Exploring the diastereoselectivity for Fischer indolization of L-menthone under different conditions, spectral characterization, and biological activities of new (2R,4aS)-2,3,4,4a-tetrahydro-1H-carbazole analogs

Abstract

Tetrahydrocarbazoles are important class of heterocycles that exhibit numerous biological properties. They are also found in several natural products. In the present study, Fischer indolization of L-menthone was investigated for diastereoselectivity using different reaction conditions. No appreciable diastereoselectivity was observed for the acids used except CuBr and boric acid at varying temperatures, where satisfactory results were obtained. In addition, a small library of new (2R,4aS)-2,3,4,4a-tetrahydro-1H-carbazole analogs was reported and structurally characterized using spectroscopic techniques herein. Additionally, the compounds were evaluated against different biological activities, such as carbonic anhydrase inhibitory, immunomodulatory, and anticancer activities and did not show any activity. As the synthesized library was found safe when tested against cytotoxicity in normal cell line, it will be explored for other biological activities in near future to identify its biological outcome.

Engaging Diastereomeric syn‐ and anti‐6‐Bromo‐4a‐isopropyl‐2‐methyl‐2,3,4,4a‐tetrahydro‐1H‐carbazoles in Suzuki Coupling Reaction: Synthesis, Spectral Characterization and DFT Studies

“…On the other hand, the structural attribute of anti-2,3,4,4a-tetrahydro-1H-carbazole (compound 4)was not resolved, however, the contrast spectral data were obtained for the reported antianalogues. [22,33] The contrast in the configuration and conformation was observed to affect their reactivity as reported in the current study since the product formation from these two compounds was found to have different kinetics. The evaluation of the configuration and conformation of these tetrahydrocarbazole compounds 3 and 4 was expected to be helpful to figure out the fundamental reason for the contrasting reaction rate of coupling viathe Suzuki-Miyauramethod.…”

“…It is pertinent to mention here that configuration of the syn ‐2,3,4,4a‐tetrahydro‐1 H ‐carbazole(compound 3 ) was elucidated based on NMR and X‐ray crystallography, which suggested that the cyclohexane ring in the compound had a chair conformation with methyl substitutent occuping an equatorial position and iso propyl group has axial disposition, hence methyl and iso propyl groups are “syn” to each other. On the other hand, the structural attribute of anti ‐2,3,4,4a‐tetrahydro‐1 H ‐carbazole (compound 4 )was not resolved, however, the contrast spectral data were obtained for the reported anti ‐analogues [22,33] . The contrast in the configuration and conformation was observed to affect their reactivity as reported in the current study since the product formation from these two compounds was found to have different kinetics.…”

“…Two sets of diastereomeric Suzuki‐coupled products were synthesized, starting from the previously reported (2 R ,4a R )‐ and (2 R ,4a S )‐6‐bromo‐4a‐ iso propyl‐2‐methyl‐2,3,4,4a‐tetrahydro‐1 H ‐carbazoles (having syn ‐ and anti ‐indolenine skeleton) ( 3 and 4 ), respectively. syn ‐ And anti ‐compounds ( 3 and 4 ) were prepared according to our previous report [22,33] in which acetic acid (AcOH)‐catalyzed Fischer indolization reaction was carried out between L‐menthone ( 1 ) and 4‐bromophenylhydrazine hydrochloride ( 2 ) (Scheme 1). The reaction was completed in half an hour at 110 °C.…”

“…[34,35] Highly remarkable was the protocol adapted by Williamson and Martin et al [36] integrated anisotropic NMR parameters with computational advances to elucidate the structure of intricate natural products. Thus, in continuation to our interest in tetrahydrocarbazole compounds, we herein report new Suzuki-coupled products via expanding an aryl ring on our previously reported compounds 3 and 4as syn-and anti-2,3,4,4a-tetrahydro-1H-carbazoles, respectively, [22,33] and inferred their conformation via spectral elucidation and DFT studies. The current study is an important addition to literature highlighting non-chair conformations as their stable form in solid state.…”