Alpha-phosphono lactone analogues of farnesyl pyrophosphate: an asymmetric synthesis via ring-closing metathesis

Yanming Du; David F Wiemer

doi:10.1021/jo0202233

Back

Alpha-phosphono lactone analogues of farnesyl pyrophosphate: an asymmetric synthesis via ring-closing metathesis

Journal article

Peer reviewed

Alpha-phosphono lactone analogues of farnesyl pyrophosphate: an asymmetric synthesis via ring-closing metathesis

Yanming Du and David F Wiemer

Journal of organic chemistry, Vol.67(16), pp.5701-5708

08/09/2002

DOI: 10.1021/jo0202233

PMID: 12153272

View Online

Abstract

An alpha-phosphono lactone derivative of farnesol has been prepared, in both racemic and nonracemic forms, to provide a new type of farnesyl pyrophosphate analogue. Attempted preparation of the racemic alpha-phosphono lactone through rearrangement of a vinyl phosphate derived from the parent lactone resulted in both rearrangement and lactone ring opening, revealing that the farnesyl lactone was not stable to the excess of strong base required for the rearrangement. A procedure for C-P bond formation based on generation of the lactone enolate, reaction with a P(III) reagent, and oxidation was successful in providing the racemic alpha-phosphono lactone, in part, because only 1 equiv of strong base was required. The same strategy for phosphonate synthesis then was applied to the nonracemic farnesyl lactone, prepared through a sequence including allylation of farnesal with a nonracemic borane reagent, reaction of the product alcohol with acryloyl chloride, and formation of an unsaturated lactone through ring-closing metathesis. A similar strategy gave the corresponding racemic alpha-phosphono lactam through a six-step sequence from farnesal.

Organophosphonates

Ether

Farnesol

Molecular Conformation

Polyisoprenyl Phosphates - chemical synthesis

Sesquiterpenes

Indicators and Reagents

Furans

Structure-Activity Relationship

Isomerism

Lactones

Details

Title: Subtitle: Alpha-phosphono lactone analogues of farnesyl pyrophosphate: an asymmetric synthesis via ring-closing metathesis
Creators: Yanming Du - Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, USA
David F Wiemer
Resource Type: Journal article
Publication Details: Journal of organic chemistry, Vol.67(16), pp.5701-5708
DOI: 10.1021/jo0202233
PMID: 12153272
NLM abbreviation: J Org Chem
ISSN: 0022-3263
eISSN: 1520-6904
Publisher: United States
Language: English
Date published: 08/09/2002
Academic Unit: Neuroscience and Pharmacology; Chemistry
Record Identifier: 9983985703402771

Metrics

26 Record Views

20 Times Cited - Web of Science