Bicyclic Conformationally Restricted Diamines

Grygorenko, Oleksandr O.; Radchenko, Dmytro S.; Volochnyuk, Dmitriy M.; Tolmachev, Andrey A.; Komarov, Igor V.

doi:10.1021/cr100352k

Cited by 106 publications

(88 citation statements)

References 266 publications

(290 reference statements)

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“…[229] Among the bifunctional reagents, (monoprotected) amino acids and diamines are mostp opular. [232] Recent years have witnessedt he publication of numerouss ynthetic works on novel advanced buildingb locks for drug discovery,f ocusingm ainly on unusual bicyclic, spirocyclic, heteroaliphatic,o rh eteroaromatic compounds, especially those with fluorine atoms; selected examples are given in Figure 44. [233][234][235][236][237][238][239][240]…”

Section: Building Blocks For Drug Discoverymentioning

confidence: 99%

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

Grygorenko

Volochnyuk

Ryabukhin

et al. 2019

Chemistry A European J

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All pharmaceutical products contain organic molecules; the source may be a natural product or a fully synthetic molecule, or a combination of both. Thus, it follows that organic chemistry underpins both existing and upcoming pharmaceutical products. The reverse relationship has also affected organic synthesis, changing its landscape towards increasingly complex targets. This Review article sets out to give a concise appraisal of this symbiotic relationship between organic chemistry and drug discovery, along with a discussion of the design concepts and highlighting key milestones along the journey. In particular, criteria for a high‐quality compound library design enabling efficient virtual navigation of chemical space, as well as rise and fall of concepts for its synthetic exploration (such as combinatorial chemistry; diversity‐, biology‐, lead‐, or fragment‐oriented syntheses; and DNA‐encoded libraries) are critically surveyed.

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Section: Building Blocks For Drug Discoverymentioning

confidence: 99%

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

Grygorenko

Volochnyuk

Ryabukhin

et al. 2019

Chemistry A European J

Self Cite

125

123

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“…Introduction of the latter to the Seyferth–Gilbert reaction with Bestmann–Ohira reagent ( 12 ) afforded terminal alkyne 13 (84 % yield) – a promising substrate for click chemistry. Another beneficial bifunctional building block – monoprotected bicyclic diamine 14 – was synthesized via modified Curtius rearrangement of 7 with subsequent hydrogenolysis of intermediate 15 (71 % yield for two steps).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 3‐Azabicyclo[3.2.0]heptane‐Derived Building Blocks via [3+2] Cycloaddition

et al. 2018

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An efficient approach to synthesis of various substituted 3‐azabicyclo[3.2.0]heptane‐derived building blocks based on [3+2] cycloaddition of cyclobut‐1‐eneraboxylic acid ester and in situ generated azomethine ylide was developed and applied on multigram scale. The utility of 1,3‐disubstituted 3‐azabicyclo[3.2.0]heptane scaffold was demonstrated by additional structural analysis using exit vector plot (EVP) tool, and tested in parallel synthesis of compound library.

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“…It should be noted that despite the fact that the synthesis of amine 12k included nine steps, it was carried out successfully on up to an 86 g scale. Therefore, this building block, a representative monoprotected bicyclic conformationally restricted diamine derivative, can now be considered to be readily available for use in drug discovery and other areas of potential application. It is a far more convenient reagent for selective modification than the free 1,3‐diaminobicyclo[1.1.1]pentane reported previously , …”

Section: Resultsmentioning

confidence: 99%

Bicyclo[1.1.1]pentane‐Derived Building Blocks for Click Chemistry

et al. 2017

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Syntheses of bicyclo[1.1.1]pentane‐derived azides and terminal alkynes – interesting substrates for click reactions – are described. With a few exceptions, these compounds were prepared in two or three steps starting from common synthetic intermediates – the corresponding carboxylic acids. The key step in the synthesis of 1‐azidobicyclo[1.1.1]pentanes is a copper‐catalysed diazo‐transfer reaction with imidazole‐1‐sulfonyl azide. The preparation of bicyclo[1.1.1]pentyl‐substituted alkynes relies on a Seyferth–Gilbert homologation with dimethyl 1‐diazo‐2‐oxopropylphosphonate (Ohira–Bestmann reagent). Both types of target compounds were found to be suitable substrates for click reactions, and thus they are promising building blocks for medicinal, combinatorial and bioconjugate chemistry. A practically important side result of this study was a multigram preparation of Boc‐monoprotected 1,3‐diaminobicyclo[1.1.1]pentane – a representative bicyclic conformationally restricted diamine derivative.

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Bicyclic Conformationally Restricted Diamines

Cited by 106 publications

References 266 publications

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

Synthesis of 3‐Azabicyclo[3.2.0]heptane‐Derived Building Blocks via [3+2] Cycloaddition

Bicyclo[1.1.1]pentane‐Derived Building Blocks for Click Chemistry

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