RT Journal Article SR Electronic T1 Process Development for the Practical Production of Eldecalcitol by Linear, Convergent and Biomimetic Syntheses JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 303 OP 309 VO 32 IS 1 A1 NOBORU KUBODERA A1 SUSUMI HATAKEYAMA YR 2012 UL http://ar.iiarjournals.org/content/32/1/303.abstract AB Eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3], an analog of calcitriol (1α,25-dihydroxyvitamin D3), possesses a hydroxypropoxy substituent at the 2β-position of calcitriol. Eldecalcitol has potent biological effects on bone disease such as osteoporosis. The marketing of eldecalcitol has very recently started in Japan. In consideration of this, we have been investigating practical synthesis of eldecalcitol for industrial-scale production. Eldecalcitol was initially synthesized in a linear manner. The 27-step linear sequence was, however, suboptimal due to its lengthiness and low overall yield (ca. 0.03%). Next, we developed a convergent approach based on the Trost coupling reaction, in which the A-ring fragment (ene-yne part obtained in 10.4% overall yield) and the C/D-ring fragment (bromomethylene part obtained in 27.1% overall yield) are coupled to produce the triene system of eldecalcitol (15.6%). Although the overall yield of the convergent synthesis was better than that of the linear synthesis, significant improvements were still necessary. Therefore, additional biomimetic studies were investigated. Process development for the practical production of eldecalcitol is described herein.