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Diversity Oriented Synthesis 2016

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Molecular Diversity".

Deadline for manuscript submissions: closed (30 July 2016) | Viewed by 25193

Special Issue Editor

Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
Interests: drug discovery; organic synthesis; medicinal chemistry; molecular imaging; diversity-oriented synthesis; peptidomimetics; chemoinformatics; enzyme inhibitors; angiogenesis; Alzheimer’s disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since its introduction, Diversity-Oriented Synthesis (DOS) has become a new paradigm for developing large collections of structurally diverse small molecules as probes to investigate biological pathways, and to provide a larger array of the chemical space in drug discovery and chemical biology issues. This strategy combines the generation of a functionalized precursor with further synthetic elaborations, in order to generate the maximum diversity and complexity from simple starting material, thus achieving molecules that differ not only for the appendages, as in traditional combinatorial chemistry, but, also, in the stereochemistry and molecular skeleton. Several DOS approaches have been proposed thus far, as divergent pathways consisting of a complexity-generating reaction followed by cyclization steps and appendage diversity, or as synthetic schemes for generating different cyclic structures through the build/couple/pair approach.

The possibility of creating new highly-diverse and complex molecular platforms, and the achievement of hundreds to thousands to millions of compounds is producing significant advances in chemical biology and drug discovery. This is mainly due to the improvement of the quality of chemical libraries, which are more stereochemically rich and structurally complex. DOS molecular collections are being applied in high-throughput screening, phenotypic assays and chemical genetics studies, leading to the discovery of both new targets and new lead compounds.

To date, many research contributions regarding diversity-oriented synthesis, covering the organic and medicinal chemistry fields, have appeared in the literature. Nevertheless, this research area is quite vibrant and many research groups are active in this field.

We invite the submission of research articles or review papers on advances in diversity-oriented synthesis through the elaboration of novel molecular scaffolds, and innovative divergent synthetic pathways. Papers related to new technologies enabling library development or to chemoinformatic characterization of DOS collections are also welcome.

Prof. Dr. Andrea Trabocchi
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Small molecules
  • Building blocks
  • Molecular diversity
  • Combinatorial chemistry
  • Drug discovery
  • Chemical biology
  • High-throughput screening

Published Papers (4 papers)

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Research

7033 KiB  
Article
Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library
by Elena Lenci, Riccardo Innocenti, Alessio Biagioni, Gloria Menchi, Francesca Bianchini and Andrea Trabocchi
Molecules 2016, 21(10), 1405; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules21101405 - 20 Oct 2016
Cited by 2 | Viewed by 4835
Abstract
The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated [...] Read more.
The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism. Full article
(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)
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5121 KiB  
Article
Combinatorial Synthesis of Structurally Diverse Triazole-Bridged Flavonoid Dimers and Trimers
by Tze Han Sum, Tze Jing Sum, Warren R. J. D. Galloway, Súil Collins, David G. Twigg, Florian Hollfelder and David R. Spring
Molecules 2016, 21(9), 1230; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules21091230 - 16 Sep 2016
Cited by 15 | Viewed by 9420
Abstract
Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a [...] Read more.
Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability) and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated. Full article
(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)
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861 KiB  
Article
Passerini Reactions on Biocatalytically Derived Chiral Azetidines
by Lisa Moni, Luca Banfi, Andrea Basso, Andrea Bozzano, Martina Spallarossa, Ludger Wessjohann and Renata Riva
Molecules 2016, 21(9), 1153; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules21091153 - 30 Aug 2016
Cited by 15 | Viewed by 5147
Abstract
The purpose of this study was to explore a series of Passerini reactions on a biocatalytically derived enantiopure azetidine-2-carboxyaldehyde in order to obtain, in a diastereoselective manner, polyfunctionalised derivatives having the potential to be cyclized to chiral bridged bicyclic nitrogen heterocycles. While diastereoselectivity [...] Read more.
The purpose of this study was to explore a series of Passerini reactions on a biocatalytically derived enantiopure azetidine-2-carboxyaldehyde in order to obtain, in a diastereoselective manner, polyfunctionalised derivatives having the potential to be cyclized to chiral bridged bicyclic nitrogen heterocycles. While diastereoselectivity was poor under classical Passerini conditions, a significant increase of diastereoselectivity (up to 76:24) was gained by the use of zinc bromide as promoter. The methodology has a broad scope and yields are always good. Full article
(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)
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2432 KiB  
Article
Enantiopure Trisubstituted Tetrahydrofurans with Appendage Diversity: Vinyl Sulfone- and Vinyl Sulfoxide-Modified Furans Derived from Carbohydrates as Synthons for Diversity Oriented Synthesis
by Debanjana Dey and Tanmaya Pathak
Molecules 2016, 21(6), 690; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules21060690 - 26 May 2016
Cited by 4 | Viewed by 5270
Abstract
Enantiomerically pure 2-substituted-2,5-dihydro-3-(aryl) sulfonyl/sulfinyl furans have been prepared from the easily accessible carbohydrate derivatives. The orientation of the substituents attached at the C-2 position of furans is sufficient to control the diastereoselectivity of the addition of various nucleophiles to the vinyl sulfone/sulfoxide-modified tetrahydrofurans, [...] Read more.
Enantiomerically pure 2-substituted-2,5-dihydro-3-(aryl) sulfonyl/sulfinyl furans have been prepared from the easily accessible carbohydrate derivatives. The orientation of the substituents attached at the C-2 position of furans is sufficient to control the diastereoselectivity of the addition of various nucleophiles to the vinyl sulfone/sulfoxide-modified tetrahydrofurans, irrespective of the size of the group. The orientation of the substituents at the C-2 center also suppresses the influence of sulfoxides on the diastereoselectivity of the addition of various nucleophiles. The strategy leads to the creation of appendage diversity, affording a plethora of enantiomerically pure trisubstituted furanics for the first time. Full article
(This article belongs to the Special Issue Diversity Oriented Synthesis 2016)
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