Short and versatile route to a key intermediate for lactacystin synthesis.
[reaction: see text] A key intermediate 14 for the synthesis of lactacystin 1 has been constructed in four steps and 33% overall yield. The key steps involve cyclization of a suitably functionalized glutamic acid derivative and concomitant alkylation of the resulting beta,beta-diketoester system, C-acylation of the cyclic alpha-amidoketone 9, and decarboxylbenzylation of 12. Alkylation of a related beta,beta-diketoester 5 was additionally achieved with several electrophiles.
Bulman Page
Philip C
PC
Department of Chemistry, Loughborough University, Loughborough, Leicestershire LE11 3TU, England. pcbpage@lboro.ac.uk
Hamzah
A Sazali
AS
Leach
David C
DC
Allin
Steven M
SM
Andrews
David M
DM
Rassias
Gerasimos A
GA
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D000215:Acylation; D000478:Alkylation; D003500:Cyclization; D018698:Glutamic Acid / Q000737:chemistry; D015394:Molecular Structure
C067713:lactacystin; D018698:Glutamic Acid; D000111:Acetylcysteine