Bioinspired Skeletal Reorganization Approach for the Synthesis of Steroid Natural Products DOI
Yu Wang, Jinghan Gui

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 1, 2024

ConspectusSteroids, termed "keys to life" by Rupert Witzmann, have a wide variety of biological activities, including anti-inflammatory, antishock, immunosuppressive, stress-response-enhancing, and antifertility steroid research has made great contributions drug discovery development. According chart compiled the Njardarson group at University Arizona, 15 top 200 small-molecule drugs (by retail sales in 2022) are steroid-related compounds. Therefore, synthetic medicinal chemists long pursued chemical synthesis natural products (SNPs) with diverse architectures, vital progress been achieved, especially twentieth century. In fact, several rewarded Nobel Prize for original isolation steroids, elucidation their structures biosynthetic pathways, synthesis. However, contrast classical which 6/6/6/5-tetracyclic framework, rearranged steroids (i.e., abeo-steroids secosteroids), derived from reorganization one or more C–C bonds tetracyclic skeleton, started gain attention community only last two decades. These unique complex frameworks high oxidation states, rich stereogenic centers, attractive rendering them popular yet formidable targets.Our strong interest efficient SNPs and, drawing inspiration nature, we found that bioinspired skeletal (BSR) is an strategy synthesizing challenging steroids. Using this strategy, recently achieved concise syntheses five different kinds (cyclocitrinols, propindilactone G, bufospirostenin A, pinnigorgiol B, sarocladione) considerably skeletons; our work also enabled us reassign originally proposed structure sarocladione. Account, summarize biosyntheses these describe BSR approach rapid construction core frameworks. described herein, information gleaned allowed develop routes cases, precursors used differed substantially intermediates biosyntheses, indicating considerable challenges encountered during campaign. It worth mentioning pursuit scalable products, developed methods accessing synthetically targets: method bridged-ring molecules means point-to-planar chirality transfer macrocyclic via novel ruthenium-catalyzed endoperoxide fragmentation. Our vividly demonstrate consideration product biosynthesis can greatly facilitate synthesis, expect will find additional applications other structurally terpenoid products.

Language: Английский

Late-stage C–H functionalization offers new opportunities in drug discovery DOI
Lucas Guillemard, Nikolaos Kaplaneris, Lutz Ackermann

et al.

Nature Reviews Chemistry, Journal Year: 2021, Volume and Issue: 5(8), P. 522 - 545

Published: July 13, 2021

Language: Английский

Citations

582
Biocatalysis DOI Open Access
Elizabeth L. Bell, William Finnigan, Scott P. France

et al.

Nature Reviews Methods Primers, Journal Year: 2021, Volume and Issue: 1(1)

Published: June 24, 2021

Language: Английский

Citations

438
Power of Biocatalysis for Organic Synthesis DOI Creative Commons
Christoph K. Winkler, Joerg H. Schrittwieser, Wolfgang Kroutil

et al.

ACS Central Science, Journal Year: 2021, Volume and Issue: 7(1), P. 55 - 71

Published: Jan. 14, 2021

Biocatalysis, using defined enzymes for organic transformations, has become a common tool in synthesis, which is also frequently applied industry. The generally high activity and outstanding stereo-, regio-, chemoselectivity observed many biotransformations are the result of precise control reaction active site biocatalyst. This achieved by exact positioning reagents relative to each other fine-tuned 3D environment, specific activating interactions between protein, subtle movements catalyst. Enzyme engineering enables one adapt catalyst desired process. A well-filled biocatalytic toolbox ready be used various reactions. Providing nonnatural conditions evolving biocatalysts play with myriad options creating novel transformations thereby opening new, short pathways target molecules. Combining several pot perform reactions concurrently increases efficiency biocatalysis even further.

