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315 results on '"Lear, Martin"'

1. Phosphine-catalyzed activation of cyclopropenones: a versatile C 3 synthon for (3+2) annulations with unsaturated electrophiles

Author

He, Xin, Ma, Pengchen, Tang, Yuhai, Li, Jing, Shen, Shenyu, Lear, Martin J, Houk, KN, and Xu, Silong

Subjects
Chemical Sciences
Abstract

We herein report a phosphine-catalyzed (3 + 2) annulation of cyclopropenones with a wide variety of electrophilic π systems, including aldehydes, ketoesters, imines, isocyanates, and carbodiimides, offering products of butenolides, butyrolactams, maleimides, and iminomaleimides, respectively, in high yields with broad substrate scope. An α-ketenyl phosphorous ylide is validated as the key intermediate, which undergoes preferential catalytic cyclization with aldehydes rather than stoichiometric Wittig olefinations. This phosphine-catalyzed activation of cyclopropenones thus supplies a versatile C3 synthon for formal cycloadditon reactions.

Published
2022

6. Synthesis and biological evaluation of anticancer agents

Author

Lear, Martin James

Subjects
540
Abstract

Within the last ten years intense research has led to a greater understanding of the signalling pathways that control normal cell division and cancerous cell proliferation. Enzymes known as protein tyrosine kinases (PTKs) play a key role in such growth-related processes by catalysing the phosphorylation of tyrosine residues on intracellular protein substrates. This knowledge has led to the search for selective PTK inhibitors in the hope of generating chemotherapeutic agents of potential use in the treatment of cancer. Particular attention has focused on the signalling events that occur at a receptor tyrosine kinase (RTK) called the epidermal growth factor (EGF) receptor since a number of studies have implicated its involvement in many types of human cancer. Compounds found to possess anticancer activity by acdng as PTK inhibitors with a structural resemblance to tyrosine are known as the tyrphostins. In this project, an extensive array of 3-arylpropenonitriles (approximately 140 compounds) akin to the tyrphostins have been synthesised and biologically evaluated in cell assays designed to correlate PTK inhibition at the EGF receptor to antiproliferative activity. Efforts were directed at producing more stable tyrphostin analogues as well as those that incorporate a heterocyclic moiety. From initial studies, tyrphostins incorporadng a nitrothiophene portion were shown to be highly potent antiproliferative agents and gave sub-nanomolar IC50 values against the breast adenocarcinoma MCF-7 cell line. Consequently, structurally isomeric tyrphostin sets were synthesised. More detailed biological analysis demonstrated that some of these compounds were acting in a non-selective cytotoxic fashion. Presently, the compound ethyl 2-cyano-3-[5-(2-nitrothienyl)]propenoate (A) has been accepted by the National Cancer Institute to undergo an in vivo evaluation and represents an interesting new cytotoxic anticancer agent. During a search for heterocyclic tyrphostins some quinoline derivatives were found to display encouraging antiproliferative activities against the MCF-7 cell line (IC50 values < 1 muM). The most potent compounds contained the 2-aminoethene-1,1-dicarbonitrile unit and, although they produced an additional cytotoxic action, they were found to inhibit selectively the phosphorylation of an unknown signalling protein that was found to be linked to EGF receptor activation. The 2-substituted quinoline (B) also displayed a certain degree of selectivity within a panel of 60 tumour cell lines (held at the US National Cancer Institute) and may act as an interesting lead for future studies. In order to determine the stereochemical requirement preferred for biological activity, attempts were made to synthesise geometric isomers of some tyrphostins. In particular, the cis- and trans- forms of the known tyrphostin (C) were synthesised and characterised by detailed NMR spectroscopy and X-ray crystallography. Interestingly, the isomer (C) was about 3.5 times more potent than its geometric panner in an antiproliferative assay against a cell line (HN5) that overexpresses the EGF receptor. Also, synthesised were other 2,3-diaryIpropenonitriles akin to compound (C) and some of these displayed equally effective IC50 values against the MCF-7 cell line.

Published
1995

18. Atypical Oxidative Methods to (A)Typically Activated Esters

Author

Lear, Martin and Lear, Martin

Abstract

The formation of amides and esters often necessitates powerful, yet mild reagent systems. New atom-economical and practical methods that achieve such goals are highly desirable. To this end, several direct oxidative methods are presented from atypical substrates. For example, amides and esters can be prepared from primary nitroalkanes or 1,1-dicyanoalkanes simply by using carbonate bases under O2 with or without I2, respectively. Such oxidative protocols can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. Unexpected, atypical mechanisms will be proposed and presented.

Published
2018

22. Activity-based proteome profiling of potential cellular targets of orlistat - an FDA-approved drug with anti-tumor activities

Author

Peng-Yu Yang, Kai Liu, Mun Hong Ngai, Lear, Martin J., Wenk, Markus R., and Yao, Shao Q.

Subjects
Gene mutations -- Analysis, Orlistat -- Health aspects, Orlistat -- Chemical properties, Proteomics -- Research, Western immunoblotting -- Usage, Cancer -- Care and treatment, Cancer -- Research, Chemistry
Abstract

The total of synthesis of orlistat, or tetrahydrolipstatin (THL)-like protein-reactive probes as an FDA-approved antiobesity drug with potential antitumor activities is reported. The findings from study have important implications in the consideration of orlistat as a potential anticancer drug at its early stages of development for cancer therapy.

Published
2010

24. Identification of the binding of sceptrin to MreB via a bidirectional affinity protocol

Author

Rodriguez, Abimael D., Lear, Martin J., and La Clair, James J.

