Alpha-phosphono lactone analogues of cytidine and cytosine arabinoside diphosphates: synthesis via ring closing metathesis

Xuemei Chen; David F Wiemer

doi:10.1021/jo0300136

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Alpha-phosphono lactone analogues of cytidine and cytosine arabinoside diphosphates: synthesis via ring closing metathesis

Journal article

Peer reviewed

Alpha-phosphono lactone analogues of cytidine and cytosine arabinoside diphosphates: synthesis via ring closing metathesis

Xuemei Chen and David F Wiemer

Journal of organic chemistry, Vol.68(17), pp.6597-6604

08/22/2003

DOI: 10.1021/jo0300136

PMID: 12919022

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Abstract

alpha-Phosphono lactone derivatives of the nucleosides cytidine and cytosine arabinoside have been prepared from the corresponding nucleoside aldehydes. The stereochemical outcome of allylation reactions with these aldehydes was found to be dependent upon both the choice of protecting groups for the 2'- and 3'-hydroxyl groups and, to some extent, the nature of the Lewis acid catalyst employed. Ultimately, conditions were found that favored either the 5'R or 5'S diastereomer from different cytidine aldehydes, and gave some stereoselectivity in additions to an aldehyde derivative of ara-C. The resulting homoallylic alcohols were used as substrates in attempted Knovenagel and Horner-Wadsworth-Emmons condensations, but elimination was found to predominate over lactone formation under the conditions employed. The desired alpha-phosphono lactones could be prepared through a reaction sequence that included ring-closing metathesis on acrylate esters of the homoallylic alcohols, followed by reduction of the resulting alpha,beta-unsaturated lactones and carbon-phosphorus bond formation on enolates generated from the saturated lactones.

Cytosine - analogs & derivatives

Arabinose - chemistry

Cytarabine - chemical synthesis

Cytidine - chemistry

Stereoisomerism

Cytidine Diphosphate - analogs & derivatives

Models, Molecular

Cytarabine - analogs & derivatives

Cytidine - analogs & derivatives

Cytosine - chemistry

Cytidine Diphosphate - chemical synthesis

Lactones

Organophosphonates

Arabinose - analogs & derivatives

Cytarabine - chemistry

Cytosine - chemical synthesis

Arabinose - chemical synthesis

Indicators and Reagents

Cytidine Diphosphate - chemistry

Details

Title: Subtitle: Alpha-phosphono lactone analogues of cytidine and cytosine arabinoside diphosphates: synthesis via ring closing metathesis
Creators: Xuemei Chen - 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.68(17), pp.6597-6604
DOI: 10.1021/jo0300136
PMID: 12919022
NLM abbreviation: J Org Chem
ISSN: 0022-3263
eISSN: 1520-6904
Publisher: United States
Language: English
Date published: 08/22/2003
Academic Unit: Neuroscience and Pharmacology; Chemistry
Record Identifier: 9983985836302771

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