synthesis and biological evaluation of fully functionalized seco-pancratistatin analogues.
The total synthesis of fully functionalized polyhydroxyamide B,C- seco-analogues of the anticancer compound pancratistatin (PST) ( 1) is reported. Key steps include an Evans' MgCl 2-promoted anti-aldol reaction between a functionalized l-threose derivative and ( R)-(+)-oxazolidinone to stereoselectively form the C-1/C-10b bond and a regiospecific radical-mediated oxidative fragmentation of a 1,3-benzylidene. The B,C- seco compounds 25 and 26 exhibited low activity (ED 50 > 30 microg/mL) for inducing apoptosis in human cancer cells.
McNulty
James
J
Department of Chemistry, McMaster University, Hamilton, Ontario, Canada. jmcnult@mcmaster.ca
Nair
Jerald J
JJ
Griffin
Carly
C
Pandey
Siyaram
S
D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism
D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D007546:Isoquinolines; C044997:pancratistatin