hz), 4 ,22-4.14 (m, 1H), 4.02 (s, 1H), 3.89-3.68 (m, 2H), 3.53 (d, 1H, J = 4.8Hz), 2.91 (d, 2H, J = 22.3Hz), 1.05 (s, 9H). <13>C-NMR (62.5 MHz, CDCl3) ? (ppm): 135.63, 135.56, 134.79, 132.45, 132.22, 130.07, 130.02, 127.92, 127.90, 127.71, 85.11, 84, 31, 79.72, 79.35, 65.07, 52.73, 29.70, 26.81, 19.11.]

Step 5: Intermediate 18 (166.0 mg, 0.400 mmol, 1.00 eq) is dissolved in 15.0 mL of anhydrous THF. Then a solution of t-BuNH4F in 1M THF (400 ?L, 0.400 mmol, 1.00 eq) is added, and the reaction mixture ? left under stirring at rt for 4h. The solvent? evaporated and the crude reaction ? purified by column chromatography (DCM/EtOAc, 1:1). The intermediate 19 ? obtained with a yield of 90% and pure by NMR analysis.

[<1>H-NMR (300 MHz, D2O) ? (ppm): 3.28-3.56 (m, 1H), 3.58-3.74 (m, 3H), 3.57-3.90 (m, 1H), 3.91-4.11 (m, 4H). <13>C-NMR (62.5 MHz, D2O) ? (ppm): 51.55, 60.93, 75.99, 77.08, 80.73, 82.32.]

Step 6: 13.7 mg (0.0700 mmol, 1.00 eq) of intermediate 19 and 32.0 mg (0.0700 mmol, 1.00 eq) of compound S1 were solubilized in 2.4 mL of 1 ,4-dioxane and a solution of sodium ascorbate 14.4 mg (0.0700 mmol, 1.00 eq) and CuSO4?5H2O 9.0 mg (0.0350 mmol, 0.500 eq) in 4.5 mL H2O. The mixture ? was left under stirring at 100°C for 15 hours. The TLC (eluent mixture EtOAc/MeOH 10:0.5) showed the disappearance of the starting glycosidic substrate and the formation of the final product F8 having Rf = 0.18. The reaction mixture? was filtered through a layer of celite eluting with MeOH. The crude obtained? was purified by preparative TLC on silica gel (eluent mixture EtOAc/MeOH 10:0.5). ? The final compound F8 (9.0 mg, 19% yield) was isolated as a white waxy solid, pure by NMR analysis.

<1>H-NMR (400 MHz, MeOD) ? (ppm): 1.45-1.52 (m, 2H), 1.66-1.73 (m, 2H), 2.18 (q, 2H, J = 6.9Hz), 2.70 ( t, 2H, J = 7.6Hz), 3.57-3.65 (m, 1H), 3.69 (dd, 1H, J = 11.9, 3.3Hz), 3.81-3 .74 (m, 2H), 4.00 (t, 1H, J = 5.9Hz), 4.11 (td, 1H, J = 6.6, 3.8Hz), 4.51-4, 63 (m, 2H), 5.43 (pseudo t, 2H, J = 2.2 Hz), 5.65 (pseudo t, 2H, J = 2.2 Hz), 5.99-6.12 (m , 2H), 7.76 (s, 1H). <13>C-NMR (400 MHz, MeOD) ? (ppm): 26.05, 29.60, 29.88, 33.14, 52.95, 63.12, 78.07, 79.40, 82.40, 82.84, 85.30, 85, 30, 85.34, 108.56, 120.80, 121.91, 124.40, 134.27, 195.87. FTIR: ? ? 1908, 2016, 2851.5, 2919.2, 2962, 3356.3. HPLC: tR = 11.89 min, peak area: 96%, MS: m/z 632 (M<+>, <187>Re, 100%), 630 (M<+>, <185>Re, 53 %).

