Soonho Hwang

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.

Identification of a potent and noncytotoxic inhibitor of melanin production

On the basis of a hit from random screening, biaryl amide derivatives were prepared in a combinatorial manner via parallel solution-phase synthesis, and their effects on melanocytes were investigated to discover new effective skin depigmenting agents. Among the 120 derivatives prepared, five members exhibited a >30% reduction of melanin production at 30 microM with a cell viability of >90%. In particular, compound A(3)/B(5) exhibited effective inhibitory activity on melanin synthesis. Although the inhibition percentage of A(3)/B(5) was slightly lower than that of the positive reference compound, phenylthiourea (PTU), A(3)/B(5) demonstrated a much better cell viability than PTU. In vivo evaluation of A(3)/B(5) also showed a significant decrease of melanin pigments. In addition, the in silico classification model was built based on the experimental data of library members. Our results suggest that these biaryl amide derivatives may act as potent skin depigmenting agents.

Surface Drainage Simulation Model for Irrigation Districts Composed of Paddy and Protected Cultivation

The objectives of this study were to develop a hydrologic simulation model to estimate surface drainage for irrigation districts consisting of paddy and protected cultivation, and to evaluate the applicability of the developed model. The model consists of three sub-models; agricultural supply, paddy block drainage, and protected cultivation runoff. The model simulates daily total drainage as the sum of paddy field drainage, irrigation canal drainage, and protected cultivation runoff at the outlets of the irrigation districts. The agricultural supply sub-model was formulated considering crop water requirement for growing seasons and agricultural water management loss. Agricultural supply was calculated for use as input data for the paddy block sub-model. The paddy block drainage sub-model simulates paddy field drainage based on water balance, and irrigation canal drainage as a fraction of agricultural supply. Protected cultivation runoff is calculated based on NRCS (Natural Resources Conservation Service) curve number method. The Idong reservoir irrigation district was selected for surface drainage monitoring and model verification. The parameters of model were calibrated using a trial and error technique, and validated with the measured data from the study site. The model can be a useful tool to estimate surface drainage for irrigated districts consisting of paddy and protected cultivation.

N-(3,5-Dimethylphenyl)-3-Methoxybenzamide (A3B5) Targets TRP-2 and Inhibits Melanogenesis and Melanoma Growth

Melanin protects the skin from harmful environmental factors such as UV light. However, excessive melanin production induces hyperpigmentation. Previously, N-(3,5-dimethylphenyl)-3-methoxybenzamide (A(3)B(5)), a biaryl amide derivative, was identified for its ability to inhibit melanin production. However, its detailed mechanism of action has not been investigated. We elucidated the inhibitory mechanisms of A(3)B(5) in melanin production. Our results showed that A(3)B(5) had no effect on the production and activity of tyrosinase, an enzyme involved in melanogenesis. However, A(3)B(5) markedly decreased both constitutively expressed and UVB-induced tyrosinase-related protein 2 (TRP-2), which plays an important role along with tyrosinase in melanogenesis. The TRP-2 downregulation caused by A(3)B(5) may occur through proteasomal degradation because the A(3)B(5)-induced TRP-2 downregulation was inhibited by the ubiquitination inhibitor, MG-132. In addition, A(3)B(5) inhibited the proliferation of melanocytes and melanoma cells by arresting cells in the G1 stage of the cell cycle and moderately suppressed tumor growth in vivo. Taken together, our results indicate that A(3)B(5) downregulates melanin production and melanoma cell growth via proteosomal degradation of TRP-2 and suggest that A(3)B(5) can be a possible therapeutic agent that effectively regulates both hyperpigmentation and melanoma growth in the skin.

Synthesis and evaluation of C-ring aromatized analogues of phenanthridone alkaloids

Phenanthridone alkaloids are envisaged as an attractive lead for the development of anticancer agents. We have prepared a series of aromatized analogues on the basis of the structure of this class of alkaloids with the hope of finding the simplified compounds with comparable activities. The obtained analogues were evaluated for their cytotoxic effect against several cancer cell lines and found to be virtually inactive. These observations together with molecular modeling studies strongly suggest that the stereochemistries of hydroxyl groups in C-ring of phenanthridone alkaloids are crucial to biological effects.

Analysis of Nutrient Load Balance in the Reservoir Irrigated Paddy Block

The objective of this study was to investigate the nutrient load balance in the reservoir irrigated paddy block during growing seasons. Idong reservoir irrigation paddy block of 10.3 ha in size was selected to collect hydrologic and water quality data. Irrigation, canal flows, and paddy field drainage were measured using a water level gauge, while water samples were collected and analysed for water quality. The water balance analysis showed that 81 % and 75 % of total outflow were through paddy and irrigation canal drainage during 2011 and 2012, respectively. The water quality of paddy field drainage varied greatly depending on rice cultivation stage ranging from 0.05 to 24.55 mg/L and from 0.01 to 0.76 mg/L for T-N and T-P, correspondently. Paddy field drainage loads during May through June account for 64 % and 76 % in 2012 and 2013, while 82 % and 81 % for T-P in 2011 and 2012, respectively. The Pearson correlation analysis showed that rainfall was significantly correlated with nutrient loads during July through August due to runoff, and irrigation was related with nutrient loads of drainage during some period of July through September due to irrigation return flow. This study results showed characteristics of inflow and outflow nutrient loads from plentiful irrigated paddy block.

