GB1321412A - Antibiotics and their preparation - Google Patents
Antibiotics and their preparationInfo
- Publication number
- GB1321412A GB1321412A GB2340771*A GB2340771A GB1321412A GB 1321412 A GB1321412 A GB 1321412A GB 2340771 A GB2340771 A GB 2340771A GB 1321412 A GB1321412 A GB 1321412A
- Authority
- GB
- United Kingdom
- Prior art keywords
- formula
- lower alkyl
- compound
- radical
- compounds
- 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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P35/00—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin
- C12P35/08—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin disubstituted in the 7 position
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Cephalosporin Compounds (AREA)
Abstract
1321412 New antibiotics MERCK & CO Inc 19 April 1971 [13 March 1970 30 June 1970 9 Dec 1970 16 Feb 1971] 23407/71 Heading C2A Novel cephalosporin-like antibiotics have the Formula I wherein R is hydrogen, halo, hydroxy, lower alkanoyloxy, mono-nuclear or bi-nuclear aromatic-carbonoyloxy, six-membered N-containing heterocyclic-carbonoyloxy, aralkanoyloxy, 5 or 6 nuclear carbon-containing cycloalkanecarbonoyloxy, α-methoxy-p-sulphooxycinnamoyloxy, α-methoxy-p-hydroxycinnamoyloxy; a carbamoyloxy radical of formula: (where R<SP>1</SP> and R<SP>2</SP> are each hydrogen, lower alkyl, halo-lower alkyl, lower alkoxycarbonyl, aryl, alkarylsulphonyl, benzhydryl, or together with the common N, form a pyrrolidino, morpholino or piperidino radical); a thio radical of formula: -SR<SP>3</SP> (where R<SP>3</SP> is lower alkyl, pyridyl, lower alkyl-substituted thiazolyl, 1,3,4- thiadiazol-2-yl, lower alkyl-substituted 1,3,4- thiadiazol-2-yl, 2-benzothiazolyl or 4-lower alkyl-pyrimidin-2-yl); a pyridinium radical of formula (where X<SP>1</SP> is hydrogen, halogen, trifluoromethyl, cyano, carboxy, carbamoyl, N-lower alkyl carbamoyl, N,N-di-lower alkyl carbamoyl, carboxymethyl, lower alkanoyl, lower alkyl, hydroxymethyl or sulpho); a thiouronium radical of formula an amidinothio radical of formula (wherein R<SP>4</SP>, R<SP>5</SP> and R<SP>6</SP> are hydrogen or lower alkyl); an amino-thio carbonylthio radical of formula (where R<SP>7</SP> and R<SP>8</SP> are hydrogen, lower alkyl, hydroxy-lower alkyl, di-lower alkylamino-lower alkyl, morpholino-lower alkyl, N-aryl-N-lower alkylaminoalkyl, or together with the common N, form a morpholino, piperidino, pyrrolidinyl or a piperazino radical of formula where R<SP>9</SP> is alkyl or phenyl); aroylthio, an oxythiocarbonylthio radical of formula (where R<SP>10</SP> is C 1 -C 6 alkyl or C 5 or C 6 cycloalkyl); alkarylsulphonyl: azido; amino, or an amino radical of formula: -NHR<SP>11</SP> (where R<SP>11</SP> is an acyl radical); polyhydroxyphenyl, N-lower alkyl-indol-3-yl, or thiocyanato. Salts, esters and amides of the compounds of Formula I are included. The word "lower" means that the relevant group contains not more than 5 carbon atoms. Compounds of Formula I wherein R is α- methoxy-p-sulphooxycinnamoyloxy or α-methoxy-p-hydroxycinnamoyloxy, i.e. compounds of Formula Ia wherein R<SP>12</SP> is sulphoxy or hydroxy respectively, are prepared by aerobically cultivating a new strain (NRRL3851) of Streptomyces griseus, when a mixture of the said compounds termed antibiotic 810A is produced. This mixture may also be produced by aerobically cultivating the following new strains:- Streptomyces griseus NRRL. 3951, 3952 and 3953; Streptomyces viridochromogenes NRRL. 3962, 3963, 3964, 3965, 3966, 3967, 3968, 3969, 3970, 3971 and 3972; Streptomyces fimbriatus NRRL. 3954, 3955, 3956, 3957 and 3958; Streptomyces halstedii NRRL. 3959, 3960 and 3961; Streptomyces rochei NRRL. 3973; Streptomyces cinnamonesis NRRL. 3974; and Streptomyces chartreusis NRRL. 3975. Compounds of Formula I wherein R is carbamoyloxy, i.e. compounds of Formula Ib are prepared by aerobically