Calcitriol lactone

Takano et al. used the Ireland-Claisen rearrangement of an allyl lactate in the total synthesis of calcitriol lactone (Scheme 4.76) [74]. The rearrangement proceeded with a 6.7 1 diastereoselectivity via O-silylation of the intermediate li-che-lated Z-enolate. Takano noted that the corresponding benzyl ether gave significantly lower de (70%) than the PMB ether. This is presumably due to the PMB ether s greater Lewis basicity and hence its greater propensity to coordinate a lithium cation. 

Nakada et al. applied the tridentate carbazole-derived ligand 15a in the methallylation of chiral aldehyde 50 to give 51, which is a key intermediate of calcitriol lactones. Ligand 15a gave 51 in 94% de (Scheme 12.37), whereas... 

Numerous substrate variations can be explored as a com-plemoit to the ether transfer. Therefore, 1,1-disubstitution in the homoallylic alcohol starting material was envisioned as an avenue to access tertiary ethers. The synthesis of such fimctionahty from stereoselective C—O bond formation is rare. To access the issue of the stereoselective synthesis of calcitriol lactone, a major metabolite of vitamin D3 developed by Hoffmann-La Roche U.C. Riverside, Jonhson and Chan synthesized tertiary ethers in high stereocontrol through iodocyclization of the coiresponding tert-butyl carbonate 161 using Barlett s procedure (Scheme 37.32). ... 

The main metabolic pathway of C. proceeds through 23- and 26-hydroxylation to 23S,26-dihydroxycal-citriol and further oxidation to calcitriol-26,23-lactone. In total over SO metabolites of calciol and ercalciol have been isolated and identified to date. Most of these secondary products have no or a very reduced antirachitic activity but do possess other interesting physiological properties the relevance of which is being investigated. 

---