Natural product inspired design and synthesis of β-carboline and γ-lactone based molecular hybrids

Abstract

β-Carboline and γ-lactone moieties have been selected by nature as privileged scaffolds and display a wide range of pharmacological properties. Following nature, we envisaged the preparation of new β-carboline and γ-lactone based molecular hybrids incorporating both the pharmacophores. In this regard, a water-assisted In-mediated environmentally benign and easy to execute single-step tandem Barbier type allylation-lactonisation process has been devised in order to afford the targeted molecular architectures. It is anticipated that aqueous medium plays the key role in allylation as well as in the subsequent lactonisation process for the diastereo-selective synthesis of these conjugates. It is believed that water drives the reaction pathway through dual activation, it increases the electrophilic character of formyl and ester functionalities and simultaneously enhances the nucleophilic potential of the hydroxyl group to facilitate the in situ intramolecular condensation. Importantly, during this synthetic strategy no column chromatographic purification was required at any stage.

A Tandem Approach towards Diastereoselective Synthesis of Quinoline C‐3 Tethered γ‐Lactones

“…However, when the isolated homoallyl alcohol 2aF was treated with p ‐TSA in anhydrous toluene at 100 o C for 5 h, it afforded the desired lactone 3aF (51% yield) as revealed by the spectroscopic data. Interestingly, the NOESY spectrum of 3aF revealed the cis ‐stereochemistry across C‐4 and C‐5 which was different from our recent results . Nevertheless, the failure to develop a one‐pot tandem approach; we were directed to explore other metal catalysts.…”

“…To identify the optimum conditions for the synthesis of desired quinoline tethered butyrolactones, 2‐chloroquinoline‐3‐carbaldehyde ( 2a ) and allyl bromide F were identified as the model substrates for Barbier‐Type allylation. In a recent study, we developed an In‐mediated water assisted green methodology for the diastereoselective synthesis of β‐carboline containing butyrolactones with trans ‐stereochemistry . During this previous study, it was observed that water played crucial role during allylation as well as in situ cyclisation and no additive was required.…”

Iodine Catalysed Synthesis of Luminescent β‐Carboline Tethered Thiazolo[4,5‐c]carbazole and Naphtho[2,1‐d]thiazole Derivatives and Estimation of their Light Emitting Properties

“…The study initiated with the synthesis of β‐carboline alkaloid, Kumujian C ( 4 ) and its derivatives ( 5–9 ) which were realized via modification in the previous procedure as depicted in Scheme . The Pictet–Spengler reaction was performed between l ‐tryptophan ( 1 ) and 2,2‐dimethoxyacetaldehyde (60 % aq.…”

Indium‐Mediated Domino Allylation‐Lactonisation Approach: Diastereoselective Synthesis of β‐Carboline C‐3 Tethered α‐Methylene γ‐Butyrolactones

“…The reaction was observed to be sluggish in aqueous medium possibly due to the solubility problem resulting in the formation of only homoallyl alcohol 5bA in low yield (10%) even after 24 h (Table , entry 1). Our recent findings guided us to explore the advantage of semi‐aqueous medium (THF: H 2 O) for the synthesis of desired prototype, so we performed the reaction in THF: H 2 O (3:2, v/v) as the solvent at room temperature. Interestingly, starting substrate, 3‐formyl 9 H ‐β‐carboline 5b disappeared and the formation of homoallyl alcohol 5bA was observed which started in situ converting into a less polar product 6bA .…”

“…The excellent pharmacological potential of these two scaffolds (β‐carboline and γ‐lactone) motivated us to construct a new molecular hybrid containing these two pharmacophores for our anticancer project. In a recent study, we achieved the synthesis of β‐carboline C‐1 substituted γ‐lactones with trans stereochemistry (Scheme ) . The preliminary biological screening studies of these compounds provided us an impetus to expand the scope of library.…”