Stereoselective synthesis of (±)-epibatidine analog: (±)-2β-(2-chloro-5-pyridinyl)-8-azabicyclo[3.2.1]octane

Stereoselective synthesis of (+/-)-epibatidine analog 2, which contains the 8-azabicyclo[3.2.1]octane ring system, was achieved by using palladium-catalyzed Heck-type coupling reaction from 3.     

Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.     

Cytotoxicity of urushiols isolated from sap of Korean lacquer tree (Rhus vernicifera stokes)

Cytotoxicities of four urushiols, congeners isolated from the sap of Korean lacquer tree (Rhus vernicifera Stokes), to 29 human cancer cell lines originated from 9 organs were evaluated. Their values of 50% growth inhibition were below 4 microg/ml, and showed cell line specific cytotoxicity. The present result is the first report on the cytotoxicity of urushiols suggesting that they would have an anticancer activity to human cancer cells.     

Another CT sign of sinonasal polyposis: truncation of the bony middle turbinate

In order to study the features of sinonasal polyposis (SNP) on CT, 100 consecutive coronasal sinus CT examinations done for chronic inflamamtory sinonasal disease were reviewed. The CT findings of the 27 fully documented SNPs were analyzed. All our SNPs were bilateral. There was a strong tendency for extensive involvement. Nasal polyps were seen in 22 of 27 (81%); bony trabecular deossification in 23 of 27 (85%); widening of infundibulum in 26 of 27(96%). We discovered a new sign truncation of the bony middle turbinate, where the bulbous part of bony middle turbinate was missing, in 51 of 26 (58 %) of SNP patients without a previous history of middle turbinectomy, 12 of 15(80%) were bilateral. The one SNP patient (1 of 27) with previous middle turbinectomy was not regarded to be real truncation. Truncation of the bony middle turbinate is a characteristic and easily recognizable ancillary sign, and is not seen in other patterns of sinusitis. Together with other features on coronal sinus CT, this adds diagnostic confidence in diagnosing sinonasal polyposis. Correspondence to: E. Y. Liang     

Relation between genotype and phenotype in Swedish phenylketonuria and hyperphenylalaninemia patients

Phenylketonuria (PKU) and hyperphenylalaninemia (HPA) are caused mostly by an inherited (autosomal recessive) deficiency in hepatic phenylalanine hydroxylase (PAH) activity. More than 50 PAH mutations have ben reported. The goal of the present study was to examine the molecular basis for the clinical heterogeneity of Swedish PKU and HPA patients. Mutations were identified through allele-specific oligonucleotide hybridization or DNA sequencing on 128 of the 176 mutant alleles (73%). Three mutations (R408W, Y414C and IVS12) together accounted for 56% of all mutant alleles and ten relatively infrequent mutations were found on another 17% of all mutant alleles. Patients from 50 of the 88 families (57%) had identified mutations in both PAH genes and allowed use to compare the clinical effects of different combinations of PAH mutations. The in vitro activity of all of these mutations, including the newly identified G272X and L364, have been tested in a eukaryotic expression system. There was a strong relationship between the average in vitro PAH activity of the two mutant enzymes and both the phenylalanine tolerance and the neonatal pretreatment serum phenylalanine concentration. This confirms previous observations in Danish and German PKU patients that disease phenotype is a consequence of the nature of the mutations at the PAH locus and not significantly influenced by other loci. The sample population in the previous study did not, however, include mild HPA patients, and the observed correlation is thus restricted to severe and moderate mutant alleles. Since a comparatively high proportion of the Swedish patients were mildly affected, we have provided additional evidence that this correlation is valid throughout a continuous spectrum of clinical varieties. PAH genotyping could therefore help predict prognosis of a recently diagnosed PKU or HPA child.     

Rotational barrier of a molybdenum-molybdenum quadruple bond

The synthesis and characterization of molybdenum(II) porphyrin dimers containing unbridged metal-metal quadruple bonds are presented. Variable temperature 300 MHz ¹H NMR studies of meso-substituted derivatives provide novel solution evidence for both the existence of quadruple bonds and for a barrier to rotation about the metal-metal bonds in these complexes. The activation energy for this rotational process is 10.1 ± 0.5 kcal·mol^-1.     

Vision through cataracts

Contrast thresholds for a range of different spatial frequencies were compared with "acuity" tests for 10 subjects with uniocular senile cataract. The results indicate that the magnitude and extent of the intra-resolution limit abnormality vary dramatically in cataract subjects and that, for some subjects, vision is abnormal for objects of all sizes. This finding indicates that the present acuity evaluation of vision with cataracts is inadequate because, in some cases, it grossly overestimates the nature of the visual world of the cataract patient.     

Deoxy derivatives of butirosin A and 5"-amino-5"-deoxybutirosin A, aminoglycoside antibiotics resistant to bacterial 3'-phosphorylative enzymatic inactivation. Synthesis and NMR studies

3'-Deoxybutirosin A (4), 5"-amino-3', 5"-dideoxybutirosin A (6), and 5"-amino-4', 5"-dideoxybutirosin A (7) were prepared by deoxygenation of the appropriate hydroxyl in suitably protected derivatives of butirosin A, using sequentially trifluoromethylsulfonylation, displacement with benzenethiolate, and hydrogenolysis. The structures of the compounds were confirmed by NMR spectroscopy, using 13C NMR and 1H NMR at up to 600 MHz. The compounds are broad-spectrum antibiotics active against resistant microorganisms which inactivate butirosin and related aminoglycosides by 3'-phosphorylation.     

Degradation of ginseng saponins under mild acidic conditions

Ginseng saponins, ginsenosides Rg (1), Re and Rb (1), decomposed under mild acidic conditions to yield prosapogenins. The structures of the prosapogenins were investigated by (13)C-NMR spectroscopy and Rg (1)-prosapogenin II was shown to be a mixture of ginsenoside Rh (1), and its C-20 epimer, produced by hydrolysis followed by epimerization at C-20. Rg (1)-prosapogenin III, the other prosapogenin derived from ginsenoside Rg (1); was a C-25,26 hydrated derivative of Rg (1)-prosapogenin II. Re-prosapogenin II was identified as a mixture of ginsenoside Rg (2) and its C-20 epimer, and Re-prosapogenine III as a C-25,26 hydrated derivative of Re-prosapogenin II.     

Biological evaluation of Korean medicinal plants(III)

The extracts of sixty Korean plants were evaluated for their biological activities such as antitumor activities against Sarcoma 180, Leukemia SN-36 and Ehrlich ascites carcinoma, antimicrobial activities and behavioral observation in mice. The results are tabulated.