Design, synthesis, and biological evaluation of a biyouyanagin compound library

Nicolaou, K. C.; Sanchini, Silvano; Šarlah, David; Lü, Gang; Wu, Tingting; Nomura, Daniel K.; Cravatt, Benjamin F.; Cubitt, Beatrice; Torre, Juan Carlos de la; Hessell, Ann J.; Burton, Dennis R.

doi:10.1073/pnas.1015258108

Cited by 31 publications

(18 citation statements)

References 38 publications

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“…Delightfully, in the presence of TMSBr reagent, the optically active ( S , S )- 2b , ( S , R )- 2b′ , ( R , S )- 2n′ and ( S , S )- 2n could participate in the transformation well, delivering hyperolactones B, C and epi -hyperolactones B, C in excellent yields with the diastereo- and enantioselectivity maintained (For details, see Supplementary Note 11 ). Accordingly, the access to natural product (−)-biyouyanagin A and its epimer is possible from the key reaction intermediates 26 , 27 29 , 31 of hyperolactone C or epi -hyperolactone C (Fig. 5 ).…”

Section: Resultsmentioning

confidence: 99%

Stereodivergent synthesis of vicinal quaternary-quaternary stereocenters and bioactive hyperolactones

Zheng

Wang

et al. 2018

Nat Commun

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Although great success has been achieved in asymmetric Claisen rearrangement for the synthesis of chiral γ,δ-unsaturated carbonyl compounds bearing vicinal tertiary-quaternary stereocenters, the development of asymmetric versions for stereodivergent construction of adjacent quaternary-quaternary stereocenters remains a formidable challenge because of the high steric hindrance. Here we report a catalytic enantioselective dearomatization Claisen rearrangement of allyl furyl ethers catalyzed by chiral N,N′-dioxide-NiII complex catalysts. A variety of chiral γ,δ-unsaturated carbonyl compounds bearing vicinal quaternary-quaternary stereocenters were obtained with excellent outcomes under mild conditions. Furthermore, we disclosed that by matching the configuration of the catalysts and the alkene unit of the substrates, four stereoisomers of the products could be prepared in excellent yields and stereoselectivities. Finally, the fascination of this strategy was demonstrated by stereodivergent synthesis of bioactive natural products hyperolactones B, C, and their epimers. A possible catalytic model was proposed to explain the origin of the asymmetric induction.

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Section: Resultsmentioning

confidence: 99%

Stereodivergent synthesis of vicinal quaternary-quaternary stereocenters and bioactive hyperolactones

Zheng

Wang

et al. 2018

Nat Commun

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“…8). 181 In conclusion, a wealth of natural products has been reported to possess antiviral properties. In the majority of these cases the chemical structure was well identified but the full antiviral activity spectrum of the compounds still needs to be evaluated, their mode of action elucidated, and, most importantly, their therapeutic value delineated.…”

Section: Natural Products With Antiviral Activitymentioning

confidence: 97%

Highlights in Antiviral Drug Research: Antivirals at the Horizon

Clercq

2012

Medicinal Research Reviews

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This review highlights ten "hot topics" in current antiviral research: (i) new nucleoside derivatives (i.e., PSI-352938) showing high potential as a direct antiviral against hepatitis C virus (HCV); (ii) cyclopropavir, which should be further pursued for treatment of human cytomegalovirus (HCMV) infections; (iii) North-methanocarbathymidine (N-MCT), with a N-locked conformation, showing promising activity against both α- and γ-herpesviruses; (iv) CMX001, an orally bioavailable prodrug of cidofovir with broad-spectrum activity against DNA viruses, including polyoma, adeno, herpes, and pox; (v) favipiravir, which is primarily pursued for the treatment of influenza virus infections, but also inhibits the replication of other RNA viruses, particularly (-)RNA viruses such as arena, bunya, and hanta; (vi) newly emerging antiarenaviral compounds which should be more effective (and less toxic) than the ubiquitously used ribavirin; (vii) antipicornavirus agents in clinical development (pleconaril, BTA-798, and V-073); (viii) natural products receiving increased attention as potential antiviral drugs; (ix) antivirals such as U0126 targeted at specific cellular kinase pathways [i.e., mitogen extracellular kinase (MEK)], showing activity against influenza and other viruses; and (x) two structurally unrelated compounds (i.e., LJ-001 and dUY11) with broad-spectrum activity against virtually all enveloped RNA and DNA viruses.

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“…216 In addition to the chemical synthesis and structural elucidation advances made in this program, the modular synthetic strategy developed toward the biyouyanagin molecular scaffold allowed us to make significant contributions to the chemical biology of these molecules. 217 Thus, a series of designed biyouyanagin analogues were designed, synthesized, and evaluated in a number of biological assays leading to the discovery of promising anti-HIV and anti-arenavirus agents, as well as a number of selective inhibitors of lipopolysaccharide (LPS)-induced cytokine production. These biological studies underscored, once again, the importance of natural products as lead compounds for chemical biology and drug discovery research efforts, and of total synthesis as a tool for implementing such studies.…”

Section: Highlights Of Contributions From the Author’s Laboratoriesmentioning

confidence: 99%

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

et al. 2012

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The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon. Although the early beginnings of organic synthesis came about serendipitously, organic chemists quickly recognized its potential and moved decisively to advance and exploit it in myriad ways for the benefit of mankind. Indeed, from the early days of the synthesis of urea and the construction of the first carbon-carbon bond, the art of organic synthesis improved to impressively high levels of sophistication. Through its practice, today chemists can synthesize organic molecules—natural and designed—of all types of structural motifs and for all intents and purposes. The endeavor of constructing natural products—the organic molecules of nature—is justly called both a creative art and an exact science. Often called simply total synthesis, the replication of nature’s molecules in the laboratory reflects and symbolizes the state of the art of synthesis in general. In the last few decades a surge in total synthesis endeavors around the world led to a remarkable collection of achievements that covers a wide ranging landscape of molecular complexity and diversity. In this article, we present highlights of some of our contributions in the field of total synthesis of natural products of biological and medicinal importance. For perspective, we also provide a listing of selected examples of additional natural products synthesized in other laboratories around the world over the last few years.

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Design, synthesis, and biological evaluation of a biyouyanagin compound library

Cited by 31 publications

References 38 publications

Stereodivergent synthesis of vicinal quaternary-quaternary stereocenters and bioactive hyperolactones

Stereodivergent synthesis of vicinal quaternary-quaternary stereocenters and bioactive hyperolactones

Highlights in Antiviral Drug Research: Antivirals at the Horizon

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

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