Enantioselective total synthesis of the antitumor macrolide rhizoxin D.
The convergent, highly enantioselective synthesis of rhizoxin D, a natural product possessing potent antitumor and antifungal bioactivity, is described. The C(1)-C(9) fragment of the molecule was synthesized utilizing a threefold pseudosymmetric intermediate ultimately derived from gamma-butyrolactone. The central core of rhizoxin D was prepared via a chiral resolution/asymmetric aldol protocol. Several methods for the generation of the polyene fragment were explored, and the side-chain was ultimately prepared from serine in six steps. The unification of the left and right wings of the molecule was achieved using a one-step olefination protocol, and the macrocyclization was carried out using a Horner-Emmons olefination at the C(2)-C(3) olefin.
Lafontaine
Jennifer A
JA
Department of Chemistry, University of California, Berkeley 94720-1460, USA.
Provencal
David P
DP
Gardelli
Cristina
C
Leahy
James W
JW
D000475:Alkenes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D003500:Cyclization; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D018942:Macrolides; D015394:Molecular Structure; D013237:Stereoisomerism
D000475:Alkenes; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D007783:Lactones; D018942:Macrolides; C479980:rhizoxin D; C041443:rhizoxin