Language: Английский

Citations

288
Shortening Synthetic Routes to Small Molecule Active Pharmaceutical Ingredients Employing Biocatalytic Methods DOI Creative Commons
Stefan Simić,

Erna Zukić,

Luca Schmermund

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(1), P. 1052 - 1126

Published: Nov. 30, 2021

Biocatalysis, using enzymes for organic synthesis, has emerged as powerful tool the synthesis of active pharmaceutical ingredients (APIs). The first industrial biocatalytic processes launched in half last century exploited whole-cell microorganisms where specific enzyme at work was not known. In meantime, novel molecular biology methods, such efficient gene sequencing and triggered breakthroughs directed evolution rapid development process-stable with broad substrate scope good selectivities tailored substrates. To date, are employed to enable shorter, more efficient, sustainable alternative routes toward (established) small molecule APIs, additionally used perform standard reactions API efficiently. Herein, large-scale synthetic containing key steps >130 APIs approved drugs drug candidates compared corresponding chemical protocols (if available) regarding steps, reaction conditions, scale. review is structured according functional group formed reaction.

Language: Английский

Citations

177
Biocatalysis making waves in organic chemistry DOI Creative Commons
Ulf Hanefeld, Frank Hollmann, Caroline E. Paul

et al.

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 51(2), P. 594 - 627

Published: Dec. 20, 2021

The many waves of biocatalysis have arisen to solve long-standing synthetic challenges. From industrially applied hydrolases enzymes catalysing selective C–C-bond formation, enables new tools access a plethora compounds.

Language: Английский

Citations

176
Electrochemical Late-Stage Functionalization DOI Creative Commons
Yulei Wang, Suman Dana, Hao Long

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(19), P. 11269 - 11335

Published: Sept. 26, 2023

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical biological activities. LSF can thus greatly accelerate development medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical synthesis has emerged as an environmentally friendly platform transformation organic compounds. Over past decade, electrochemical late-stage (eLSF) gained major momentum, which is summarized herein up to February 2023.

Language: Английский

Citations

141
A tautomeric ligand enables directed C‒H hydroxylation with molecular oxygen DOI
Zhen Li, Zhen Wang, Nikita Chekshin

et al.

Science, Journal Year: 2021, Volume and Issue: 372(6549), P. 1452 - 1457

Published: June 24, 2021

Easing oxygen into arenes Although is all around us, it often surprisingly difficult to use for selective chemical oxidations, necessitating more expensive, wasteful alternatives. Li et al. report that careful ligand optimization produces palladium catalysts can efficiently activate hydroxylate a variety of aryl and heteroaromatic rings adjacent carboxylic acid substituent. The binds through pyridine pyridone components, the authors posit tautomerization between dative anionic coordination modes plays role in its effectiveness. Science , abg2362, this issue p. 1452

Language: Английский

Citations

129
Catalytic enantioselective C(sp3)–H functionalization involving radical intermediates DOI Creative Commons
Chi Zhang, Zhong‐Liang Li, Qiang‐Shuai Gu

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 20, 2021

Abstract Recently, with the boosted development of radical chemistry, enantioselective functionalization C( sp 3 )–H bonds via a pathway has witnessed renaissance. In principle, two distinct catalytic modes, distinguished by steps in which stereochemistry is determined (the formation step or step), can be devised. This Perspective discusses state-of-the-art area involving intermediates as well future challenges and opportunities.

Language: Английский

Citations

116
Biocatalytic oxidative cross-coupling reactions for biaryl bond formation DOI
Lara Zetzsche, Jessica Yazarians, Suman Chakrabarty

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7899), P. 79 - 85

Published: March 2, 2022

Language: Английский

Citations

110
State-of-the-Art Biocatalysis DOI Creative Commons
Joshua B. Pyser, Suman Chakrabarty, Evan O. Romero

et al.

ACS Central Science, Journal Year: 2021, Volume and Issue: 7(7), P. 1105 - 1116

Published: June 25, 2021

The use of enzyme-mediated reactions has transcended ancient food production to the laboratory synthesis complex molecules. This evolution been accelerated by developments in sequencing and DNA technology, bioinformatic protein engineering tools, increasingly interdisciplinary nature scientific research. Biocatalysis become an indispensable tool applied academic industrial spheres, enabling synthetic strategies that leverage exquisite selectivity enzymes access target In this Outlook, we outline technological advances have led field's current state. Integration biocatalysis into mainstream chemistry hinges on increased well-characterized permeation retrosynthetic logic. Ultimately, anticipate is poised enable molecules at new levels efficiency throughput.

Language: Английский

Citations

106