苏北盆地油源判别指标研究

苏北盆地有上白垩统泰州组二段、古新统阜宁组二段、四段3套油源,母岩干酪根性质和地质环境十分接近,通过一般的地球化学指标很难彻底区分它们,为此因地制宜采用了多参数联合图版以及正烷烃分布、原生甾烷分布、三芳甾系列、二甲基咔唑系列等指标,使3套油源达到有效区分。值得提出的是,用于运移研究的二甲基咔唑系列分布在同源油之间也表现出惊人的稳定性,并且提供出进一步细分油源的指纹信息。      

CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.     

Aggregation arrestant pheromone of the German cockroach,Blattella germanica (L.) (Dictyoptera: Blattellidae): Isolation and structure elucidation of blattellastanoside-A and -B

The aggregation pheromone of the German cockroach,Blattella germanica, consists of attractant and arrestant, which can be detected by olfactometer and choice-chamber assay, respectively. Both were extracted from the frass-contaminated filter paper being used as a shelter. They were separated by solvent partition withn-butanol and water. The arrestant from then-butanol phase was purified by open column chromatography and then successive HPLC isolated two major arrestant components. Spectral evidence from SI-MS, HR-EI-MS, and NMR experiments with pulse techniques provided possible structures as 1-(6-chloro-4,5-epoxy-5-stigmast-3-yl)--d-glucopyranoside and 1-(6-chloro-5-hydroxy-5-stigmast-3-yl)--d-glu-copyranoside, denoted as blattellastanoside-A and blattellastanoside-B, respectively. They represented arrestant activity as median effective doses (ED₅₀) at 0.044 (A) and 3.2 (B) nmol on 1.0 cm² of Whatman No. 1 filter paper.     

Stereoselective asymmertric synthesis and characterization of 17α-acetoxy-19-nor-progesterone

17α-actoxy-19-nor-progesterone was synthesized by a new efficient stereoselective asymmertric pathway from 19-nor-androst-4-en-3,17-dione in 5-steps reactions with overall yield 63.3%. Consequently, a strategy was used to produce of 17-α-hydroxyl compound stereoselectively by addition 17-keto steroid with hydrogen cyanide, at the same time, the conditions of this asymmertric reaction were optimized. The titled compound and the intermediate were fully characterized by 1H, one dimension and two dimension 13C-nuclear magnetic resonance, and infrared spectrum. The results show that the rate of 17-α-hydroxyl compound isomeride is sensitively affected by the solution system and the best volume ratio of CH3 OH to H2 O is 36%. After the carbonyl and hydroxyl groups were protected by ethylenediol and vinyl butyl ether respectively, organometallic addition to CN group with CH3 Li, androstance compound was converted to pregnane compound. After removing the protective groups by a mild hydrolytic procedure with high yield, the titled compound was obtained by esterified the above intermidiate. The new pathway gives a good purity of 98% as determined by high performance liquid chromatography.     

Investigation of injectable drospirenone organogels with regard to their rheology and comparison to non-stabilized oil-based drospirenone suspensions

The objective of this study was to evaluate organogels as potential injectable drug-delivery systems for drospirenone (DRSP). Recently, studies on organogel characterization with focus on the parenteral injection are rarely to find in the literature. DRSP organogels contained the drug suspended in medium-chain triglycerides and were stabilized by various organogelators. The DRSP organogels were assessed in comparison to non-stabilized DRSP microcrystal suspensions (MCSs). Furthermore, rheological properties of the organogels, in particular the elastic modulus (G′), the complex viscosity (η*) and the elasticity, were evaluated with respect to the long-term stability, syringeability/injectability and in vitro release. DRSP organogels showed significantly improved storage stability compared to non-stabilized MCSs with regard to sedimentation and particle growth. Furthermore, all of the DRSP organogels showed shear-thinning behavior. Thus, ejection from syringes was possible by an autoinjector using 23G needles comparable to non-stabilized MCSs. Nevertheless, DRSP organogels exhibited significantly more sustained drug release than non-stabilized MCSs most likely caused by partial recovery of the organogelator structures at 37?°C after destruction. Consequently, DRSP organogels were evaluated to be superior to conventional non-stabilized MCSs. Silica organogels, which provided the highest elasticity, moderate G' and η* and avoided most efficiently particle growth, are slightly more preferable compared to the other DRSP organogels.     

