Chulbom Lee

β-Alkoxyacrylates in radical cyclizations: Remarkably efficient oxacyle synthesis

Abstract β-Alkoxyacrylates were found to be exceptionally efficient radical acceptors in radical-mediated intramolecular cyclizations. For example, reaction of 5-bromo-2-pentanol with ethyl propiolate, tributylstannane-mediated radical cyclization, and hydrolysis yielded (±) ( cis -6-methyltetrahydropyran-2-yl)acetic acid, a known component of civet.

Nitrogen budgets for the Republic of Korea and the Yellow Sea region

Growing populations in northeast Asia have greatly altered the nitrogencycle, with increases in agricultural production to feed the population, andwith increases in N emissions and transboundary air pollution. For example,during the 1900s over 50% of the N deposition over Republic of Korea wasimported from abroad. In this paper, we present biogeochemical budgets ofN for the South Korean peninsula (the Republic of Korea) and for the YellowSea region. We quantify N inputs from atmospheric deposition, fertilizers,biological fixation, and imports of food, feed, and products. We quantifyoutputs in riverine export, crop uptake, denitrification, volatilization,runoff, sedimentation and sea water exchange. Calculations were conductedusing mean values from 1994–1997. All of the nitrogen budgets werepositive, with N inputs exceeding outputs. The excess N inputs gave rise toincreases in N storage in landfills and in groundwater. Annual accumulationof N in the Yellow sea, including inputs from South Korea and otherdrainage areas, was 1229 kt yr−1 with a residence time for N ofapproximately 1.5 years, thus doubling N content in marine waters every 3years during 1994–1997. The human derived N inputs leads to excessiveeutrophication and pollution of the Yellow Sea.

Nickel-catalyzed reductive cyclization of organohalides.

A mild and convenient nickel-catalyzed method for free-radical cyclization of organohalides is described. The use of a NiCl(2)•DME/Pybox complex as the catalyst and zinc powder in methanol efficiently promotes the reductive cyclization of various unsaturated alkyl halides to give carbo-, oxa-, and azacycles as products in high yields.

Rhodium-Catalyzed Oxygenative [2 + 2] Cycloaddition of Terminal Alkynes and Imines for the Synthesis of β-Lactams

A rhodium-catalyzed oxygenative [2 + 2] cycloaddition of terminal alkynes and imines has been developed, which gives β-lactams as products with high trans diastereoselectivity. In the presence of a Rh(I) catalyst and 4-picoline N-oxide, a terminal alkyne is converted to a rhodium ketene species via oxidation of a vinylidene complex and subsequently undergoes a [2 + 2] cycloaddition with an imine to give rise to the 2-azetidinone ring system. Mechanistic studies suggest that the reaction proceeds through a metalloketene rather than free ketene intermediate. The new method taking advantage of catalytic generation of a ketene species directly from a terminal alkyne provides a novel and efficient entry to the Staudinger synthesis of β-lactams under mild conditions.

Rhodium‐Catalyzed Oxygenative Addition to Terminal Alkynes for the Synthesis of Esters, Amides, and Carboxylic Acids

A gem of a couple: The title reaction of terminal alkynes with O and N nucleophiles proceeds in the presence of [{Rh(cod)Cl}2], P(4-FC6H4)3, and 4-picoline N-oxide. Alcohols, amines, and water add to the terminal alkynes to give esters, amides, and carboxylic acids, respectively. The reaction involves formation of a rhodium vinylidene, oxidation to a ketene by oxygen transfer, and nucleophilic addition.

Concise Synthesis of the Erythrina Alkaloid 3-Demethoxyerythratidinone via Combined Rhodium Catalysis

The total synthesis of the erythrina alkaloid 3-demethoxyerythratidinone has been achieved via a strategy based on combined rhodium catalysis. The catalytic tandem cyclization effected by the interplay of alkynyl and vinylidene rhodium species allows for efficient access to the A and B rings of the tetracyclic erythrinane skeleton in a single step. The synthesis also features rapid preparation of the requisite precursor for the double ring closure and thus has been completed in only 7 total steps in 41% overall yield.

