title: Synthesis of the northern sector (C8-C19) of rapamycin via Chan rearrangement and oxidation of an alpha-acyloxyacetate.
abstract: Two routes to the masked tricarbonyl segment of the immunosuppressant rapamycin comprising C8-C19 were explored beginning from D-xylose. The first approach employed a protected form of 2,4,5-trihydroxypentanol to obtain dithiane 43, which failed to react with dimethyl oxalate to give a 1,2,3-tricarbonyl unit corresponding to the northern sector of rapamycin. A second approach employing carboxylic acid 61 derived from 43 utilized base-mediated (Chan) rearrangement of alpha-acyloxyacetate 62 with trapping of the resultant enediolate as bis silyl ether 63. Epoxidation of this diene afforded masked tri-keto ester 65 which underwent acid-catalyzed methanolysis to produce cyclic ketal 67.
authors.affiliation: Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003.
authors.forename: James D
authors.initials: JD
authors.lastname: White
authors.forename: Scott C
authors.initials: SC
authors.lastname: Jeffrey