Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1992532 | The Journal of Steroid Biochemistry and Molecular Biology | 2007 | 7 Pages |
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 1α,25-dihydroxyvitamin D3 (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-1α,25-dihydroxy-19-norvitamin D3 (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.