711028-98-7Relevant articles and documents
Identification of Small-Molecule Modulators of Diguanylate Cyclase by FRET-Based High-Throughput Screening
Christen, Matthias,Kamischke, Cassandra,Kulasekara, Hemantha D.,Olivas, Kathleen C.,Kulasekara, Bridget R.,Christen, Beat,Kline, Toni,Miller, Samuel I.
, p. 394 - 407 (2019/01/04)
The bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP) is a key regulator of cellular motility, the cell cycle, and biofilm formation with its resultant antibiotic tolerance, which can make chronic infections difficult to treat. Therefore, diguanylate cyclases, which regulate the spatiotemporal production of c-di-GMP, might be attractive drug targets for control of biofilm formation that is part of chronic infections. We present a FRET-based biochemical high-throughput screening approach coupled with detailed structure–activity studies to identify synthetic small-molecule modulators of the diguanylate cyclase DgcA from Caulobacter crescentus. We identified a set of seven small molecules that regulate DgcA enzymatic activity in the low-micromolar range. Subsequent structure–activity studies on selected scaffolds revealed a remarkable diversity of modulatory behavior, including slight chemical substitutions that reverse the effects from allosteric enzyme inhibition to activation. The compounds identified represent new chemotypes and are potentially developable into chemical genetic tools for the dissection of c-di-GMP signaling networks and alteration of c-di-GMP-associated phenotypes. In sum, our studies underline the importance of detailed mechanism-of-action studies for inhibitors of c-di-GMP signaling and demonstrate the complex interplay between synthetic small molecules and the regulatory mechanisms that control the activity of diguanylate cyclases.
Derivatives and application to the asymmetric synthesis of unnatural α-amino acid derivative
Inokuma, Tsubasa,Jichu, Takahisa,Nishida, Kodai,Shigenaga, Akira,Otaka, Akira
, p. 573 - 581 (2017/06/07)
We describe herein a manganese(IV) oxide-mediated oxidation of N-p-methoxyphenyl (PMP)-protected glycine derivatives for the synthesis of a-imino carboxylic acid derivatives. Using this methodology, utilization of unstable glyoxic acid derivatives was avoided. Furthermore, using this methodology we synthesized novel a-imino carboxylic acid derivatives such as a-imino phenyl ester, perfluoroalkyl etsers, imides, and thioester. The asymmetric Mannich reaction of those novel imine derivatives with 1,3-dicarbonyl compound is also described, and the novel a-imino imide gave improved chemical yield and stereoselectivity compared with those obtained by the use of the conventional a-imino ester-type substrate.
A convenient method for preparation of α-imino carboxylic acid derivatives and application to the asymmetric synthesis of unnatural α-amino acid derivative
Inokuma, Tsubasa,Jichu, Takahisa,Nishida, Kodai,Shigenaga, Akira,Otaka, Akira
, p. 573 - 581 (2019/12/26)
We describe herein a manganese(IV) oxide-mediated oxidation of N-p-methoxyphenyl (PMP)-protected glycine derivatives for the synthesis of α-imino carboxylic acid derivatives. Using this methodology, utilization of unstable glyoxic acid derivatives was avo
Enantioselective Michael addition to α,β-unsaturated imides catalyzed by a bifunctional organocatalyst
Hoashi, Yasutaka,Okino, Tomotaka,Takemoto, Yoshiji
, p. 4032 - 4035 (2007/10/03)
(Chemical Equation Presented) High enantioselectivities (up to 94 % ee) were attained in the Michael addition of a variety of α,β-unsaturated imides 1 and malononitrile (2) catalyzed by bifunctional thiourea 4. The pyrrolidinone moiety of 1 plays a key ro
Application of enantioselective radical reactions: Synthesis of (+)-ricciocarpins A and B
Sibi, Mukund P.,He, Liwen
, p. 1749 - 1752 (2007/10/03)
Matrix presented. Enantioselective synthesis of (+)-ricciocarpins A and B has been achieved in 41 and 45% overall yields, respectively, starting from a β-substituted oxazolidinone. The key steps in the strategy are an enantioselective conjugate radical ad
