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Second generation synthesis of C27-C35 building block of E7389, a synthetic halichondrin analogue.

ABSTRACT: A practical method is reported to synthesize E7389 C27-C35 building block 13 from 1,2-O-isopropylidene-alpha-D-5-deoxyglucurono-6,3-lactone (3). This synthesis relies on two key processes: (1) C34/C35-diol is introduced via asymmetric dihydroxylation with dr = 3:1, with the undesired C34-diastereomer effectively removed by crystallization of 11, and (2) the C30 PhSO2CH2 group is introduced stereoselectively (>100:1) via hydrogenation of 12 in the presence of the Crabtree catalyst. The reported synthesis is practically free from chromatographic separation.

SUBMITTER: Yang YR

PROVIDER: S-EPMC2759418 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Second generation synthesis of C27-C35 building block of E7389, a synthetic halichondrin analogue.

Yang Yu-Rong YR Kim Dae-Shik DS Kishi Yoshito Y

Organic letters 20091001 20

A practical method is reported to synthesize E7389 C27-C35 building block 13 from 1,2-O-isopropylidene-alpha-D-5-deoxyglucurono-6,3-lactone (3). This synthesis relies on two key processes: (1) C34/C35-diol is introduced via asymmetric dihydroxylation with dr = 3:1, with the undesired C34-diastereomer effectively removed by crystallization of 11, and (2) the C30 PhSO2CH2 group is introduced stereoselectively (>100:1) via hydrogenation of 12 in the presence of the Crabtree catalyst. The reported s ...[more]

PMID: 19754145

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