Synthesis of putative metabolites of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71)

Steroids
Yoshiyuki OnoN Kubodera

Abstract

1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is under phase III clinical trials in Japan for the treatment of osteoporosis and bone fracture prevention. Since ED-71 has a substituent at the 2beta-position of the A-ring, it is recognized that the metabolic pathway of ED-71 might be more complicated than 1,25(OH)(2)D(3) because of metabolism at the 2beta-position substituent in addition to the inherent metabolism of the side chain. To clarify the metabolism of hydroxypropoxy substituent of the 2beta-positon and a combination of metabolism between side chain and 2beta-positon, four putative metabolites of ED-71 have been prepared as authentic samples. The metabolites at the 2beta-positon, the methyl ester derivative considered as an ester standard of the oxidized metabolite and the tetraol derivative as the truncated metabolite were synthesized from alpha-epoxide, a key intermediate of ED-71 synthesis. The combination metabolites between side chain and 2beta-positon, the 24(S)- and 24(R)-pentaols were synthesized using Trost's convergent method.

References

Apr 1, 1995·Endocrine Reviews·R BouillonA W Norman
Jul 18, 2001·Journal of the American Chemical Society·I HijikuroT Takahashi
Jan 24, 1997·The Journal of Organic Chemistry·Subhash C. Sinha, Ehud Keinan

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Citations

Nov 23, 2007·Natural Product Reports·James R Hanson
Oct 22, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Yoshiyuki Ono
Jun 4, 2015·Pharmacology Research & Perspectives·Kaori YasudaToshiyuki Sakaki
Sep 18, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Kaori YasudaToshiyuki Sakaki
Jul 13, 2021·Chembiochem : a European Journal of Chemical Biology·Ryota SakamotoKazuo Nagasawa

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