Enantioselective, biocatalytic reduction of 3-substituted cyclopentenones: application to the asymmetric synthesis of an hNK-1 receptor antagonist

Kevin R Campos; Artis Klapars; Yoshinori Kohmura; David Pollard; Hideaki Ishibashi; Shinji Kato; Akihiro Takezawa; Jacob H Waldman; Debra J Wallace; Cheng-yi Chen; Nobuyoshi Yasuda

doi:10.1021/ol1030348

Enantioselective, biocatalytic reduction of 3-substituted cyclopentenones: application to the asymmetric synthesis of an hNK-1 receptor antagonist

Org Lett. 2011 Mar 4;13(5):1004-7. doi: 10.1021/ol1030348. Epub 2011 Feb 8.

Authors

Kevin R Campos¹, Artis Klapars, Yoshinori Kohmura, David Pollard, Hideaki Ishibashi, Shinji Kato, Akihiro Takezawa, Jacob H Waldman, Debra J Wallace, Cheng-yi Chen, Nobuyoshi Yasuda

Affiliation

¹ Department of Process Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA. [email protected]

PMID: 21302901
DOI: 10.1021/ol1030348

Abstract

A convergent and enantioselective route to the hNK-1 receptor antagonist (1) is described, which sets all six stereogenic centers with high diastereoselectivity and delivers 1 in only 11 steps and 23% overall yield. The process was enabled by the development of the enantioselective enzymatic reduction of 3-functionalized cyclopentenones and stereospecific Pd-catalyzed etherification coupling of fragments 6 and 7.

MeSH terms

Catalysis
Cyclopentanes
Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
Heterocyclic Compounds, 4 or More Rings / chemistry
Heterocyclic Compounds, 4 or More Rings / pharmacology*
Humans
Molecular Structure
Neurokinin-1 Receptor Antagonists*
Palladium / chemistry
Stereoisomerism

Substances

Cyclopentanes
Heterocyclic Compounds, 4 or More Rings
Neurokinin-1 Receptor Antagonists
Palladium
cyclopentenone