Scheme 8

Example 1.5 ? Synthesis of compound F9

The reaction, exemplified in Scheme 9 below, is performed in a microwave vial: 60.0 mg of compound S1 (0.136 mmol, 1.30 eq) and 40.0 mg of commercial azide (s)-5-azido -2-(Fmocamino)-pentanoic acid (0.105 mmol, 1.00 eq) was dissolved in a 1:1 (v/v) H2O/t-BuOH (0.4 mL) mixture. After that? a freshly prepared aqueous solution of sodium ascorbate (2.1 mg, 0.0105 mmol, 0.100 eq in 0.1 mL H2O) and CuSO4?5H2O (0.3 mg, 0.00105 mmol, 0.0100 eq in 4 ?L of H2O). The heterogeneous mixture is vigorously stirred and subjected to several cycles in a microwave reactor:

- 1? cycle: 150 ?C for 10 minutes;

- 2? cycle: 150 ?C for 15 minutes;

- 3? cycle: 150 ?C for 30 minutes;

- 4? cycle: 200 ?C for 2 minutes.

The analytical TLC (eluent mixture CHCl3/MeOH 95:5) showed the disappearance of the starting substrate and the formation of the final product F9. The reaction mixture? was diluted with H2O and extracted with EtOAc (three times); the organic phase was washed with NaCl saturated solution (once), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude obtained? was purified by column chromatography (CHCl3/MeOH 95:5 eluent mixture). The final F9 product? was isolated (17.5 mg, 20% yield) as a beige glassy solid, pure by NMR analysis.

<1>H-NMR (400MHz, DMSO-d6) ? (ppm): 1.31-1.42 (m, 2H), 1.50-1.61 (m, 3H), 1.63-1.70 (m, 1H), 1.73-1.83 (m, 2H), 2.04-2.13 (m, 2H), 2.56 (t, 2H, J = 7.3Hz), 3.73 (bs, 1H), 4.17-4, 34 (m, 5H), 5.60 (pseudo t, 2H, J = 2.1 Hz), 5.86 (pseudo t, 2H, J = 2.2 Hz), 6.00 (d, 1H, J = 16.0Hz), 6.11 (dt, 1H, J = 15.8, 6.6Hz), 6.82 (bs, 1H), 7.27-7.35 (m, 2H), 7 .40 (t, 2H, J = 7.3Hz), 7.65-7.72 (m, 2H), 7.75 (s, 1H), 7.88 (d, 2H, J = 7.2 Hz). <13>C-NMR (400 MHz, DMSO-d6) ? (ppm): 24.81, 26.48, 28.11 (2C), 28.40 (2C), 31.55, 46.76, 49.13, 65.33, 82.02 (2C), 85 ,19 (2C), 107.32, 120.09, 120.22 (2C), 121.38, 121.50, 125.17, 125.22, 127.05 (2C), 127.29, 127, 59, 128.92, 133.16, 140.70, 143.82, 143.97, 146.58, 155.52, 195.48 (3C). FTIR:?? 740, 1048, 1575, 1697, 1903, 2015, 2927, 3067, 3338 (br) cm<-1>.

Scheme 9

Example 1.6 ? Synthesis of compound F10

Step 1: The reaction, exemplified in Scheme 10 below, is performed by suspending commercially available D-glucose (500.0 mg, 2.77 mmol, 1.00 eq) in 1.0 mL of propargyl alcohol, and leaving under stirring at 65 ?C for a few minutes. After that? the activated silica SiO2<.>H2SO4 (14.0 mg) is added and the reaction mixture is left under stirring at 65?C for 3h. After 3h, the presence of the starting product is still noted, therefore it is left under stirring at 50?C for 16h. The reaction mixture was filtered through a layer of silica eluting first with DCM and then with a 5:1 DCM/MeOH mixture. The raw reaction is dried to the mechanical pump thus obtaining? the intermediate 20 as a mixture of anomers without further purifications (500.0 mg, 83% yield).

