Stereoselective Substrate-Controlled Asymmetric Syntheses of both 2,5-cis
- and 2,5-trans
-Tetrahydrofuranoid Oxylipids: Stereodivergent Intramolecular Amide Enolate Alkylation

A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (JDP-107) with an optimal combination of potency (IC<sub>50</sub>= 0.16 𝜇M in a Kv7.2 thallium flux assay), efficacy in a Kv7.2/7.3 patch clamp assay, and drug-like properties.

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Enantioselective Syntheses of Flavonoid Diels-Alder Natural Products: A Review

Current Organic Synthesis ◽

10.2174/1570179414666170821120234 ◽

2018 ◽

Vol 15 (2) ◽

pp. 221-229 ◽

Cited By ~ 3

Author(s):

Shah Bakhtiar Nasir ◽

Noorsaadah Abd Rahman ◽

Chin Fei Chee

Keyword(s):

Natural Products ◽

Organic Synthesis ◽

Lewis Acid ◽

Alder Reaction ◽

Diels Alder ◽

Enantioselective Synthesis ◽

Chiral Ligand ◽

Asymmetric Syntheses ◽

Diels Alder Reaction ◽

Enantioselective Syntheses

Background: The Diels-Alder reaction has been widely utilised in the syntheses of biologically important natural products over the years and continues to greatly impact modern synthetic methodology. Recent discovery of chiral organocatalysts, auxiliaries and ligands in organic synthesis has paved the way for their application in Diels-Alder chemistry with the goal to improve efficiency as well as stereochemistry. Objective: The review focuses on asymmetric syntheses of flavonoid Diels-Alder natural products that utilize chiral ligand-Lewis acid complexes through various illustrative examples. Conclusion: It is clear from the review that a significant amount of research has been done investigating various types of catalysts and chiral ligand-Lewis acid complexes for the enantioselective synthesis of flavonoid Diels-Alder natural products. The results have demonstrated improved yield and enantioselectivity. Much emphasis has been placed on the synthesis but important mechanistic work aimed at understanding the enantioselectivity has also been discussed.

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ChemInform Abstract: ORIGINS OF STEREOSELECTIVITY IN ASYMMETRIC SYNTHESES USING CHIRAL OXAZOLINES

Chemischer Informationsdienst ◽

10.1002/chin.197912122 ◽

1979 ◽

Vol 10 (12) ◽

Author(s):

M. A. HOOBLER ◽

D. E. BERGBREITER ◽

M. NEWCOMB

Keyword(s):

Asymmetric Syntheses

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l-Prolinal Dithioacetal: A Highly Effective Organocatalyst for the Direct Nitro-Michael Addition to Selected Cyclic and Aromatic Ketones

Synthesis ◽

10.1055/s-0037-1611531 ◽

2019 ◽

Vol 51 (17) ◽

pp. 3356-3368

Author(s):

Piotr Pomarański ◽

Zbigniew Czarnocki

Keyword(s):

Michael Addition ◽

Ring Size ◽

Cyclic Ketones ◽

Asymmetric Syntheses ◽

Aromatic Ketones ◽

Ring Systems ◽

Effective Catalyst ◽

Acetophenone Derivatives ◽

Highly Effective ◽

Related Compounds

The synthesis of novel l-prolinal dithioacetal and its application as an organocatalyst for the direct Michael addition of cyclic ketones and acetophenone derivatives to trans-β-nitrostyrene and related compounds is described. The prolinal dithioacetal acts as effective catalyst in the case of cyclic ketones of different ring size, in particular five- and six-membered examples, as well as larger and smaller ring systems. High enantioselectivity and diastereoselectivity is observed for different substrates and trans-β-nitrostyrenes. Also, the first asymmetric syntheses of selected 2-methyl-4-nitro-1,3-diphenylbutan-1-one derivatives by application of the obtained organocatalyst is presented.

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