Total synthesis of the potent microtubule-stabilizing agent (+)-discodermolide.
The total synthesis of the potent microtubule-stabilizing, antimitotic agent (+)-discodermolide is described. The convergent synthetic strategy takes advantage of the diastereoselective alkylation of a ketone enolate to establish the key C15-C16 bond. The synthesis is amenable to preparation of gram-scale quantities of (+)-discodermolide and analogues.
Harried
Scott S
SS
Department of Chemistry and Biochemistry, UCLA, Los Angeles, California 90095, USA.
Lee
Christopher P
CP
Yang
Ge
G
Lee
Tony I H
TI
Myles
David C
DC
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000478:Alkylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure*; D008958:Models, Molecular; D008968:Molecular Conformation; D011753:Pyrones
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D007202:Indicators and Reagents; D007783:Lactones; D011753:Pyrones; C071229:discodermolide