Resolution of Atropisomeric Cyclic Catechol Monoether O-Sulfate Esters by a Molluscan Sulfatase.

Atropisomeric cyclic catechol ethers are notoriously difficult to resolve by classical chiral phase high-performance liquid chromatography. Here, we show the first application of sulfatase enzymes for the kinetic resolution of O-sulfato-catechol ethers with enantioselectivities ranging from 30 to 65% ee, as determined by preparation of their Marfey's ether derivatives. Substrate-structure dependence was briefly explored.

Relationship between tongue pressure and maxillofacial morphology in Japanese children based on skeletal classification.

During childhood, perioral muscle function is closely associated with malocclusion. To clarify the effects of tongue function on maxillofacial morphology in children, tongue pressure and maximum lip-closing force (LCF) were measured and the relationship between perioral muscle function and maxillofacial morphology was evaluated according to the skeletal classification. Maximum tongue pressure (MTP) and swallowing tongue pressure (STP) were measured on the anterior palatine rugae in 100 children (Hellman's dental stages IIIA-IIIC) using a balloon-type tongue pressure measurement device. Lip-closing force was measured using an LCF measurement device. Lateral cephalograms were examined to classify subjects into skeletal (S)-I, S-II and S-III groups. Correlations of skeletal classification with tongue pressure and LCF were examined. Correlations of lateral cephalometric measurements with palatal volume (PV), measured using a three-dimensional optical scanner, were evaluated. Maximum tongue pressure was significantly lower in the S-II group than in other groups. Swallowing tongue pressure was significantly lower in the S-II group than in the S-III group. Lip-closing force was significantly higher in the S-III group than in other groups. Swallowing tongue pressure was positively correlated with MTP and PV. Correlations between tongue pressure and anteroposterior skeletal classification indicated the importance of quantitative tongue function assessment.

The true distal posterior inferior cerebellar artery aneurysm: clinical characteristics and strategy for treatment.

OBJECTIVE: A series of aneurysms located at the 4 (th) or 5 (th) segment of the posterior inferior cerebellar artery (PICA) has not been previously reported in the literature. We report six such cases and analyze their clinical characteristics and outcomes from three different treatment strategies. MATERIAL AND METHODS: We reviewed six patients with a diagnosis of distal PICA aneurysm. The following data were analyzed: age, sex, aneurysm size, Hunt-Hess grade at presentation, angiographic characteristics, and clinical treatment outcome determined by Glascow outcome scores (GOS). Treatments performed included clipping and wrapping, sacrificing the parent arteries of the aneurysms, and selective coiling. RESULTS: Six patients (5 females, 1 male; mean age: 61.2 years; mean aneurysm size: 6.2 mm) presented at our facility with subarachnoid hemorrhage (SAH) caused by aneurysm rupture. Two patients presented with Hunt-Hess grades 4 and 5; all others were in Hunt-Hess grades 2 or 3. One patient died before surgery. Treatment outcomes of the surviving five patients were as follows: three patients had GOS of 5, one improved by operation, and another died from re-bleeding after selective coiling. CONCLUSION: Surgery for the true distal PICA aneurysm results in good clinical outcomes. Clipping or wrapping should be considered as the first choice for treatment, and sacrificing the parent artery of the distal PICA aneurysm is relatively safer than selective coiling. The type of parent artery and particularly the collateralization of its distal part should be considered as an essential factor to take into consideration when choosing a treatment strategy.

Amaranzole A, a new N-imidazolyl steroid from Phorbas amaranthus.

An unprecedented 24-N-imidazolyl steroidal alkaloid, amaranzole A, was isolated from a tropical sponge, Phorbas amaranthus. The structure was solved by interpretation of MS, NMR, including a novel exciton-coupled CD spectrum due to an allyl imidazole, and comparison with model compounds.

Simplified cyclic analogues of bastadin-5. Structure-activity relationships for modulation of the RyR1/FKBP12 Ca2+ channel complex.

Bastadin-5, a brominated macro-dilactam from the marine sponge Ianthella basta, enhances release of Ca2+ from stores within the sarcoplasmic reticulum (SR) of muscle and nonmuscle cells by modulating RyR1/FKBP12 complex. Analogues of bastadin-5 present desirable targets for SAR studies to shed light on the gating mechanism and locus of bastadin-5 binding on these heteromeric channels that mediate essential steps in early coupling of membrane excitation to Ca2+ signaling cascades. Simple, ring-constrained analogues of bastadin-5 were synthesized from substituted benzaldehydes in a convergent manner, featuring an efficient S(N)Ar macroetherification, and evaluated in an assay that measures [3H]-ryanodine that is known to correlate with the functional open state of the Ca2+ channel. The simplified 14-membered ring, atropisomeric analogue (+/-)-7, like bastadin-5, enhanced ryanodine binding to the RyR1/FKBP12 complex (EC50 11 microM), however, unexpectedly, the corresponding achiral 18-membered ring analogue 14 potently inhibited binding (IC50 6 microM) under the same conditions. Structure-activity relationships of both families of cyclic analogues showed activity in a ryanodine binding assay that varied with substitutions of the Br atom on the trisubstituted aryl ring by various functional groups. The most active analogues were those that conserved the dibromocatechol ether moiety that corresponds to the 'western edge' of the bastadin-5 structure. These data suggest that cyclic analogues of bastadin-5 interact with the channel complex in a complex manner that can either enhance or inhibit channel activity.

