Enantioselective Synthesis and Antimicrobial Activities of Tetrahydro‐Β‐Carboline Diketopiperazines

Abstract

A series of single isomers tetrahydro-β-carboline diketopiperazines were stereoselectively synthesized starting from l-tryptophan methyl ester hydrochloride and six aldehydes through a four-step reaction including Pictet-Spengler reaction, crystallization-induced asymmetric transformations (CIAT), Schotten-Baumann reaction, and intramolecular ester amidation. The chemical structures were characterized by nuclear magnetic resonance (NMR) and elemental analysis, among which two compounds were determined by x-ray single crystal diffraction. Moreover, antimicrobial activities of all the compounds were also tested.

Synthesis, Antimicrobial Activity, Structure-Activity Relationship, and Molecular Docking Studies of Indole Diketopiperazine Alkaloids

“…The synthetic routes of indole DKPs 2a−2f , 3a−3d , 4a−4d , and 5a−5e are outlined in Scheme 2 and 3. General procedure for the synthesis of these compounds have been described in our previous research (Ma et al, 2013, 2014, 2017).…”

The Pictet-Spengler Reaction Updates Its Habits

“…Phenanthroindolizidines (50 [71,72]), phenanthroquinolizidines (51 [72]), tetrahydroprotoberberines (53 [67,68]), pyrroloisoquinolines (55 [69,70]), and diketopiperazine-fused THIQs (65 [73], vide infra) embody the tetrahydroisoquinoline skeleton, while indolizinoindoles (57 [74,75]), THBC-imidazolinediones (59 [76]), THBC-piperazinedione (61 [77,78]), the tetracyclic indole alkaloids (S)-harmicine (pyrrole-fused THBC, [66,79]), and (S)-eleagnine (1-methyl THBC, [66,80] represent the THBC-containing polyheterocycles. The additional ring can be already present in the imine substrate before the P-S reaction (type A) or can be built on the THIQ/THBC skeleton exploiting the functionality of some substituents (type B).…”

“…25, x FOR PEER REVIEW 61 of 8477). The optimized process afforded (S)-norcoclaurine (R = H; ee 93%) in 81% yield and allowed for the recycling of the enzyme[259].…”

The Chiral Pool in the Pictet–Spengler Reaction for the Synthesis of β-Carbolines

“…Finally, HR22C16, a mitotic kinesin Eg5 inhibitor, could be readily synthesized from the enantiomerically pure (1R,3S)-1,3-disubstituted tetrahydro-β-carboline [41]. This procedure was also efficiently applied to the synthesis of a series of tetrahydro-β-carboline diketopiperazines as single isomers starting from L-tryptophan methyl ester hydrochloride and six aldehydes [42]. Then, the reaction was extended to thirteen aldehydes, both aromatic and aliphatic, and high stereoselectivities and yields could be obtained, but the predominance of the cis-or trans-isomer was not predictable.…”