[<1>H-NMR (300 MHz, MeOD) ? (ppm): 2.86 (m, 1H, J = 2.5Hz), 3.16-3.45 (m, 1H), 3.53-3.70 (m, 5H), 3.84 ( m, 1H), 4.30 (d, 2H, J = 2.1Hz), 4.41-4.47 (m, 1H), 5.00 (d, 1H, J = 3.7Hz). ]

Step 2: Intermediate 20 (500.0 mg, 2.29 mmol, 1.00 eq) is solubilized in 8.0 mL of pyridine. After that? 8.0 mL of Ac2O are added and the reaction mixture is left under stirring at rt for 4h. The reaction mixture is co-evaporated with toluene and the reaction crude (mixture of anomers) is purified by column chromatography with n-hexane/EtOAc 8:2 eluent mixture thus isolating the ? Intermediate anomer 21 with Rf = 0.17 (73.0 mg, 8% yield) pure by NMR analysis.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 2.01 (s, 3H), 2.03 (s, 3H), 2.06 (s, 3H), 2.09 (s, 3H), 2.47 (t, 1H, J = 2.4Hz), 3.70-3.76 (m, 1H), 4.15 (dd, 1H, J = 12.6, 2.6Hz), 4.24-4.31 (m, 1H ), 4.38 (d, 2H, J = 2.4Hz), 4.78 (d, 1H, J = 8.0Hz), 5.02 (dd, 1H, J = 9.6, 7, 6Hz), 5.07-5.14 (m, 1H), 5.21-5.28 (m, 1H).]

Step 3: 46.4 mg (0.120 mmol, 1.00 eq) of Intermediate 21 and 52.0 mg (0.120 mmol, 1.00 eq) of compound S6 were solubilized in 2.1 mL of 1,4-dioxane and a solution of sodium ascorbate 23.8 mg (0.120 mmol, 1.00 eq) and CuSO4?5 H2O 15.0 mg (0.0600 mmol, 0.500 eq) in 4.0 mL H2O. The mixture ? was left under stirring at 100°C for 3 hours. The TLC (n-hexane/ethyl acetate 4:6 eluent mixture) showed the disappearance of the starting glycosidic substrate and the formation of the intermediate 22 having Rf = 0.10. The reaction mixture? was filtered through a layer of celite and taken up with ethyl acetate. The crude obtained? was purified by column chromatography (n-hexane/ethyl acetate eluent mixture 4:6). ? the intermediate (72.5 mg, 74% yield) was isolated as a pale yellow solid, pure by NMR analysis.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.48-1.57 (m, 2H), 1.93-2.02 (m, 2H), 1.99 (s, 3H), 2.00 (s, 3H), 2, 03 (s, 3H), 2.09 (s, 3H), 2.42-2.49 (m, 2H), 3.71-3.76 (m, 1H), 4.16 (dd, 1H, J = 12.3, 2.4Hz), 4.27 (dd, 1H, J = 12.3, 4.7Hz), 4.34-4.40 (m, 2H), 4.68 (d , 1H, J = 8.0Hz), 4.82 (d, 1H, J = 12.5Hz), 4.95 (d, 1H, J = 12.5Hz), 5.01 (dd, 1H , J = 9.6, 8.0 Hz), 5.06-5.13 (m, 1H), 5.19 (d, 1H, J = 9.4 Hz), 5.21-5.27 ( m, 4H), 7.51 (s, 1H). <13>C-NMR (400 MHz, CDCl3) ? (ppm): 20.72 (2C), 20.82, 20.89, 27.61, 28.75, 29.96, 50.05, 61.95, 63.23, 68.46, 71.37 , 72.06, 72.86, 83.17 (2C), 83.88 (2C), 90.80, 100.13, 110.21, 161.18, 169.51, 169.58, 170.32 , 170.78, 194.43 (3C).].

Step 4: 50.0 mg of intermediate 22 (0.0611 mmol, 1.00 eq) solubilized in 2.1 mL of anhydrous MeOH are introduced into a flamed flask under a flow of Ar, equipped with a magnetic stirrer and a cooler. The reaction mixture is cooled to 0°C and then 29.7 mg of solid MeONa (0.550 mmol, 9.00 eq) is added. The mixture is left under stirring at room temperature for about 4 hours. The progress of the reaction is monitored by analytical TLC CHCl3/MeOH 9:1. After 21h, the mixture was diluted with MeOH and filtered through a layer of celite. The crude is purified by flash chromatography with CHCl3/MeOH 9:1 eluent mixture. The final compound F10 ? a white solid obtained in 75% yield (30.0 mg) and pure by NMR analysis.

