Yutaka Aoyagi

Palladium-catalyzed arylation of furan, thiophene, benzo[b]furan and benzo[b]thiophene

Treatment of π-electron sufficient aromatic heterocycles such as title compounds with aryl bromides in the presence of tetrakis(triphenylphosphine)palladium gave the corresponding 2-aryl aromatic heterocycles.

Palladium-catalyzed cross-coupling reactions of chloropyrazines with aromatic heterocycles

In the presence of tetrakis(triphenylphosphine) palladium, chloropyrazines were treated with aromatic heterocycles such as furan, thiophene, pyrrole, N-substituted pyrroles, benzo[b]furan, benzo[b]thiophene, oxazole, thiazole, N-methylimidazoles, benz[b]oxazole and benzo[b]thiazole. The corresponding coupling products were obtained in moderate to good yields. The structures of the coupling products were determined

Separation and characterization of individual mycolic acids in representative mycobacteria

Total mycolic acid methyl ester fractions were isolated from 24 representatives of Mycobacterium tuberculosis, Mycobacterium bovis (including BCG), Mycobacterium microti, Mycobacterium kansasii and Mycobacterium avium. The total mycolate functional group composition was estimated from (1)H-NMR spectra. Mycolates were separated into alpha-mycolates, methoxymycolates and ketomycolates and each class was further separated by argentation chromatography into mycolates with no double bonds, with one trans-double bond and with one cis-double bond. Mass spectrometry revealed the mycolate chain lengths and (1)H-NMR the cis- and trans-double bond and cyclopropane ring content. The same species had similar mycolate profiles; the major type of each class had cis- or trans-cyclopropane rings and lacked double bonds. Minor proportions of possible unsaturated precursors of the cyclopropane mycolates were commonly encountered. Among unusual alpha-mycolates, many strains had tricyclopropyl components with chains extended by 6 to 8 carbons. Significantly, M. tuberculosis (Canetti) and M. avium had alpha-mycolates with a trans-double bond and cyclopropane ring, whose chain lengths suggested a relationship to possible precursors of oxygenated mycolates. The methoxy- and ketomycolates from a majority of M. tuberculosis strains had minor amounts of components with additional cyclopropane rings, some of whose chains were also extended by 6 to 8 carbons. These latter mycolates were major components in the attenuated M. tuberculosis H37Ra strain, whose mycolate profile was distinct from those of other strains of M. tuberculosis.

Location of functional groups in mycobacterial meromycolate chains; the recognition of new structural principles in mycolic acids.

Mycobacterial alpha-, methoxy- and keto-mycolic acid methyl esters were separated by argentation chromatography into mycolates with no double bond, with one trans double bond or with one cis double bond. Meromycolic acids were prepared from each methyl mycolate fraction by pyrolysis, followed by silver oxide oxidation, and analysed by high-energy collision-induced dissociation/fast atom bombardment MS to reveal the exact locations of the functional groups within the meromycolate chain. The locations of cis and trans double bonds, cis and trans cyclopropane rings, methoxy and keto groups, and methyl branches within the meromycolate chain were determined from their characteristic fragment ion profiles, and the structures of the meromycolic acids, including those with three functional groups extracted from Mycobacterium tuberculosis H37Ra, Mycobacterium bovis BCG and Mycobacterium microti, were established. Meromycolic acids with one cis double bond were structurally closely related to those with one cis cyclopropane ring, whereas the meromycolic acids with one trans cyclopropane ring were closely related to the corresponding meromycolic acids with one cis cyclopropane ring. A close relationship between methoxy- and keto-meromycolic acids was also implied. The relationship between the meromycolic acids with a trans double bond and the other meromycolic acids was not clearly revealed, and they did not appear to be immediate substrates for trans cyclopropanation.

Salvileucalin B, a novel diterpenoid with an unprecedented rearranged neoclerodane skeleton from Salvia leucantha Cav.

Salvileucalin B (2), having an unprecedented rearranged neoclerodane skeleton, was isolated from the aerial parts of Salvia leucantha Cav. (Labiatae) along with salvileucalin A (1). The absolute structures were elucidated by spectroscopic analysis, X-ray crystallographic analysis, and vibrational circular dichroism. Compound 2 represents a novel neoclerodane, characterized by a tricyclo[3.2.1.0 (2,7)]octane substructure incorporating the exocyclic C-20 methylene of 1. This molecule exerted cytotoxic activity against A549 and HT-29 cells with IC50 values of 5.23 and 1.88 microg/mL, respectively.

