Stereocontrolled and versatile total synthesis of bispyrrolidinoindoline diketopiperazine alkaloids: structural revision of the fungal isolate (+)-asperdimin.
Homo- and heterodimeric bispyrrolidinoindoline diketopiperazine alkaloids have been synthesized following a concise, versatile, and stereoselective route. Highlights of the sequence are a diastereoselective construction of the C3a-bromo-hexahydropyrrolo[2,3-b]indole nucleus, its Co(I)-induced C3a-C3a' dimerization, and the twofold or sequential amide-bond formation before cyclization to the diketopiperazine of the homo- or heterodimeric alkaloids, respectively. Stereochemical diversity is achieved through the choice of the appropriate amino acids combined with the base-induced epimerization of the C2-acyl-hexahydropyrrolo[2,3-b]indole at C2. According to this strategy, the natural products (+)-WIN 64821 1, (+)-WIN 64745 2 and (+)-asperdimin 6 as well as analogues (5, 22, 32, 44) with different relative and absolute configuration have been efficiently synthesized. The flexibility of this synthetic methodology has facilitated the structural revision of the natural product (+)-asperdimin, whose structure has been corrected to diastereomer 6.
Pérez-Balado
Carlos
C
Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, As Lagoas/Marcosende, 36310 Vigo, Spain.
Rodríguez-Graña
Paula
P
de Lera
Angel R
AR
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D054659:Diketopiperazines / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry*; D013237:Stereoisomerism
D000470:Alkaloids; D054659:Diketopiperazines; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D010879:Piperazines; D011760:Pyrrolidinones; C546076:asperdimin; C087461:WIN 64821