<1>H-NMR (400 MHz, CD3CN) ? (ppm): 1.43-1.52 (m, 2H), 1.90 (quint, 2H, J = 7.4Hz), 2.41-2.47 (m, 2H), 2.93- 3.00 (m, 1H), 3.09-3.16 (m, 1H), 3.19-3.31 (m, 2H), 3.34 (bs, 1H), 3.43 (bs, 2H), 3.54-3.62 (m, 1H), 3.73-3.80 (m, 1H), 4.36 (t, 2H, J = 7.1Hz), 4.37 (d , 1H, J = 7.8 Hz), 4.72 (d, 1H, J = 12.5 Hz), 4.87 (d, 1H, J = 12.5 Hz), 5.37 (pseudo t, 2H, J = 2.1Hz), 5.41 (pseudo t, 2H, J = 2.1Hz), 7.78 (s, 1H). <13>C-NMR (400 MHz, CD3CN) ? (ppm): 27.97, 29.47, 30.38, 50.43, 62.84 (2C), 71.49, 74.56, 77.25, 77.67, 84.96 (2C), 85.24 (2C), 103.01, 112.18, 124.56, 145.11, 196.22 (3C). FTIR: ? ? 594, 1034, 1438, 1891, 2012, 2924, 3342 (br) cm<-1>.

Scheme 10

Example 1.6 ? Synthesis of compound F11

Step 1: The reaction, exemplified in Scheme 11 below, is carried out in a flaming two-neck flask under Ar, to which EtOH (19.5 mL) is added and cooled with an ice and water bath to 0 ? c. After that, the acetyl chloride (0.98 mL, 13.7 mmol, 3.10 eq) is added dropwise, obtaining a clear and transparent solution which is left under stirring at 0 ?C for 30 minutes. Commercially available D-propargylglycine (500.0 mg, 4.42 mmol, 1.00 eq) is then added and the reaction mixture turns white and cloudy. It is left under stirring at 100 ?C for 3h. After the foreseen time, the reaction mixture is taken up with CHCl3, the solvent is eliminated by evaporation under reduced pressure. The residue is triturated with Et2O and the filtrate is collected and drawn to the vacuum pump. The intermediate 23 ? obtained with a yield of 93% (725.1 mg, beige solid).

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.33 (t, 1H, J = 7.0 Hz, 2.29 (t, 1H), 3.02 (bd, 1H, J = 16.0 Hz), 3.18 (bd, 1H, J = 15.8Hz), 4.25-4.43 (m,3H), 8.83 (bs, 3H).]

Step 2: Intermediate 23 (722.1 mg, 4.07 mmol, 1.00 eq) is solubilized in 10.4 mL of anhydrous DCM. The solution is cooled to 0?C and after which? 1.7 mL of Et3N (12.2 mmol, 3.00 eq) and (Boc)2O (1.30 g, 6.11 mmol, 1.50 eq) are added. The reaction mixture is left under stirring at rt for 16h. After the expected time, the reaction mixture is diluted with DCM, washed with NaHCO3 (three times), washed with distilled H2O (once) and washed with NaCl saturated solution (once). The organic phase is dried over Na2SO4, filtered and concentrated under reduced pressure. The raw reaction product is purified by column chromatography with n-hexane/EtOAc 95:5 eluent mixture thus isolating intermediate 24 as a clear oil (653.4 mg, 67% yield) pure by NMR analysis.

[<1>H-NMR (400 MHz, CDCl3) ? (ppm): 1.29 (t, 3H, J = 7.1Hz), 1.45 (s, 9H), 2.03 (t, 1H, J = 2.6Hz), 2.67-2 .81 (m, 2H), 4.17-4.31 (m, 2H), 4.41-4.49 (m, 1H), 5.35 (bd, 1H, J = 8.1Hz). ]

Step 3: 28.0 mg (0.116 mmol, 1.00 eq) of intermediate 24 in 1.8 mL of tBuOH and 50.0 mg (0.116 mmol, 1.00 eq) of compound S6 in 2.0 were solubilized mL of 1,4-dioxane and 1.8 mL. To this mixture? adding a solution of sodium ascorbate 23.0 mg (0.116 mmol, 1.00 eq) and CuSO4?5 H2O 14.5 mg (0.0580 mmol, 0.500 eq) in 3.9 mL of H2O. The mixture ? was left under stirring at 80°C for 3 hours. The TLC (eluent mixture CH3Cl/MeOH 99:1) showed the disappearance of the starting glycosidic substrate and the formation of the final compound 11 having Rf = 0.15. The reaction mixture? was filtered through a layer of celite and taken up with ethyl acetate. The crude obtained? was purified by column chromatography (CH3Cl/MeOH 99:1 eluent mixture). ? The final compound F11 (59.9 mg, 77% yield) was isolated as a pale yellow oil, pure by NMR analysis.

