Hyeung-geun Park

Trimeric Cinchona alkaloid phase-transfer catalyst: α,α′,α′′-tris[O(9)-allylcinchonidinium]mesitylene tribromide

A trimeric Cinchona alkaloid ammonium salt, α,α′,α′′-tris[O(9)-allylcinchonidinium]mesitylene tribromide has been prepared as a novel phase-transfer catalyst. The catalytic enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester using the trimer catalyst showed high enantioselectivity (90–97% ee).

Structure–activity relationship study of asiatic acid derivatives against beta amyloid (Aβ)-induced neurotoxicity

8 Semi-synthetic derivatives of asiatic acid were prepared and their protective effect against Aβ-induced neurotoxicity was evaluated. Among them, asiatic acid (2), and 4, 16 showed 97, 92 and 87% of protective effect, respectively.

Highly efficient ortho-fluoro-dimeric cinchona-derived phase-transfer catalysts

A series of cinchona alkaloid-derived dimeric quaternary ammonium salts were prepared as chiral phase-transfer catalysts by the introduction of various functional groups on the phenyl ligand. Among them, the 2-F-substituted derivative 21 showed the highest enantioselectivity in the alkylation of the glycine anion equivalent 1 (97 to >99% ee).

The highly enantioselective phase-transfer catalytic mono-alkylation of malonamic esters.

The phase-transfer catalytic alkylation of N,N-dialkylmalonamic tert-butyl esters in the presence of 1 mol% of (S,S)-3,4,5-trifluorophenyl-NAS bromide afforded highly enantioselective (S)-mono-alpha-alkylated products (up to 96% ee), which could be readily converted into versatile chiral building blocks without loss of chirality.

Enantioselective synthesis of (2R,3S)-(+)-catechin

Abstract A new enantioselective synthetic method for catechin from trans-methyl cinnamate derivative was developed via asymmetric dihydroxylation (ADH), the addition of an aryllithium species, followed by the Barton–McCombie reaction and an intramolecular Mitsunobu reaction as key steps.

An enantioselective synthesis of (+)-polyoxamic acid via phase-transfer catalytic conjugate addition and asymmetric dihydroxylation.

A new enantioselective synthetic method of (+)-polyoxamic acid is reported. (+)-Polyoxamic acid could be obtained in 7 steps with 46% overall yield from diphenylmethyl-glycineimine tert-butyl ester via an enantioselective phase-transfer conjugate addition (99% yield, 96% ee) and an asymmetric dihydroxylation (98% yield, 94% de) as the key reactions.

RORα decreases oxidative stress through the induction of SOD2 and GPx1 expression and thereby protects against nonalcoholic steatohepatitis in mice.

AIMS Increased hepatic oxidative stress and inflammation is the main cause of exacerbating nonalcoholic steatohepatitis (NASH). Retinoic acid-related orphan receptor α (RORα) regulates diverse target genes associated with lipid metabolism, and its expression level is low in the liver of patients with NASH. Here, we investigated the role of RORα in regulating hepatic oxidative stress and inflammation. RESULTS First, cholesterol sulfate (CS), an agonist of RORα, lowered oxidative stress that was induced by 1.5 mM oleic acid in the primary cultures of hepatocytes. Second, exogenously introduced RORα or CS treatment induced the mRNA level of antioxidant enzymes, superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPx1), through the RORα response elements located in the upstream promoters of Sod2 and Gpx1. Third, RORα significantly decreased reactive oxygen species levels and mRNA levels of tumor necrosis factor α (TNFα) and interleukin-1β that were induced by lipopolysaccharide or TNFα in Kupffer cells. Finally, the administration of JC1-40 decreased the signs of liver injury, lipid peroxidation, and inflammation in the MCD diet-induced NASH mice. INNOVATION AND CONCLUSION We showed for the first time that RORα and its ligands protect NASH in mice by reducing hepatic oxidative stress and inflammation. Further, the molecular mechanism of the protective function of RORα against oxidative stress in the liver was revealed. These findings may offer a rationale for developing therapeutic strategies against NASH using RORα ligands.

Enantioselective synthetic method for 3-hydroxyflavanones: an approach to (2R,3R)-3′,4′-O-dimethyltaxifolin

A new enantioselective synthetic method for (2R,3R)-3-hydroxyflavanone (1a) was developed via asymmetric dihydroxylation (ADH) and intramolecular Mitsunobu reaction as key reactions and the application to synthesis of (2R,3R)-3′,4′-O-dimethyltaxifolin (1b) is described.

Synthesis and in vitro cytotoxicity of C(20)(RS)-camptothecin analogues modified at both B (or A) and E ring

A series of C(7) and C(20)-substituted camptothecin derivatives (12-14, 16-18) are prepared. Their syntheses and in vitro cytotoxicities are reported.

Highly Enantioselective Total Synthesis of (+)-Isonitramine

A new efficient enantioselective synthetic method of (+)-isonitramine is reported. (+)-Isonitramine was obtained in 12 steps (98% ee and 43% overall yield) from δ-valerolactam via enantioselective phase-transfer catalytic alkylation, Dieckman condensation, and diastereoselective reduction as key steps.