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Synthesis of L‐[4,5,5,5‐D 4 ]isoleucine: determination of approximate rotamer population about the C β ‐C γ bond
Author(s) -
Oba Makoto,
Miyakawa Akiko,
Shionoya Masanobu,
Nishiyama Kozaburo
Publication year - 2001
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.439
Subject(s) - chemistry , moiety , stereochemistry , nucleophile , derivative (finance) , hydroxymethyl , conformational isomerism , medicinal chemistry , organic chemistry , molecule , financial economics , economics , catalysis
An asymmetric synthesis of regio‐ and stereoselectively deuterium‐labelled L‐isoleucine was examined. An unsaturated γ‐lactam readily available from L‐pyroglutamic acid was stereoselectively methylated by the Gilman reagent and subsequent oxidation of the hydroxymethyl moiety afforded a 3‐methylpyroglutamate derivative. Introduction of a deuterium atom into the γ‐position was achieved via a radical‐based deuteriation of the corresponding phenyl selenide by tributyltin deuteride. Then, the deuteriated 3‐methylpyroglutamate derivative was converted to L‐[4,5,5,5‐D 4 ]isoleucine via a base‐promoted ring opening and a reductive deuteriation of the terminal carboxyl moiety. Copyright © 2001 John Wiley & Sons, Ltd.