<1>H-NMR (400 MHz, MeOD) ? (ppm): 1.24 (t, 3H, J = 7.1Hz), 1.42 (s, 9H), 1.45-1.55 (m, 2H), 1.95 (quint, 2H, J = 7.3Hz), 2.42-2.49 (m, 2H), 3.06 (dd, 1H, J = 14.7, 8.5Hz), 3.20 (dd, 1H, J = 14.9, 5.2), 4.16 (q, 2H, J = 7.1 Hz), 4.40 (t, 3H, J = 6.9 Hz), 5.40 (pseudo t, 2H , J = 2.2 Hz), 5.45 (pseudo t, 2H, J = 2.1 Hz), 7.78 (s, 1H). <13>C-NMR (400 MHz, MeOD) ? (ppm): 14.47, 28.47 (4C), 28.68, 28.89, 29.75, 30.81, 50.89, 55.05, 62.45, 80.73, 84.66 , 84.68, 85.01, 85.03, 112.25, 124.65, 157.75, 173.08, 195.93 (3C). FTIR: ? ? 596, 1161, 1366, 1705, 1899, 2014, 2935, 3103cm<-1>.

Scheme 11

Example 1.7 ? Synthesis of compound F12

Step 1: The reaction, exemplified in Scheme 12 below, is carried out by solubilizing 78.9 mg (0.189 mmol, 1.00 eq) of intermediate 9 in 3.0 mL of tBuOH and 83.0 mg (0.189 mmol, 1 .00 eq) of compound S6 in 3.3 mL of 1,4-dioxane. To this mixture? adding a solution of sodium ascorbate 37.4 mg (0.189 mmol, 1.00 eq) and CuSO4?5 H2O 23.6 mg (0.0945 mmol, 0.500 eq) in 6.0 mL H2O. The mixture ? was left under stirring at 80°C for 3 hours. The TLC (nexane/EtOAc 4:6 eluent mixture) showed the disappearance of the starting glycosidic substrate and the formation of intermediate 25 with Rf = 0.15. The reaction mixture? was filtered through a layer of celite and taken up with ethyl acetate.

The crude obtained? was purified by column chromatography (n-hexane/EtOAc 4:6 eluent mixture). ? Intermediate 25 (133.2 mg, 82% yield) was isolated as a light green oil.

[<1>H-NMR (400 MHz, MeOD) ? (ppm): 1.57-1.67 (bm, 2H), 1.80-1.90 (bm, 2H), 1.94 (s, 3H), 1.97 (s, 3H), 2, 00 (s, 3H), 2.06 (s, 3H), 2.43 (pseudo t, 2H, J = 6.6Hz), 2.71-2.82 (bm, 2H), 3.83- 3.90 (m, 1H), 3.97-4.05 (m, 1H), 4.11-4.16 (m, 1H), 4.17-4.24 (m, 1H), 4, 27 (dd, 1H, J = 12.3, 4.5Hz), 4.56-4.63 (bm, 2H), 4.67 (d, 1H, J = 7.9Hz), 4.86 (dd, 1H, J = 9.6, 8.1Hz), 5.00 (pseudo t, 1H, J = 9.7Hz), 5.23 (pseudot, 1H, J = 9.5Hz) , 5.46 (pseudo t, 2H, J = 2.2 Hz), 5.73 (pseudo t, 2H, J = 2.2 Hz), 7.89-8.03 (bs, 1H).

<13>C-NMR (400 MHz, MeOD) ? (ppm): 19.25, 20.34 (4C), 20.49, 20.56, 28.77, 62.81, 64.05, 66.79, 68.41, 69.54, 71.14, 72.37, 72.64, 72.77, 73.85, 85.20, 86.88), (21.88C), , 101.39, 170.79, 171.01, 171.33, 172.05, 194.91 (3C).]

