Carboxyalthioacrylates

Halphen, Paul D.; Owen, Terence C.

doi:10.1021/jo00960a015

“…For many decadest he reactivity of electron deficient acetylenes with thiols hasb een explored both in organic [68][69][70] and Scheme17. Application of diarylthiomaleimidesint he generation of peptideconjugates for therapy and study of biological systems.…”

Section: Arylpropionitrilesmentioning

confidence: 99%

Bioconjugation with Maleimides: A Useful Tool for Chemical Biology

Ravasco

¹

,

Faustino

²

,

Trindade

³

et al. 2018

Chemistry A European J

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Maleimide chemistry stands out in the bioconjugation toolbox by virtue of its synthetic accessibility, excellent reactivity, and practicability. The second-generation of clinically approved antibody-drug conjugates (ADC) and much of the current ADC pipeline in clinical trials contain the maleimide linkage. However, thiosuccinimide linkages are now known to be less robust than once thought, and ergo, are correlated with suboptimal pharmacodynamics, pharmacokinetics, and safety profiles in some ADC constructs. Rational design of novel generations of maleimides and maleimide-type reagents have been reported to address the shortcomings of classical maleimides, allowing for the formation of robust bioconjugate linkages. This review highlights the main strategies for rational reagent design that have allowed irreversible bioconjugations in cysteines, reversible labelling strategies and disulfide re-bridging.

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“…[6] Application of this method to step-growth polymerization has allowed us to access high molar mass polymers with control over double bond stereochemistry,m onomer composition, and chain-end functionality to create elastomeric materials with independently tuneable mechanical and physical properties.…”

mentioning

confidence: 99%

Independent Control of Elastomer Properties through Stereocontrolled Synthesis

Bell

¹

,

Yu

²

,

Barker

³

et al. 2016

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In most synthetic elastomers,c hanging the physical properties by monomer choice also results in ac hange to the crystallinity of the material, which manifests through alteration of its mechanicalperformance.Using organocatalyzed stereospecific additions of thiols to activated alkynes,h igh-molarmass elastomers were isolated via step-growth polymerization. The resulting controllable double-bond stereochemistry defines the crystallinity and the concomitant mechanical properties as well as enabling the synthesis of materials that retain their excellent mechanical properties through changing monomer composition. Using this approacht oe lastomer synthesis,f urther end group modification and toughening through vulcanization strategies are also possible.The organocatalytic control of stereochemistry opens the realm to an ew and easily scalable class of elastomers that will have unique chemical handles for functionalization and post synthetic processing.Nature has evolved the ability to create large and complex molecules in which the precise control over the spatial arrangement of the atoms is critical to their performance.The three-dimensional control over the arrangement of bonds is as important to the function and behavior of molecules as any other factor and is critical to the structure-function relationships that govern the role of arange of molecules.While the effect of stereochemistry on functionality is probably best known in the examples of small molecule drugs such as thalidomide (one enantiomer is effective against morning sickness,t he other is teratogenic) or naproxen (one enantiomer is used to treat arthritis pain, the other causes liver poisoning with no analgesic effect), it is less well-studied with respect to materials design.Elastomeric materials are applied widely to demanding applications on account of their inherent reversible deformation behavior. Many synthetic elastomer materials are tri-or multi-block copolymers that are based on the concept of an amorphous-crystalline or hard-soft phase-separated system in which organization of the hard and soft domains endows the strong but elastic properties upon the materials.[1] While these materials have found widespread application, changes to the monomers or stoichiometry designed to elicit ac hange in physical properties also alter the chain packing and hence the mechanical properties of the materials.I nterestingly,n atural rubber and gutta percha are homopolymers of poly(cisisoprene) and poly(trans-isoprene) respectively.W hile these materials differ by only the double bonds of the backbone,the superior elastomeric properties of natural rubber [2] are attributed to the enhanced chain packing afforded by its stereochemical orientation.[3] While the design principles to control crystallinity and the associated mechanical properties in these materials are clear,the inability to incorporate awide range of functional groups in ac ontrolled manner or rationally define the chain end functionality limits the applications of both these materials a...

