GB1298295A - Improvements in or relating to antibiotic derivatives and the preparation thereof - Google Patents
Improvements in or relating to antibiotic derivatives and the preparation thereofInfo
- Publication number
- GB1298295A GB1298295A GB2565571A GB2565571A GB1298295A GB 1298295 A GB1298295 A GB 1298295A GB 2565571 A GB2565571 A GB 2565571A GB 2565571 A GB2565571 A GB 2565571A GB 1298295 A GB1298295 A GB 1298295A
- Authority
- GB
- United Kingdom
- Prior art keywords
- methyl
- acetyl
- deoxy
- compound
- thiolincosaminide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/14—Acyclic radicals, not substituted by cyclic structures attached to a sulfur, selenium or tellurium atom of a saccharide radical
- C07H15/16—Lincomycin; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
1298295 Lincomycin and lincosaminide derivatives UPJOHN CO 19 April 1971 [20 April 1970] 25655/71 Headings C2C and C2P The invention comprises compounds of the Formula I the zwitterion form thereof and the salts thereof, where Y is -SR, 2-(2-hydroxyphenylcarbonyloxy)ethylthio or 2-hydroxyethylthio, R 1 is H or cis or trans C 1-8 alkyl, R 2 is H, methyl or ethyl, X is OH, Cl, Br, I or OR 3 , each in the (R) or (S) configuration, R is C 1-6 alkyl, R 3 is C 1-6 alkyl or cycloalkyl, alkoxyalkyl, or hydroxyalkyl, and Z is a nucleoside-5<SP>1</SP>- phosphate group where the nucleoside is adenosine, guanosine, cytidine or uridine. The compounds of the invention may be prepared by incorporating a compound of the Formula I in which Z is hydrogen in the fermentation medium of a Streptomyces fermentation, and may be subsequently isolated from the fermentation medium by (a) filtering the fermentation medium, (b) absorbing the filtrate on a suitable absorbent to remove water-soluble impurities, (c) chromatographing the eluate from the absorbent on an anion exchange resin, (d) subjecting fractions from the anion exchange resin to countercurrent distribution and (e) separating the individual 3-nucleotides by chromatography. Methyl - 6,7 - aziridino - 6 - deamino - 7 - deoxy- α-thio -lincosaminide, (Compound VI) is prepared by reacting methyl 7(S)-chloro-7-deoxy-α-thiolincosaminide with sodium carbonate. Methyl N acetyl 6,7 - aziridino - 6 - deamino - 7 - deoxy - α - thiolincosaminide (Compound XIII) is prepared by reacting compound VI with acetic anhydride in isopropyl alcohol. Methyl N - acetyl - 7(S) - methoxy - 7 - deoxy- α-thiolincosaminide (Compound VII) is prepared by reacting compound VI with methanol and acetic anhydride, or by reacting compound XIII with methanol and acetic acid under reflux. Methyl N - acetyl - 6,7 - aziridino - 6 - deamino- 7 - deoxy - 2,3,4 - tri - O - acetyl - α - thiolincosaminide (Compound X) is prepared by reacting compound VI with acetic anhydride in pyridine. Methyl N - acetyl - 2,3,4 - tri - O - acetyl - 7- deoxy - 7(S) - methoxy - α - thiolincosaminide (Compound XI) is prepared by reacting compound X with methanol and glacial acetic acid. A mixture of compound XI and the 2,3-di-O- acetyl compound is obtained by reacting compound VII with acetic anhydride in pyridine. The 2,3-di-O-acetyl compound is converted to compound XI by acetylation. Methyl - 7 - deoxy - 7(S) - methoxy - α - thiolincosaminide (Compound VIII) is obtained by hydrazinolysis of compound VII or of compound XI. 7 - Deoxy - 7(S) - methoxy lincomycin hydrochloride