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
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
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
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
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
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
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)