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“…[4] Combination of the control over degree of crystallinity and mechanical properties through backbone double-bond stereochemistry,a se xemplified by natural rubber/gutta percha, with the tunability of materials properties of synthetic materials via monomer selection and end group modification, presents an ew method by which to undertake the rational design of elastomers and presents an entire new design space for functional materials.Acritical deficiencyofsynthetic methods in the ability to control double-bond stereochemistry using monomers with diverse functional groups limits the development of novel materials that mimic the method of mechanical property control exemplified in natural rubber and gutta percha elastomers.T he application of click chemistry,r eactions that are so categorized because of their modular nature,s ingle reaction trajectory,equimolarity,high yields,simple purification, chemoselectivity,and fast timescales, [5] could potentially address the synthetic pitfalls and afford access to high-molarmass polymers with defined stereochemistry.Indeed, we and others have recently demonstrated that the organobasecatalyzed addition of thiols to activated alkynes could be stopped after asingle addition and furthermore,byjudicious choice of catalyst or solvent polarity,t he stereochemistry of the resultant alkene could be controlled. [6] Application of this method to step-growth polymerization has allowed us to access high molar mass polymers with control over double bond stereochemistry,m onomer composition, and chain-end [*] Dr.…”

mentioning

confidence: 99%

Independent Control of Elastomer Properties through Stereocontrolled Synthesis

Bell

¹

,

Yu

²

,

Barker

³

et al. 2016

View full text Add to dashboard Cite

In most synthetic elastomers,c hanging the physical properties by monomer choice also results in ac hange to the crystallinity of the material, which manifests through alteration of its mechanicalperformance.Using organocatalyzed stereospecific additions of thiols to activated alkynes,h igh-molarmass elastomers were isolated via step-growth polymerization. The resulting controllable double-bond stereochemistry defines the crystallinity and the concomitant mechanical properties as well as enabling the synthesis of materials that retain their excellent mechanical properties through changing monomer composition. Using this approacht oe lastomer synthesis,f urther end group modification and toughening through vulcanization strategies are also possible.The organocatalytic control of stereochemistry opens the realm to an ew and easily scalable class of elastomers that will have unique chemical handles for functionalization and post synthetic processing.Nature has evolved the ability to create large and complex molecules in which the precise control over the spatial arrangement of the atoms is critical to their performance.The three-dimensional control over the arrangement of bonds is as important to the function and behavior of molecules as any other factor and is critical to the structure-function relationships that govern the role of arange of molecules.While the effect of stereochemistry on functionality is probably best known in the examples of small molecule drugs such as thalidomide (one enantiomer is effective against morning sickness,t he other is teratogenic) or naproxen (one enantiomer is used to treat arthritis pain, the other causes liver poisoning with no analgesic effect), it is less well-studied with respect to materials design.Elastomeric materials are applied widely to demanding applications on account of their inherent reversible deformation behavior. Many synthetic elastomer materials are tri-or multi-block copolymers that are based on the concept of an amorphous-crystalline or hard-soft phase-separated system in which organization of the hard and soft domains endows the strong but elastic properties upon the materials.[1] While these materials have found widespread application, changes to the monomers or stoichiometry designed to elicit ac hange in physical properties also alter the chain packing and hence the mechanical properties of the materials.I nterestingly,n atural rubber and gutta percha are homopolymers of poly(cisisoprene) and poly(trans-isoprene) respectively.W hile these materials differ by only the double bonds of the backbone,the superior elastomeric properties of natural rubber [2] are attributed to the enhanced chain packing afforded by its stereochemical orientation.[3] While the design principles to control crystallinity and the associated mechanical properties in these materials are clear,the inability to incorporate awide range of functional groups in ac ontrolled manner or rationally define the chain end functionality limits the applications of both these materials a...

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Carboxyalthioacrylates

Abstract: for the microanalyses, Dr. T. Williams for the nmr spectra, Mr. S. Traiman for the ir spectra, Dr. W.Benz for the mass spectra, and Dr. V. Toome for the uv spectra.

Cited by 34 publications

References 14 publications

Bioconjugation with Maleimides: A Useful Tool for Chemical Biology

Bioconjugation with Maleimides: A Useful Tool for Chemical Biology

Independent Control of Elastomer Properties through Stereocontrolled Synthesis

Independent Control of Elastomer Properties through Stereocontrolled Synthesis

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