Reaction of bromomethylazoles and tosylmethyl isocyanide. A novel heterocyclization method for the synthesis of the core of marine alkaloids variolins and related azolopyrimidines.
A novel and efficient synthesis of the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine system, the heterocyclic core of the variolin family of marine alkaloids, is described. The route involves the reaction of 3-bromo-2-(bromomethyl)pyrrolo[2,3-b]pyridine and tosylmethyl isocyanide (TosMIC) under phase-transfer conditions. This unprecedented reaction was also used to synthesize a series of new methoxycarbonyl azolopyrimidines by reaction of TosMIC with bromomethylindoles, bromomethylbenzimidazole, and bromomethylpyrazole. Hydrolysis and decarboxylation of 5-bromo-7-methoxycarbonylpyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine obtained by this heterocyclization process and installation of the pyrimidine moiety in the C5 position open an alternative approach to complete a total synthesis of variolin B.
Mendiola
Javier
J
Departamento de Química Orgánica, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.
Baeza
Alejandro
A
Alvarez-Builla
Julio
J
Vaquero
Juan J
JJ
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D001393:Azoles / Q000737:chemistry*; D003486:Cyanides / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D014105:Tosyl Compounds / Q000737:chemistry*
D000470:Alkaloids; D001393:Azoles; D003486:Cyanides; D011743:Pyrimidines; D014105:Tosyl Compounds