title: Total synthesis of halichondrin A, the missing member in the halichondrin class of natural products.
abstract: A total synthesis of halichondrin A, the phantom member in the halichondrin class of natural products, is reported. The highlights of synthesis include: (1) synthesis of C1-C19 building block 6b via a catalytic asymmetric Cr-mediated coupling of 12 and 13b; (2) synthesis of the right-half of 19 via an asymmetric Ni/Cr-mediated coupling, followed by base-induced furan formation, and Shiina macrolactonization; (3) synthesis of enone 20 via Ni/Cr-mediated coupling of 5 with 19, followed by oxidation; (4) synthesis of halichondrin A from 20, with use of a newly discovered, highly selective TMSOTf-mediated equilibration of C38-epi-halichondrin A to halichondrin A. Two pieces of evidence are presented unambiguously to establish the structure of halichondrin A thus synthesized: one is the synthesis of norhalichondrin A (24) from 19 and 23, and the other is the study of the proton chemical shift difference between synthetic halichondrin A and known members of this class of natural products.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ueda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kato
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kishi
mesh_terms: D000818:Animals; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D011161:Porifera / Q000737:chemistry; D000095662:Polyether Polyketides
chemical_list: D001688:Biological Products; D004988:Ethers, Cyclic; D018942:Macrolides; C000597650:halichondrin A; D000095662:Polyether Polyketides