Addition of Cl2C: to (-)-O-menthyl acrylate under sonication-phase-transfer catalysis. Efficient synthesis of (+)- and (-)-(2-chlorocyclopropyl)methanol.

[reaction: see text] Dichlorocyclopropanation of (-)-O-menthyl acrylate under conditions of phase-transfer catalysis (CHCl3, KOH, tetramethylammonium bromide), with sonication, gives excellent yields (85-94%) of the corresponding dichlorocyclopropanecarboxylate ester compared to thermal conditions (90 degrees C, 56%). No diastereoselectivity was observed, but one isomer was isolated pure by fractional crystallization. The measured kinetic isotope effect (initial rate (CHCl3)/rate (CDCl3) approximately 1.7) suggests deprotonation of CHCl3 as the rate-limiting step.

Arabidopsis glucosyltransferase UGT74B1 functions in glucosinolate biosynthesis and auxin homeostasis.

Glucosinolates are a class of secondary metabolites with important roles in plant defense and human nutrition. Here, we characterize a putative UDP-glucose:thiohydroximate S-glucosyltransferase, UGT74B1, to determine its role in the Arabidopsis glucosinolate pathway. Biochemical analyses demonstrate that recombinant UGT74B1 specifically glucosylates the thiohydroximate functional group. Low Km values for phenylacetothiohydroximic acid (approximately 6 microm) and UDP-glucose (approximately 50 microm) strongly suggest that thiohydroximates are in vivo substrates of UGT74B1. Insertional loss-of-function ugt74b1 mutants exhibit significantly decreased, but not abolished, glucosinolate accumulation. In addition, ugt74b1 mutants display phenotypes reminiscent of auxin overproduction, such as epinastic cotyledons, elongated hypocotyls in light-grown plants, excess adventitious rooting and incomplete leaf vascularization. Indeed, during early plant development, mutant ugt74b1 seedlings accumulate nearly threefold more indole-3-acetic acid than the wild type. Other phenotypes, however, such as chlorosis along the leaf veins, are likely caused by thiohydroximate toxicity. Analysis of UGT74B1 promoter activity during plant development reveals expression patterns consistent with glucosinolate metabolism and induction by auxin treatment. The results are discussed in the context of known mutations in glucosinolate pathway genes and their effects on auxin homeostasis. Taken together, our work provides complementary in vitro and in vivo evidence for a primary role of UGT74B1 in glucosinolate biosynthesis.

Phorbasterones A-D, cytotoxic nor-ring A steroids from the sponge Phorbas amaranthus.

The sponge Phorbas amaranthus from Florida contains the new ring A-contracted steroids, phorbasterones A-D, and the known anthosterones A and B. The structures of phorbasterones A-D were determined by interpretation of their spectroscopic data. Phorbasterones show moderate cytotoxicity against HCT-116 tumor cells.

Cationic reduction of bastadin-4 to bastadin-5. Preparation of 5-[2h]-bastadin-5 by site-specific isotopic labeling.

A chemoselective conversion of bastadin-4 to the important Ca2+ channel modulator bastadin-5 (1a) has been achieved using cationic hydrogenation (Et3SiH, TFA, 60%). Specifically deuterated bastadin-5 (1b, >95 at. %) was prepared following this method and the simplified 1H NMR H-5/H2-6 spin system of 1b exploited to study temperature-dependent macrocyclic ring dynamics.

A cDNA clone with anti-oncogene activity.

A cDNA clone, p14-6, which has an anti-oncogene activity on the v-Ki-Ras oncogene-transformed malignant cell line DT, was found. This clone was recovered from the revertant R14 cells, which had been isolated by transfections of DT cells with a normal human fibroblast cDNA library cloned in pcD2, an Okayama-Berg vector. When transfected into DT cells, p14-6 clone gave rise to phenotypical flat reversion in 5-15% of DT transfectant colonies. The p14-6-transfected flat cell line, RR, was proven to be a true revertant with significantly reduced malignancy by in vitro and in vivo malignancy tests. All other clones recovered from R14 cells were unable to cause this reversion. Molecular hybridizations showed that the p14-6 was inserted into RR genome as tandem repeats, and no structural change was found in the v-Ki-Ras oncogene in RR genome. These facts suggest that the anti-oncogene activity of the p14-6 clone on the DT cells may be exerted through expression of the cDNA contained in this clone.