A(1,3)-strain enabled retention of chirality during bis-cyclization of beta-ketoamides: total synthesis of (-)-salinosporamide A and (-)-homosalinosporamide A.
A concise, enantioselective synthesis of the Phase I anticancer agent, (-)-salinosporamide A, is described. The brevity of the described strategy stems from a key bis-cyclization of a beta-keto tertiary amide, accomplished on gram scale, which retains optical purity enabled by A(1,3)-strain rendering epimerization slow relative to the rate of bis-cyclization. The versatility of the strategy for derivative synthesis is demonstrated by the synthesis of (-)-homosalinosporamide A.
Nguyen
Henry
H
Department of Chemistry, Texas A&M University, College Station, TX 77840, USA.
Ma
Gil
G
Romo
Daniel
D
D000577:Amides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D000970:Antineoplastic Agents; D007783:Lactones; D011758:Pyrroles; C520957:beta-ketoamide; C475865:marizomib