Acid promoted cyclodehydration of amino alcohols with amide acetal

A convenient acid-promoted cyclization protocol for the formation of azaheterocycles from amino alcohols is described. The reaction involves the use of N,N-dimethylacetamide dimethyl acetal (DMADA) as the activating reagent of the hydroxyl group. Using this protocol, pyrrolidines or piperidines with various substituents can be synthesized in good to high yields.

Assessment of Flood Impact on Downstream of Reservoir Group at Hwangryong River Watershed

Works for dam heightening plan have dual purposes: flood disaster prevention by securing additional storage volume and river ecosystem conservation by supplying stream maintenance flow. Now, the dam heightening project is in progress and there are 93 dam heightened reservoir. After the dam heightening project, 2.2 hundred million ton of flood control volume in reservoirs will be secured. Thus it is necessary to evaluate the effects of the dam heightening project on watershed hydrology and stream hydraulics, and resulting flood damages. This study was aimed to assess the impact of outflow from the dam heightened reservoir group on the Whangryong river design flood. The HEC-HMS (Hydrologic Engineering Center-Hydrologic Modeling System) model was used for estimating flood discharge, while HEC-5 (Hydrologic Engineering Center-5) was used for reservoir routing. This study analysed flood reduction effect on 100yr and 200yr return periods about the before and after heightening of agricultural dams. Based on the results of this study, the reduction of flood peak discharge at downstream of the reservoir group was estimated to be about 41% and 53% for 100yr and 200yr frequencies, respectively.

Characteristics and EMCs of NPS Pollutants Runoff from a Forest-Paddy Composite Watershed

This study was aimed to characterize non-point source (NPS) pollutant runoff and estimate event mean concentrations (EMCs) from a small rural watershed located at the headwater area of the Gyeongan stream. The study watershed consists of the two major landuse, forest (72 %) and paddy field (28 %). The nine rainfall events ranging from 18.5 to 192.6 mm in amount were monitored in this study. Stream flow was measured at the watershed outlet using a water level gauge, while a number of water samples for each event were collected and analysed for water quality. Event pollutant loads varied greatly depending on rainfall events varying from 22.6 to 3,134.2 mg/L, 0.32 to 24.56 mg/L, 0.090 to 1.320 mg/L, and 2.3 to 149.8 mg/L for SS, TN, TP, and COD, correspondently. The respective mean EMCs were estimated by 104.2, 1.00, 0.168, and 7.9 mg/L. The Pearson correlation analysis showed that COD EMC was significantly correlated with those of SS, TN, and TP. Rainfall runoff ratio appeared to be negatively correlated with EMCs of SS, TP, and COD, although not statistically significant. The event loads from the largest rainfall was greater than the sum of those from the remaining eight events. The study results suggest that the appropriate management of intensified storm events are of greater importance in curbing NPS loads, while the estimated EMCs provide base data for the unit pollutant loads determination for the forest-paddy composite upstream watershed.

Silver‐Mediated exo‐Selective Tandem Desilylative Bromination/Oxycyclization of Silyl‐Protected Alkynes: Synthesis of 2‐Bromomethylene‐Tetrahydrofuran

Tandem reactions are one-pot multi-step processes and are thus among the most useful synthetic methods. Recently, the use of transition metals in tandem reactions has received considerable attention and has revolutionized the synthetic strategies in organic chemistry. Among the transition metal-based tandem reactions, the processes that involve heterocyclization reactions of unsaturated substrates are of particular interest, as they provide a direct method for the construction of synthetically and biologically valuable heterocycles. The intramolecular heterocyclization of g or d-hydroxyalkynes promises to be a convenient way to access the functionalized tetrahydrofurans and pyrans, which are common motifs in a variety of natural products. This cyclization can be driven by transition metal catalysts, and the regioselectivity of these reactions varies depending on the metal and the conditions employed. Among the metals thus far reported for these reactions, silver and gold have been demonstrated to be the most effective and selective for the formation of exo-dig products. These metals can promote heterocyclization of both internal and terminal alkynes. Even halogenated and silylated alkynes can be converted into the corresponding exo-dig products using these metals. The exocyclic enol ether function, created by the exo-dig heterocyclization of hydroxyalkynes, is synthetically useful because it is amenable to further chemical transformations, such as hetero-Diels–Alder reactions and electrophilic additions. In the synthesis of functionalized oxygen heterocycles, the exocyclic b-bromo enol ether 1 (Scheme 1) is more