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Synlett 2010(4): 535-538  
DOI: 10.1055/s-0029-1219207
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Enantioselective Formal Synthesis of (+)-Lactacystin from Hydroxymethyl Glutamic Acid (HMG)

Abdul Hameed, Alexander J. Blake, Christopher J. Hayes*
School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
Fax: +44(115)9513564; e-Mail: chris.hayes@nottingham.ac.uk;
Further Information

Publication History

Received 10 November 2009
Publication Date:
19 January 2010 (online)

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Abstract

A formal synthesis of (+)-lactacystin from hydroxymethylglutamic acid (HMG), with an alkylidene carbene insertion reaction being used to construct the key nitrogen-bearing quaternary centre has been completed. Our route intercepts that of Shibasaki at an advanced pyrrolidinone intermediate, from which the synthesis can be completed following Donohoe’s route.

Key words

Lactacystin - hydroxymethyl glutamic acid - alkylidene carbene - CH insertion

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CCDC 753698 and 753699 contain the supplementary crystallographic data for this paper (for 19 and 20). These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.