6-(1'-Hydroxyethyl)-2-substituted-pen-2-em-3-carboxylic acid
AssigneeMerck & Co., Inc.
InventorsBurton G. Christensen, Frank P. DiNinno
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Abstract
Disclosed are 6-(1'-hydroxyethyl)-2-substituted-pen-2-em-3-carboxylic acids of the following structure: ##STR1## wherein R is, inter alia, hydrogen, --OR, --SR, --NR.sub.2, alkyl, aryl, aralkyl, or heterocylcyl; n is 0 or 1; when n=1 R is as defined but not --SR. Such compounds and their pharmaceutically acceptable salt and ester derivatives are useful as antibiotics. Also disclosed are processes for the preparation of such compounds, pharmaceutical compositions comprising such compounds and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.
Claims1
A process for preparing a compound having the structure:
- ##STR123## and the pharmaceutically acceptable salts thereof;
- wherein R' is hydrogen, --R, --OR, --SR, --NR.sub.2 ;
- wherein R is substituted and unsubstituted:
- alkyl, having 1-6 carbon atoms, phenyl, phenylalkyl having 7-12 carbon atoms, heterocyclyl and heterocyclylalkyl wherein the alkyl has 1-3 carbon atoms and the heterocycle has 1-4 hetero atoms selected from O, N, and S;
- and wherein the chain or nuclear substituent on R is selected from amino, mono-, di- and trialkylamino (each alkyl having 1-6 carbon atoms), hydroxyl, alkoxyl, having 1-6 carbon atoms, mercapto, alkylthio having 1-3 carbon atoms, phenylthio, sulfamoyl, amidino, guanidino, nitro, chloro, bromo, fluoro, cyano, and carboxyl;
- n is 0 or 1;
- when n=1, R' is not --SR;
- comprising the steps of
- oxidizing:
- ##STR124## to form:
- ##STR125## followed by treating with a phosphine in the presence of the anhydride (R.sup.3 CO).sub.2 O to form:
- ##STR126## followed by oxidizing to form:
- ##STR127## followed by treating with a glyoxalate ester to form:
- ##STR128## followed by halogenating to form:
- ##STR129## wherein X is halo;
- followed by treating with triphenylphosphine to form:
- ##STR130## followed by cyclizing:
- ##STR131## by heating, followed by deblocking;
- wherein R.sup.2 is a readily removable protecting group;
- R.sup.3 is a readily removable protecting group;
- and .phi. is phenyl.
Dependencies are inferred from the claim text.