Heme-binding-mediated negative regulation of the tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) by IDO2

Indoleamine 2,3-dioxygenases (IDOs) are tryptophan-catabolizing enzymes with immunomodulatory functions. However, the biological role of IDO2 and its relationship with IDO1 are unknown. To assess the relationship between IDO2 and IDO1, we investigated the effects of co-expression of human (h) IDO2 on hIDO1 activity. Cells co-expressing hIDO1 and hIDO2 showed reduced tryptophan metabolic activity compared with those expressing hIDO1 only. In a proteomic analysis, hIDO1-expressing cells exhibited enhanced expression of proteins related to the cell cycle and amino acid metabolism, and decreased expression of proteins related to cell survival. However, cells co-expressing hIDO1 and hIDO2 showed enhanced expression of negative regulators of cell apoptosis compared with those expressing hIDO1 only. Co-expression of hIDO1 and hIDO2 rescued the cell death induced by tryptophan-depletion through hIDO1 activity. Cells expressing only hIDO2 exhibited no marked differences in proteome profiles or cell growth compared with mock-transfectants. Cellular tryptophan metabolic activity and cell death were restored by co-expressing the hIDO2 mutant substituting the histidine 360 residue for alanine. These results demonstrate that hIDO2 plays a novel role as a negative regulator of hIDO1 by competing for heme-binding with hIDO1, and provide information useful for development of therapeutic strategies to control cancer and immunological disorders that target IDO molecules.

Tandem Diels–Alder and Retro-Ene Reactions of 1-Sulfenyl- and 1-Sulfonyl-1,3-dienes as a Traceless Route to Cyclohexenes

A pericyclic approach for the synthesis of six-membered ring structures is described. The method employs 1,3-dienes with a 1-sulfur substituent in a tandem sequence of Diels-Alder and retro-ene reactions. In this pairing of [4 + 2] cycloaddition and 1,5-sigmatropic rearrangement, 1-sulfenyl-1,3-dienes engage in Diels-Alder reactions with electron-deficient dienophiles. Subsequently, the sulfenyl group of the cycloadducts is oxidized and unmasked to form allylic sulfinic acids, which undergo sterospecific reductive transposition via sulfur dioxide extrusion. The sequence can also include an inverse electron demand Diels-Alder reaction by using a 1-sulfonyl-1,3-diene. This combination of two pericyclic events offers novel stereocontrolled access to cyclohexenes that are inaccessible via a direct [4 + 2] cycloaddition route.

A paradoxical pattern of indoleamine 2,3-dioxygenase expression in the colon tissues of patients with acute graft-versus-host disease

Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan catabolism that plays an important role in the induction of immune tolerance. It is induced in the colon and exerts its effects there, regulating T-cell proliferation and survival. To address the role of IDO in acute graft-versus-host disease (AGVHD) after human allogeneic hematopoietic stem cell transplantation, we analyzed the relationship between IDO expression in colon tissues and clinical outcomes among 41 AGVHD patients who were diagnosed as gut AGVHD by a colon mucosal biopsy within 100 days posttransplantation. By in situ immunohistochemical analyses, IDO expression was measured in colon mucosal mononuclear cells (MNCs) and endothelial cells (ECs) in GVHD areas. High IDO expression in MNCs and low IDO expression in ECs had a trend toward a lower nonrelapse mortality (p = 0.157 and p = 0.062, respectively). Multivariate analysis showed that high MNC combined with low EC IDO expression (p = 0.046), as well as low disease risk (p = 0.012), are associated with lower nonrelapse mortality. Paradoxical upregulation of IDO expression in colon MNCs and ECs may represent a new predictive factor for prognosis in gut AGVHD after human allogeneic hematopoietic stem cell transplantation.

The role of regulatory T cells during the attenuation of graft-versus-leukemia activity following donor leukocyte infusion in mice

We investigated how the graft-versus-leukemia (GVL) effect is attenuated in the tumor microenvironment using a murine model of non-myeloablative allo-HSCT (NM-HSCT) plus delayed donor leukocyte infusion (DLI) in a haploidentical B6→F1 strain combination. In-line with aggravated leukemia growth, the proportions of effector T cells expressing IFN-γ (Teffs) in spleen were reduced and attenuated GVL activity was found to be accompanied by a rebound in CD4(+)Foxp3(+) regulatory T cells (Tregs) in tumor-draining lymph nodes and tumor tissues. DLI-derived Tregs and Teffs may be potential indicators of presence of leukemic progression after DLI in this GVL model.