Total Synthesis of (+)-Sieboldine A: Evolution of a Pinacol-Terminated Cyclization Strategy

Abstract

This article describes synthetic studies that culminated in the first total synthesis of the Lycopodium alkaloid sieboldine A. During this study a number of pinacol-terminated cationic cyclizations were examined to form the cis-hydrindanone core of sieboldine A. Of these, a mild Au(I)-promoted 1,6-enyne cyclization that was terminated by a semipinacol rearrangement proved to be most efficient. Fashioning the unprecedented N-hydroxyazacyclononane ring embedded within the bicyclo[5.2.1]decane-N,O-acetal moiety of sieboldine A was a formidable challenge. Ultimately, the enantioselective total synthesis of (+)-sieboldine A was completed by forming this ring in good yield by cyclization of a protected-hydroxylamine thioglycoside precursor.

Rapid Photoactivated Generation of Nitroxyl (HNO) under Neutral pH Conditions

“…Zuschriften spectroscopy (Supporting Information, Figure S8). As shown in Scheme 2, the desired pathway leading to HNO generation (Pathway 1) was accompanied by ac ompeting potentially solvent-assisted [20] O À Nb ond cleavage to form CF 3 SO 2 NH 2 and aldehyde 10 [21] (Pathway 2).…”

Recent Advances in Substrate-Controlled Asymmetric Cyclization for Natural Product Synthesis

“…Cation-induced cyclization has been a powerful tool for controlling the stereochemistry of various ring structures in natural product synthesis. The total synthesis of (+)-siebolidine A ( 37 ), which is an alkaloid of club moss Lycopodium sieboldii [ 23 ], was firstly reported by Overman et al [ 24 , 25 ]. This landmark synthesis was accomplished with a pinacol-terminated cyclization cascade as depicted in Scheme 5 .…”

Eine Conia‐En‐artige Cyclisierung unter basischen Bedingungen ermöglicht die effiziente Synthese von (−)‐Lycoposerramin R

“…Hier fingen wir Overmans elegante Route zu Sieboldin Aa b, welche komplett unterschiedliche Prins-Pinakolchemie verwendet, um zum Hydrindan zu gelangen. [16] Mit unserer Route ist 48 in 8S chritten von kommerziellen Startmaterialien zugänglich, was einen signifikanten Fortschritt gegenüber den 16 Schritten der Originalroute darstellt.…”