Asymmetric synthesis of substituted 1-aminocyclopropane-1-carboxylic acids via diketopiperazine methodology.
Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N,N'-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-(2)H2]-1-aminocyclopropane-1-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.
Buñuel
Elena
E
Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford, UK OX1 3QY.
Bull
Steven D
SD
Davies
Stephen G
SG
Garner
A Christopher
AC
Savory
Edward D
ED
Smith
Andrew D
AD
Vickers
Richard J
RJ
Watkin
David J
DJ