GB1426717A - Penicillins - Google Patents
PenicillinsInfo
- Publication number
- GB1426717A GB1426717A GB1169272A GB1169272A GB1426717A GB 1426717 A GB1426717 A GB 1426717A GB 1169272 A GB1169272 A GB 1169272A GB 1169272 A GB1169272 A GB 1169272A GB 1426717 A GB1426717 A GB 1426717A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- reacting
- formula
- acid
- defined above
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
1426717 Carbonic esters of penicillins ASTRA LAKEMEDEL AB 12 March 1973 [13 March 1972] 11692/72 Heading C2C [Also in Division A5] Novel penicillins comprise compounds of formula or pharmaceutically acceptable salts thereof, wherein R is phenyl, thienyl or furyl; R<SP>1</SP> is H or R<SP>2</SP> is as for R<SP>1</SP> or C 1 -C 8 alkyl, aryl or aralkyl; R<SP>3</SP> is H or CH 3 ; R<SP>4</SP> is a C 1 -C 8 alkyl, alkenyl or alkynyl, C 3 -C 7 cycloalkyl, phenyl, benzyl, indanyl, thienyl, furyl, furfuryl, pyridyl, pyridylmethyl or 2-methyl-1,3-dioxanyl group, these groups being optionally substituted with one or more amino, substituted amino or nitro groups or halogen; provided that R<SP>2</SP> is where R<SP>1</SP> is H. The compounds are prepared (a) by reacting 6-aminopenicillanic acid with a compound R<SP>7</SP>'Y, wherein R<SP>7</SP>' is R<SP>7</SP>, wherein R<SP>7</SP> is wherein R<SP>3</SP> and R<SP>4</SP> are as defined above or R<SP>7</SP>' is a protected R<SP>7</SP> group and Y is halogen or a functionally equivalent group, to provide esters of Formula IV wherein R<SP>7</SP>' is as defined above, which are reacted with a compound of formula wherein R is as defined above, R<SP>2</SP>' is R<SP>2</SP> or a protected R<SP>2</SP> group and -COZ is an amideforming group and, if necessary, removing protecting groups, or (b) by reacting an ester of formula wherein RCO is the acyl group of a natural or biosynthetic penicillin, and R<SP>7</SP> is as defined above with a phosphorus halide to form an imino halide, reacting this with a lower alcohol and reacting the imino ether produced with a compound of Formula III as above or (c) by esterifying a compound of formula wherein R and R<SP>2</SP> are as defined above with a compound R<SP>7</SP>'Y, wherein Y is an esterifying group or halogen and R<SP>7</SP>' is as defined above, or (d) by reacting a compound of formula wherein R and R<SP>2</SP>' are as defined above, with a compound of Formula IV as above, or (e) by esterifying a compound of formula wherein R is as defined above, Q is H or a cation and R<SP>8</SP>' is an R<SP>1</SP> or protected R<SP>1</SP> group, with a compound R<SP>6</SP>'Y, R<SP>6</SP>' being an R<SP>2</SP> or protected R<SP>2</SP> group, neither R<SP>1</SP> nor R<SP>2</SP> being H, or (f) by reacting a compound of formula wherein R is as defined above with a compound wherein R<SP>4</SP> is R<SP>4</SP>' as defined above or a protected R<SP>4</SP> group, and R<SP>3</SP> is as defined above or (g) by reacting a suitable activated malonic acid ester with 6-APA or (h) by reacting an α-carboxy, 3-protected carboxy penicillin with a compound of formula wherein Y, R<SP>3</SP> and R<SP>4</SP>' are as defined above or (i) by reacting a 6-N-acylated natural or biosynthetic penicillin having a protected carboxy group with a phosphorus halide to give an imino halide which is treated with a lower alcohol to give an imino ether, which is reacted with a suitable malonic acid ester derivative or (j) by reacting a compound of formula wherein R, R<SP>4</SP>' and R<SP>3</SP> have the above-defined meanings with 6-APA having the carboxy group protected or (k) by reacting an acid α-carboxy 6-acylated penicillanic