112 research outputs found
A 2,2′-bipyridine-palladacycle catalyzed the coupling of arylboronic acids with nitroarenes
AbstractA novel palladium-catalyzed protocol for the synthesis of diaryl ethers derivatives has been developed. In the presence of 2,2′-bipyridine-cyclopalladated ferrocenylimine complex (Cat. Ic), diaryl ethers were selectively generated by adjusting reaction parameters through the coupling of arylboronic acids and nitroarenes with yields ranging from poor to good. The efficiency of this reaction was demonstrated by its compatibility with a range of groups. Moreover, the rigorous exclusion of air or moisture was not required in these transformations
Synthesis and anti-HIV activity of 2′-deoxy-2′-fluoro-4′-C-ethynyl nucleoside analogs
Based on the favorable antiviral profiles of 4′-substituted nucleosides, novel 1-(2′-deoxy-2′-fluoro-4′-C-ethynyl-β-D-arabinofuranosyl)-uracil (1a), -thymine (1b), and – cytosine (2) analogues were synthesized. Compounds 1b and 2 exhibited potent anti-HIV-1 activity with IC50 values of 86 and 1.34 nM, respectively, without significant cytotoxicity. Compound 2 was 35-fold more potent than AZT against wild-type virus, and also retained nanomolar antiviral activity against resistant strains, NL4-3(K101E) and RTMDR. Thus, 2 merits further development as a novel NRTI drug
Synthesis of new 2′-deoxy-2′-fluoro-4′-azido nucleoside analogues as potent anti-HIV agents
We prepared 1-(4′-azido-2′-deoxy-2′-fluoro-β -D-arabinofuranosyl)cytosine (10) and its hydrochloride salt (11) as potential antiviral agents based on the favorable antiviral profiles of 4′-substituted nucleosides. Compounds 10 and 11 were synthesized from 1,3,5-O-tribenzoyl-2-deoxy-2-fluoro-D-arabinofuranoside in multiple steps, and their structures were unequivocally established by IR, 1H NMR, 13C NMR, and 19F NMR spectroscopy, HRMS, and X-ray crystallography. Compounds 10 and 11 exhibited potent anti-HIV-1 activity (EC50: 0.3 and 0.13 nM, respectively) without significant cytotoxicity in concentrations up to 100 μM. Compound 11 exhibited extremely potent anti-HIV activity against NL4-3 (wild-type), NL4-3 (K101E), and RTMDR viral strains, with EC50 values of 0.086, 0.15, and 0.11 nM, respectively. Due to the high potency of 11, it was also screened against an NIH Reagent Program NRTI-resistant virus panel containing eleven mutated viral strains and for cytotoxicity against six different human cell lines. The results of this screening indicated that 11 is a novel NRTI that could be developed as an anti-AIDS clinical trial candidate to overcome drug-resistance issues
Establishing chromosomal design-build-test-learn through a synthetic chromosome and its combinatorial reconfiguration
Chromosome-level design-build-test-learn cycles (chrDBTLs) allow systematic combinatorial reconfiguration of chromosomes with ease. Here, we established chrDBTL with a redesigned synthetic Saccharomyces cerevisiae chromosome XV, synXV. We designed and built synXV to harbor strategically inserted features, modified elements, and synonymously recoded genes throughout the chromosome. Based on the recoded chromosome, we developed a method to enable chrDBTL: CRISPR-Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE). CRIMiRE allowed the creation of customized wild-type/synthetic combinations, accelerating genotype-phenotype mapping and synthetic chromosome redesign. We also leveraged synXV as a "build-to-learn" model organism for translation studies by ribosome profiling. We conducted a locus-to-locus comparison of ribosome occupancy between synXV and the wild-type chromosome, providing insight into the effects of codon changes and redesigned features on translation dynamics in vivo. Overall, we established synXV as a versatile reconfigurable system that advances chrDBTL for understanding biological mechanisms and engineering strains. </p
Insights into the Unexpected Chemoselectivity for the N‑Heterocyclic Carbene-Catalyzed Annulation Reaction of Allenals with Chalcones
Lewis
base N-heterocyclic carbene (NHC)-catalyzed annulation is
the subject of extensive interest in synthetic chemistry, but the
reaction mechanisms, especially the unexpected chemoselectivity of
some of these reactions, are poorly understood. In this work, a systematic
theoretical calculation has been performed on NHC-catalyzed annulation
between allenals and chalcone. Multiple possible reaction pathways
(A–E) leading to three different products have been characterized.
The calculated results reveal that NHC is more likely to initiate
the reaction by nucleophilic attack on the center carbon atom of the
allene group but not the carbonyl carbon atom in allenals leading
to the Breslow intermediate, which is remarkably different from the
other NHC-catalyzed annulations of unsaturated aldehydes with chalcones.
The computed energy profiles demonstrate that the most energetically
favorable pathway (A) results in polysubstituted pyranyl aldehydes,
which reasonably explains the observed chemoselectivity in the experiment.
The observed chemoselectivity is demonstrated to be thermodynamically
but not kinetically controlled, and the stability of the Breslow intermediate
is the key for the possibility of homoenolate pathway D and enolate
pathway E. This work can improve our understanding of the multiple
competing pathways for NHC-catalyzed annulation reactions of unsaturated
aldehydes with chalcones and provide valuable insights for predicting
the chemoselectivity for this kind of reaction
Cp*Rh(III)-Catalyzed Mild Addition of C(sp(3))-H Bonds to alpha,beta-Unsaturated Aldehydes and Ketones
A Rh(III)-catalyzed addition of benzylic C(sp(3))-H bond to alpha,beta-unsaturated ketones/aldehydes has been realized, leading to efficient synthesis of gamma-aryl ketones/aldehydes. This atom-economic reaction proceeded under mild and redox-neutral conditions with a broad substrate scope. Besides benzylic C-H, allylic C-H bonds are also applicable when assisted by O-methyl ketoxime directing groups
Computational insights into the origin of decrease/increase in potency of <i>N</i>-CDPCB analogues toward FTO
Computational insights into the origin of decrease/increase in potency of <i>N</i>-CDPCB analogues toward FT
Co(III)/Zn(II)-catalyzed dearomatization of indoles and coupling with carbenes from ene-yne ketones via intramolecular cyclopropanation
A straightforward and efficient protocol for dearomatizing indoles is described. The reaction, catalyzed by an inexpensive Co(III)/Zn(II) catalyst, starts from easily accessible N-pyrimidinyl indoles and ene-yne ketones. Mild reaction conditions, high diastereoselectivity, a broad substrate scope, effective functional group tolerance, and reasonable to remarkable yields were observed. (C) 2018, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved
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