Gram-scale synthesis of (+)-spongistatin 1: development of an improved, scalable synthesis of the F-ring subunit, fragment union, and final elaboration.
In a quest to develop an effective, scalable synthesis of (+)-spongistatin 1 ( 1), we devised a concise, third-generation scalable synthesis of (+)- 7, the requisite F-ring tetrahydropyran aldehyde, employing a proline-catalyzed cross-aldol reaction. Subsequent elaboration to (+)-EF Wittig salt (+)- 3, followed by union with advanced ABCD aldehyde (-)- 4, macrolactonization and global deprotection permitted access to >1.0 g of totally synthetic (+)-spongistatin 1 ( 1).
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Tomioka
Takashi
T
Risatti
Christina A
CA
Sperry
Jeffrey B
JB
Sfouggatakis
Chris
C