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.
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.
Chochrek
Paweł
P
Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw 48, Poland.
Wicha
Jerzy
J
D018360:Crystallography, X-Ray; D006900:Hydroxylation; D007192:Indenes / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D014807:Vitamin D / Q000138:chemical synthesis* / Q000737:chemistry
D007192:Indenes; D014807:Vitamin D; D010100:Oxygen