is prepared by reacting compound VIII with trans - 1 - methyl - 4 - propyl - L - 2 - pyrrolidine-carboxylic acid hydrochloride, and subsequently dissolving the free base formed in hydrochloric acid. 7 - Deoxy - 7(S) - ethoxylincomycin hydrochloride is prepared in a similar way from compound XIII, via methyl N-acetyl-7-deoxy-7(S)- ethoxy - 1 - thio - α - lincosaminide, methyl N- acetyl - 2,3,4 - triacetyl (or 2,3 - diacetyl) - 7- deoxy - 7(S) - ethoxy - α - thiolincosaminide and 7 - deoxy - 7(S) - ethoxy - α - thiolincosaminide. 7 - Deoxy - 7(S) - propoxylincomycin hydrochloride is prepared from compound XIII via methyl N - acetyl - 7 - deoxy - 7(S) - propoxy- α-thiolmcosaminide, methyl N-acetyl-2,3,4-tri- O - acetyl (or 2,3 - diacetyl) - 7(S) - propoxy - 7- deoxy-α-thiolincosaminide and methyl 7-deoxy- 7(S)-propoxy-α-thiolincosaminide. 7 - Deoxy - 7(S) - isopropoxylincomycin hydrochloride is obtained from compound XIII via methyl N - acetyl - 2,3,4 - tri - O - acetyl - 7- deoxy - 7(S) - isopropoxy - α - thiolincosaminide and methyl 7 - deoxy - 7(S) - isopropoxy - α- thiolincosaminide. 7(S) -Cyclohexyloxy - 7 - deoxylincomycin hydrochloride is obtained from compound XIII via methyl N - acetyl - 2,3,4 - tri - O - acetyl- 7 - deoxy - 7(S) - cyclohexyloxy - α - thiolincosaminide and methyl 7-deoxy-7(S)-cyclohexyloxy-α-thiolincosaminide. 7 - Deoxy - 7(S) - 2<SP>1</SP> - hydroxyethoxylincomycin hydrochloride is prepared from compound VI in a similar way to compound IX via methyl N- acetyl - 7 - deoxy - 7(S) - 2<SP>1</SP> - hydroxyethoxy - α- thiolincosaminide, its 2,3,4-tri-O-acetyl derivative and methyl 7-deoxy-7(S)-2<SP>1</SP>-hydroxy-eth - oxy-α-thiolincosaminide. 7 - Deoxy - 7(S) - 2<SP>1</SP> - methoxyethoxylincomycin hydrochloride is prepared from compound VI via methyl N - acetyl - 7 - deoxy - 7(S) - 2<SP>1</SP>- methoxyethoxy - α - thiolincosaminide, its 2,3,4- tri-O-acetyl derivative and methyl 7-deoxy-7(S)- 2<SP>1</SP>-methoxyethoxy-a-thiolincosaminide. Methyl 7 - deoxy - 7(S) - hydroxy - α - thiolincosaminide is prepared from compound VI via methyl N - acetyl - 7 - deoxy - 7(S)- hydroxy -α-thiolincosaminide. A mixture of methyl N.acetyl.2,3,4-tri-O. acetyl - 7(S) - ethoxy - 7 - deoxy - α - thiolincosaminide and methyl N-acetyl-2,3,4-tri-O-acetyl- 7(S) - acetoxy - 7 - deoxy - α - thiolincosaminide is prepared by reacting compound X with glacial acetic acid and ethanol. 7 - O - Methyllincomycin hydrochloride is prepared from 2<SP>1</SP>-hydroxyethyl 1-thio-α-celestosaminide via 2<SP>1</SP>-hydroxyethyl N-acetyl-2<SP>1</SP>,2,3,4. tetra - O - acetyl - 7 - O - methyl - 1 - thio - α- lincosaminide, 1 - bromo - 7 - O - methyl - #. lincosamine tetraacetate, methyl N-acetyl-2,3, 4 - tri - O - acetyl - 7 - O - methyl - 1 - thio - α- and #-lincosaminides and methyl 7-O-methyl-1- thio-α-lincosaminide. Methyl' N - acetyl - 7 - O - methyl - 1 - thio - α- lincosaminide and its triacetate are prepared from methyl 6 - N,7 - O - ethylidyne - 3,4 - O-, isopropylidene - 1 - thio - α - lincosaminide via its 2-O-acetyl derivative, methyl N-acetyl-2-O- acetyl - 3,4 - O - isopropylidene - 1 - thio - α- lincosaminide and its 7-O-methyl derivative. Compounds of the Formula II and the corresponding 7-O-ethyl, propyl, butyl, isobutyl, sec-butyl and tert-butyl derivatives are prepared by methods similar to those described above. The compounds of the invention are antibacterial agents and may be made up into pharmaceutical compositions with suitable carriers.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3025470A | 1970-04-20 | 1970-04-20 |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1298295A true GB1298295A (en) | 1972-11-29 |
