Total synthesis of apoptolidin A.
A highly convergent, enantioselective total synthesis of the potent antitumor agent apoptolidin A has been completed. The key transformations include highly selective glycosylations to attach the C27 disaccharide and the C9 6'-deoxy-l-glucose, a cross-metathesis to incorporate the C1-C10 trienoate unit, and a Yamaguchi macrolactonization to complete the macrocycle. Twelve stereocenters in the polypropionate segments and sugar units were established through diastereoselective chlorotitanium enolate aldol reactions.
Crimmins
Michael T
MT
Venable and Kenan Laboratories of Chemistry, Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA. crimmins@email.unc.edu
Christie
Hamish S
HS
Long
Alan
A
Chaudhary
Kleem
K
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D018942:Macrolides; D011753:Pyrones; C506738:apoptolidin A; D005947:Glucose