The asymmetric total synthesis of (−)-leuconoxine has been achieved. The desymmetrization of a prochiral diester using a chiral phosphoric acid catalyst produced a highly enantioenriched lactam with excellent yield. The ring construction featuring an intramolecular N-acyliminium cyclization and the one-step pyrrolidone formation using Bestmann’s ylide was successfully accomplished.

The cross-coupling of tryptamine with substituted aniline to access C3a–nitrogen-linked pyrroloindolines has been developed via the consecutive cyclization of tryptamine with DMSO/Tf2O and the substitution of 3a-pyrroloindolylthionium intermediate with aniline. The use of 2,3-dihydrotryptamine instead of aniline enabled easy access to 3a-(1-indolyl)pyrroloindoline and the concise synthesis of C3a–N1′-linked pyrroloindoline alkaloid (±)-psychotriasine was accomplished.

An efficient and versatile synthesis of 5-N-acetylardeemin (1a) and sixteen 2-, 3- and 13-substituted derivatives 1b–q was achieved through Ugi three-component reaction of 3,3a,8,8a-tetrahydropyrrolo[2,3-b]indole and cyclization/epimerization. Their inhibitory activity on the drug efflux of breast cancer resistance protein (ABCG2) was evaluated by flow cytometric analysis of accumulation of Hoechst 33342 stain in Flp-In-293/ABCG2 cells. Most of the derivatives exhibited a stronger ABCG2 inhibitory effect compared with natural product 1a. The derivative 1m with a 4-tolyl substituent at the C-13 position exhibited the most potent ABCG2 inhibition. This preliminary structure–activity relationship study indicates that an electron-rich aryl moiety as the 13-substituent is key to increasing the inhibitory activity.

We report a one-pot procedure for forming a dimeric pyrroloindoline framework with a thionium reagent. The cyclization of tryptamine with DMSO and Tf2O, followed by substitution with indole derivatives, produced racemic 3a-indolylpyrroloindolines. The method enables rapid access to heterodimeric pyrroloindolines as well as to homodimeric pyrroloindolines.

Aliphatic C–H functionalization at indole 2α-position mediated by acyloxythionium species 1 generated from sulfoxide and acid anhydride has been developed. The combination of sulfoxide and TFAA with O-, N- and C-nucleophiles enabled introduction of various substituents in a one-pot procedure. Especially on utilizing DMSO, the combination provided a practical and efficient method for the synthesis of a wide range of 2α-substituted indoles.

Phenserine is a potentially attractive drug for Alzheimer’s disease. In order to further expand SAR study for inhibitions of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), the methyl group at the 3a-position of phenserine was replaced with an alkyl or alkenyl group, and its phenylcarbamoyl moiety was substituted at the o- or p-position. The synthetic methodology for these phenserine analogues includes the efficient cascade reactions for introduction of the 3a-substituent and assembly of the quaternary carbon center followed by reductive cyclization to the key pyrroloindoline structure. The bulkiness of the substituent at 3a-position of phenserine derivatives tends to reduce the inhibitory effect on AChE activity in the following order: methyl > ethyl > vinyl > propyl ≈ allyl > reverse-prenyl groups. Among the series synthesized, the 3a-ethyl derivative demonstrated the highest AChE selectivity. In construct, the 3a-reverse-prenyl derivative indicated modest BuChE selectivity.

A combination of dimethyl sulfoxide (DMSO) and trifluoroacetic anhydride (TFAA) mediates functionalization at the 2α-position of indole derivatives. Carbon and heteroatom nucleophiles were directly introduced via a one-pot procedure in excellent yields.

An efficient approach to spirocyclic oxindole architecture with vicinal quaternary carbon centers is described. The reaction of 2-allyloxyindolin-3-ones with cyanomethylphosphonate at low reaction temperature proceeds smoothly with consecutive olefination, isomerization, deacylation, and anion-accelerated Claisen rearrangement to give the 3,3-disubstituted oxindoles with vicinal quaternary all-carbon centers in high yield and diastereoselectivity. The oxindoles are readily converted into more synthetically advanced spiro-products.

We describe the first total synthesis of the reported and revised structures of okaramine M (1 and 7) through the Ugi three-component reaction of pyrroloindole imine 10 with p-methoxyphenyl isonitrile and N-Boc-l-tryptophan, followed by cyclization and epimerization.

Covering: 2005. Previous review: Nat. Prod. Rep., 2005, 22, 761

The concise total synthesis of marine alkaloids, (−)-flustramines A and B, and (−)-flustramides A and B has been achieved through the domino olefination/isomerization/Claisen rearrangement (OIC) for highly enantioselective construction of the asymmetric quaternary carbon center and the chemoselective reduction–cyclization (RC) for pyrrolidine formation as key steps.

Covering: 2004

The cross-coupling of tryptamine with substituted aniline to access C3a–nitrogen-linked pyrroloindolines has been developed via the consecutive cyclization of tryptamine with DMSO/Tf2O and the substitution of 3a-pyrroloindolylthionium intermediate with aniline. The use of 2,3-dihydrotryptamine instead of aniline enabled easy access to 3a-(1-indolyl)pyrroloindoline and the concise synthesis of C3a–N1′-linked pyrroloindoline alkaloid (±)-psychotriasine was accomplished.

A combination of dimethyl sulfoxide (DMSO) and trifluoroacetic anhydride (TFAA) mediates functionalization at the 2α-position of indole derivatives. Carbon and heteroatom nucleophiles were directly introduced via a one-pot procedure in excellent yields.

Aliphatic C–H functionalization at indole 2α-position mediated by acyloxythionium species 1 generated from sulfoxide and acid anhydride has been developed. The combination of sulfoxide and TFAA with O-, N- and C-nucleophiles enabled introduction of various substituents in a one-pot procedure. Especially on utilizing DMSO, the combination provided a practical and efficient method for the synthesis of a wide range of 2α-substituted indoles.