US 5,204,459 AGranted

Process for preparing carbapenem compounds

AssigneeAjinomoto Co., Inc.

InventorsShigeo Nozoe, Tomihisa Ohta

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Abstract

Novel amino acid derivatives of the formula ##STR1## wherein R.sup.1 is a protecting group removable under reducing or acid conditions, and R.sup.2 and R.sup.5 are hydrogen or carboxylic protecting groups, are useful as intermediates in preparing stereospecific carbapenam/carbapenem derivatives. R.sup.1 is removed under reducing conditions to form a pyrrolidine derivative, which is further cyclized from the R.sup.5 =H compound to form a .beta.-lactam ring. Stereospecificity at the 6-position is achieved by treatment with lithium diisopropylamide (LDA) and quenching at different temperatures. Compound (I) can be prepared by treating R.sup.1 -protected R.sup.3 -pyrrolidone carboxylic acid R.sup.2 -ester with a lithium enolate of the formula R.sup.4 CHLiCO.sub.2 R.sup.5. The lithium enolate can be formed from R.sup.4 CH.sub.2 CO.sub.2 R.sup.5 by treatment with LDA.

Claims5

Dependent claims

A process comprising

(i) selectively cleaving the substituent R.sup.5 from a compound of the formula (II) ##STR16## wherein R.sup.2 is hydrogen or a carboxylic-protecting group, R.sup.5 is a carboxylic-protecting group, R.sup.3 is hydrogen, alkyl, hydroxyl, methoxy or acetoxy, R.sup.4 is methyl, ethyl, i-propyl, benzyl or a CH.sub.3 CR.sup.6 (OR.sup.7)-group in which R.sup.6 is hydrogen or methyl and R.sup.7 is hydrogen or a hydroxyl-protecting group and having, respectively 2(S) and 5(R) configurations in the 2 and 5 positions thereof;
to give a compound of the formula (V) ##STR17## (ii) .beta.-lactam cyclizing the compound of the formula (V) to produce a compound of the formula (VI);
##STR18## (iii) treating the compound of the formula (VI) with lithium diisopropylamide at about -78.degree. C. and quenching said
treated compound with acetic acid/methanol at about 0.degree. C. to give predominantly the (3R, 5R, 6R) carbapenem compound (VII) ##STR19## or quenching the compound of the formula (VI) at about -78.degree. C. to give predominantly the (3R, 5R, 6S) carbapenam compound (IX) ##STR20##

1 more element

Dependencies are inferred from the claim text.

Facts

Application: 07/853,069Filed 17 Mar 1992 · division
Priority: JP 61-21509312 Sep 1986
Granted: 20 Apr 1993
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07C 271/22
With the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms: to carbon atoms of hydrocarbon radicals…
C07D 207/16
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07D 477/04
Preparation: by forming the ring or condensed ring systems
Y02P 20/55
Improvements relating to the production of bulk chemicals: design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Family

Serial95,445Parent of this division · filed 11 Sep 1987
Serial360,534Parent of this division · filed 2 Jun 1989
Serial661,246Parent of this division · filed 27 Feb 1991
US 5,118,831 AParent of this division
US 5,028,718 AParent of this division
US 4,876,383 AParent of this division
US 5,204,459 AThis patent

From the US filing history. Foreign family members aren’t listed.