Deukjoon Kim

Design and synthesis of highly potent fumagillin analogues from homology modeling for a human MetAP-2.

New fumagillin analogues were designed through structure-based molecular modeling with a human methionine aminopeptidase-2. Among the fumagillin analogues, cinnamic acid ester derivative CKD-731 showed 1000-fold more potent proliferation inhibitory activity on endothelial cell than TNP-470.

Simultaneous determination of anti‐diabetes/anti‐obesity drugs by LC/PDA, and targeted analysis of sibutramine analog in dietary supplements by LC/MS/MS

The safety of dietary supplements is questionable as there have been occasional reports of products contaminated with illegal adulterants. The present study was carried out to develop trustworthy methodologies to screen for six anti-diabetic drugs (phenformin, rosiglitazone, glipizide, glimepiride, glybenclamide and gliclazide) and six anti-obesity drugs (ephedrine, fenfluramine, T3, T4, fluoxetine and sibutramine) in dietary supplements. A simultaneous determination method of the 12 drugs by liquid chromatography coupled with a photodiode array (LC/PDA) was established and was validated for linearity (r(2) > 0.99), precision (RSD <13.3%), recoveries (88.8-115.9%) and reproducibility. Sibutramine and its analogs, N-desmethylsibutramine, were subject to further investigation by LC/MS/MS because they were one of the major illegal adulterants. Our proposed method to monitor illegal drug adulterations in dietary supplements using LC/PDA is a simple and reliable, and therefore applicable to routine drug-adulteration screening.

Biomimetic asymmetric total synthesis of (-)-laurefucin via an organoselenium-mediated intramolecular hydroxyetherification.

The first asymmetric total synthesis of (-)-laurefucin (1), a unique C-15 acetogenin with a 2,8-dioxabicyclo[5.2.1]decane skeleton, has been accomplished in nine steps in 31% overall yield from known oxocene 10. Highlights of the highly stereoselective synthesis include a novel organoselenium-mediated biomimetic hydroxyetherification.

An asymmetric total synthesis of (−)-fumagillol

Abstract (−)-Fumagillol (2), a hydrolysis product of fumagillin (1), has been synthesized in a highly stereoselective manner utilizing a glycolate Claisen rearrangement and an intramolecular ester enolate alkylation as key steps starting from carbohydrate-based precursor 5.

Asymmetric Total Synthesis of (+)‐Bermudenynol, a C15 Laurencia Metabolite with a Vinyl Chloride Containing Oxocene Skeleton, through Intramolecular Amide Enolate Alkylation

A substrate-controlled asymmetric total synthesis of (+)-bermudenynol, a compact and synthetically challenging C15 Laurencia metabolite that contains several halogen atoms, is reported. The oxocene core, which contains a vinyl chloride, was constructed by an efficient and highly stereoselective intramolecular amide enolate alkylation (IAEA). This result showcases the broad utility of the IAEA methodology as a useful alternative for cases in which the ring-closing metathesis is inefficient.

Magneto thermoelectric power of the doped polyacetylene

Abstract Thermoelectric power (TEP) and electrical conductivity of the metallic polyacetylene (PA) doped with AuCl 3 and I 2 are measured under high magnetic field up to 17 Tesla. We have observed the following two remarkable behaviors in the TEP results; (1) the temperature dependence of TEP for the iodine and metal-halide doped polyacetylene show clear difference at T

Stereocontrolled Total Synthesis of (+)‐trans‐Dihydronarciclasine

A highly stereoselective and efficient total synthesis of trans-dihydronarciclasine from a readily available chiral starting material was developed. The synthesis defines two of the five stereogenic centers of the natural product by an amino acid ester-enolate Claisen rearrangement. The other three stereogenic centers are created in a highly stereocontrolled fashion via a six-ring vinylogous ester intermediate, which is generated from the γ,δ-unsaturated ester functional group of the Claisen rearrangement product in an efficient three-step sequence. This concise total synthesis exemplifies the use of a highly regioselective Friedel-Crafts-type cyclization to form the B ring via an isocyanate intermediate derived from an N-Boc group, which is superior to the conventional method using an imino triflate intermediate. This same N-Boc group is employed to give high selectivity in the Claisen rearrangement earlier in the sequence.

Stereoselective synthesis of (±)-β-elemene by a doubly diastereodifferentiating internal alkylation: a remarkable difference in the rate of enolization between syn and anti esters

Abstract A total synthesis of the sesquiterpene (±)- β -elemene ( 1 ) has been achieved starting from a simple acyclic precursor 4 . Key transformations include a ‘doubly diastereodifferentiating folding and allylic strain-controlled’ intramolecular ester enolate alkylation. In the course of the synthesis, we encountered remarkably different reactivity between syn and anti diastereomeric esters in the enolization step.

Total synthesis and determination of the absolute configuration of (+)-neoisoprelaurefucin

The first total synthesis of the seven-membered ring ether marine natural product (+)-neoisoprelaurefucin (1) has been achieved employing a regioselective internal alkylation of amide 3, a novel sequence for removal of the triethylsilyl group from the resulting triethylsilyloxepene 2, and a bromoetherification of alcohol 16 as key steps. In addition, the absolute stereochemistry of the natural product was assigned.

Highly stereoselective intramolecular alkylation of ester enolate: an approach to trans-hydrindane system

Abstract Highly diastereoselective intramolecular alkylation of acyclic ester system was developed based upon allylic strain concept as an approach to trans-hydrindane system.