with a compound of formula wherein Y, R<SP>3</SP>, X and R<SP>4</SP>' have the meanings defined above to yield a mixture of compounds of formulae wherein R, R<SP>3</SP> and R<SP>4</SP> have the above meanings. Chloromethylethyl carbonate is prepared by reacting chloromethyl chloroformate with ethanol and is then reacted with potassium phenylacetate to form ethoxycarbonyloxymethylphenyacetate, from which phenylmalonic acid ethoxycarbonyloxymethyl monoester is prepared by reaction with dry ice (CO 2 ) in the presence of n-butyllithium. The acid chloride of the monoester is prepared by reaction with thionyl chloride. Ethoxycarbonyloxymethyl - (3 - thienyl) - acetate, 3- thienylmalonic acid ethoxycarbonyloxymethyl monoester, its acid chloride, chloromethylphenyl carbonate, phenylacetic acid phenoxycarbonyloxymethyl ester, its acid chloride, phenylmalonic acid phenoxycarbonyloxymethyl monoester, its acid chloride, chloromethyl-2-N- benzyloxycarbonylmethylamino ethyl carbonate, and α - chloroethylcyclopentyl carbonate are produced by similar methods 3-thienylacetic acid acid chloride is produced by reacting 3-thienylacetic acid with thionyl chloride and the product is esterified to yield benzyl-(3-thienyl) acetate. N-benzyloxycarbonyl methylamino ethanol is prepared by reacting chloroformic acid with 2 - methyamino ethanol. Phenylmalonic acid (1<SP>1</SP> - ethoxycarbonyloxyethyl)monoester is produced from the diester by hydrogenation, the diester being produced by methods similar to those above. Pharmaceutical compositions comprise a compound of the invention and a pharmaceutically acceptable carrier. Other antibiotics may be present (see Division A5).
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1169272A GB1426717A (en) | 1972-03-13 | 1972-03-13 | Penicillins |
DE2312041A DE2312041A1 (en) | 1972-03-13 | 1973-03-10 | PENICILLIN, THE METHOD OF MANUFACTURING THEIR PRODUCTS AND THE PHARMACEUTICAL PRODUCTS CONTAINING IT |
AU53209/73A AU5320973A (en) | 1972-03-13 | 1973-03-12 | Penicillins |
JP48028906A JPS49289A (en) | 1972-03-13 | 1973-03-12 | |
FR7308754A FR2201870A1 (en) | 1972-03-13 | 1973-03-12 | |
AT214273A AT332540B (en) | 1972-03-13 | 1973-03-12 | METHOD FOR MANUFACTURING NEW PENICILLIN |
NL7303489A NL7303489A (en) | 1972-03-13 | 1973-03-13 | |
DK543774A DK543774A (en) | 1972-03-13 | 1974-10-17 | |
NO750668A NO750668L (en) | 1972-03-13 | 1975-02-27 | |
AT632575A AT332974B (en) | 1972-03-13 | 1975-08-14 | METHOD FOR MANUFACTURING NEW PENICILLIN |
SE7512141A SE7512141L (en) | 1972-03-13 | 1975-10-30 | NEW ORGANIC ASSOCIATIONS |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1169272A GB1426717A (en) | 1972-03-13 | 1972-03-13 | Penicillins |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1426717A true GB1426717A (en) | 1976-03-03 |
Family
ID=9990955
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB1169272A Expired GB1426717A (en) | 1972-03-13 | 1972-03-13 | Penicillins |
Country Status (9)
Country | Link |
---|---|
JP (1) | JPS49289A (en) |
AT (1) | AT332540B (en) |
AU (1) | AU5320973A (en) |
DE (1) | DE2312041A1 (en) |
FR (1) | FR2201870A1 (en) |
GB (1) | GB1426717A (en) |
NL (1) | NL7303489A (en) |
NO (1) | NO750668L (en) |
SE (1) | SE7512141L (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4606865A (en) * | 1982-09-20 | 1986-08-19 | Astra Lakemedel Aktiebolag | Methods for the preparation of α-bromodiethylcarbonate |
US4614829A (en) * | 1983-08-26 | 1986-09-30 | Societe Nationale Des Poudres Et Explosifs | Process for the preparation of α-chlorinated chloroformates |
US4619785A (en) * | 1982-06-29 | 1986-10-28 | Astra Lakemedel Aktiebolag | Novel synthesis route for bacampicillin |
