IE36448L - Cephalosporin esters - Google Patents
Cephalosporin estersInfo
- Publication number
- IE36448L IE36448L IE65272A IE65272A IE36448L IE 36448 L IE36448 L IE 36448L IE 65272 A IE65272 A IE 65272A IE 65272 A IE65272 A IE 65272A IE 36448 L IE36448 L IE 36448L
- Authority
- IE
- Ireland
- Prior art keywords
- cephalosporin
- compound
- azido
- sulphoxide
- salt
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Abstract
1335317 Cephalosporin esters LOVENS KEMISKE FABRIK PRODUKTIONSAKTIESELSKAB 23 May 1972 [23 June 1971] 29449/71 Headings C2A and C2C The invention relates to novel cephalosporin esters having the general Formula (I) and salts thereof, wherein the asterisk indicates that the carbon atom can be asymmetric, n is an integer from 0 to 5 ; R 1 is a radical corresponding to the equivalent radical of a known semisynthetic cephalosporin ; R 2 is a hydrogen atom, an optionally substituted alkyl radical or an optionally substituted phenyl radical; R 3 , R 4 and R 5 each represents H or C 1 -C 6 alkyl; or R 2 and R 5 together with the intermediate carbon atom can form a 5-, 6- or 7-membered carbocyclic ring and either R 3 , R 4 and the intermediate nitrogen atom or R 4 , R 5 and the intermediate carbon and nitrogen atoms form a heterocyclic ring system: and R 6 is H, alkoxy, alkylthio, aryloxy, arylthio, acyloxy, acylthio, azido, pyridyl or 2-(1,3,4- thiadiazolyl)-thio. The cephalosporin esters (I) are produced by a procedure comprising: (1) reacting a cephalosporin salt of Formula II in which R 1 and R 6 are as defined above and X is a cation (e.g. Na<SP>+</SP>, K<SP>+</SP>, ammonium or trialkylammonium) with a compound of Formula III wherein Hal is a halogen atom (Cl or Br), Z is an amino group, a substituted or protected amino group or a group (e.g. azido, nitro or halogen) which is directly convertible to an amino group, by hydrogenation, hydrolysis or amination, and R 2 , R 5 and n are as previously defined; to give a mixture of #<SP>2</SP> and #<SP>3</SP> isomers of Formulae (IVa) and (IVb) (2) oxidizing these mixed isomers with a per-acid (e.g. peracetic acid or m-chloroperbenzoic acid) to the corresponding #<SP>2</SP>- and #<SP>3</SP>-cephem sulphoxides and treating the mixed sulphoxide isomers with a hydroxylic solvent (e.g. methanol) to convert the #<SP>2</SP> compound to the #<SP>3</SP> compound, thus yielding a pure #<SP>3</SP>-cephem sulphoxide of general Formula VII (these compounds, wherein R 1 , R 2 , R 5 and R 6 are as defined previously and Z is an unsubstituted, substituted or protected amino group, an azido group, a nitro group or a halogen atom, being novel and forming an aspect of the invention); (3) reducing the compound VII (e.g. with sodium dithionite in the presence of acetyl chloride) to give a compound (IVa) as set forth above, which is identical with the desired compound (I) when Z is amino or substituted amino; and (4) when Z is protected amino, or the aforesaid group which is directly convertible to an amino group, converting the compound IVa to a compound (I) by hydrolysis, hydrogenation or amination. In an alternative procedure the compound VII is prepared by either (a) reacting a cephalosporin sulphoxide salt of Formula VIII wherein R 1 , R 6 and X are as previously defined, with a compound (III) hereinbefore; or (b) reacting a chloromethyl ester of a cephalosporin sulphoxide, of Formula (IX) wherein R 1 and R 6 are as before, with an acid of Formula (V) in which R 2 , R 5 , Z and n are as defined above. The cephalosporin sulphoxide chloromethyl esters (IX) are said to be novel. They may be prepared by either reacting a cephalosporin salt (II) with chloroiodomethane or chlorobromomethane to give a mixture of #<SP>2</SP> and #<SP>3</SP> isomeric cephalosporin chloromethyl esters, which mixture is converted to the pure #<SP>3</SP> cephem sulphoxide ester (IX) by the oxidation/hydroxylic solvent treatment described above in step (2); or else by reacting the cephalosporin sulphoxide salt (VIII) above with chloroiodomethane or chlorobromomethane. N-tert. Butoxycarbonyl-L-valine chloromethyl ester is produced by esterifying the protected amino-acid with chloroiodomethane. Chloromethyl α-azido-α-methylpropionate is prepared by correspondingly esterifying α-azido-α- methylpropionic acid sodium salt. D,L-α-azido-iso valeric acid is resolved into the L-( - )- and D-( + )-isomers by fractional crystallization of the L-ephedrine salt. The isomeric ephedrine salts are converted to the corresponding free acids by treatment with HCl, and the acids are then used to prepare the sodium salts. The L-( - )- and D-( + )-isomers (as the Na salts) are reacted with chloroiodomethane to give chloromethyl L-α-azido-isovalerate (containing 25% methylene di-L-α-azido-isovalerate), and chloromethyl D-α-azido-isovalerate. Pharmaceutical compositions having broad spectrum antibacterial activity comprise a cephalosporin ester of Formula I as defined above or a salt thereof, together with a pharmaceutical carrier or diluent. The compositions are preferably in forms suitable for oral administration.
