Convergent synthesis of double point modified analogs of 1α,25-dihydroxyvitamin D2 for biological evaluation

Research output: Contribution to journalArticle

Authors

  • Sharmin Nadkarni
  • Michał Chodyński
  • Krzysztof Krajewski
  • Piotr Cmoch
  • Ewa Marcinkowska
  • Andrzej Kutner

Colleges, School and Institutes

Abstract

There is a long lasting controversy over the biological activity of vitamin D2 as compared to vitamin D3 in terms of maintaining of calcium homeostasis and raising the level of circulating 25-OH-D. To shed more light on this relationship we synthesized 1α,25-dihydroxyvitamin D2, by a novel convergent strategy, to compare this compound directly with the activity of 1α,25-dihydroxyvitamin D3. The same synthetic strategy also provided a series of (5E,7E) geometric isomers of the natural 1α,25-dihydroxyvitamin D2 as well as a series of double point modified analogs of its (24R)-epimer, including C-22 hydroxy derivatives. The structure of the new analogs was determined by 1H and 13C NMR as well as by mass spectrometry. The influence of (5E,7E) modification, alone or in combination with additional modifications in the side chain, on the activity profile and metabolic deactivation of analogs of 1α,25-dihydroxyvitamin D2 still remains unknown. (5E,7E) modification in the structure of new analogs of 1α,25-dihydroxyvitamin D2 is expected to give analogs with no influence on calcium level, as was previously obtained for the analogs of 1α,25-dihydroxyvitamin D3. Investigation of the affinities for the vitamin D receptor and cell differentiation, transcriptional and calcium activities of the most active form of vitamin D2 and of (5E,7E) analogs, compared to 1α,25-dihydroxyvitamin D3, is underway in the collaborating laboratories.

Details

Original languageEnglish
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Early online date24 Aug 2015
Publication statusE-pub ahead of print - 24 Aug 2015

Keywords

  • 1α,25-dihydroxyvitamin D2, Double point modified analogs, (5E,7E) geometric isomers, convergent synthesis, Modified Julia olefination, Dess–Martin oxidation