Expedited approach to the vitamin D trans-hydrindane building block from the Hajos dione. Comparative study on various methods for the selective deoxygenation of one of the hydroxy groups in a diol.
Paweł Chochrek, Jerzy Wicha
Index: J. Org. Chem. 72 , 5276, (2007)
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Abstract
1 alpha,25-Dihydroxyvitamin D3 (calcitriol, 1) is a bioregulator important for the treatment of various human metabolic diseases and biomedical research. Herein, we report an efficient diastereoselective approach to the key trans-hydrindane building block for calcitriol synthesis (2a) starting from the readily accessible optically active tetrahydroindenedione derivative (Hajos dione, 3). It was found that epoxide ring opening in a related hydroxy epoxide (7) with sodium cyanoborohydride-BF3 x Et2O occurs by hydride anion addition at the ring juncture position to produce a vicinal diol with the trans-hydrindane ring system (6a). Four methods for selective deoxygenation of the sterically less shielded hydroxy group in diol 6a were examined with an approach based on a cyclic sulfate of the diol as the most efficient and operationally convenient method.