Second generation synthesis of C27-C35 building block of E7389, a synthetic halichondrin analogue.
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.
Yang
Yu-Rong
YR
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Kim
Dae-Shik
DS
Kishi
Yoshito
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry; D018942:Macrolides; D000095662:Polyether Polyketides
D000970:Antineoplastic Agents; D002244:Carbon; D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D007783:Lactones; D018942:Macrolides; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin