Premium
Substitution der 6‐Aminopenicillansäure am Kohlenstoffatom 6
Author(s) -
Reiner R.,
Zeller P.
Publication year - 1968
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19680510812
Subject(s) - chemistry , benzaldehyde , salicylaldehyde , formaldehyde , oxazolidine , hydrolysis , schiff base , penicillin , acid hydrolysis , medicinal chemistry , organic chemistry , stereochemistry , catalysis , antibiotics , biochemistry
Abstract The hydroxyalkylation of the penicillin nucleus at C‐6 with benzaldehyde and formaldehyde is reported. 6‐aminopenicillanic acid (6‐APA) ( 2 ) was used as starting material. Protection of the functional groups and activation of the C‐6 position were effected by converting 6‐APA successively into the Schiff base 13 , the methyl ester 14 and the copper complex 15 . The latter gave with benzaldehyde the C‐6 monosubstituted complex 17 , and with formaldehyde the disubstituted complex 18 . The direct α‐hydroxybenzylation of 6‐APA at C‐6 was also carried out with an excess of benzaldehyde at pH 7,5 leading to the S CHIFF base 19 . Mild hydrolysis of 19 gave 6‐amino‐6‐(α‐hydroxybenzyl)‐penicillanic acid ( 21 ). Phenylacetylation of the latter yielded the penicillin G analogue 22 . Direct reaction of 6‐APA with formaldehyde took place only in the presence of salicylaldehyde, giving the oxazolidine 24 , from which the amino acid 25 could not be obtained. The new compounds showed only weak antibacterial activity as compared with penicillin G.