303015-32-9Relevant academic research and scientific papers
Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3
Ikeda, Masahiko,Takahashi, Kazuhiko,Dan, Akihito,Koyama, Kohji,Kubota, Katsumi,Tanaka, Tomoyuki,Hayashi, Masaji
, p. 2157 - 2166 (2007/10/03)
The activated vitamin D3 derivative 26,27-F6-1α,25(OH)2D3 (2a), its three A-ring diastereomers (2b, 2c, 2d), and 5,6-trans isomer (2e) were prepared. Two analogues (2b, 2c) of these isomers were synthesized by a palladium catalyzed coupling reaction using vinyl bromide 5 and enynes (6a, 6b), which were derived from readily commercially available 2S-(+)-glycidyl p-toluenesulfonate 7, as a common starting material. Competitive vitamin D receptor (VDR) binding affinities of these diastereomers of 2a were evaluated. Interestingly, the stereochemical effects at C-1,3 of 2a were considerably more moderate than those of 1α,25(OH)2D3 (1). In particular, isomerization at the 5,6-double bond of 2a only slightly reduced VDR affinity, whereas 5,6-trans-1α,25(OH)2D3 had a significantly lower binding affinity than 1. Copyright (C) 2000 Elsevier Science Ltd.
New strategies for the synthesis of vitamin D metabolites via Pd-catalyzed reactions
Trost, Barry M.,Dumas, Jacques,Villa, Marco
, p. 9836 - 9845 (2007/10/02)
The invention of new palladium-catalyzed reactions offers new insights into synthetic strategies directed toward the vitamin D system. The palladium-catalyzed cycloisomerization of 1,6- and 1,7-enynes to dialkylidenecycloalkanes permits a lynchpin approach to the A ring of vitamin Ds. Using the thioacetal of formaldehyde, the proper subunits containing the olefin and the acetylene were attached. Pd(2+) effected cycloisomerization to an A ring subunit. A more effective strategy evolved from the evolution of a Pd-catalyzed alkylative cyclization of enynes. Whereas prior work established the feasibility of this process for 1,6-enynes, model studies reported herein demonstrate the feasibility of its extension to 1,7-enynes. This reaction permits the creation of a new concept for vitamin D synthesis wherein A ring formation is concomitant with its attachment to an appropriate CD fragment. An asymmetric synthesis of the requistite 1,7-enyne required six steps. Bromomethylenation of Grundmann's ketone and its side chain hydroxylated derivative proceeded with excellent geometrical selectivity (>30:1) using the Wittig reaction. A Pd catalyst generated from (dba)3Pd2·CHCl3 and triphenylphosphine stitched together these two units in a single step resulting in syntheses of alphacalcidiol and calcitriol.
