Asymmetric synthesis of (4R,5R)-cytoxazone and (4R,5S )-epi-cytoxazone

Stephen G. Davies*, Deri G. Hughes, Rebecca L. Nicholson, Andrew D. Smith, Angela J. Wright

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

(4R,5R)-Cytoxazone has been prepared in four steps and in 61% overall yield and >98% ee. Conjugate addition of lithium (R)-N-benzyl-.N-α- methylbenzylamide to tert-butyl (E)-3-(p-methoxyphenyl)prop-2-enoate and subsequent in situ diastereoselective enolate oxidation with (+)-(camphorsulfonyl)oxaziridine gave tert-butyl (2R,3R,αR)-2-hydroxy-3- (p-methoxyphenyl)-3-(N-benzyl-N-α-methylbenzylamino)propanoate in >98% de. Subsequent N-benzyl deprotection to the primary β-amino ester via hydrogenolysis, oxazolidinone formation with C(2)-retention by treatment with diphosgene and chemoselective ester reduction furnishes (4R,5R)-cytoxazone. The synthesis of the C(5)-epimer, (4R,5S)-epi-cytoxazone in 44% overall yield, has also been completed via a protocol involving N-Boc protection of the primary β-amino ester, utilization of the N-Boc group to facilitate simultaneous C(2)-inversion and oxazolidinone formation, and subsequent reduction.

Original languageEnglish
Pages (from-to)1549-1553
Number of pages5
JournalOrganic and Biomolecular Chemistry
Volume2
Issue number10
DOIs
Publication statusPublished - 21 May 2004

Fingerprint

Dive into the research topics of 'Asymmetric synthesis of (4R,5R)-cytoxazone and (4R,5S )-epi-cytoxazone'. Together they form a unique fingerprint.

Cite this