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Synthesis of Optically Active, Ring‐Substituted N‐Benzyloxycarbonylphenylalanines via 2‐Benzyloxycarbonylamino‐2‐arylalkylmalonates
Author(s) -
Bosshard Hans Rudolf,
Berger Arieh
Publication year - 1973
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.19730560603
Subject(s) - chemistry , phenylalanine , hydrolysis , decarboxylation , racemization , amino acid , alkaline hydrolysis , organic chemistry , medicinal chemistry , stereochemistry , catalysis , biochemistry
Diethyl or dimethyl benzyloxycarbonylaminomalonate was reacted with ring substituted benzyl halides and the resulting arylalkyl derivatives ( 3 to 6 ) half‐saponified to the DL ‐monoacid‐monoesters ( 7 to 10 ). Decarboxylation by refluxing in dioxane afforded the N‐benzyl oxycarbonyl‐ DL ‐amino acid esters ( 11 to 14 ), which were resolved into their optical antipodes by enzymic hydrolysis of the ester group with Subtilisin, type Carlsberg . Enzymic hydrolysis led to the N‐benzyloxycarbonyl‐ L ‐amino acids ( 15 to 18 ) and to the corresponding D ‐amino acid esters. The latter were converted to the N‐benzyloxycarbonyl‐ D ‐amino acids ( 19 and 20 ) by alkaline hydrolysis of the ester groups. These derivatives could be used directly for further peptide synthesis. The following compounds were prepared: N‐benzyloxycarbonyl derivatives of p ‐methyl‐ L ‐phenylalanine ( 15 ), p ‐methyl‐ D ‐phenylalanine ( 19 ), p ‐fluoro‐ L ‐phenylalanine ( 16 ), m ‐fluoro‐ L ‐phenylalanine ( 17 ), m ‐fluoro‐ D ‐phenylalanine ( 20 ) and penta‐fluoro‐ L ‐phenylalanine ( 18 ). The free amino acids were obtained by removal of the benzyloxycarbonyl group with HBr in acetic acid.