synthesis and biological evaluation of fully functionalized seco-pancratistatin analogues
- J Nat Prod. 2008 Mar;71(3):357-63. doi: 10.1021/np0705460.
Affiliations
- 1. Department of Chemistry, McMaster University, Hamilton, Ontario, Canada. [email protected]
PMID: 18225861
DOI: 10.1021/np0705460
Abstract
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.