<p>Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.</p>

Shiv Nadar University

The application of small molecules to modulate proteins by direct interactions has evolved as a powerful tool for the study of complex biological systems. Conventional genetic approaches have examined biological systems by generating random mutations which were then screened in search of a precise cellular phenotype. Analogous to the genetic approach, large random collections of small molecules can be used to elucidate the roles of specific proteins in many biological pathways. The crux of this 'chemical genetic' approach is the design and synthesis of libraries of compounds which span large tracts of biologically relevant chemical space. Diversity-oriented asymmetric synthesis (DOAS) is an exceptional methodology for preparing structurally and stereochemically diverse small molecule libraries which show a greater variety not only in their physiochemical properties but also in their biological activities. Herein, we describe some of the most effective strategies that have been used in asymmetric diversity-oriented synthesis library design and preparation. 1 Introduction 2 Philosophy of DOAS 3 Stoichiometric Reactions 3.1 DOAS with Chiral Auxiliaries 3.2 DOAS with Chiral Templates 3.3 DOAS with Chiral 'Linchpins' 3.4 DOAS from Natural Products via a Ring-Distortion Strategy 3.5 DOAS via Chiral Reactions 4 DOAS towards Peptidomimetics 5 Catalytic Reactions 6 Conclusion. © Georg Thieme Verlag Stuttgart. New York.

Chemistry

(SoNS) School of Natural Sciences

Synthesis (Germany)

Diversity-oriented asymmetric synthesis

World University root node

Chemistry - An Asian Journal

Erratum: Synthesis of privileged scaffolds by using diversity-oriented synthesis (Chemistry - An Asian Journal (2013) 8 DOI: 10.1002/asia.201201203)

The intramolecular Dötz benzannulation with alkyne-tethered aryloxy Fischer carbenes has been applied to synthesize a nine membered diaryl ether linked macrocyclic library. Insilico tools, that is, shape space analysis was used to assess the diversity of the library, and polar surface area (PSA) of the compounds were deduced to understand the range of their surface electrostatic potential. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asian Journal of Organic Chemistry

Diversity Oriented Synthesis of Macrocyclic Diaryl Ethers by Dötz Benzannulation

In the present study, we have demonstrated the diversity oriented synthesis of nitrogen heterocycles viz. chiral piperidinones, quinolizidinones and diaryl pyrrolidinones from Michael adducts generated via a TiCl4-catalyzed highly stereoselective Michael reaction with nitrostyrenes and an Evans chiral auxiliary. We also reported a Cu-4,4'-(isopropyl)-substituted isopropylidene-bridged 2,2'-bis-1,3'-oxazoline catalyst mediated catalytic asymmetric version of this reaction. In silico analysis is utilized to evaluate the diversity of the set of compounds against shape space (PMI), polar surface area (PSA) calculations and relevant drug like properties (viz. HBA, HBD, PSA, mol. wt., log P and log D). Finally, the molecules were screened against microorganisms to assess their antimicrobial properties. © 2013 The Royal Society of Chemistry.

Fulltext

RSC Advances

A reagent based DOS strategy via Evans chiral auxiliary: Highly stereoselective Michael reaction towards optically active quinolizidinones, piperidinones and pyrrolidinones

An elegant reagent-controlled strategy has been developed for the generation of a diverse range of biologically active scaffolds from a chiral bicyclic lactam. Reduction of the chiral lactam with LAH or alkylation with LHMDS to trigger different cyclization reactions have been shown to generate privileged scaffolds, such as pyrrolidines, indolines, and cyclotryptamines. Their amenability to substitution allows us to create various compound libraries by using these scaffolds. In silico studies were used to estimate the drug-like properties of these compounds. Selected compounds were subjected to anticancer screening by using three different cell lines. In addition, all these compounds were subjected to antibacterial screening to gauge the spectrum of biological activity that was conferred by our DOS methodology. Gratifyingly, with no additional iterative cycles, our method directly generated anticancer compounds with potency at low nanomolar concentrations, as represented by spiroindoline 14. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of privileged scaffolds by using diversity-oriented synthesis

Herein, we report a diversity-oriented-synthesis (DOS) approach for the synthesis of biologically relevant molecular scaffolds. Our methodology enables the facile synthesis of fused N-heterocycles, spirooxoindolones, tetrahydroquinolines, and fused N-heterocycles. The two-step sequence starts with a chiral-bicyclic-lactam-directed enolate-addition/substitution step. This step is followed by a ring-closure onto the built-in scaffold electrophile, thereby leading to stereoselective carbocycle- and spirocycle-formation. We used in silico tools to calibrate our compounds with respect to chemical diversity and selected drug-like properties. We evaluated the biological significance of our scaffolds by screening them in two cancer cell-lines. In summary, our DOS methodology affords new, diverse scaffolds, thereby resulting in compounds that may have significance in medicinal chemistry. Uno, DOS, tres: An enolate-mediated strategy was used to synthesize biologically relevant cyclic scaffolds. In silico analysis was used to evaluate the compounds in terms of, for example, polar surface area and chemical diversity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reagent-based DOS: Developing a diastereoselective methodology to access spirocyclic- and fused heterocyclic ring systems

A highly efficient enantioselective SNAr reaction of chiral acyl bicyclic lactam with substituted-2,4-dinitrobenzenes was developed, affording products containing quarternary stereogenic centers. They are further utilized towards an enantioselective synthesis of spirooxoindoles. © 2011 The Royal Society of Chemistry.

Organic and Biomolecular Chemistry

Enantioselective synthesis of spirooxoindoles via chiral auxiliary (bicyclic lactam) controlled SNAr reactions

We report a facile diversity oriented synthesis of α- and β-amino acids, by utilizing the pluripotent α-methylene group in a chiral bicyclic lactam as our key point of transformation. © 2011 Elsevier Ltd. All rights reserved.

Tetrahedron Letters

Diversity-oriented synthesis of amino acids using chiral enolates

Journal of Organic Chemistry

<p>Blue Light-Emitting Diode-Mediated In Situ Generation of Pyridinium and Isoquinolinium Ylides from Aryl Diazoesters: Their Application in the Synthesis of Diverse Dihydroindolizine</p>