Total synthesis and stereochemistry of cytoblastin.
The first total synthesis and stereochemical assignment of cytoblastin were reported. Key steps included the palladium-mediated coupling of N-SEM-7-bromoindolactam V ((-)-11) with allylstannane c-13, and osmium tetroxide-mediated dihydroxylation of 14, both of which were stereoselective. The stereochemistry of cytoblastin was determined as 1A via spectroscopic analysis of the pentacyclic derivative 21 of cytoblastin. A connection was then made between the stereochemistry so elucidated and the Kishi/Rando hypothesis for the structural correlation between (S)-1,2-diacylglycerol and tumor promoters for the process of protein kinase C activation.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
O A
OA
Moreno
Y
Y
Kishi
D002273:Carcinogens / Q000138:chemical synthesis* / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D002273:Carcinogens; D007211:Indoles; D007769:Lactams; C071412:cytoblastin