Step 2: 60.0 mg of intermediate 25 (0.0700 mmol, 1.00 eq) solubilized in 2.4 mL of anhydrous MeOH are introduced into a flamed flask under a flow of Ar, equipped with a magnetic stirrer and a cooler. The reaction mixture is cooled to 0°C and then 34.0 mg of solid MeONa (0.630 mmol, 9.00 eq) is added. The mixture is left under stirring at room temperature for about 4 hours. The progress of the reaction is monitored by analytical TLC CHCl3/MeOH 9:1. After 21h, the mixture was diluted with MeOH and filtered through a layer of celite. The crude is purified by flash chromatography with CHCl3/MeOH 9:1 eluent mixture. The final compound F12 ? a white solid obtained in 78% yield (37.5 mg) and pure by NMR analysis.

<1>H-NMR (400 MHz, MeOD) ? (ppm): 1.59 (quint, 2H, J = 7.3Hz), 1.80 (quint, 2H, J = 7.6Hz), 2.39 (t, 2H, J = 7.0Hz ), 2.72 (t, 2H, J = 7.5Hz), 3.18 (dd, 1H, J = 9.0, 7.8Hz), 3.25-3.29 (m, 2H) , 3.35 (dd, 1H, J = 8.9, 6.8 Hz), 3.62-3-68 (m, 1H), 3.87 (dd, 1H, J = 11.6, 1, 6Hz), 3.94-4.02 (m, 1H), 4.19-4.27 (m, 1H), 4.30 (d, 1H, J = 7.8Hz), 4.61 ( t, 2H, J = 5.1 Hz), 5.45 (pseudo t, 2H, J = 2.2 Hz), 5.72 (pseudo t, 2H, J = 2.1 Hz), 7.87 ( s, 1H).

<13>C-NMR (400MHz, DMSO-d6) ? (PPM): 19.37, 25.74, 28.92, 29.58, 51.51, 62.72, 69.13, 71.56, 72.70, 74.96, 77.97, 78.08, 85.35 (2C), 88.76 (2C), 88.98, 91.16, 104.59, 124.30, 148.68, 3C). FTIR: ? ? 593, 1031, 1429, 1897, 2016, 2931, 3332 (br) cm<-1>.

Scheme 12

Example 2 ? In vitro visualization under the FT-IR microscope to evaluate the highlighting of portions (cells/tissues) of pancreatic adenocarcinoma (PDAC)

Primary pancreatic tumor cell cultures (PCC-PDAC) and tumor tissue (TT-PDAC) were deposited on glass slides by trans-reflectance MirrIR slide Kevley Technologies. For the two types of material indicated above, two different procedures were used. For PCC-PDAC, chamber-slides were mounted on MirrIR slides, in such a way as to be able to create 8 cell spots on each slide, in order to be able to test the same compound at different doses and times or to evaluate different compounds in the same preparation. In particular, the same PCC-PDACs were treated with three different compounds (report which ones) for three different periods of time: 15 min, 30 min, 60 min. The combination of this type of support with the slides for MirrIP analysis has allowed to improve the experimentation by reducing the quantities? of compounds used for cell culture treatments. At the same time, in a single support (slide+chamber-slide) ? it was possible to compare the different exposure times of the various compounds. For each individual experiment ? a relative control test has always been evaluated.

The TT-PDAC tissues, on the other hand, were placed on the same MirrIR slides, following the normal histological procedures for the preparation of cryostatic sections of a few ?m (typical, but not limiting, range: 1-10 ?m). However, ? Particular attention was paid to tissue sampling and related exposure to compounds. Every sample ? was cut into two symmetrical parts and the cut surfaces obtained were used for the assay (experimental test) and the relative control (same solvent, first of the compounds). Therefore, in order to properly compare the treatments on cells and tissues, concerning the same pathology, two identical procedures were performed, but reversed in the single phases of the experimentation.

The cells were first prepared and then exposed to treatments. For fabrics? the opposite happened: first they were treated and then prepared for the analyses. The biological material used for the experiments? was subsequently preserved at -80 ?C.

