Catalytic Enantioselective Synthesis of Guvacine Derivatives through [4 + 2] Annulations of Imines with α-Methylallenoates

Qihai Xu; Nathan J Dupper; Andrew J Smaligo; Yi Chiao Fan; Lingchao Cai; Zhiming Wang; Adam D Langenbacher; Jau-Nian Chen; Ohyun Kwon

doi:10.1021/acs.orglett.8b02489

Catalytic Enantioselective Synthesis of Guvacine Derivatives through [4 + 2] Annulations of Imines with α-Methylallenoates

Org Lett. 2018 Oct 5;20(19):6089-6093. doi: 10.1021/acs.orglett.8b02489. Epub 2018 Sep 24.

Authors

Qihai Xu¹, Nathan J Dupper¹, Andrew J Smaligo¹, Yi Chiao Fan¹, Lingchao Cai¹, Zhiming Wang¹, Adam D Langenbacher², Jau-Nian Chen², Ohyun Kwon¹

Affiliations

¹ Department of Chemistry and Biochemistry , University of California , Los Angeles , California 90095-1569 , United States.
² Department of Molecular Cellular and Developmental Biology , University of California , Los Angeles , California 90095 , United States.

Abstract

P-Chiral [2.2.1] bicyclic phosphines (HypPhos catalysts) have been applied to reactions between α-alkylallenoates and imines, producing guvacine derivatives. These HypPhos catalysts were assembled from trans-4-hydroxyproline, with the modular nature of the synthesis allowing variations of the exocyclic P and N substituents. Among them, exo-( p-anisyl)-HypPhos was most efficacious for [4 + 2] annulations between ethyl α-methylallenoate and imines. Through this method, ( R)-aplexone was identified as being responsible for the decrease in the cellular levels of cholesterol.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Catalysis
Chemistry Techniques, Synthetic
Imines / chemistry*
Naphthalenes / chemistry*
Nicotinic Acids / chemical synthesis*
Nicotinic Acids / chemistry*
Stereoisomerism
Substrate Specificity

Substances

Imines
Naphthalenes
Nicotinic Acids
guvacine
allenolic acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding