- Total synthesis of 1α,25-dihydroxyvitamin D3 analogs modified at the side chain and D-ring
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Herein, we describe a synthetic strategy to access 1α,25-dihydroxyvitamin D3 (calcitriol) analogs with natural or unnatural configuration at C20 and unsaturation at the D-ring. The synthetic approach is exemplified by the synthesis of two potent analogs, namely 1α,25-dihydroxy-16-en-23-yne-vitamin D3 and 1α,25-dihydroxy-20-epi-24a-homo-26,27-dimethyl-vitamin D3. A key feature of the synthetic strategy is the generation of an unnatural configuration at C20 by a catalytic asymmetric reduction of an α,β,γ,δ-unsaturated ester with the CuH species in a micellar system.
- López-Pérez, Borja,Maestro, Miguel A.,Mouri?o, Antonio
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p. 4563 - 4569
(2018/06/29)
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- Parallel synthesis of a vitamin D3 library in the solid-phase
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A highly efficient synthesis of the vitamin D3 system on solid support is described. Two synthetic strategies for the solid-phase synthesis of vitamin D3 were developed. One is for 11-hydroxy analogues, and the other is for most other synthetic analogues. In the latter strategy, the sulfonate-linked CD-ring 58 was initially immobilized on PS-DES resin to give solid-supported CD-ring 63 (Scheme 10). Similarly, solid-supported CD-ring 63 was prepared by attachment of the CD-ring 10 to the chlorosulfonate resin 64. The vitamin D3 system was synthesized by Horner-Wadsworth-Emmons reaction of the A-ring phosphine oxide to a solid-supported CD-ring, followed by simultaneous introduction of the side chain and cleavage from resin with a Cu1-catalyzed Grignard reagent. Parallel synthesis of the vitamin D3 analogues was accomplished by a split and pool methodology utilizing radio frequency encoded combinatorial chemistry, and a manual parallel synthesizer for side chain diversification and deprotection. Additionally, we demonstrated the synthesis of various A-rings in a similar protocol for efficient preparation of building blocks.
- Hijikuro,Doi,Takahashi
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p. 3716 - 3722
(2007/10/03)
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