US4960881A (en) * | 1984-02-16 | 1990-10-02 | Societe Nationale Des Poudres Et Explosifs | α-chlorinated carbonates, their method of manufacture and application in the protection of the amine functions of amino acids |
WO2004067536A2 (en) * | 2003-01-28 | 2004-08-12 | Sandoz Ag | Carboxylic acid esters to improve bioavailability of pharmaceutical compounds |
US7091197B2 (en) | 2002-08-23 | 2006-08-15 | Pfizer Inc. | Beta-lactamase inhibitor prodrug |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2482587A1 (en) * | 1980-05-14 | 1981-11-20 | Poudres & Explosifs Ste Nale | PROCESS FOR THE SYNTHESIS OF A-CHLORINATED CHLOROFORMIATES AND NEW A-CHLORINATED CHLOROFORMIATES |
IL68992A (en) * | 1982-06-29 | 1991-06-10 | Astra Laekemedel Ab | Alpha-bromo diethyl carbonate and process for the preparation of ethoxycarbonyloxy esters of penicillanic acids |
GB8400024D0 (en) * | 1984-01-03 | 1984-02-08 | Glaxo Group Ltd | Cephalosporin antibiotics |
FR2559766B1 (en) * | 1984-02-16 | 1986-05-16 | Poudres & Explosifs Ste Nale | PROCESS FOR THE PREPARATION OF CARBAMIC ACID DERIVATIVES |
US4916230A (en) * | 1984-07-02 | 1990-04-10 | Merck & Co., Inc. | Process for preparing novel N-(acyloxy-alkoxy)carbonyl derivatives useful as bioreversible prodrug moieties for primary and secondary amine functions in drugs |
-
1972
- 1972-03-13 GB GB1169272A patent/GB1426717A/en not_active Expired
-
1973
- 1973-03-10 DE DE2312041A patent/DE2312041A1/en active Pending
- 1973-03-12 JP JP48028906A patent/JPS49289A/ja active Pending
- 1973-03-12 FR FR7308754A patent/FR2201870A1/fr not_active Withdrawn
- 1973-03-12 AU AU53209/73A patent/AU5320973A/en not_active Expired
- 1973-03-12 AT AT214273A patent/AT332540B/en not_active IP Right Cessation
- 1973-03-13 NL NL7303489A patent/NL7303489A/xx unknown
-
1975
- 1975-02-27 NO NO750668A patent/NO750668L/no unknown
- 1975-10-30 SE SE7512141A patent/SE7512141L/en not_active Application Discontinuation
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4619785A (en) * | 1982-06-29 | 1986-10-28 | Astra Lakemedel Aktiebolag | Novel synthesis route for bacampicillin |
US4606865A (en) * | 1982-09-20 | 1986-08-19 | Astra Lakemedel Aktiebolag | Methods for the preparation of α-bromodiethylcarbonate |
US4820857A (en) * | 1982-09-20 | 1989-04-11 | Astra Lakemedel Aktiebolag | α-bromodiethylcarbonate |
US4614829A (en) * | 1983-08-26 | 1986-09-30 | Societe Nationale Des Poudres Et Explosifs | Process for the preparation of α-chlorinated chloroformates |
US4960881A (en) * | 1984-02-16 | 1990-10-02 | Societe Nationale Des Poudres Et Explosifs | α-chlorinated carbonates, their method of manufacture and application in the protection of the amine functions of amino acids |
US7091197B2 (en) | 2002-08-23 | 2006-08-15 | Pfizer Inc. | Beta-lactamase inhibitor prodrug |
WO2004067536A2 (en) * | 2003-01-28 | 2004-08-12 | Sandoz Ag | Carboxylic acid esters to improve bioavailability of pharmaceutical compounds |
WO2004067536A3 (en) * | 2003-01-28 | 2004-12-23 | Sandoz Ag | Carboxylic acid esters to improve bioavailability of pharmaceutical compounds |
Also Published As
Publication number | Publication date |
---|---|
NL7303489A (en) | 1973-09-17 |
DE2312041A1 (en) | 1973-10-11 |
AU5320973A (en) | 1974-09-12 |
FR2201870A1 (en) | 1974-05-03 |
AT332540B (en) | 1976-10-11 |
SE7512141L (en) | 1975-10-30 |
ATA214273A (en) | 1976-01-15 |
NO750668L (en) | 1973-09-14 |
JPS49289A (en) | 1974-01-05 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PS | Patent sealed [section 19, patents act 1949] | ||
PLNP | Patent lapsed through nonpayment of renewal fees |