Stereoselective Synthesis of <i>cis</i>-2,5-Disubstituted THFs: Application to Adjacent Bis-THF Cores of Annonaceous Acetogenins

Fujioka, Hiromichi; Maehata, Ryota; Wakamatsu, Shintaro; Nakahara, Kenji; Hayashi, Tatsuya; Oki, Tomohiro

doi:10.1021/ol203425p

Cited by 20 publications

(10 citation statements)

References 30 publications

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“…For the diastereoselective synthesis of cis-iodomethyl tetrahydrofurans rac-18b,d, a modified literature procedure was applied. 60 Homo allyl alcohols rac-15b,d were protected with a triethylsilyl group to give derivatives rac-16b,d. Subsequent NIS-promoted cyclization gave the desired intermediates rac-Table 2.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Fragment-Based Discovery of 2-Aminoquinazolin-4(3H)-ones As Novel Class Nonpeptidomimetic Inhibitors of the Plasmepsins I, II, and IV

et al. 2015

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2-Aminoquinazolin-4(3H)-ones were identified as a novel class of malaria digestive vacuole plasmepsin inhibitors by using NMR-based fragment screening against Plm II. Initial fragment hit optimization led to a submicromolar inhibitor, which was cocrystallized with Plm II to produce an X-ray structure of the complex. The structure showed that 2-aminoquinazolin-4(3H)-ones bind to the open flap conformation of the enzyme and provided clues to target the flap pocket. Further improvement in potency was achieved via introduction of hydrophobic substituents occupying the flap pocket. Most of the 2-aminoquinazolin-4(3H)-one based inhibitors show a similar activity against digestive Plms I, II, and IV and >10-fold selectivity versus CatD, although varying the flap pocket substituent led to one Plm IV selective inhibitor. In cell-based assays, the compounds show growth inhibition of Plasmodium falciparum 3D7 with IC50 ∼ 1 μM. Together, these results suggest 2-aminoquinazolin-4(3H)-ones as perspective leads for future development of an antimalarial agent.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Fragment-Based Discovery of 2-Aminoquinazolin-4(3H)-ones As Novel Class Nonpeptidomimetic Inhibitors of the Plasmepsins I, II, and IV

et al. 2015

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“…Intermediate 16 was further treated with vinyl MgBr/CuI followed by an acetonide deprotection to yield compound 13, [25] which is a precursor for cyclization. An iodoetherification [26,27] reaction on compound 13 produced trans-and cis-2,5-disubstituted tetrahydrofuran derivatives, (12 a and 12 b) in 4 : 1 ratio. These two diastereomers were easily separated by column chromatography and the pure products were then thoroughly analysed by 1D and 2D NMR studies (see supporting information).…”

Section: Resultsmentioning

confidence: 99%

Stereoselective Approaches for Building the C14‐C21 Fragment of Eribulin

et al. 2021

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“…41 This method is based on a TMS transfer, triggered by trimethylsiloxycyclohexene, to generate a steric bulk that will allow the cis-selectivity (Scheme 11). In this case, the cis-THF products are obtained in very good yields and good diastereoselectivies (dr up to 15:1).…”

Section: Scheme 10: Diastereospecific Iodocyclization To Form Trans-thfmentioning

confidence: 99%

Recent advances in the synthesis of tetrahydrofurans and applications in total synthesis

et al. 2016

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Mousseron. His research interests include the total synthesis of oxygenated cyclic and non cyclic metabolites of polyunsaturated fatty acids, mainly leukotrienes, iso-, phyto-and neuroprostanes, as well as dihydroxylated PUFAs and more recently lipophenols and the understanding of the role of such bioactive lipids and lipophenols by developing collaborations with chemists, biochemists, biologists and clinicians across the world. Jean-Marie Galano studied chemistry at Paul Cézanne Université Marseille and obtained his PhD under the supervision of Honoré Monti in 2001. He then moved to the University of Oxford to pursue a postdoctoral fellowship with David H. Hodgson on the development of new methods for the total synthesis of natural products. In October 2005 he joined the CNRS as a Chargé de Recherche at Université of Montpellier. His research focuses on the total synthesis and discovery of new lipid metabolites, and to discover their potential implications in human health. AbstractMany natural products contain tetrahydrofuran (THF) moieties. Those molecules, often biologically active, may be structurally diverse, e.g. cis or trans THF, mono-, di-, tri-or tetrasubstituted on the furan ring. Thus, the construction of THF is of great interest for the community of organic chemists; especially in developing new methodologies, and applying them in the total synthesis of natural products. The aim of this review is to report recent advances in the field of THF synthesis, as well as the application of these methods to the synthesis of bioactive compounds.

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Stereoselective Synthesis of cis-2,5-Disubstituted THFs: Application to Adjacent Bis-THF Cores of Annonaceous Acetogenins

Cited by 20 publications

References 30 publications

Fragment-Based Discovery of 2-Aminoquinazolin-4(3H)-ones As Novel Class Nonpeptidomimetic Inhibitors of the Plasmepsins I, II, and IV

Fragment-Based Discovery of 2-Aminoquinazolin-4(3H)-ones As Novel Class Nonpeptidomimetic Inhibitors of the Plasmepsins I, II, and IV

Stereoselective Approaches for Building the C14‐C21 Fragment of Eribulin

Recent advances in the synthesis of tetrahydrofurans and applications in total synthesis

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