Synthesis of amphidinolide T1 via catalytic, stereoselective macrocyclization.
Two nickel-catalyzed reductive coupling reactions of alkynes were instrumental in a modular, stereoselective synthesis of amphidinolide T1 (1). The C13-C21 fragment was prepared from two simple starting materials that were joined in a catalytic alkyne-epoxide fragment coupling operation, whereas an intramolecular aldehyde-alkyne reductive coupling simultaneously formed the final carbon-carbon bond of the macrocycle and established the C13 carbinol configuration with complete selectivity in the desired fashion.
Colby
Elizabeth A
EA
Massachusetts Institute of Technology, Department of Chemistry, Cambridge, Massachusetts 02139, USA.
O'Brien
Karen C
KC
Jamison
Timothy F
TF
D000480:Alkynes / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D007783:Lactones / Q000138:chemical synthesis*; D018942:Macrolides; D009532:Nickel / Q000737:chemistry; D013237:Stereoisomerism; D000097442:Amphidinolides
D000480:Alkynes; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; D018942:Macrolides; D009532:Nickel; C414522:amphidinolide T; D000097442:Amphidinolides