Total synthesis of (+)-spongistatin 1. An effective second-generation construction of an advanced EF Wittig salt, fragment union, and final elaboration.
A stereocontrolled, total synthesis of (+)-spongistatin 1 (1) has been achieved. Union of a second-generation EF Wittig salt (+)-3 with the advanced ABCD aldehyde (-)-4, followed by regioselective macrolactonization and global deprotection afforded (+)-spongistatin 1 (1). The longest linear sequence, 29 steps, proceeded in 0.5% overall yield.
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center, Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Zhu
Wenyu
W
Shirakami
Shohei
S
Sfouggatakis
Chris
C
Doughty
Victoria A
VA
Bennett
Clay S
CS
Sakamoto
Yasuharu
Y
D000447:Aldehydes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D004988:Ethers, Cyclic / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides; D013237:Stereoisomerism; D000095702:Polyether Toxins
D000447:Aldehydes; D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D007783:Lactones; D018942:Macrolides; C083856:spongistatin 1; D000095702:Polyether Toxins