Probing the Catalytic Promiscuity of a Regio‐ and Stereospecific C‐Glycosyltransferase from Mangifera indica

The catalytic promiscuity of the novel benzophenone C‐glycosyltransferase, MiCGT, which is involved in the biosynthesis of mangiferin from Mangifera indica, was explored. MiCGT exhibited a robust capability to regio‐ and stereospecific C‐glycosylation of 35 structurally diverse druglike scaffolds and simple phenolics with UDP‐glucose, and also formed O‐ and N‐glycosides. Moreover, MiCGT was able to generate C‐xylosides with UDP‐xylose. The OGT‐reversibility of MiCGT was also exploited to generate C‐glucosides with simple sugar donor. Three aryl‐C‐glycosides exhibited potent SGLT2 inhibitory activities with IC₅₀ values of 2.6×, 7.6×, and 7.6×10⁻⁷ M , respectively. These findings demonstrate for the first time the significant potential of an enzymatic approach to diversification through C‐glycosidation of bioactive natural and unnatural products in drug discovery.     

Synthesis and Crystal Structure of a Novel 14,20-Annulated Pentacyclic Steroid 17(S)-Methyl-13β-hydroxyl-14(R),20(S)-epoxy-pregn-4-en-3-one

The title compound 17(S)-methyl-13β-hydroxyl-14(R),20(S)-epoxy-pregn-4-en-3-one was synthesized by an improved tandem reaction, and its structure was determined by IR, NMR, HR MS and X-ray single-crystal diffraction. The crystal belongs to orthorhombic, space group P212121 with a = 10.55248(15), b = 12.14700(16), c = 14.56841(18) ?, V = 1867.39(4) ?3, Z = 4, Dc= 1.175 g/cm3, μ= 0.604 mm-1, F(000) = 720, the final R = 0.0400 and w R = 0.1072 for 3610 observed reflections with I 2σ(I).     

Liquid chromatography mass spectrometry simultaneous determination of vindoline and catharanthine in rat plasma and its application to a pharmacokinetic study

Vinblastine and vincristine, both of which are bisindole alkaloids derived from vindoline and catharanthine, have been used for cancer chemotherapy; their monomeric precursor molecules are vindoline and catharanthine. A simple and selective liquid chromatography mass spectrometry method for simultaneous determination of vindoline and catharanthine in rat plasma was developed. Chromatographic separation was achieved on a C₁₈ (2.1 × 50 mm, 3.5 µm) column with acetonitrile–0.1% formic acid in water as mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification. Mean recoveries were in the range of 87.3–92.6% for vindoline in rat plasma and 88.5–96.5% for catharanthine. Matrix effects for vindoline and catharanthine were measured to be between 95.3 and 104.7%. Coefficients of variation of intra‐day and inter‐day precision were both <15%. The accuracy of the method ranged from 93.8 to 108.1%. The method was successfully applied in a pharmacokinetic study of vindoline and catharanthine in rats. The bioavailability of vindoline and catharanthine were 5.4 and 4.7%, respectively. Copyright © 2014 John Wiley & Sons, Ltd.     

浙江丽水地区畲族与汉族成人头影测量分析对比研究

目的 比较畲族和汉族成人头影测量标准值的差别，为临床正畸治疗错牙合畸形提供依据。方法 按照准入标准选择浙江丽水地区汉族和畲族成人正常牙合各40 例，均拍摄头颅X线侧位片,采用北京大学口腔医院头影测量分析法进行测量分析。结果 测量结果显示，畲族成人的面角、上下中切牙夹角、Y 轴角以及下颌平面角（MP-FH）和上中切牙突距均较汉族显著增加（P＜0.05 或0.01），而颌凸角及下中切牙突距显著减小（P＜0.01）；畲族女性成人下颌平面角（MP-SN）和面角均较男性成人显著增加（P＜0.05），其他测量指标差异无统计学意义（P＞0.05）。结论 畲族成人较汉族相对是长面型，垂直生长型较多。而畲族男女比较，女性长面型较男性更明显。