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A convenient synthesis of 2S, 3S‐[3‐ 2 H]‐serine and 2S, 3R‐[2, 3‐ 2 H 2 ]‐serine
Author(s) -
Slieker Lawrence,
Benkovic Stephen J.
Publication year - 1982
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580190505
Subject(s) - chemistry , serine , hydrolysis , acrylate , yield (engineering) , stereochemistry , derivative (finance) , methyl acrylate , alkyl , medicinal chemistry , organic chemistry , enzyme , materials science , monomer , copolymer , economics , financial economics , metallurgy , polymer
Both 2S, 3R‐[2, 3‐ 2 H 2 ]‐serine 5 and 2S, 3S‐[3‐ 2 H]‐serine 6 have been prepared from (E)‐methyl‐[2, 3.‐ 2 H 2 ]‐acrylate and (Z)‐ethyl‐[3‐ 2 H]‐acrylate, respectively. The acrylate esters were converted to a mixture of isomeric bromohydrins by treatment with N‐bromoacetamide. The ratio of 2‐bromo‐3‐hydroxy species to the 2‐hydroxy‐3‐bromo isomer was approximately 3:1. Conversion to the corresponding azido alcohols by treatment with NaN 3 followed by catalytic reduction over Pd gave the alkyl esters of serine and isoserine. Purification and hydrolysis yielded serine in typically 20–25% yield from methyl or ethyl acrylate. Resolution was accomplished enzymatically by hog kidney acylase I treatment of the N‐acetyl derivative. Absolute configuration was determined by 1 H NMR and the ratio of proton intensity in the diastereotopic positions at C–3 were measured to be H S /H R = 11 for 5 and H R /H S = 4.4 for 6 .