3d Transition Metals for C–H Activation

Chemical Reviews, Journal Year: 2018, Volume and Issue: 119(4), P. 2192 - 2452

Published: Nov. 27, 2018

C–H activation has surfaced as an increasingly powerful tool for molecular sciences, with notable applications to material crop protection, drug discovery, and pharmaceutical industries, among others. Despite major advances, the vast majority of these functionalizations required precious 4d or 5d transition metal catalysts. Given cost-effective sustainable nature earth-abundant first row metals, development less toxic, inexpensive 3d catalysts gained considerable recent momentum a significantly more environmentally-benign economically-attractive alternative. Herein, we provide comprehensive overview on until summer 2018.

Language: Английский

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Towards the sustainable discovery and development of new antibiotics

Nature Reviews Chemistry, Journal Year: 2021, Volume and Issue: 5(10), P. 726 - 749

Published: Aug. 19, 2021

An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast current level investment their development, particularly fields natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry modes action are desperately needed worldwide tackle public health menace posed antimicrobial resistance. Here, our consortium presents a strategic blueprint substantially improve ability discover develop new antibiotics. We propose both short-term long-term solutions overcome most urgent limitations various sectors research funding, aiming bridge gap between academic, industrial political stakeholders, unite interdisciplinary expertise order efficiently fuel translational pipeline benefit future generations.

Language: Английский

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Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(7), P. 3887 - 3964

Published: April 2, 2018

New methods for preparation of tailor-made fluorine-containing compounds are in extremely high demand nearly every sector chemical industry. The asymmetric construction quaternary C-F stereogenic centers is the most synthetically challenging and, consequently, least developed area research. As a reflection this apparent methodological deficit, pharmaceutical drugs featuring constitute less than 1% all medicines currently on market or clinical development. Here we provide comprehensive review current research activity area, including such general directions as electrophilic fluorination via organocatalytic and transition-metal catalyzed reactions, elaboration substrates alkylations, Mannich, Michael, aldol additions, cross-coupling biocatalytic approaches.

Language: Английский

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Marine natural products

Natural Product Reports, Journal Year: 2019, Volume and Issue: 36(1), P. 122 - 173

Published: Jan. 1, 2019

A comprehensive review of 1490 new MNPs including the first naturally occurring blue zwitterionic quinoids dactylocyanines A–H is presented.

Language: Английский

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Same Substrate, Many Reactions: Oxygen Activation in Flavoenzymes

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(4), P. 1742 - 1769

Published: Jan. 11, 2018

Over time, organisms have evolved strategies to cope with the abundance of dioxygen on Earth. Oxygen-utilizing enzymes tightly control reactions involving O2 mostly by modulating reactivity their cofactors. Flavins are extremely versatile cofactors that capable undergoing redox accepting either one electron or two electrons, alternating between oxidized and reduced states. The physical chemical principles flavin-based chemistry been investigated widely. In following pages we summarize state art a key area research in flavin enzymology: molecular basis for activation flavin-dependent oxidases monooxygenases. general terms, use as an acceptor produce H2O2, while monooxygenases activate forming intermediate insert oxygen atom into substrate. First, analyze how reaches cofactor embedded protein matrix through dedicated access pathways. Then approach from perspective monooxygenases, preferred intermediate, C(4a)-(hydro)peroxyflavin, cases which other intermediates described. Finally, focus understanding architectures developed active sites promote factors operate its reactivity.

Language: Английский

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Strategies to diversify natural products for drug discovery

Medicinal Research Reviews, Journal Year: 2017, Volume and Issue: 38(4), P. 1255 - 1294

Published: Oct. 24, 2017

Natural product libraries contain specialized metabolites derived from plants, animals, and microorganisms that play a pivotal role in drug discovery due to their immense structural diversity wide variety of biological activities. The strategies greatly extend natural scaffolds through available chemical approaches offer unique opportunities access new series analogues, enabling the construction diverse product-like libraries. affordability these structurally molecules has been crucial step accelerating discovery. This review provides an overview various exploit compounds for product-based development, drawing upon examples illustrate each strategy.

Language: Английский

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Enzyme function prediction using contrastive learning

Science, Journal Year: 2023, Volume and Issue: 379(6639), P. 1358 - 1363

Published: March 31, 2023

Enzyme function annotation is a fundamental challenge, and numerous computational tools have been developed. However, most of these cannot accurately predict functional annotations, such as enzyme commission (EC) number, for less-studied proteins or those with previously uncharacterized functions multiple activities. We present machine learning algorithm named CLEAN (contrastive learning-enabled annotation) to assign EC numbers enzymes better accuracy, reliability, sensitivity compared the state-of-the-art tool BLASTp. The contrastive framework empowers confidently (i) annotate understudied enzymes, (ii) correct mislabeled (iii) identify promiscuous two more numbers-functions that we demonstrate by systematic in silico vitro experiments. anticipate this will be widely used predicting thereby advancing many fields, genomics, synthetic biology, biocatalysis.

Language: Английский

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Discovery of a pathway for terminal-alkyne amino acid biosynthesis

Nature, Journal Year: 2019, Volume and Issue: 567(7748), P. 420 - 424

Published: March 1, 2019

Language: Английский

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Neurotoxicity of polychlorinated biphenyls and related organohalogens

Acta Neuropathologica, Journal Year: 2019, Volume and Issue: 138(3), P. 363 - 387

Published: April 11, 2019

Language: Английский

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Flavoprotein monooxygenases: Versatile biocatalysts

Biotechnology Advances, Journal Year: 2021, Volume and Issue: 51, P. 107712 - 107712

Published: Feb. 15, 2021

Flavoprotein monooxygenases (FPMOs) are single- or two-component enzymes that catalyze a diverse set of chemo-, regio- and enantioselective oxyfunctionalization reactions. In this review, we describe how FPMOs have evolved from model in mechanistic flavoprotein research to biotechnologically relevant catalysts can be applied for the sustainable production valuable chemicals. After historical account development FPMO field, explain classification system, which is primarily based on protein structural properties electron donor specificities. We then summarize most appealing reactions catalyzed by each group with focus different types oxygenation chemistries. Wherever relevant, report engineering strategies been used improve robustness applicability FPMOs.

Language: Английский

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