An efficient chiral moderator prepared from inexpensive (+)-3-carene: synthesis of the HIV-1 non-nucleoside reverse transcriptase inhibitor DPC 963

G S Kauffman; G D Harris; R L Dorow; B R Stone; R L Parsons Jr; J A Pesti; N A Magnus; J M Fortunak; P N Confalone; W A Nugent

doi:10.1021/ol006321x

An efficient chiral moderator prepared from inexpensive (+)-3-carene: synthesis of the HIV-1 non-nucleoside reverse transcriptase inhibitor DPC 963

Org Lett. 2000 Oct 5;2(20):3119-21. doi: 10.1021/ol006321x.

Authors

G S Kauffman¹, G D Harris, R L Dorow, B R Stone, R L Parsons Jr, J A Pesti, N A Magnus, J M Fortunak, P N Confalone, W A Nugent

Affiliation

¹ DuPont Pharmaceuticals Company, Chemical Process R&D, Chambers Works, PRF Building S1, Deepwater, New Jersey 08023, USA.

PMID: 11009360
DOI: 10.1021/ol006321x

Abstract

The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a chiral moderator for the addition of lithium cyclopropylacetylide to an unprotected N-acylketimine. This reaction provides an efficient route to the second generation NNRTI drug candidate DPC 963.

MeSH terms

HIV-1 / enzymology*
Quinolones / chemical synthesis*
Reverse Transcriptase Inhibitors / chemical synthesis*
Stereoisomerism

Substances

DPC 963
Quinolones
Reverse Transcriptase Inhibitors