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Synthesis and biological evaluation of a des-C,D-analog of 2-methylene-19-nor-1alpha,25-(OH)2D3.

Authors
Type
Published Article
Journal
The Journal of Steroid Biochemistry and Molecular Biology
0960-0760
Publisher
Elsevier
Publication Date
Volume
103
Issue
3-5
Pages
298–304
Identifiers
PMID: 17223343
Source
Medline
License
Unknown

Abstract

Structure-activity studies directed at novel Vitamin D compounds of potential therapeutic value has long attracted an attention of numerous research groups. To date more than 3000 analogs of the natural hormone 1alpha,25-dihydroxyvitamin D(3) (1) have been synthesized and tested. As a continuation of our studies on 19-norvitamin D compounds we have obtained (20S)-des-C,D-2-methylene-1alpha,25-dihydroxy-19-norvitamin D(3) (6) and examined its biological activity. This Vitamin D compound was efficiently prepared in a convergent synthesis. The "upper" fragment was synthesized starting with methyl (R)-(-)-3-hydroxy-2-methylpropionate (9). The key synthetic step involved Lythgoe type Wittig-Horner coupling of the protected hydroxy aldehyde 19 with the phosphine oxide 20. The prepared Vitamin D analog 6 exhibited limited binding ability to the rat intestinal Vitamin D receptor being ca. 80 times less potent when compared to the natural hormone 1. Although the analog 6 did retain some cell differentiating and transcriptional activities, preliminary in vivo tests do not show any activity of this analog in animals.

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