Parallel synthesis of a vitamin D(3) library in the solid-phase.
A highly efficient synthesis of the vitamin D(3) system on solid support is described. Two synthetic strategies for the solid-phase synthesis of vitamin D(3) 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 D(3) 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 Cu(I)-catalyzed Grignard reagent. Parallel synthesis of the vitamin D(3) 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
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Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan.
Doi
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Takahashi
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D000465:Algorithms; D002117:Calcitriol / Q000138:chemical synthesis; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D020650:Combinatorial Chemistry Techniques; D008956:Models, Chemical; D015394:Molecular Structure; D011846:Radio Waves; D013237:Stereoisomerism; D013451:Sulfonic Acids / Q000737:chemistry
D013451:Sulfonic Acids; D002762:Cholecalciferol; D002117:Calcitriol