Multistep Microwave-Assisted Divergent Synthesis of Indolo-Fused Pyrazino-/Diazepinoquinoxalinones on PEG Support

Lai, Jiun-I; Salunke, Deepak B.; Sun, Chung‐Ming

doi:10.1021/ol100436r

Cited by 40 publications

(16 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: New Compound Collectionsmentioning

confidence: 99%

“…Th e known universe of organic chemistry is generally dominated by a remarkably small number of molecular scaff olds; for example, in a recent study of known cyclic molecules, 0.25 % of the molecular frameworks were found in 50 % of known compounds 9,42 . Th is scenario demonstrates a clear need for novel molecular scaff olds to explore and exploit uncharted regions of chemical space 43 .In this context, a less-focused approach is required. Th e use of non-biased, diversity-driven synthetic approaches, which aim to access a wider range of chemical space by virtue of increased library structural diversity, may thus be more useful 10 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Diversity-oriented synthesis as a tool for the discovery of novel biologically active small molecules

2010

View full text Add to dashboard Cite

Biologically active molecules can be identifi ed through the screening of small-molecule libraries. Defi ciencies in current compound collections are evidenced by the continuing decline in drugdiscovery successes. Typically, such collections are comprised of large numbers of structurally similar compounds. A general consensus has emerged that library size is not everything; library diversity, in terms of molecular structure and thus function, is crucial. Diversity-oriented synthesis (DOS) aims to generate such structural diversity in an effi cient manner. Recent years have witnessed signifi cant achievements in the fi eld, which help to validate the usefulness of DOS as a tool for the discovery of novel, biologically interesting small molecules.S mall molecular mass chemical entities (so-called small molecules) have always been of interest in chemistry and biology because of their ability to exert powerful eff ects on the functions of macromolecules that comprise living systems 1 -3 . Indeed, the small-molecule modulation of protein function represents the basis for both medicinal chemistry (wherein molecules are sought to chemically modify disease states) and chemical genetics (wherein molecules are used as ' probes ' to study biological systems 3 -8 . Such chemical modulators are most commonly identifi ed by screening collections or ' libraries ' of small molecules. However, a crucial consideration is what compounds to use 3,9,10 . A general consensus has emerged that library size is not everything; library diversity, in terms of molecular structure and more importantly function, is a crucial consideration. Th e effi cient creation of functionally diverse small-molecule collections presents a formidable challenge.Traditionally, when a specifi c biological molecule or family of molecules is targeted, the compounds used in the screening process are usually selected or designed on the basis of knowledge of the target structure or the structure of known natural ligands 3,9,11 . Th e selection criteria are dramatically complicated if the subsequent screening is ' unbiased ' ; that is, when the precise nature of the biological target is unknown (for example, in a random drug-discovery screen) 4,3,12 . In such situations, the structural features required in the small molecules cannot be defi ned a priori and it can be argued that the screening of a library of compounds that has been designed to interact with one specifi c biological target (or family of related targets) is not logical, whereas the random screening of many such ' focused ' collections can be extremely time and cost demanding.In general, the identifi cation of biologically active small molecules may be aided by screening functionally diverse compound libraries (that is, libraries that display a broad range of biological activities), as it has been argued that a greater sample of the bioactive chemical universe (that is, of all bioactive molecules) increases the chance of identifying a compound with the desired properties 3,10,13,14 . As a corollary, ...

show abstract

Section: New Compound Collectionsmentioning

confidence: 99%

mentioning

confidence: 99%

Diversity-oriented synthesis as a tool for the discovery of novel biologically active small molecules

2010

View full text Add to dashboard Cite

show abstract

“…MW-assisted reduction of arylnitro derivatives yielded the corresponding anilines that were submitted "in situ" to a Pictet-Spengler-type condensation with different ketones furnishing these novel heterocycle scaffolds [66]. The use of Pd/C with formates under MWs also led to the double bond reduction of an intermediate for the synthesis of enantiopure 7-substituted azepane-2-carboxylic acids [60].…”

Section: Scheme 18mentioning

confidence: 99%

“…MW-assisted reduction of arylnitro derivatives yielded the corresponding anilines that were submitted "in situ" to a Pictet-Spengler-type condensation with different ketones furnishing these novel heterocycle scaffolds [66]. The reaction was performed under Pd/C catalysis in polyethylene glycol-200 (PEG-200) under MWs using ammonium formate or alkyl/arylammonium formates, as a joint source of reductant and nitrogen nucleophile for the ring closure (Scheme 19) [61].…”

Section: Scheme 18mentioning

confidence: 99%

“…A Pd/C-catalyzed nitro reduction with ammonium formate was also applied to the synthesis of amino acids and indoline-substituted dinitrobenzenes supported on a soluble polymer (PEG6000) via a reductive double-ring closure, to yield the structurally diverse indolo fused pyrazino-/diazepino-quinoxalinones (72 in Scheme 21). MW-assisted reduction of arylnitro derivatives yielded the corresponding anilines that were submitted "in situ" to a Pictet-Spengler-type condensation with different ketones furnishing these novel heterocycle scaffolds [66]. This reaction was also applied to the combinatorial synthesis of a library of benzimidazolealkyloxypyrrolo[1,2-a]quinoxalinones [67].…”

Section: Scheme 20 Pd/c Hydrogen Transfer Reduction Of Nitro Derivatmentioning

confidence: 99%

See 1 more Smart Citation

Pd/C Catalysis under Microwave Dielectric Heating

2017

View full text Add to dashboard Cite

Microwave-assisted organic synthesis (MAOS) provides a novel and efficient means of achieving heat organic reactions. Nevertheless, the potential arcing phenomena via microwave (MW) interaction with solid metal catalysts has limited its use by organic chemists. As arcing phenomena are now better understood, new applications of Pd/C-catalyzed reactions under MW dielectric heating are now possible. In this review, the state of the art, benefits, and challenges of coupling MW heating with heterogeneous Pd/C catalysis are discussed to inform organic chemists about their use with one of the most popular heterogeneous catalysts.

show abstract

Solid‐Supported Synthesis

Yellol

Sun

2012

Green Techniques for Organic Synthesis and Medicinal Chemistry

View full text Add to dashboard Cite

Multistep Microwave-Assisted Divergent Synthesis of Indolo-Fused Pyrazino-/Diazepinoquinoxalinones on PEG Support

Cited by 40 publications

References 23 publications

Diversity-oriented synthesis as a tool for the discovery of novel biologically active small molecules

Diversity-oriented synthesis as a tool for the discovery of novel biologically active small molecules

Pd/C Catalysis under Microwave Dielectric Heating

Solid‐Supported Synthesis

Contact Info

Product

Resources

About