64700-65-8Relevant articles and documents
Revised Structure of Anthelvencin A and Characterization of the Anthelvencin Biosynthetic Gene Cluster
Aubry, Céline,Clerici, Paolo,Gerbaud, Claude,Lautru, Sylvie,Micouin, Laurent,Pernodet, Jean-Luc
, p. 945 - 951 (2020/05/19)
Anthelvencins A and B are pyrrolamide metabolites produced by Streptomyces venezuelae ATCC 14583 and 14585. Isolated in 1965, they were reported to exhibit anthelmintic and moderate antibacterial activities. In this study, we revise the structure of anthelvencin A and identify a third anthelvencin metabolite, bearing two N-methylated pyrrole groups, which we named anthelvencin C. We sequenced the genome of S. venezuelae ATCC 14583 and identified a gene cluster predicted to direct the biosynthesis of anthelvencins. Functional analysis of this gene cluster confirmed its involvement in anthelvencin biosynthesis and allowed us to propose a biosynthetic pathway for anthelvencins. In addition to a nonribosomal peptide synthetase (NRPS), the assembly of anthelvencins involves an enzyme from the ATP-grasp ligase family, Ant23. We propose that Ant23 uses a PCP-loaded 4-aminopyrrole-2-carboxylate as substrate. As observed for the biosynthesis of the other pyrrolamides congocidine (produced by Streptomyces ambofaciens ATCC 25877) and distamycin (produced by Streptomyces netropsis DSM 40846), the NRPS assembling anthelvencins is composed of stand-alone domains only. Such NRPSs, sometimes called type II NRPSs, are less studied than the classical multimodular NRPSs. Yet, they constitute an interesting model to study protein-protein interactions in NRPSs and are good candidates for combinatorial biosynthesis approaches.
Design and Synthesis of 56 Shape-Diverse 3D Fragments
Atobe, Masakazu,Blakemore, David C.,Bond, Paul S.,Chan, Ngai S.,De Fusco, Claudia,Downes, Thomas D.,Firth, James D.,Hubbard, Roderick E.,Jones, S. Paul,Klein, Hanna F.,O'Brien, Peter,Roughley, Stephen D.,Vidler, Lewis R.,Waddelove, Laura,Whatton, Maria Ann,Wheldon, Mary C.,Woolford, Alison J.-A.,Wrigley, Gail L.
supporting information, (2020/07/13)
Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under-represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning design feature of this fragment collection is that assessment of fragment shape and conformational diversity (by considering conformations up to 1.5 kcal mol?1 above the energy of the global minimum energy conformer) is carried out prior to synthesis and is also used to select targets for synthesis. The 3D fragments were designed to contain suitable synthetic handles for future fragment elaboration. Finally, by comparing our 3D fragments with six commercial libraries, it is clear that our collection has high three-dimensionality and shape diversity.
INHIBITORS OF APOL1 AND METHODS OF USING SAME
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Paragraph 00311, (2020/07/14)
The disclosure provides at least one entity chosen from compounds of formula (I), solid state forms of the same, compositions comprising the same, and methods of using the same, including use in treating focal segmental glomerulosclerosis (FSGS) and/or non-diabetic kidney disease (NDKD).
Method for efficiently preparing azaindole CRTH2 receptor antagonist intermediate
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Paragraph 0048-0051, (2020/10/21)
The invention provides a method for preparing an azaindole compound shown as a formula (I). The method comprises the following steps: carrying out simple conversion on an initial raw material D-pyroglutamic acid to obtain an intermediate shown as a formula (II); carrying out ring opening on the intermediate shown as the formula (II) by 2-(N-tert-butyloxycarbonylamino)-3-methylpyridine under the action of organic alkali; and adding organic acid to directly obtain an azaindole compound shown as a formula (III), protecting secondary amine, activating hydroxyl or performing Mitsunobu reaction, andperforming ring closing to obtain the formula (I). According to the method provided by the invention, D-pyroglutamic acid is used as a starting material, so that complex processes such as chiral auxiliary synthesis, chiral resolution or introduction of chiral amino by enzyme catalytic reaction are avoided; therefore, the synthesis steps are greatly shortened, the cost is greatly reduced, and themethod is suitable for industrial large-scale production.
Catalytic Enantioselective Total Synthesis of (+)-Lycoperdic Acid
Kortet, Sami,Claraz, Aurélie,Pihko, Petri M.
supporting information, p. 3010 - 3013 (2020/04/10)
A concise enantio- and stereocontrolled synthesis of (+)-lycoperdic acid is presented. The stereochemical control is based on iminium-catalyzed Mukaiyama-Michael reaction and enamine-catalyzed organocatalytic α-chlorination steps. The amino group was introduced by azide displacement, affording the final stereochemistry of (+)-lycoperdic acid. Penultimate hydrogenation and hydrolysis afforded pure (+)-lycoperdic acid in seven steps from a known silyloxyfuran.
2-PYRROLIDINE PHENYLHYDRAZIDES ANTIBACTERIAL AGENTS
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Page/Page column 54, (2018/02/28)
2-Pyrrolidine phenylhydrazides antibacterial agents The present invention relates to 2-pyrrolidine phenylhydrazide compounds of formula (I), which are selective antibacterials specifically agalnstAcineto barter baumannii.The invention also relates to their therapeutic use as antibacterials, to a process for their preparation and to pharmaceutical compositions containing them.
Zirconium-catalysed N-acylation of lactams using unactivated carboxylic acids
Hulsbosch, Joris,Claes, Laurens,De Vos, Dirk E.
supporting information, p. 1646 - 1650 (2018/04/06)
A large number of chemicals including surfactants, nootropic drugs and pesticides contain an N-acylated lactam moiety in their molecular structure. In this work, the direct, catalytic N-acylation of a number of lactams with various unactivated carboxylic
FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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Paragraph 1803, (2017/05/14)
The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION
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Paragraph 0156, (2017/02/24)
The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto- temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
Impact of Functional Groups on the Copper-Initiated N-Arylation of 5-Functionalized Pyrrolidin-2-ones and Their Vinylogues
Baudelet, Davy,Da?ch, Adam,Rigo, Beno?t,Lipka, Emmanuelle,Gautret, Philippe,Homerin, Germain,Claverie, Christelle,Rousseau, Jolanta,Abuhaie, Cristina-Maria,Ghinet, Alina
supporting information, p. 2226 - 2244 (2016/07/15)
The electronic effects governing the N-arylation of pyrrolidone were investigated. The generalization of our preliminary findings on a copper(I)-catalyzed Csp2-N coupling process was first improved with a wide variety of aryl and heteroaryl halides and methyl pyroglutamate. The optimized protocol was further extended to pyrrolidin-2-ones substituted at the C5-position with an aryl group bearing an electron-donating or electron-withdrawing group as well as to some of their substituted enaminoester vinylogues. The impact of substituents at the N- and C5-position on these coupling processes seemed to be pivotal for determining both the reaction profiles and yields.
