Total syntheses of mitragynine, paynantheine and speciogynine via an enantioselective thiourea-catalysed Pictet–Spengler reaction

Abstract

The pharmacologically interesting indole alkaloids (-)-mitragynine, (+)-paynantheine and (+)-speciogynine were synthesised in nine steps from 4-methoxytryptamine by a route featuring (i) an enantioselective thiourea-catalysed Pictet-Spengler reaction, providing the tetrahydro-β-carboline ring and (ii) a Pd-catalysed Tsuji-Trost allylic alkylation, closing the D-ring.

Psychopharmacological Indole Alkaloids from Terrestrial Plants

“…The most recent synthesis was reported by Kerschgens et al, which involved nine steps using an enantioselective Pictet-Spengler reaction catalyzed by chiral thiourea with 4-methoxytryptamine as a starter (Kerschgens et al 2012).…”

Facile Efficient Synthesis of New Alkoxymethylphosphonium Tetrafluoroborates; Valuable Alternative to Their Halide Analogues

“…They can use as soluble supports [7], ionic liquids [8][9][10], ligands [11][12][13], counterions [14,15] and deep eutectic solvents (DES) [16][17][18][19]. Among functionalized phosphonium salts, α-alkoxyphosphonium salts illustrate many applications, though methods for their synthesis have certain limitations [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Alkoxymethyltriphenylphosphonium tetrafluoroborates are less studied and only few methodologies have been reported such as the reaction of triphenylphosphine with α-alkoxy ethers in the presence of fluoroboric acid or tertafluoroboric acid [35,36].…”

“…Optimization of reaction conditions for synthesis of α-butoxymethyl triphenylphosphonium tetrafluoroborates (2a)Table 2). Alkoxymethylphosphonium tetrafluoroborates synthesized in current studies can be valuable alternative to their halide analogues, which have certain limitations of tedious methodology, long reaction time and toxic intermediate as well as side products[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]41]. Moreover, these salts are relatively more stable due to presence of nonnucleophilic tetrafluoroborate ( − BF 4 ) counterion.…”

The Pictet-Spengler Reaction Updates Its Habits

“…25, x FOR PEER REVIEW 20 of Asymmetric total synthesis of (−)-saframycin A by two P-S ring closures. The key intermediate 81, containing the THBC ring of mitragynine, paynantheine, and speciogynine (Scheme 22), was constructed via an enantioselective thiourea-catalyzed P-S cyclization involving the tryptamine derivative 79 and the aldehyde 80[89]. Enantioselective thiourea-catalyzed P-S reaction in the route to corynantheidine alkaloids.…”