Facile and efficient synthesis of pyrroles and indoles via palladium-catalyzed oxidation of hydroxy-enamines and -amines

The palladium-catalyzed oxidation of hydroxy-enamines, which were obtained by the condensation of β-aminoalcohols and carbonyl compounds, proceeded to give the corresponding polysubstituted pyrroles and 4,5,6,7-tetrahydroindoles in good yields. The treatment of o-(2-hydroxyethyl)aniline with the palladium catalyst also gave indole in 78% yield.

Blockade of interferon-γ-inducible protein-10 attenuates chronic experimental colitis by blocking cellular trafficking and protecting intestinal epithelial cells

The role of chemokines, especially CXCL10/interferon‐γ‐inducible protein 10 kDa (IP‐10), a chemokine to attract CXCR3+ T‐helper 1‐type CD4+ T cells, is largely unknown in the pathophysiology of inflammatory bowel disease; ulcerative colitis and Crohns disease. The authors have earlier shown that IP‐10 neutralization protected mice from acute colitis by protecting crypt epithelial cells of the colon. To investigate the therapeutic effect of neutralization of IP‐10 on chronic colitis, an anti‐IP‐10 antibody was injected into mice with newly established murine AIDS (MAIDS) colitis. Anti‐IP‐10 antibody treatment reduced the number of colon infiltrating cells when compared to those mice given a control antibody. The treatment made the length of the crypt of the colon greater than control antibody. The number of Ki67+ proliferating epithelial cells was increased by the anti‐IP‐10 antibody treatment. Terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL)+ apoptotic cells were observed in the epithelial cells of the luminal tops of crypts in control MAIDS colitis, whereas TUNEL+ apoptotic epithelial cells were rarely observed with anti‐IP‐10 antibody treatment. In conclusion, blockade of IP‐10 attenuated MAIDS colitis through blocking cellular trafficking and protecting intestinal epithelial cells, suggesting that IP‐10 plays a key role in the development of inflammatory bowel disease as well as in chronic experimental colitis.

Lipase TL®-mediated kinetic resolution of benzoin: facile synthesis of (1R,2S)-erythro-2-amino-1,2-diphenylethanol

Abstract The lipase TL®-mediated kinetic resolution of (±)-benzoin ( 1 ) proceeded to give the corresponding optically pure benzoin ( R )- 1 . On the other hand, ( S )-benzoin- O -acetate ( 5 ) could be hydrolyzed without epimerization to give ( S )-benzoin ( S )- 1 , under alkaline conditions. Further, ( R )- 1 was converted to (1 R ,2 S )-2-amino-1,2-diphenylethanol (99:1 er) according to the procedure reported previously.

First total synthesis of pyrrolam A

First synthesis of pyrrolam A (1), a pyrrolizidine alkaloid from Streptomyces olivaceus, was accomplished. The SmI2-mediated intramolecular coupling reaction between a bromoalkyl and ynamide group gave solely a cyclized product, which was converted to pyrrolam A (1) efficiently.

Hepatic Angiomyolipoma: Diagnostic Findings and Management

Angiomyolipoma (AML) is a benign mesenchymal tumor that is frequently found in the kidney and, rarely, in the liver. The natural history of hepatic AML has not been clarified, and, because of the similar patterns in imaging studies, such as ultrasonography, computed tomography, and magnetic resonance imaging, some of these tumors have been overdiagnosed as hepatocellular carcinoma in the past. With an increase in the number of case reports showing detailed imaging studies and immunohistochemical staining of the tumor with human melanoma black-45, the diagnostic accuracy is also increasing. In this paper, we focused on the role of noninvasive imaging studies and histological diagnosis showing distinctive characteristics of this tumor. In addition, because several reports have described tumor progression in terms of size, recurrence after surgical resection, metastasis to other organs, and portal thrombosis, we summarized these cases for the management and discussed the indications for the surgical treatment of this tumor.