Antiproliferative Hybrid Analogs of the Hormone 1α,25-Dihydroxyvitamin D3:  Design, Synthesis, and Preliminary Biological Evaluation

Antiproliferative Hybrid Analogs of the Hormone 1α,25-Dihydroxyvitamin D3:  Design, Synthesis, and Preliminary Biological Evaluation

The combination of 10−12 kbar pressure plus Lewis acidic zinc dichloride promotes highly regioselective and stereoselective Diels−Alder cycloaddition between 3-bromo-2-pyrone, prepared in a new way, and unactivated terminal alkene 4-(tert-butyldimethylsiloxy)-1-butene. The conjugate base of A-ring a...

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Veröffentlicht in:Journal of organic chemistry 1997-05, Vol.62 (10), p.3299-3314
Hauptverfasser: Posner, Gary H, Lee, Jae Kyoo, White, M. Christina, Hutchings, Richard H, Dai, Haiyan, Kachinski, Joseph L, Dolan, Patrick, Kensler, Thomas W
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container_end_page 3314
container_issue 10
container_start_page 3299
container_title Journal of organic chemistry
container_volume 62
creator Posner, Gary H
Lee, Jae Kyoo
White, M. Christina
Hutchings, Richard H
Dai, Haiyan
Kachinski, Joseph L
Dolan, Patrick
Kensler, Thomas W
description The combination of 10−12 kbar pressure plus Lewis acidic zinc dichloride promotes highly regioselective and stereoselective Diels−Alder cycloaddition between 3-bromo-2-pyrone, prepared in a new way, and unactivated terminal alkene 4-(tert-butyldimethylsiloxy)-1-butene. The conjugate base of A-ring allylic phosphine oxide 20 adds chemospecifically to the C-8 keto group of some C-8,C-24-diketones to form directly metabolically resistant 24-oxo analogs of 1α,25-dihydroxyvitamin D3 (calcitriol). Several of these new hybrid analogs are as efficacious in vitro as calcitriol at inhibiting growth of murine keratinocytes even at physiologically relevant 10−100 nanomolar concentrations.
doi_str_mv 10.1021/jo970049w
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title Antiproliferative Hybrid Analogs of the Hormone 1α,25-Dihydroxyvitamin D3:  Design, Synthesis, and Preliminary Biological Evaluation
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