[GB1335317A]
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB2944971 | 1971-06-23 |
Publications (2)
Publication Number | Publication Date |
---|---|
IE36448L true IE36448L (en) | 1972-12-23 |
IE36448B1 IE36448B1 (en) | 1976-11-10 |
Family
ID=10291750
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE65272A IE36448B1 (en) | 1971-06-23 | 1972-05-15 | New cephalosporin esters salts thereof and methods for their preparation |
Country Status (8)
Country | Link |
---|---|
AU (1) | AU457864B2 (en) |
BE (1) | BE785275A (en) |
DE (1) | DE2230620A1 (en) |
FR (1) | FR2143318B1 (en) |
GB (1) | GB1335317A (en) |
IE (1) | IE36448B1 (en) |
LU (1) | LU65565A1 (en) |
NL (1) | NL7208407A (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1425933A (en) * | 1972-03-13 | 1976-02-25 | Astra Laekemedel Ab | Cephalosporins |
US5481011A (en) * | 1994-12-13 | 1996-01-02 | Bristol-Myers Squibb Company | Process for preparing N-protected amino acid α-halomethyl ketones and alcohols from N-protected amino acid esters |
ES2547258T3 (en) | 2006-12-10 | 2015-10-02 | Chongxi Yu | Systems of transdermal administration of beta-lactam antibiotics |
US9969751B2 (en) | 2009-06-10 | 2018-05-15 | Techfields Pharma Co., Ltd. | High penetration prodrug compositions of antimicrobials and antimicrobial-related compounds |
JP6445967B2 (en) | 2012-05-16 | 2018-12-26 | テックフィールズ ファーマ カンパニー リミテッド | Highly osmotic prodrug compositions for the treatment of pulmonary diseases and pharmaceutical compositions thereof |
JP5795343B2 (en) * | 2013-01-23 | 2015-10-14 | チョンシー ユー | Transdermal delivery system for β-lactam antibiotics |
-
1971
- 1971-06-23 GB GB1335317D patent/GB1335317A/en not_active Expired
-
1972
- 1972-05-15 IE IE65272A patent/IE36448B1/en unknown
- 1972-05-30 AU AU42874/72A patent/AU457864B2/en not_active Expired
- 1972-06-20 NL NL7208407A patent/NL7208407A/xx unknown
- 1972-06-22 DE DE19722230620 patent/DE2230620A1/en active Pending
- 1972-06-22 LU LU65565D patent/LU65565A1/xx unknown
- 1972-06-22 BE BE785275A patent/BE785275A/en unknown
- 1972-06-22 FR FR7222623A patent/FR2143318B1/fr not_active Expired
Also Published As
Publication number | Publication date |
---|---|
FR2143318B1 (en) | 1975-10-31 |
IE36448B1 (en) | 1976-11-10 |
LU65565A1 (en) | 1972-10-26 |
FR2143318A1 (en) | 1973-02-02 |
BE785275A (en) | 1972-12-22 |
AU4287472A (en) | 1973-12-06 |
DE2230620A1 (en) | 1972-12-28 |
GB1335317A (en) | 1973-10-24 |
AU457864B2 (en) | 1975-01-22 |
NL7208407A (en) | 1972-12-28 |
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