713522-38-4Relevant academic research and scientific papers
Formal desymmetrization of the diastereotopic chains in gemini calcitriol derivatives with two different side chains at C-20
Maehr, Hubert,Uskokovic, Milan R.
, p. 1703 - 1713 (2004)
Derivatives of calcitriol with two equal side chains emanating at C-20, also known as gemini, have emerged as interesting compounds, either as instruments for assessing the steric requirements of the vitamin D receptor or as drug candidates. We now describe the syntheses of gemini analogs where the two side chains differ from each other. While retaining the 2-hydroxy-2- methylpentyl moiety, common to both calcitriol and gemini, as one chain, we replaced the other with a 1,1,1-trifluoro-2-hydroxy-2-(trifluoromethyl)-3- pentynyl group. The features comprising this chain modification are commonly regarded to improve toxicity profiles and drug performance. The resulting epimeric pairs with a new stereogenic center at C-20 were resolved and the absolute configurations assigned. The side-chain desymmetrization protocols described herein serve as a basis for additional synthesis activity in this area. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
