An efficient semi-synthesis of 1-hydroxyl oleanolic acid analogs

An efficient route for the semi-synthesis of either 1α- or 1β-OH epimers of 1-hydroxy-3-deoxyolean-12-en-28-oic acid (1), 6–8 steps from oleanolic acid is reported. The synthesis involves stereoselective formation of α,β-unsaturated epoxy ketone and subsequent Wharton reaction as key steps, offering a new access to the 1-O-substituted oleanolic acid-type pentacyclic triterpenoids.     

A new diimide derivative from the co-culture broth of two mangrove fungi (strain no. E33 and K38)

A new diimide derivative, named ( ? )-byssochlamic acid bisdiimide (1), was isolated from the mixed broth of two mangrove fungi (strain no. K38 and E33) from the South China sea coast. The structure of 1 was determined by comprehensive spectroscopic methods, including 1D and 2D NMR (COSY, HMQC, and HMBC) and semi-synthesis. Primary bioassays showed that 1 had weak cytotoxic activity against Hep-2 and HepG2 cells.     

白花前胡丙素C-3′和C-4′反式结构类似物的半合成白花前胡丙素C-3′和C-4′反式结构类似物的半合成

目的对白花前胡丙素［(+)-praeruptorin A］进行结构修饰,半合成C-3′和C-4′反式结构类似物,寻找活性化合物。方法首先从白花前胡(Peucedanum praeruptorum)根中分离得到白花前胡丙素,从白花前胡丙素出发,运用碱水解及各种酰化反应,半合成各种结构修饰产物。结果首次合成了17个白花前胡丙素C-3′和C-4′反式结构类似物,通过IR,¹HNMR,MS等方法确定它们的结构。结论17个化合物均为新化合物,其中一些新化合物有显著的钙离子拮抗活性,首次证明C-3′和C-4′反式结构的这类化合物同样具有活性。     

Isolation,identification, semi-synthesis of aziditaxel derivatives and their biological evaluation

Two new taxoids (5 and 6) were obtained by isolating impurities in aziditaxel, and their structures were characterized based on data analysis of ¹H NMR, ¹³C NMR, HPLC-MS, and through comparison with literature. In order to test their cytotoxicities against human nonsmall lung cancer cell lines (A549), sufficient amounts of compounds 5 and 6 were obtained by semi-synthesis and both of them showed equipotent cytotoxiesty compared with taxol, docetaxel, and aziditaxel.     

硅烷化剂苯基二甲基氯硅烷的合成及应用

用氯苯和二甲基二氯硅烷经格氏反应和取代反应制得硅烷化试剂苯基二甲基氯硅烷，总收率72％。将其应用于辛伐他汀的半合成，收率49％。     

Enzymatic semisynthesis of [Leu B30] insulin

Experimental conditions for the preparation of [Leu^B30] insulin by coupling of des-Ala^B30 insulin with Leu-OBu^t were determined using Achromobacter protease I and trypsin as catalysts. Successful coupling required a large excess of the amine component (0.8 M), a high concentration of organic cosolvent (35–50%) and neutral pH of the reaction mixture. The coupling yield of Achromobacter protease I after 24 h at 37°C was almost the same or a little higher than that at 25°C. With trypsin, the coupling yield at 37°C after 24 h was considerably lower than at 25°C. This was partly ascribed to the difference in concentration of organic cosolvent at 37°C and 25°C; 35% and 50%, respectively, or possibly of enzyme stability at these temperatures. The maximum product yield was about 90% with both enzymes under optimal conditions. A preparative scale experiment was performed with Achromobacter protease I; the yield of [Leu^B30] insulin was 51% using porcine insulin as the starting material. This semisynthetic insulin was identified by HPLC and amino acid analysis. No difference was observed in CD spectra between [Leu^B30] insulin and human insulin.     

源头与末端治理相结合处理半合成抗生素原料药生产废水

半合成抗生素原料药生产废水难降解,治理难度大。通过对半合成抗生素原料药生产过程污水排放节点分析,根据各类污水的性质采用不同的处理方法,回收了产品和溶剂,大幅降低了源头污水量和COD排放量。同时,结合原有污水处理工艺,采用Fenton氧化和膜生物反应器（MBR）处理技术,最终实现排放污水满足COD≤120mg／L的要求。     

对HPLC法测定紫杉醇有关物质方法的探讨

目的紫杉醇为《中国药典》2010年版二部新增品种,通过对国内外现行标准紫杉醇有关物质检测方法的探讨,建立准确、可行的有关物质质控方法。方法对已有的质量标准进行了综合对比,在流动相梯度程序、色谱柱、供试品溶剂的选择和已知杂质的定位等方面进行了相关试验,就单个杂质、总杂质的计算方法和控制限度等问题进行了探讨。结果与结论本文拟定的有关物质检查方法,将国家标准与国外药典标准作了相应的结合,拟定了切实可行的紫杉醇有关物质检查方法。     

PHOTOLABILE MULTI-DETACHABLE p-ALKOXYBENZYL ALCOHOL RESIN SUPPORTS FOR PEPTIDE FRAGMENT OR SEMI-SYNTHESIS

Two photolabile multi-detachable alkoxybenzyl alcohol resins, 2-[4-(oxymethyl)phenoxy]propionyl-resin 4 and 4-[4-(oxymethyl)phenoxymethyl]-3-nitrobenzamidomethyl-resin 5 have been synthesized. Bpoc-peptide attached to resin 4 or 5 when treated with 50% trifluoroacetic acid provided the free, unprotected peptide, but on photolysis gave Bpoc-peptide p-hydroxybenzyl ester. Removal of the p-hydroxybenzyl ester in aqueous base or by oxidative work up gave a protected Bpoc-peptide suitable for fragment synthesis at its C-terminus. However, methylation of the ester to Bpoc-peptide p-methoxybenzyl ester followed by removal of the Bpoc-group gave a protected peptide p-methoxybenzyl ester suitable for fragment coupling at its N-terminus. The efficacies of these resins were evaluated in the syntheses of a model tetrapeptide and an octapeptide by using N^α-Bpoc-, Fmoc- and Nps-amino acids. The use of 2-thiopyridine with pyridinium hydrochloride as a new and efficient thiolytic reagent for the deprotection of the Nps-group was studied.     

HPLC测定吲哚美辛亚微乳胶含量及其体外经皮渗透评价

目的建立测定吲哚美辛亚微乳胶含量的高效液相色谱法,并评价其在离体大鼠皮肤中的渗透性。方法采用Hypersil BDS C18柱（4．6mm×200mm,5μm）;流动相为乙腈-水-冰乙酸（50：50：0．06）;流速1.0mL·min^-1,检测波长228nm,柱温40℃,外标法定量计算结果。改良Franz扩散池测定药物在离体大鼠皮肤中的渗透量。结果吲哚美辛在8．46～126．90μg·mL^-1内线性关系良好（r=0．9999）,平均回收率为99．60％,RSD为1.35％（月=9）。吲哚美辛亚微乳胶24h平均累积透过量为（1311．38±74．95）μg·cm^-2,渗透系数为（54．17±4．91）μg·cm^-2·h,渗透行为经拟合符合零级动力学过程。结论本试验建立的方法准确可靠、简单快速,适用于该制剂的含量测定及体外经皮特性研究。