6 research outputs found

    Organocatalyzed Asymmetric Michael Addition of 1‑Acetylindolin-3-ones to β,γ-Unsaturated α‑Ketoesters: An Access to Chiral Indolin-3-ones with Two Adjacent Tertiary Stereogenic Centers

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    Asymmetric Michael addition of 1-acetylindolin-3-ones to β,γ-unsaturated α-ketoesters was investigated for the synthesis of chiral indolin-3-ones with two adjacent tertiary stereogenic centers. Under the catalysis of a chiral bifunctional squaramide derived from l-<i>tert</i>-leucine, a wide range of 1-acetylindolin-3-ones and β,γ-unsaturated α-ketoesters were well-tolerated in this transformation to provide the corresponding novel densely functionalized chiral indolin-3-one derivatives in high yield with excellent diastereo- and enantioselectivity under mild reaction conditions

    Stereocontrolled Construction of Tetrahydro­pyrano­[2,3‑<i>c</i>]pyrazole Scaffold via an Organocatalyzed Formal [3 + 3] Annulation

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    A bifunctional squaramide catalyzed enantioselective formal [3 + 3] annulation reaction with pyrazolin-5-ones and nitroallylic acetates has been developed. Densely substituted tetrahydro­pyrano­[2,3-<i>c</i>]­pyrazoles with two adjacent stereogenic centers are obtained in a highly stereocontrolled manner. Representative transformation of the annulation product to a biologically important fused dihydroisoquinoline is achieved without any appreciable loss in the diastereo- and enantioselectivity

    Application of “Hydrogen Bonding Interaction” in New Drug Development: Design, Synthesis, Antiviral Activity, and SARs of Thiourea Derivatives

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    A series of simple thiourea derivatives were designed based on the structure of natural product harmine and lead compound and synthesized from amines in one step. The antiviral activity of these thiourea derivatives was evaluated. Most of them exhibited significantly higher anti-TMV activity than commercial plant virucides ribavirin, harmine, and lead compound. The hydrogen bond was found to be important but not the more the better. The optimal compound (<i>R</i>,<i>R</i>)-<b>20</b> showed the best anti-TMV activity in vitro and in vivo (in vitro activity, 75%/500 μg/mL and 39%/100 μg/mL; inactivation activity, 71%/500 μg/mL and 35%/100 μg/mL; curative activity, 73%/500 μg/mL and 37%/100 μg/mL; protection activity, 69%/500 μg/mL and 33%/100 μg/mL), which is significantly higher than that of Ningnanmycin. The systematic study provides strong evidence that these simple thiourea derivatives could become potential TMV inhibitors

    Application of “Hydrogen-Bonding Interaction” in Drug Design. Part 2: Design, Synthesis, and Structure–Activity Relationships of Thiophosphoramide Derivatives as Novel Antiviral and Antifungal Agents

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    On the basis of the structure of natural product harmine, lead compound <b>18</b>, and the structure of compounds in part 1, a series of thiophosphoramide derivatives <b>1</b>–<b>17</b> were designed and synthesized from various amines in one step. Their antiviral and antifungal activities were evaluated. Most of the compounds showed significantly higher antiviral activity against tobacco mosaic virus (TMV) than commercial virucide ribavirin. Compound (<i>R</i>,<i>R</i>)-<b>17</b> showed the best anti-TMV activity <i>in vitro</i> (70%/500 μg/mL and 33%/100 μg/mL) and <i>in vivo</i> (inactivation effect, 68%/500 μg/mL and 30%/100 μg/mL; curative effect, 64%/500 μg/mL and 31%/100 μg/mL; protection effect, 66%/500 μg/mL and 31%/100 μg/mL), which is higher than that of ningnanmycin and lead compound <b>18</b>. The antiviral activity of (<i>R</i>,<i>R</i>)-<b>17</b>·HCl is about similar to that of (<i>R</i>,<i>R</i>)-<b>17</b>. However, the antifungal activity of (<i>R</i>,<i>R</i>)-<b>17</b>·HCl against Puccinia sorghi is slightly lower than that of (<i>R</i>,<i>R</i>)-<b>17</b>. The systematic study provides compelling evidence that these simple thiophosphoramide compounds could become efficient antiviral and antifungal agents

    Asymmetric Formal [4 + 2] Annulation of <i>o</i>‑Quinone Methides with β‑Keto Acylpyrazoles: A General Approach to Optically Active <i>trans</i>-3,4-Dihydrocoumarins

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    An asymmetric cascade reaction between β-keto acylpyrazoles and <i>o</i>-quinone methides in a formal [4 + 2] fashion to access potentially pharmacological active <i>trans</i>-3,4-dihydrocoumarins has been achieved efficiently by using a quinine-based chiral squaramide as the catalyst. The desired products were obtained in high yields with excellent diastereo- and enantioselectivities (up to 96% yield, >19/1 dr and 96% ee) under mild reaction conditions

    Enantioselective Synthesis of <i>trans</i>-Dihydrobenzofurans via Primary Amine-Thiourea Organocatalyzed Intramolecular Michael Addition

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    A primary amine-thiourea organocatalyzed intramolecular Michael addition access was developed for the synthesis of <i>trans</i>-dihydrobenzofurans. Under the catalysis of an (<i>R</i>,<i>R</i>)-1,2-diphenylethylamine derived primary amine-thiourea bearing a glucosyl scaffold, the corresponding <i>trans</i>-dihydrobenzofurans were obtained in high yields with excellent level of enantioselectivities (94 to >99% ee). Moreover, an in situ isomerization occurring at high temperature gave good to excellent <i>trans</i>/<i>cis</i> ratios as well (<i>trans</i>/<i>cis</i>: 84/16–96/4)
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