Family
ID=21853299
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB2565571A Expired GB1298295A (en) | 1970-04-20 | 1971-04-19 | Improvements in or relating to antibiotic derivatives and the preparation thereof |
Country Status (4)
Country | Link |
---|---|
BE (1) | BE766008A (en) |
DE (1) | DE2118636A1 (en) |
FR (1) | FR2092060B1 (en) |
GB (1) | GB1298295A (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005012320A2 (en) * | 2003-06-17 | 2005-02-10 | Vicuron Pharmaceuticals, Inc. | Novel lincomycin derivatives possessing antimicrobial activity |
US7164011B2 (en) | 2002-08-15 | 2007-01-16 | Vicuron Pharmaceuticals, Inc. | Lincomycin derivatives possessing antibacterial activity |
US7199106B2 (en) | 2003-06-17 | 2007-04-03 | Vicuron Pharmaceuticals, Inc. | Lincomycin derivatives possessing antimicrobial activity |
US7199105B2 (en) | 2002-08-15 | 2007-04-03 | Vicuron Pharmaceuticals, Inc. | Lincomycin derivatives possessing antibacterial activity |
US7256177B2 (en) | 2003-06-17 | 2007-08-14 | Vicuron Pharmaceuticals, Inc. | Lincomycin derivatives possessing antibacterial activity |
US7361743B2 (en) | 2004-02-11 | 2008-04-22 | Pfizer Inc | Lincomycin derivatives possessing antibacterial activity |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3544552A (en) * | 1968-10-18 | 1970-12-01 | Upjohn Co | 3-phosphate esters of lincomycin |
-
1971
- 1971-04-17 DE DE19712118636 patent/DE2118636A1/en active Pending
- 1971-04-19 GB GB2565571A patent/GB1298295A/en not_active Expired
- 1971-04-19 FR FR7113813A patent/FR2092060B1/fr not_active Expired
- 1971-04-20 BE BE766008A patent/BE766008A/en unknown
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7164011B2 (en) | 2002-08-15 | 2007-01-16 | Vicuron Pharmaceuticals, Inc. | Lincomycin derivatives possessing antibacterial activity |
US7199105B2 (en) | 2002-08-15 | 2007-04-03 | Vicuron Pharmaceuticals, Inc. | Lincomycin derivatives possessing antibacterial activity |
WO2005012320A2 (en) * | 2003-06-17 | 2005-02-10 | Vicuron Pharmaceuticals, Inc. | Novel lincomycin derivatives possessing antimicrobial activity |
WO2005012320A3 (en) * | 2003-06-17 | 2005-10-20 | Vicuron Pharm Inc | Novel lincomycin derivatives possessing antimicrobial activity |
US7199106B2 (en) | 2003-06-17 | 2007-04-03 | Vicuron Pharmaceuticals, Inc. | Lincomycin derivatives possessing antimicrobial activity |
JP2007516172A (en) * | 2003-06-17 | 2007-06-21 | ビキュロン・ファーマシューティカルズ・インコーポレイテッド | Novel lincomycin derivatives with antibacterial activity |
US7256177B2 (en) | 2003-06-17 | 2007-08-14 | Vicuron Pharmaceuticals, Inc. | Lincomycin derivatives possessing antibacterial activity |
US7361743B2 (en) | 2004-02-11 | 2008-04-22 | Pfizer Inc | Lincomycin derivatives possessing antibacterial activity |
Also Published As
Publication number | Publication date |
---|---|
FR2092060B1 (en) | 1974-10-18 |
FR2092060A1 (en) | 1972-01-21 |
BE766008A (en) | 1971-09-16 |
DE2118636A1 (en) | 1971-11-04 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PS | Patent sealed | ||
PCNP | Patent ceased through non-payment of renewal fee |