The slides what? obtained were analyzed by Agilent Techonlogies FTIR 620 microscope with Focal Plane Array (FPA) detector cooled with liquid nitrogen. Each analysis ? was carried out in mode? reflectance, with 64 scans, both for the samples and for the background, at 4 cm<-1 > of resolution in a spectral range that goes from 3500 to 900 cm<-1>. For each spectrum analysed, both the false color image (FPA image) and the visible image are present, both 350X350 ?m in size.

The areas of the spectra cos? obtained were subsequently analyzed and compared with the help of Prism GraphPad. The ratios between the areas (band at 2100 cm<-1>/band amide I) compared using an ANOVA test, gave P=0.0005, demonstrating significance of the analysis performed.

The collected images are shown in Figures 1-9.

Claims (12)

CLAIMS 1. A compound of general formula (I): Formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof, in which Y ? selected from the group consisting of: glucose and its derivatives, preferably alpha- and beta-O-glycosides comprising units of D-glucose; fructose and its derivatives, preferably fructopyranose nuclei; 2,5-anhydrous D-mannitol and its derivatives; arginine-glycine-aspartate (RGD) tripeptides, glycine, alanine, norvaline, or a combination thereof; X ? selected from the group consisting of: C1-C20 linear alkyl or C3-C20 branched alkyl; said C1-C20 linear alkyl or C3-C20 branched alkyl possibly presenting one or more? groups selected from: aryl, heteroaryl, alkene, alkyne, amine, amide, ether, ester, ketone, thioether, sulfide, sulphone, sulfoxide, or a combination thereof. A compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof according to claim 1, wherein: Y ? a cycle with 5 or 6 carbon atoms. A compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof according to claim 1 or 2, wherein: X ? chosen from one of the groups having one of the following general formulas: in which p ? an integer between 0 and 18, q ? an integer between 0 and 18, r ? an integer between 0 and 1. 4. Compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof according to any one of the preceding claims selected from: 5. Pharmaceutical composition comprises the compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof according to any one of the preceding claims and one or more? pharmaceutically acceptable excipients, diluents and/or carriers, said composition being preferably formulated as an aqueous solution. A compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof according to any one of claims 1 to 4 or a pharmaceutical composition according to claim 5 for use in the diagnosis of a pathological or metabolic condition by infrared spectroscopy (IR) 7. Compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof according to any one of claims 1 to 4 or pharmaceutical composition according to claim 5 for use according to claim 6 wherein said pathological or metabolic condition ? selected from the group consisting of: a tumor, an infection, preferably bacterial or viral, an inflammation, a metabolic disorder, preferably metabolic syndrome, a MAGL-mediated condition, an autoimmune disease, and a combination thereof. 8. Compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof according to any one of claims 1 to 4 or pharmaceutical composition according to claim 5 for use according to claim 6 or 7 in which said pathological condition ? a tumor, preferably selected from the group consisting of: pancreatic cancer, lung cancer, colorectal cancer, breast cancer, ovarian cancer, liver cancer, and a combination thereof, plus preferably a carcinoma or an adenocarcinoma, even more? preferably said tumor being primary or metastatic. 9. Method for the detection, by infrared spectroscopy (IR), of cells and/or tissues affected by a pathological or metabolic condition in isolated biological samples, said method comprising the steps of: i) making available an isolated biological sample, preferably deposited on a support suitable for being analyzed by IR spectroscopy, said support preferably being a slide; ii) contacting the compound of general formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof according to any one of claims 1 to 4 or the pharmaceutical composition according to claim 5 with said isolated biological sample; iii) analyzing the sample obtained in step ii) by means of an IR microscope, preferably an FTIR microscope, obtaining at least one spectrum of said sample; iv) analyzing said at least one spectrum obtained in step iii) and possibly comparing it with a control model. The method according to claim 9, wherein said detection comprises the detection of alterations of protein components of said cells and/or tissues. 11. A method according to claim 9 or 10 wherein said pathological condition ? a tumor and said cells and/or tissues are tumor cells and/or tissues 12. A method according to claim 9 or 10 wherein said pathological condition ? a bacterial or viral infection and said detection includes the detection of antigenic components resulting from infections caused by viruses or bacteria.