Stephacidin A and its congeners are a collection of secondary metabolites that possess intriguing structural motifs. They stem from unusual biosynthetic sequences that lead to the incorporation of a prenyl or reverse-prenyl group into a bicyclo[2.2.2]diazaoctane framework, a chromene unit or the vestige thereof. To complement biosynthetic studies, which normally play a significant role in unveiling the biosynthetic pathways of natural products, here we demonstrate that chemical synthesis can provide important insights into biosynthesis. We identify a short total synthesis of congeners in the reverse-prenylated indole alkaloid family related to stephacidin A by taking advantage of a direct indole C6 halogenation of the related ketopremalbrancheamide. This novel strategic approach has now made possible the syntheses of several natural products, including malbrancheamides B and C, notoamides F, I and R, aspergamide B, and waikialoid A, which is a heterodimer of avrainvillamide and aspergamide B. Our approach to the preparation of these prenylated and reverse-prenylated indole alkaloids is bioinspired, and may also inform the as-yet undetermined biosynthesis of several congeners.

Organocatalytic access to N-tosylaziridines catalyzed by diarylprolinol trimethylsilyl ether [Ar = 3,5-(CF 3 ) 2 C 6 H 3 ] starting from different α-substituted-α,β-unsaturated aldehydes is described. The products were obtained in good yields (up to 86 %) and enantioselectivities (up to 90 % ee) and could

Last decades have witnessed the golden rush of organocatalysis, which opened an effective and efficient way to high yielding, metal free, stereoselective strategies toward the synthesis of a plethora of natural products. The present review provides an overview of the current achievements of those organocatalytic methodologies in which active methylene compounds have been used as key intermediates. Ranging from covalent to non-covalent activation mode, from monofunctional to bifunctional catalysts, recent results suggest a variety of new powerful tools to accomplish the formal and total synthesis of both the simplest and the most complex natural compounds with facile procedures in high yields and excellent stereoselectivities. At the same time, it is clear how the organocatalytic approach might offer an outstanding and impressive answer to unsolved longstanding synthetic challenges. Finally the possible application to industrial protocols and to the preparation of novel potential drugs has been highlighted