Asymmetric catalytic ene-cyclization approach to 2-fluoro-19-nor-1,25-dihydroxyvitamin D(3) A-ring analog with significant transactivation activity.

Abstract:

:1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)2D3) has been shown to modulate not only proliferation and differentiation, but also apoptosis in malignant cells, indicating that it could be useful for the treatment of cancer and psoriasis. However, little information has been available on the binding conformation of the 1alpha,25(OH)2D3 molecule and its analogs with the vitamin D receptor (VDR). Therefore, we synthesized 2alpha-fluorinated A-ring analogs of 19-nor-1alpha,25(OH)2D3 in order to investigate the VDR-binding conformation of the A-rings on the basis of the (19)F NMR analysis. The 2alpha-fluoro-19-nor-1alpha,25-dihydroxyvitamin D3 A-ring analog thus synthesized via a asymmetric catalytic carbonyl-ene cyclization, shows significant activity in transactivation.

journal_name

Chirality

journal_title

Chirality

authors

Mikami K,Ohba S,Ohmura H,Kubodera N,Nakagawa K,Okano T

doi

10.1002/chir.1046

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

366-71

issue

7

eissn

0899-0042

issn

1520-636X

pii

10.1002/chir.1046

journal_volume

13

pub_type

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