cultivating a new species (NRRL. 3802) of Streptomyces, S. lactamdurans. The said compound is referred to as antibiotic 842A. Other compounds of Formula I are obtained by appropriate chemical conversions of the 3- carbamoyloxy group of compound (Ib), if necessary after conventionally protecting the free amino group and both carboxyl groups. By reacting the protected compound (Ib) with nitrosyl halide, the 3-hydroxymethylanalogueis obtained. N-Mono-substituted and N,N-disubstituted 3-carbamoyloxy compounds are prepared by first reacting the protected compound (Ib) with a carbonyl halide to give the corresponding 3-(haloformyloxymethyl) compound which is then treated with the appropriate mono- or di-substituted amine. Reaction of compound (Ib) with an isocyanate gives the N-monosubstituted analogue. 3-Methyl derivatives are prepared by catalytic hydrogenation of compound (Ib). Other 3-substituted compounds may be obtained by acylation of the 3-hydroxymethyl compound to give the corresponding 3-acyloxymethyl compound. This compound or the compound (Ib) may then be reacted with any of the following: thiourea, N- substituted thiourea; N,N-di-substituted thiourea, alkali metal azide, thiazole, thiadiazole, halogenating agent or alkali metal thiocyanate, to give the corresponding 3-thiouroniummethyl, 3-azidomethyl, 3-thiazolylmercaptomethyl, 3- thiadiazolylmercaptomethyl, halomethyl or 3- cyanatomethyl derivatives. In addition, the 3-acyloxymethyl compound may be reacted with a thiol, dithiocarbamate, dithiocarboxylate, amine, pyridine or nuclear substituted pyridine, alkali metal sulphinate, N-alkyl-indole or polyhydroxybenzene to give the remaining derivatives of Formula I. Antibiotic 810A may be separated into its component antibiotics by chromatography e.g. on strongly hydrophilic anion exchange resin with 0À5M ammonium bromide-0À1M formic acid; on weakly basic anion exchange resin with pH1-2 aqueous acid; or on non-ionic crosslinked polystyrene polymer with aqueous methanol or aqueous acetone. Antibiotic 842A may be purified by chromatography on quaternary ammonium or sulphonic acid exchange resins, eluting with aqueous or aqueous alcoholic ammonium or sodium chloride. Pharmaceutical compositions having broad spectrum antibiotic activity comprise a compound of Formula I as defined hereinbefore or a pharmacologically acceptable non-toxic salt, ester or amide thereof in a pharmaceutically acceptable carrier. The compositions may be in forms for oral, parenteral, injectable or topical administration.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US1949670A | 1970-03-13 | 1970-03-13 | |
US5131970A | 1970-06-30 | 1970-06-30 | |
US9659470A | 1970-12-09 | 1970-12-09 | |
US05/115,779 US4302578A (en) | 1970-12-09 | 1971-02-16 | Cephalosporin antibiotics |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1321412A true GB1321412A (en) | 1973-06-27 |
Family
ID=27486855
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB2340771*A Expired GB1321412A (en) | 1970-03-13 | 1971-04-19 | Antibiotics and their preparation |
Country Status (19)
Country | Link |
---|---|
JP (1) | JPS581919B1 (en) |
AR (3) | AR200370A1 (en) |
BE (1) | BE764160A (en) |
CA (1) | CA960169A (en) |
CH (5) | CH586226A5 (en) |
DD (3) | DD96254A5 (en) |
DE (3) | DE2166462B2 (en) |
DK (1) | DK131639C (en) |
FI (1) | FI51484C (en) |
FR (1) | FR2085702B1 (en) |
GB (1) | GB1321412A (en) |
IE (1) | IE35110B1 (en) |
IL (1) | IL36281A (en) |
IT (1) | IT1045524B (en) |
NL (1) | NL171285C (en) |
NO (1) | NO134219C (en) |
PH (1) | PH12292A (en) |
SE (1) | SE385713B (en) |
YU (1) | YU35164B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4065356A (en) | 1976-02-12 | 1977-12-27 | Merck & Co., Inc. | Production of antibiotic FR-02A (efrotomycin) by streptomyces lactamdurans |
EP0028511A1 (en) * | 1979-10-31 | 1981-05-13 | Glaxo Group Limited | Cephalosporins, processes for their preparation and microorganisms capable of their production |
