Exploiting the borono-Mannich reaction in bioactive alkaloid synthesis

Abstract

Abstract:We have demonstrated that the borono-Mannich reaction is a versatile and efficient reaction for the diastereoselective preparation of chiral 1,2-amino alcohols. These Mannich products are valuable starting materials as shown in this report by the synthesis of bioactive polyhydroxylated pyrrolizidine and indolizidine alkaloids. Initial studies, directed at the more complex Stemona alkaloids and using the borono-Mannich reaction on cyclic N-acyliminium ions, are encouraging, as demonstrated by the synthesis of the pyrido[1,2-a]azepine core structure of stemocurtisinol.

Scaffold Diversity from N-Acyliminium Ions

“…The single most widely applied method for NAI formation involves the release of a leaving group from the α-position of the acyl nitrogen under acidic reaction conditions, a process that proceeds in a reversible manner (Scheme ). Hydroxyl compounds, such as the hydroxylated pyrrolidine, pyrrolizidine, and indolizidine alkaloids reported by Pyne and co-workers, − have been commonly used as NAI precursors. A protonated hydroxyl group is the most common leaving group, but halogen, alkyloxy, aryloxy, acetoxy, alkylthio, arylthio, arylsulfonyl, carbamate, and benzotriazolyl moieties have also been utilized.…”

Boronic Acids and Esters in the Petasis-Borono Mannich Multicomponent Reaction

“…The exclusive formation of the anti-β-amino alcohols diastereomer was observed starting from racemic α-hydroxy aldehydes, while a single enantiomer was formed from enantiomerically pure analogues . Pyne and co-workers, suggested that, for the case of vinyl boronic acids, the diastereocontrol arises from the reactive conformation E of the ate complex, where the 1,3-allylic strain is minimized (Scheme ). , …”

A theoretical study of the nornicotine-catalyzed Mannich reaction in wet solvents and water

“…The Mannich reaction is an important reaction for the consecutive formation of C-N and C-C bonds yielding β-aminocarbonyl compounds (Mannich bases), and it is frequently applied in the synthesis 1,2 of pharmaceuticals and natural products. Volatile organic compounds such as benzene, THF, acetone and DMSO are common solvents in these procedures.…”