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Total synthesis
About: Total synthesis is a research topic. Over the lifetime, 25578 publications have been published within this topic receiving 489319 citations.
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TL;DR: This review aims to highlight the origins, structures, biological potencies, and synthetic approaches of those natural products bearing at least one benzofuran in their complex structures and especially focus on the step in which this key heterocycle is installed during the total synthesis of a natural product as the desired target.
Abstract: Research on natural products containing benzofuran has remarkably increased during the past few decades. Newly isolated natural products with complex structures are being studied, characterized and screened for possible biological activities. Several of such compounds have exhibited various biological activities, thus their total syntheses have attracted much attention from synthetic organic chemists. In this review, we aim to highlight the origins, structures, biological potencies, and synthetic approaches of those natural products bearing at least one benzofuran in their complex structures. Furthermore, we especially focus on the step in which this key heterocycle is installed during the total synthesis of a natural product as the desired target.
111 citations
TL;DR: The potent bryostatin antitumor agents are currently in phase II clinical trials for the treatment of a variety of forms of cancer.
Abstract: The potent bryostatin antitumor agents are currently in phase II clinical trials for the treatment of a variety of forms of cancer. Aldol reactions and directed reductions are among the essential steps for the formation of fragments A-C in the total synthesis of the title compound. Coupling of these fragments by sulfone-based olefination and alkylation reactions was followed by macrocyclization and introduction of the enoate moieties on rings B and C.
110 citations
TL;DR: In this paper, an enantioselective first total synthesis of laulimalide (1) was described, which involved the assembly of C3−C16 segment 4 and C17−C28 segment 5 by Julia olefination and photoisomerization to a mixture of cis- and trans-isomers.
Abstract: An enantioselective first total synthesis of laulimalide (1) is described. Laulimalide, a remarkably potent antitumor macrolide, has been isolated from the Indonesian sponge Hyattella sp. and the Okinawan sponge Fasciospongia rimosa. Laulimalide represents a new class of antitumor agents with significant clinical potential. The synthesis is convergent and involved the assembly of C3−C16 segment 4 and C17−C28 segment 5 by Julia olefination. The sensitive C2−C3 cis-olefin functionality was installed by Yamaguchi macrolactonization of a hydroxy alkynic acid followed by hydrogenation of the resulting alkynoic lactone over Lindlar's catalyst. Initial attempts of intramolecular Still's variant of Horner−Emmons olefination between the C19-phosphonocetate and C3-aldehyde provided a 1:2 mixture of cis- and trans-macrolactones. The trans-isomer was photoisomerized to a mixture of cis- and trans-isomers. The other key steps involved ring-closing olefin metathesis to construct both dihydropyran units, stereoselective...
110 citations
TL;DR: Dramatic solvent effects observed in the macrolactonization reaction suggest that hydrogen-bonding effects play a critical role in the biologically active marine natural product leucascandrolide A.
Abstract: The total synthesis of the biologically active marine natural product leucascandrolide A is reported. A convergent strategy is employed, allowing for the rapid assembly of the macrolide moiety. Key steps of our approach include the diastereoselective addition of a zinc alkynilide to (R)-isopropylidene glyceraldehyde, the enantioselective copper(I) fluoride catalyzed aldol addition of a TMS-dienolate to crotonaldehyde, and the formation of a 2,6-trans-substituted tetrahydropyran by selenium-mediated intramolecular cyclization. Moreover, dramatic solvent effects observed in the macrolactonization reaction suggest that hydrogen-bonding effects play a critical role. An improved route to a key intermediate of our synthesis is documented.
110 citations
TL;DR: The ability to halogenate the pyrrole core in a regioselective fashion, even in the presence of highly electron-rich aryl substituents, has been established and the compatibility of Suzuki coupling conditions with free alcohols and phenols in the boronic acids has been employed to reduce the number of protection/deprotection steps.
Abstract: A modular synthesis of the lamellarin family of natural products has been developed that is based on the application of three iterative halogenation/cross-coupling reaction sequences. The ability to halogenate the pyrrole core in a regioselective fashion, even in the presence of highly electron-rich aryl substituents, has been established. The compatibility of Suzuki coupling conditions with free alcohols and phenols in the boronic acids has been employed to reduce the number of protection/deprotection steps. Indeed, the presence of a free phenol on boronic acid 3 has been determined to be critical for the successful final coupling in route to lamellarin G trimethyl ether, since protected versions fail to undergo coupling.
110 citations