EP0137365A2 (en) * | 1983-09-06 | 1985-04-17 | Takeda Chemical Industries, Ltd. | Cephalosporins and their production |
WO2004106347A1 (en) | 2003-05-28 | 2004-12-09 | Dsm Ip Assets B.V. | Cephem compound |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1040620A (en) * | 1972-11-14 | 1978-10-17 | Frank J. Urban | 6-alkoxy-6-acylamidopenicillins 7-alkoxy-7-acylamido acetoxycephalosporins and process |
US4327093A (en) | 1978-10-24 | 1982-04-27 | Fujisawa Pharmaceutical Co., Ltd. | 3,7-Disubstituted-2 or 3-cephem-4-carboxylic acid compounds |
JPS5931517B2 (en) * | 1978-12-12 | 1984-08-02 | 山之内製薬株式会社 | New 7↓-methoxycephalosporin derivative |
EP0160745A3 (en) * | 1984-05-07 | 1986-11-05 | Takeda Chemical Industries, Ltd. | Cephem compounds and their production |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4945594A (en) * | 1972-09-08 | 1974-05-01 |
-
1971
- 1971-02-24 IL IL36281A patent/IL36281A/en unknown
- 1971-03-02 DE DE19712166462 patent/DE2166462B2/en active Granted
- 1971-03-02 DE DE2109854A patent/DE2109854C3/en not_active Expired
- 1971-03-02 DE DE19712166463 patent/DE2166463A1/en active Pending
- 1971-03-08 CH CH1273175A patent/CH586226A5/xx not_active IP Right Cessation
- 1971-03-08 AR AR234333A patent/AR200370A1/en active
- 1971-03-08 CH CH1294275A patent/CH589655A5/xx not_active IP Right Cessation
- 1971-03-08 CH CH1273075A patent/CH587911A5/xx not_active IP Right Cessation
- 1971-03-08 CH CH1294175A patent/CH587856A5/de not_active IP Right Cessation
- 1971-03-08 CH CH333371A patent/CH579576A5/xx not_active IP Right Cessation
- 1971-03-08 PH PH12269A patent/PH12292A/en unknown
- 1971-03-10 IE IE303/71A patent/IE35110B1/en unknown
- 1971-03-11 SE SE7103119A patent/SE385713B/en unknown
- 1971-03-11 FI FI710711A patent/FI51484C/en active
- 1971-03-12 FR FR7108668A patent/FR2085702B1/fr not_active Expired
- 1971-03-12 DD DD153734A patent/DD96254A5/xx unknown
- 1971-03-12 DD DD164639A patent/DD99166A5/xx unknown
- 1971-03-12 IT IT49017/71A patent/IT1045524B/en active
- 1971-03-12 DK DK118171A patent/DK131639C/en not_active IP Right Cessation
- 1971-03-12 YU YU626/71A patent/YU35164B/en unknown
- 1971-03-12 DD DD164638A patent/DD100002A5/xx unknown
- 1971-03-12 NO NO932/71A patent/NO134219C/no unknown
- 1971-03-12 BE BE764160A patent/BE764160A/en not_active IP Right Cessation
- 1971-03-12 NL NLAANVRAGE7103360,A patent/NL171285C/en not_active IP Right Cessation
- 1971-03-12 CA CA107,642A patent/CA960169A/en not_active Expired
- 1971-03-13 JP JP46013630A patent/JPS581919B1/ja active Pending
- 1971-04-19 GB GB2340771*A patent/GB1321412A/en not_active Expired
-
1972
- 1972-05-31 AR AR242279A patent/AR212149A1/en active
-
1974
- 1974-04-29 AR AR253505A patent/AR201142A1/en active
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4065356A (en) | 1976-02-12 | 1977-12-27 | Merck & Co., Inc. | Production of antibiotic FR-02A (efrotomycin) by streptomyces lactamdurans |
EP0028511A1 (en) * | 1979-10-31 | 1981-05-13 | Glaxo Group Limited | Cephalosporins, processes for their preparation and microorganisms capable of their production |
EP0137365A2 (en) * | 1983-09-06 | 1985-04-17 | Takeda Chemical Industries, Ltd. | Cephalosporins and their production |
EP0137365A3 (en) * | 1983-09-06 | 1986-01-15 | Takeda Chemical Industries, Ltd. | Cephalosporins and their production |
WO2004106347A1 (en) | 2003-05-28 | 2004-12-09 | Dsm Ip Assets B.V. | Cephem compound |
Also Published As
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
414F | Notice of opposition given (sect. 14/1949) | ||
414A | Case decided by the comptroller ** specification amended (sect. 14/1949) | ||
49R | Reference inserted (sect. 9/1949) | ||
SPA | Amended specification published | ||
PS | Patent sealed [section 19, patents act 1949] | ||
PE20 | Patent expired after termination of 20 years |