Buchi Reddy Vaddula

A simple and facile Heck-type arylation of alkenes with diaryliodonium salts using magnetically recoverable Pd-catalyst

The Heck-type arylation of alkenes was achieved in aqueous polyethylene glycol using a magnetically recoverable heterogenized palladium catalyst employing diaryliodonium salts under ambient conditions. The benign reaction medium and the stability of the catalyst are the salient features of this simple and facile protocol.

One-pot synthesis and anticancer studies of 2-arylamino-5-aryl-1,3,4-thiadiazoles.

A series of 2-arylamino-5-aryl-1,3,4-thiadiazoles 1a-j were synthesized and screened for their anticancer activity against various human cancer cell lines. The novel one-pot synthesis of 1,3,4-thiadiazoles was achieved by refluxing aryl aldehydes, hydrazine hydrate, and aryl isothiocyanates in methanol followed by oxidative cyclization with ferric ammonium sulfate. The compounds 1g-j with trimethoxyphenyl at the C-5 position displayed extremely potent anticancer activity with at least twofold selectivity (IC(50): 4.3-9.2 μM). The nature of substituent on the C-2 arylamino ring may be critical in opting for the selectivity towards a particular cancer cell.

N-Allylation of amines with allyl acetates using chitosan-immobilized palladium

A simple procedure for N-allylation of amines with allyl acetates has been developed using a biodegradable and easily recyclable heterogeneous chitosan-supported palladium catalyst. The general methodology, applicable to a wide range of substrates, has sustainable features that include a ligand-free reaction with simple workup, recycling and reusability of the catalyst.

The copper–nicotinamide complex: sustainable applications in coupling and cycloaddition reactions

The crystalline copper(II)–nicotinamide complex, synthesized via simple mixing of copper chloride and nicotinamide solution at room temperature, catalyzes the C–S, C–N bond forming and cycloaddition reactions under a variety of sustainable reaction conditions.

An efficient and more sustainable one-step continuous-flow multicomponent synthesis approach to chromene derivatives

A simple and rapid one-step continuous-flow synthesis route has been developed for the preparation of chromene derivatives from the reaction of aromatic aldehydes, α-cyanomethylene compounds, and naphthols. In this contribution, a one-step continuous-flow protocol in a ThalesNano H-Cube Pro™ has been developed for the preparation of these chromene derivatives. This arises from the multicomponent one-step reaction of aromatic aldehydes, α-cyanomethylene compounds, and naphthols. This flow protocol was optimized in 2-methyltetrahydrofuran, which is a more environment-friendly solvent. The faster residence times (<2 min) coupled with elevated pressure (~25 bar) results in an efficient, safer, faster, and modular reaction. Results obtained illustrate that this base-catalyzed reaction affords the respective chromene derivative products in very high yields. The products can then be easily purified by recrystallization, if desired.

One-pot synthesis and in-vitro anticancer evaluation of 5-(2′-indolyl)thiazoles

A series of 5-(2′-indolyl)thiazoles were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of thioamides 3 with 3-tosyloxypentane-2,4-dione 4 led to in situ formation of 5-acetylthiazole 5 which upon treatment with arylhydrazines 6 in polyphosphoric acid resulted in the formation of 5-(2′-indolyl)thiazoles 2. Among the synthesized 5-(2′-indolyl)thiazoles, compounds 2d–f, and 2h exhibited encouraging anticancer activity and also selectivity towards particular cell lines (IC50 = 10–30 μM). Further studies on the SAR of compound 2e may result in good anticancer activity.

Multi-Component Reactions in Drug Discovery

This presentation will discuss approaches to enhance the rate of molecular probe discovery and close the growing knowledge gap between chemical and biological space created by recent advances in systems biology. As such, multi-component reactions are advocated as tools to build proprietary compound collections, founded on the central tenets of efficiency in medicinal chemistry: (1) the potential for increased “iterative speed” around the “hypothesis–synthesis–screening” loop and (2) reduced numbers of required iterations for expedited value chain progression. Front-loading collections, in this respect, have afforded several successful “bench-to-bedside” studies with no required intermediate “scaffold hopping.” Such examples may be viewed as the original “holy grail” of combinatorial chemistry, now enabled by the exponentially increasing MCR-derived “chemical diversity space” made accessible in recent years.