Process development for the practical production of eldecalcitol by linear, convergent and biomimetic syntheses.

Abstract:

:Eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D(3)], an analog of calcitriol (1α,25-dihydroxyvitamin D(3)), 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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Kubodera N,Hatakeyama S

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

303-9

issue

1

eissn

0250-7005

issn

1791-7530

pii

32/1/303

journal_volume

32

pub_type

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