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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.

SUBMITTER: White JD

PROVIDER: S-EPMC2722752 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Synthesis of the northern sector (C8-C19) of rapamycin via Chan rearrangement and oxidation of an alpha-acyloxyacetate.

White James D JD Jeffrey Scott C SC

Tetrahedron 20090801 33

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 ...[more]

PMID: 20161171

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