新技术在甾体药物微生物转化中的应用

主要综述了固定化细胞和原生质体转化、双水相转化、超临界流体技术、有机介质中微生物转化以及磁场和超声处理等新技术应用于甾体药物微生物转化的研究进展。简要介绍了相应的反应器研究开发趋势。     

Investigation of the role of diterpenes produced by marine pulmonatesTrimusculus reticulatus andT. conica

The intertidal pulmonate limpetTrimusculus reticulatus, which is found in caves or crevices along the California coast, was previously reported to contain two novel diterpenoids, 6-isovaleroxylabda-8,13-dien-7,15-diol (1) and 2,7-diacetoxy-6-isovaleroxylabda-8,13-dien-15-ol (2). Dissection of the animals prior to extraction revealed that the diterpenoids were concentrated in the mantle, foot, and mucus, but not in the viscera. The presence ofT. reticulatus or its mucus was toxic to veliger larvae of the sabellariid reef-building tube wormPhragmatopoma californica. The major diterpenoid1 was responsible for the observed larvicidal activity. Protection against overgrowth by settling invertebrate larvae is important for the survival of this sessile filter-feeding pulmonate. A related pulmonate,T. conica, which was found in similar intertidal habitats in New Zealand, contained 6-acetoxy-7-isovaleroxylabda-8,13-dien-15-oic acid (3) and 1,7,12,18-tetraacetoxy-cholest-5-en-3-ol (4). The diterpene3 was also localized in the foot, mantle, and mucus ofT. conica but was not larvicidal toP. californica.     

Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes.

Allopregnanolone is a neuroactive steroid that, like ethanol (EtOH), has stimulant, anxiolytic, ataxic, and depressant effects. Two experiments tested the hypothesis that sensitivity to the locomotor stimulant effects of these drugs is influenced by a common set of genes. Sensitivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant inbred (RI) strains. Strain means were positively correlated with extant means for EtOH stimulation in 20 of the same strains. Quantitative trait locus (QTL) analysis provisionally identified many loci, including several known to influence sensitivity to EtOH. Sensitivity to allopregnanolone was also measured in FAST and SLOW mice, which were selectively bred for differential locomotor response to EtOH, to determine whether selection has also altered allopregnanolone sensitivity. FAST mice were more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice. These data suggest that sensitivity to the locomotor stimulant effects of these drugs is influenced by common genes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microbial conversion of androst‐1,4‐dien‐3,17‐dione by Mucor racemosus to hydroxysteroid‐1,4‐dien‐3‐one derivatives

BACKGROUND: A large number of bacterial, fungal and microalgal species are able to bio‐transform steroid compounds. Among them, fungi from the Mucor genus have been shown to mediate hydroxylation, oxidation, and desaturation by the double bond formation and epoxidation of various steroid substances. Mucor racemocus has not been studied for its ability to modify androst‐1,4‐dien‐3,17‐dione, a pharmaceutically important steroid precursor. RESULTS: The filamentous fungus M. racemosus was applied for bioconversion of androst‐1,4‐dien‐3,17‐dione (ADD, I ) in a 5‐day fermentation. Microbial metabolites were purified chromatographically and identified on the basis of their spectral data as 17β‐hydroxyandrost‐1,4‐dien‐3‐one ( II ), 14α‐hydroxyandrost‐1,4‐dien‐3,17‐dione ( III ), 15α‐hydroxyandrost‐1,4‐dien‐3,17‐dione ( IV ), 15α,17β‐dihydroxyandrost‐1,4‐dien‐3‐one ( V ), 14α,17β‐dihydroxyandrost‐1,4‐dien‐3‐one ( VI ), and 6β,17β‐dihydroxyandrost‐1,4‐dien‐3‐one ( VII ). CONCLUSION: Observed modifications included hydroxylation at C‐6β, C‐14α, C‐15α positions and 17‐carbonyl reduction. The best fermentation conditions for production of hydroxysteroid‐1,4‐dien‐3‐one derivatives were found to be 25 °C at 150 rpm for 5 days with a substrate concentration of 0.5 g L^?1. Copyright © 2009 Society of Chemical Industry