Novel Concurrent Synthesis of Side-Chain Analogues of Vitamins D2 and D3: 24,24-Dihomo-25-hydroxycholecalciferol and (22E)-22-Dehydro-24,24-dihomo-25-hydroxycholecalciferol
✍ Scribed by A. Kutner; M. Chodynski; S.J. Halkes; J. Brugman
- Publisher
- Elsevier Science
- Year
- 1993
- Tongue
- English
- Weight
- 485 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0045-2068
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✦ Synopsis
A novel method for the preparation of side-chain extended analogues of vitamins (D) is described. Both 24,24-dihomo- and (22E)-22-dehydro-24,24-dihomo-25-hydroxycholecalciferols were efficiently prepared from the same intermediates, i.e., the phenyltriazolinedione adduct of previtamin D with a C-22 aldehyde group and a side-chain alkyl sulfone. The key steps in this synthesis involve the Julia coupling of the vitamin (D) synthon with the sidechain sulfone followed by Barton radical deoxygenation of the C-22 alcohol or dehydroxydesulfonylation of the respective (\beta)-hydroxysulfone. All four (\beta)-hydroxysulfones of the Julia reaction were separated and characterized for the first time. The absolute configurations at (\mathrm{C}-22) and (\mathrm{C}-23) in these compounds were tentatively assigned by high-field proton magnetic resonance. The synthetic method allows a highly efficient concurrent preparation of analogues with a modified side chain attached to the vitamin D nucleus via both single and double bonds. 1993 Academic Press. Inc.