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This work describes our studies on the functionalization at C11 of CD-ring fragments of vitamin D3 using organocopper reagents. As an application, an efficient, convergent synthesis of 11α-[3,3-(dimethoxy)propyl] calcitriol analogue 2, which may be useful for the construction of affinity columns for the purification of 1α,25-(OH)2-vitamin D3 receptors, is described.

1 α ,24( R )-Dihydroxyvitamin D 3 ( 5e ) was synthesized. The key step in the preparation of the side-chain was opening of the chiral epoxide 10 by the α-anion of the nitrile 9 . The triene system was synthesized by the dienyne route.

Coupling of the CD fragment, ketone 6 (obtained by partial synthesis from vitamin D2), either directly (Horner-Wittig route) or via the derived enol triflate (dienyne route) with the appropriate A-ring fragment, phosphine oxide anion 7 or enyne 10, is the key step in the syntheses of 24-oxavitamin D3 (1d) and 1α-hydroxy-24-oxavitamin D3 (1e), respectively. © 1993.

We describe a general approach, based on the palladium-catalysed coupling of enynes with vinyl triflates, for the construction of dienynes related to vitamin D metabolites and analogues. As an application of this method, an efficient convergent synthesis of 1α,25-dihydroxyvitamin D3 starting from the Inhoffen-Lythgoe diol (6a) and natural carvones has been carried out (11 steps, 28% overall yield from 6a). This strategy allows labelling of the side chain in the final steps of the synthesis. © 1991.