Enantioselective synthesis of (+)-cryptophycin 52 (LY355703), a potent antimitotic antitumor agent.
A highly enantioselective and convergent synthesis of cryptophycin 52 (2), an exceedingly potent cytotoxic agent, is described. Cryptophycin 52, a synthetic variant of the cryptophycin family, is currently undergoing clinical trials. The synthesis is convergent and involves assembly of three fragments, phenyl hexenal 3, d-tyrosine phosphonate 4, and protected beta-amino acid derivative 5. The synthesis of fragment 3 involves an efficient and stereocontrolled construction of both stereogenic centers at C-3 and C-4 by cleavage of a substituted tetrahydrofuran ring via an acyloxycarbenium ion intermediate. Both of these stereogenic centers were derived from optically active 4-phenylbutyrolactone, synthesized enantioselectively by Corey-Bakshi-Shibata reduction.
Ghosh
Arun K
AK
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA. arunghos@uic.edu
Swanson
Lisa
L
D015107:4-Butyrolactone / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D047630:Depsipeptides; D005663:Furans / Q000737:chemistry; D006591:Hexobarbital / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D010654:Phenylbutyrates / Q000737:chemistry; D013237:Stereoisomerism; D014443:Tyrosine / Q000737:chemistry
D000596:Amino Acids; D000970:Antineoplastic Agents; D047630:Depsipeptides; D005663:Furans; D007769:Lactams; D007783:Lactones; D010654:Phenylbutyrates; C018674:tetrahydrofuran; D014443:Tyrosine; C075773:4-phenylbutyric acid; D006591:Hexobarbital; C114033:cryptophycin 52; D015107:4-Butyrolactone