General access to the vinca and tacaman alkaloids using a Rh(II)-catalyzed cyclization/cycloaddition cascade.
The total synthesis of several members of the vinca and tacaman classes of indole alkaloids has been accomplished. The central step in the synthesis consists of an intramolecular [3+2]-cycloaddition reaction of an alpha-diazo indoloamide which delivers the pentacyclic skeleton of the natural product in excellent yield. The acid lability of the oxabicyclic structure was exploited to establish the trans-D/E ring fusion of (+/-)-3H-epivincamine (3). Finally, a base induced keto-amide ring contraction was utilized to generate the E-ring of the natural product. A variation of the cascade sequence of reactions used to synthesize (+/-)-3H-epivincamine was also employed for the synthesis of the tacaman alkaloids (+/-)-tacamonine and (+/-)-apotacamine.
England
Dylan B
DB
Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
Padwa
Albert
A
D002384:Catalysis; D003500:Cyclization; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism; D031053:Vinca / Q000737:chemistry*; D014748:Vinca Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry
D026121:Indole Alkaloids; D007211:Indoles; D014748:Vinca Alkaloids; C520379:tacaman; D012238:Rhodium