SYNTHESIS OF 4-ARYL SUBSTITUTED CANTHIN-6-ONE WITH β-CARBOLINE SKELETON VIA PICTET-SPENGLER CONDENSATION AND CYCLIZATION REACTION; [Sintesis 4-Aril Gantian Kantin-6-One dengan Rangka β-Karbolina Melalui Kondensasi Pictet-Spengler dan Tindak Balas Kitaran]

• Published in: Malaysian Journal of Analytical Sciences
• Main Author: Pungot N.H.; Tarmizi N.H.M.; Zulkifli S.Z.
• Format: Article
• Language: English
• Published: Malaysian Society of Analytical Sciences 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185117089&partnerID=40&md5=5af312fd4f1a0b0583edec5c7f27a26f

This study presents a comprehensive synthesis of 4-aryl substituted canthin-6-one through a versatile Pictet-Spengler condensation and subsequent cyclization, involving the formation of 1-aroyl substituted β-carbolines as pivotal intermediates. β-Carbolines, as indole alkaloids, serve as fundamental building blocks with diverse biological activities. In particular, canthin-6-one and its derivatives exhibit a wide range of promising biological properties, which include anti-cancer, antibacterial, anti-inflammatory, and cytotoxic effects, thus making them valuable in pharmaceutical and medicinal chemistry applications. The method outlined herein involves the utilization of readily available starting materials in a direct reaction sequence, resulting in an efficient and moderate-yield access to 4-aryl substituted canthin-6-one. Synthesizing canthine was initiated by forming the intermediates, 1-aroyl substituted β-carbolines via Pictet-Spengler condensation of different substituted aromatic glyoxals with 5-hydroxy tryptophan in the presence of trifluoroacetic acid. This synthesis route avoids the formation of tetrahydro-β-carbolines. Subsequently, the series of 1-aroyl substituted β-carboline intermediates were cyclized to yield the desired 4-aryl substituted canthin-6-one derivatives. The reaction mechanism and key intermediates are discussed, providing insights into the synthesis pathway. The structure of the synthesized compounds were confirmed by using Infrared Radiation (IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. This research not only contributes to the understanding of synthetic methodologies but also paves the way for the development of novel compounds with promising pharmaceutical properties. © 2023, Malaysian Society of Analytical Sciences. All rights reserved.