Concise Total Synthesis of (−)‐Affinisine Oxindole, (+)‐Isoalstonisine, (+)‐Alstofoline, (−)‐Macrogentine, (+)‐N_a‐Demethylalstonisine, (−)‐Alstonoxine A, and (+)‐Alstonisine

Abstract

A highly enantio- and diastereoselective strategy to access any member of the sarpagine/macroline family of oxindole alkaloids via internal asymmetric induction was developed from readily available D-(+)-tryptophan. At the center of this approach was the diastereospecific generation of the spiro[pyrrolidine-3,3’-oxindole] moiety at an early stage via a tert-butyl hypochlorite-promoted oxidative rearrangement of a chiral tetrahydro-β-carboline derivative. This key branching point determined the spatial configuration at the C-7 spiro center to be entirely 7R or 7S. Other key stereospecific processes were the asymmetric Pictet-Spengler reaction and Dieckmann cyclization, which were scalable to the 600 gram and 150 gram levels, respectively. Execution of this approach resulted in first enantiospecific total synthesis of (+)-isoalstonisine and (−)-macrogentine from the chitosenine series (7R), as well as (+)-alstonisine, (+)-alstofoline, (−)-alstonoxine A and (+)-Na-demethylalstonisine from the alstonisine series (7S).

Completion of the Total Synthesis of Several Bioactive Sarpagine/Macroline Alkaloids including the Important NF-κB Inhibitor N4-Methyltalpinine

“…In addition, one looked for inspiration from similar transformations in related systems. Inspired by the methods in the total synthesis of the oxindole alkaloid isoalstonisine by Fonseca [ 31 ], fortunately, the chloroformate was successfully used to N -dealkylate the N b -methyl group in a congested system at the final stage of the synthesis. It was then decided to employ the well-known N -dealkylation process developed by Olofson et al [ 32 ].…”

Short, Scalable Access to Pyrrovobasine

“…The resulting compound was then reacted with α-ketoglutaric acid 11 to afford the cyclized compound 12 in 49% yield (2 steps) (trans/cis = 2:1). − The isomers were separated by chromatography at this stage, and the route continued with the trans isomer 12 . This trans/cis ratio resembles the trans/cis ratio occurring in the general Pictet–Spengler reaction with tryptophan derivatives. , Compound 12 was successfully used for the synthesis of tetracyclic compound 13 in 88% yield (40 g) via Dieckmann condensation, which proved to be very useful in the synthesis of 1,3-dicarbonyl compounds. ,− Subsequent decarboxylation of 13 followed by Boc protection led to the synthesis of 6 .…”

A Platform for the Synthesis of Corynantheine-Type Corynanthe Alkaloids

“…In this context, intermediate 9 was initially subjected to oxidative rearrangement conditions (Scheme ). While the oxidative rearrangement reaction of indoles is relatively well studied, ,− our attempts to forge spirooxindole 17 from tertiary amine 9 proved inefficient, generating mainly undesired 18 in low yields (see the Supporting Information for details, Scheme A). Thus, we revised our original plan to establish the spirooxindole moiety at the stage of lactam 8 .…”