Intramolecular macrolactonization, photophysical and biological studies of new class of polycyclic pyrrole derivatives

Abstract

Herein, we report an efficient synthesis of N-substituted pyrrole derivatives and their application to construct macrocyclic oxazocinone via a two-component coupling reaction followed by base mediated intramolecular cyclization. This methodology provides an easy two-step approach to constitute a library of fused pyrrolo-oxazocinone derivatives in good yields under mild reaction conditions. The present methodology offers an easy access to the synthesis of a library of fluorescent pyrole derivatives. Among them, tert-butyl 2-(2-(3-hydroxypropyl)-7-methoxy-4,5-dihydro-2H-benzo[e]isoindol-1-yl)acetate has been employed in bio-analytical imaging which shows efficient cellular internalization along with no obvious cellular toxicity.

NaN3/NH4Cl‐Promoted Aza‐Cyclization: A Convenient Route for Bio‐Active Diverse Isoindolinone Derivatives

“…To be a useful bio‐annalytical fluorophore, the fluorophore needs to be non‐toxic in nature. Therefore, firstly, we performed in vitro cellular cytotoxicity studies with compound 2 e in CHO ( Chinese hamster ovary) cell lines . The cytotoxicity in vitro was measured using the MTT assay on the CHO cell line.…”

Palladium-Catalyzed Intramolecular Cyclization: Access to Rare PentacyclicN-Fused Heterocycles

“…Treatment of compound 1 with 2‐bromo benzylamine hydrochloride in dry Et 3 N at room temperature was the optimum condition for intramolecular aza‐cyclization to provide N ‐benzyl pyrroles 2 in good yields as shown in Table . It was noted that the early developing procedure as hydroxyl amine hydrochloride did not give any fruitful result . A series of structurally diversified bicyclic/tricyclic pyrrole derivatives ( 2 a‐2 m) were prepared utilizing the conditions as shown in Table .…”

“…Another heteroarylation scaffold obtained from 1 via two steps. The pyrrole ring was constructed using previously developed procedure . Then, the N ‐hydroxy pyrroles 3 was converted to N ‐benzyloxy pyrrole precursors 4 in the presence of 2‐bromo benzylbromide and K 2 CO 3 in 1,4 dioxane at 80 °C.…”

“…Among them, pyrazolone and pyrrolo‐oxazocione are the similar scaffolds where pyrrole ring is fused at 3,4 postion . After the successful synthetic and biological study on the aza/oxa cyclisation product, using ester functionality of pyrrole derivatives, we wish to construct a rare pentacyclic N ‐fused rings using hetroarylation process via the metal activation of pyrrole C−H bond (Scheme ).…”

Concise strategy for diastereoselective annulation to afford fused [5:7] oxazepanone γ-lactams

“…Eventually, with compounds 6 in hand, the intramolecular annulations to the corresponding title compounds were attempted using different methods either under basic or acidic conditions. 34,35 By utilizing potassium tert-butoxide as the base in THF at 0°C, compounds 6 successfully gave the anticipated [5:7] oxazepanone γ-lactams (8) in 70-83% yields (Scheme 3). Earlier attempts at the lactonization of 6 with the aid of acid catalyst, ρ-toluenesulfonic acid in tetrahydrofuran or 1,4-dioxane, only led to the recovery of the starting material.…”