Subjects
Escherichia coli -- Physiological aspects, Gums and resins -- Chemical properties, Protein binding -- Analysis, Chemistry
Abstract

A newly designed method with affinity resins was used to biologically evaluate sponge extracts for natural products that bind to Escherichia coli proteins. The method would help to construct a library of affinity resins that could be used as a simple high-throughput tool to screen the connectivity between natural products and proteins.

Published
2008

25. Microparticle assembly

Author

Trau, Dieter, Lear, Martin, and Ochs, Christopher

Subjects
F110 Applied Chemistry, H810 Chemical Engineering, F100 Chemistry
Abstract

A bead construct includes a bead, a fluorophore molecule, first and second linker molecules and a ligand molecule. The fluorophore molecule comprises at least two subunits connected to each other by at least one internal linker that provides conformational freedom to the at least two subunits. An optical signal emitted by the fluorophore molecule changes when reducing the conformational freedom of the at least two subunits to each other. The first linker molecule is connected to the bead and to one of the subunits of the flurophore molecule. The second linker molecule is connected to another one of the subunits of the fluorophore molecule. The ligand molecule is connected to the second linker molecule.

Published
2015

32. A microparticle assembly

Author

Trau, Dieter, Lear, Martin, and Ochs, Christopher

Subjects
F170 Physical Chemistry, F200 Materials Science, F160 Organic Chemistry
Abstract

A microarray, comprising a plurality of bead constructs disposed thereon, wherein the bead constructs comprise: (a) a bead; (b) a fluorophore molecule, wherein the fluorophore molecule comprises at least two subunits connected to each other by at least one internal linker that provides conformational freedom to the at least two subunits, and wherein the optical signal emitted by the flurophore changes when reducing the conformational freedom of the at least two subunits to each other; (c) a first linker molecule connected to the bead and to one of the subunits of the flurophore molecule; (d) a second linker molecule connected to another subunit of the fluorophore molecule; and (e) a ligand molecule connected to the second linker.

Published
2013

33. Autoinductive conversion of α,α-diiodonitroalkanes to amides and esters catalysed by iodine byproducts under O2.

Author

Li, Jing, Lear, Martin J., and Hayashi, Yujiro

Subjects
*AMIDES, *ESTERS, *IODINE, *AUTOCATALYSIS, *NITROALKANES
Abstract

Studies to convert nitroalkanes into amides and esters using I2 and O2 revealed in situ-generated iodine species facilitate the homolytic C–I bond cleavage of α,α-diiodonitroalkanes, arguably in an autoinductive or autocatalytic manner. Consequently, we devised a rapid and economical I2/O2-based method to synthesise sterically hindered esters directly from primary nitroalkanes. [ABSTRACT FROM AUTHOR]

Published
2018
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34. Autoinductive conversion of α,α-diiodonitroalkanes to amides and esters catalysed by iodine byproducts under O2.

Author

Li, Jing, Lear, Martin J., and Hayashi, Yujiro

Subjects
AMIDES, ESTERS, IODINE, AUTOCATALYSIS, NITROALKANES
Abstract

Studies to convert nitroalkanes into amides and esters using I2 and O2 revealed in situ-generated iodine species facilitate the homolytic C–I bond cleavage of α,α-diiodonitroalkanes, arguably in an autoinductive or autocatalytic manner. Consequently, we devised a rapid and economical I2/O2-based method to synthesise sterically hindered esters directly from primary nitroalkanes. [ABSTRACT FROM AUTHOR]

Published
2018
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36. Synthesis and use of fluorophore-tagged antimalarials

Author

Lear, Martin and Tan, Kevin S. W.

Subjects
F165 Biomolecular Chemistry, C500 Microbiology, F160 Organic Chemistry
Abstract

This invention includes a fluorophore-tagged antimalarial represented by the following structural formula (1) or a salt thereof. This invention relates to the synthesis of fluorophore-tagged antimalarials and describes the synthesis of a fluorophore-tagged antimalarial. These fluorophore-tagged antimalarials can be used to image live cells to determine the location of the antimalarial in the cell, identify drug resistance and growth related pathways in Plasmodium isolates, identify new drug targets and chemo-sensitizers to reverse drug resistance.

Published
2012

41. The first total synthesis of N1999-A2: Absolute stereochemistry and stereochemical implications into DNA cleavage

Author

Kobayashi, Shoji, Ashizawa, Shukuko, Takahashi, Yusuke, Sugiura, Yukio, Nagaoka, Makoto, Lear, Martin J., and Hirama, Masahiro

Subjects
Thiols -- Chemical properties, DNA -- Research, Stereochemistry -- Research, Chemistry
Abstract

The realization of a concise and efficient strategy that has culminated in the first total synthesis of N1999-A2 and the chemical evidence of a thiol-triggered aromatization of N1999-A2 are described. The results show that the (S)-configured C11-naphthoate unit plays a dominant role in not only controlling the trans-orientation of thiol attack, which triggers aromatization, but also in the efficient recognition and base-specific cleavage of DNA.

Published
2001

42. Characterization of the Commercially-Available Fluorescent Chloroquine-BODIPY Conjugate, LynxTag-CQGREEN, as a Marker for Chloroquine Resistance and Uptake in a 96-Well Plate Assay

Author

Loh, Cheryl C. Y., primary, Suwanarusk, Rossarin, additional, Lee, Yan Quan, additional, Chan, Kitti W. K., additional, Choy, Kit-Ying, additional, Rénia, Laurent, additional, Russell, Bruce, additional, Lear, Martin J., additional, Nosten, François H., additional, Tan, Kevin S. W., additional, and Chow, Larry M. C., additional

Published
2014
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