Seok-Ho Kim

Hepatoprotective pyrrole derivatives of Lycium chinense fruits

As a part of our search for hepatoprotective compounds from Lycium chinense fruits, three new pyrrole derivatives (1-3) were isolated. These compounds and a related synthetic methylated compound (4) were evaluated for their biological activity and structure-activity relationship, and compounds 1 and 2 showed hepatoprotective effects comparable to silybin at the concentration of 0.1 microM (64.4 and 65.8%, respectively).

Total Synthesis of (+)-Brefeldin A

(+)-Brefeldin A was synthesized through an efficient route, which features (1) construction of the five-membered ring from a Crimmins aldol via tandem Li-I exchange and carbanion-mediated cyclization with concurrent removal of the chiral auxiliary, (2) introduction of the lower side chain (C10 to C16) via a Rh-catalyzed Michael addition of a vinyl boronic acid, (3) stereoselective reduction of the C7 ketone with SmI2, and (4) a 2-methyl-6-nitrobenzoic anhydride-mediated (Shiina) lactonization.

The versatile conversion of lactams to the α-alkylated azacycles via cyclic N,O-acetal TMS ether

The efficient preparation of the cyclic N,O-acetals from lactams by DIBAL reduction followed by direct trapping of the resulting N,O-hemiacetals using TMSOTf/pyridine system is described. In addition, the facile nucleophilic addition of various carbon nucleophiles at the carbonyl carbons of the lactams through the corresponding N,O-acetals is also reported.

Chalcones, inhibitors for topoisomerase I and cathepsin B and L, as potential anti-cancer agents.

In order to diversify the pharmacological activity of chalcones and extend the scaffold of topoisomerase and cathepsins B and L inhibitors, we have designed and synthesized total 18 chalcone compounds and tested their biological activity. In the topoisomerase inhibition test, most analogues in group III and IV except compound 11 exhibited more efficient topoisomerase I inhibitory activity than camptothecin at 20 μM. Compounds 15, 16 and 18 in group IV showed significant cathepsin B and L inhibitory activity. Among the compounds, compound 15 was most active with IC50 values of 1.81±0.05 μM on cathepsin B and 3.15±0.07 μM on cathepsin L, respectively. Compound 15 also showed most potent cytotoxic activity against T47D and SNU638 cells with IC50 values of 1.37±0.05 μM and 0.62±0.01 μM, respectively. Overall, although more compounds should be tested and analyzed for clear SAR against topoisomerase I and cathepsin B and L, compound 15 showed consistent inhibitory ability on the tested assays, which can implicate the cytotoxic activity of compound 15 on topoisomerase I and cathepsin B and L inhibitory pathways.

First total synthesis and structural confirmation of fluvirucinine A2 via an iterative ring expansion strategy.

The first asymmetric total synthesis of fluvirucinine A(2) has been accomplished. A key feature of the synthesis is an iterative lactam ring expansion to provide rapid access to the 14-membered lactam skeleton and three stereogenic centers. The excellent remote control of the three stereogenic centers relied on stereoselective amidoalkylation followed by an amide-enolate-induced aza-Claisen rearrangement. In addition, the structure of fluvirucinine A(2) has been completely elucidated by our total synthesis.

A versatile asymmetric synthesis of highly enantiomerically enriched 12(s)-HETE via a combination of enzymatic and chemical processes

This paper describes a versatile asymmetric synthesis of highly enantiomerically enriched 12(S)-HETE via enzymatic kinetic resolution of the key allylic alcohol synthon and the facile introduction of three alkyne units which were concomitantly converted to three alkenes units.

The versatile conversion of acyclic amides to α-alkylated amines

A general and efficient method for the versatile functionalization of acyclic amide via N,O-acetal TMS ether, an excellent precursor for the N-acyliminium ion, has been developed.

Xanthohumol prevents dextran sulfate sodium-induced colitis via inhibition of IKKβ/NF-κB signaling in mice

Xanthohumol (XN), a prenylated chalcone isolated from the hop plant, has been reported to exhibit multiple biological functions including anti-inflammation. However, the pharmacological function of XN on colitis remains unknown. In this study, we investigated the anti-inflammatory effect of synthesized XN and molecular mechanism on dextran sulfate sodium (DSS)-induced experimental colitis. XN attenuated the colitis symptoms along with the prevention of colonic lesions after DSS challenge. XN inhibited the production of pro-inflammatory cytokines, oxidative stress and cyclooxygenase-2 expression in DSS-treated mice. Moreover, XN inhibited the phosphorylation of IκBα, the nuclear translocation of NF-κB subunits and the transcriptional activity of NF-κB in vivo and in vitro. In contrast to XN, isoXN showed much less effects on the kinase activity of IKKβ and IκBα phosphorylation induced by XN in this study, suggesting that an electrophilic carbon center present in XN is critical for the anti-inflammation in colitis, especially inhibition of IKKβ/NF-κB signaling pathway. Consistently, our docking analysis revealed that XN could bind to the active site, presumably at the Cys99 of IKKβ. Taken together, these findings demonstrate a new function of XN to inhibit IKKβ/NF-κB signaling, suggesting XN could be the potential therapeutic agent for the prevention of colitis.

Recent Advances in Substrate-Controlled Asymmetric Cyclization for Natural Product Synthesis

Asymmetric synthesis of naturally occurring diverse ring systems is an ongoing and challenging research topic. A large variety of remarkable reactions utilizing chiral substrates, auxiliaries, reagents, and catalysts have been intensively investigated. This review specifically describes recent advances in successful asymmetric cyclization reactions to generate cyclic architectures of various natural products in a substrate-controlled manner.

Asymmetric Synthesis of (−)-6-Desmethyl-Fluvirucinine A1 via Conformationally-Controlled Diastereoselective Lactam-Ring Expansions

The versatile synthesis of (−)-6-desmethyl-fluvirucinine A1 was accomplished at a 24% overall yield through a thirteen-step process from a known vinylpiperidine. The key part involved the elaboration of the distal stereocenters and a macrolactam skeleton via conformationally-induced diastereocontrol and the iterative aza-Claisen rearrangements of lactam precursors.