The aminating reagent O-mesitylsulfonylhydroxylamine (MSH) has a known potential hazard since it contains high-energy functional groups in its structure. There are references in the literature that report several incidents involving the use of pure and crystalline MSH. The preparation and safe use of this reagent at kilo scale are described herein.

Critical parameters affecting the stereoselective amination of (hetero)aromatic ketones using transaminases have been studied such as temperature, pH, substrate concentration, cosolvent and source and percentage of amino donor, to further optimize the production of enantiopure amines using both (S)-and (R)-selective biocatalysts from commercial suppliers.Interesting enantiopure amino building blocks have been obtained overcoming some limitations of traditional chemical synthetic methods. Representative processes were scaled-up affording halogenated and heteroaromatic amines in enantiomerically pure form and good isolated yields.

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.

A new reaction of N-protected 2-bromomethylazoles and tosylmethyl isocyanide (TosMIC) leading to the preparation of azolopyrimidines is described. This domino sequence was used to synthesize the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine core of alkaloids variolins from 4-methoxy-2-methylpyrrolo[2,3-b]pyrimidine in two steps.

A new total synthesis of the alkaloid variolin B is achieved by a selective and sequential palladium-mediated functionalization of a trihalo-substituted pyrido