CuBr₂-Catalyzed Mild Oxidation of 3,4-Dihydro-β-Carbolines and Application in Total Synthesis of 6-Hydroxymetatacarboline D

Abstract

A green chemical method for the conversion of 3,4-dihydro-β-carbolines to β-carbolines has been developed using air as the oxidant. With 15 mol % CuBr 2 as the catalyst, 3,4-dihydro-β-carbolines could be efficiently oxidized to β-carbolines in dimethyl sulfoxide at room temperature in the presence of 1,8-diazabicyclo[5,4,0]undec-7-ene (or Et 3 N). By applying this method, the first total synthesis of 6-hydroxymetatacarboline D was performed through 12 steps in 22% overall yield starting from l -5-hydroxy-tryptophan.

Total Synthesis of 6-Hydroxymetatacarboline-d Discovered from Mycena metata via the Pictet–Spengler Reaction Followed by the Horner–Wadsworth–Emmons Reaction

“…In Scheme 4, chain extension on the formyl group was achieved using the Horner−Wadsworth−Emmons (HWE) reaction with tert-butyl 2-(diethoxyphosphoryl)acetate (19) and NaH to obtain the desired product (20) with 85−90% yields. Further, the selective hydrolysis of tert-butyl ester was done using TFA in DCM to obtain the desired acid (21), which was coupled with tert-butyl L-prolinate (22) using HATU to get the desired amide product (23) in 66% yield.…”

“…The total synthesis of 6-hydroxymetatacarboline- d has been reported previously via a different approach. 23 In the present research work, we wish to report the novel route for the synthesis of 6-hydroxymetatacarboline- d via the Pictet–Spengler and Horner–Wadsworth–Emmons (HWE) reactions.…”

“…In 2013 Robert J. R. Jaeger et al isolated an alkaloid, 6-hydroxymetatacarboline- d , from the fruiting bodies of Mycena metata and assigned its structure, on the basis of various range of spectroscopic studies. The total synthesis of 6-hydroxymetatacarboline- d has been reported previously via a different approach . In the present research work, we wish to report the novel route for the synthesis of 6-hydroxymetatacarboline- d via the Pictet–Spengler and Horner–Wadsworth–Emmons (HWE) reactions.…”

Recent Advances in the Synthesis of β-Carboline Alkaloids

“…First, the coupling of 177b with various amino acid esters was performed, then a formyl moiety was formed via acidic treatment of the acetal, followed by the same three steps described previously to form the other four metatacarbolines (32)(33)(34)(35). The first total synthesis of 6-hydroxymetatacarboline D (36) has been developed in 12 steps by Meng et al via CuBr2-catalyzed mild oxidation method by the dehydrogenation of the DHβC's C-ring (Scheme 17) [129]. The synthesis starts from 5-hydroxytryptophan (179), which was converted into Boc-and benzyl-protected compound 182 by applying protecting group chemistry.…”

“…The first total synthesis of 6-hydroxymetatacarboline D ( 36 ) has been developed in 12 steps by Meng et al via CuBr 2 -catalyzed mild oxidation method by the dehydrogenation of the DHβC’s C-ring ( Scheme 17 ) [ 129 ]. The synthesis starts from 5-hydroxytryptophan ( 179 ), which was converted into Boc- and benzyl-protected compound 182 by applying protecting group chemistry.…”