阿伐他汀手性中间体合成研究进展

综述了近年来阿伐他汀手性中间体的合成研究进展,从手性池反应、不对称合成、外消旋体拆分三个方面介绍了阿伐他汀手性中间体合成的工艺路线和研究水平,对其工业化前景进行了展望.     

HMG—CoA还原酶抑制剂类血脂调节药物的合成与应用

本文介绍了ＨＭＧ－ＣｏＡ还原酶抑制剂类血脂调节药物的开发和应用，重点综述了近年上市的新药氟代他汀，西伐他汀和阿伐他汀的合成与临床应用。     

专利选登

标题：智能絮凝投药系统；标题：作为阿立新受体拮抗药的N—芳酰基环胺衍生物；标题：7-酰氨基-3-杂芳硫基-3-头孢羧酸抗生素的前药；标题：辉伐他汀及其合成方法和以辉伐他汀为原料药的制剂；标题：用于制备一类取代的二噁嗪的中间体……     

浅谈阿托伐他汀的作用机理及合成

阿托伐他汀是一种他汀类的药物,在降低心血管疾病和死亡风险方面,有着高效、安全的长期临床效益。本文对阿托伐他汀的药动力学机理进行分析,在此基础上,对阿托伐他汀合成路径研究综述。研究表明:阿托伐他汀主要有线性、收敛性两种合成策略,Paal-Knorr吡咯法通常被认为是最广泛的使用方法。     

氟伐他汀钠的电化学行为和测定

研究了在pH值为5.10的醋酸-醋酸钠缓冲液中,氟伐他汀钠在玻碳电极上的电化学行为,并依此建立了氟伐他汀钠的微分脉冲伏安测定法。在微分脉冲伏安模式下,于 0.64 V(vs.Ag/AgCl)电位处产生一灵敏的阳极氧化峰,用循环伏安法、线性扫描极谱法、微分脉冲伏安法等手段研究了其电化学行为和机理。结果表明,该峰电流值与氟伐他汀钠的质量浓度在2.0~40 mg/L范围内呈良好的线性关系,其最低检测限为0.24 mg/L,该法应用于来适可胶囊中氟伐他汀钠含量的测定,回收率达到98.0%~101.2%,并讨论了氟伐他汀钠在玻碳电极上的电极过程。     

氟伐他汀对糖尿病大鼠肾脏CTGF表达的影响

目的观察氟伐他汀对糖尿病大鼠肾脏结缔组织生长因子(CTGF)表达的影响。方法用链脲佐菌素复制糖尿病大鼠模型,成模后给予氟伐他汀治疗。采用ELISA法检测尿微量白蛋白浓度;Western blot和RT-PCR法检测大鼠肾皮质CT-GF蛋白及mRNA的表达水平;免疫组化法检测肾小球内CTGF和FN的表达。结果氟伐他汀治疗组大鼠尿白蛋白排泄率、肾脏肥大指数(KHI)、肾皮质中CTGF的mRNA及蛋白表达、肾小球内CTGF和FN的表达较糖尿病组大鼠均明显降低。结论氟伐他汀能降低肾小球内CTGF及FN的表达,减轻肾小球肥大,起到抑制和延缓糖尿病肾病进展的作用。     

顶空毛细管气相色谱法测定瑞舒伐他汀钙的残留溶剂

目的:建立瑞舒伐他汀钙残留有机溶剂的检测方法。方法:采用顶空毛细管气相色谱法;色谱柱为DB-624(30 m×0.53 mm×3μm),FID检测器,测定瑞舒伐他汀钙中残留的甲醇、乙醚和丙酮。结果:各被测溶剂均能良好分离,各溶剂线性关系良好,精密度RSD均小于10%,平均回收率为95%~105%之间。结论:该法适用于瑞舒伐他汀钙原料药的残留溶剂测定。     

灯盏花素对阿托伐他汀药物体内转运过程的影响

研究灯盏花素对阿托伐他汀药物体内转运过程的影响,为两药在临床的合理联用提供一定的实验依据,为指导临床合理用药提供科学依据。方法:将小鼠/大鼠随机分为阿托伐他汀单独给药组,灯盏花素注射液联合阿托伐他汀给药组,分别于给药后不同时间点/时间段采集组织及胆汁样品,样品经处理后进行HPLC分析。结果:阿托伐他汀与灯盏花素注射液联合用药后,阿托伐他汀迅速进入小鼠体内后,0.5h即可被检测到。灯盏花素显著增加阿托伐他汀在各组织中的浓度。排泄研究中,灯盏花素显著降低阿托伐他汀的胆汁排泄量。结论:灯盏花素影响了阿托伐他汀药物的组织分布、胆汁排泄,增强了阿托伐他汀对心脑血管的药理作用。     

瑞舒伐他汀治疗冠心病心绞痛临床观察

目的观察瑞舒伐他汀治疗冠心病心绞痛的疗效。方法入选冠心病心绞痛患者120例,随机分成瑞舒伐他汀组和对照组。2组均给予阿司匹林/氯吡格雷、硝酸酯类、钙拮抗剂、β受体阻滞剂及基础病因治疗。瑞舒伐他汀组加用瑞舒伐他汀10mg,qd,连用3个月。观察2组治疗前后各症状变化及不良反应。结果瑞舒伐他汀组治疗后较对照组心绞痛发作次数明显减少,持续时间明显缩短,硝酸甘油耗量减少,总胆固醇、低密度脂蛋白胆固醇及C-反应蛋白明显降低,心电图缺血改善。与治疗前相比、与对照组治疗后相比有统计学差异。结论瑞舒伐他汀治疗冠心病心绞痛有显著疗效。     

阿伐那非的合成研究进展

阿伐那非是一种用于治疗男性勃起功能障碍的磷酸二酯酶5抑制剂。目前有关阿伐那非的合成方法报道较少。本文简单介绍了阿伐那非的作用机理,阿伐那非的合成方法研究进展,并对其市场前景进行了展望。     

Enzymes-Assisted Extraction of Plants for Sustainable and Functional Applications

The scientific community and industrial companies have discovered significant enzyme applications to plant material. This rise imparts to changing consumers’ demands while searching for ‘clean label’ food products, boosting the immune system, uprising resistance to bacterial and fungal diseases, and climate change challenges. First, enzymes were used for enhancing production yield with mild and not hazardous applications. However, enzyme specificity, activity, plant origin and characteristics, ratio, and extraction conditions differ depending on the goal. As a result, researchers have gained interest in enzymes’ ability to cleave specific bonds of macroelements and release bioactive compounds by enhancing value and creating novel derivatives in plant extracts. The extract is enriched with reducing sugars, phenolic content, and peptides by disrupting lignocellulose and releasing compounds from the cell wall and cytosolic. Nonetheless, depolymerizing carbohydrates and using specific enzymes form and release various saccharides lengths. The latest studies show that oligosaccharides released and formed by enzymes have a high potential to be slowly digestible starches (SDS) and possibly be labeled as prebiotics. Additionally, they excel in new technological, organoleptic, and physicochemical properties. Released novel derivatives and phenolic compounds have a significant role in human and animal health and gut-microbiota interactions, affecting many metabolic pathways. The latest studies have contributed to enzyme-modified extracts and products used for functional, fermented products development and sustainable processes: in particular, nanocellulose, nanocrystals, nanoparticles green synthesis with drug delivery, wound healing, and antimicrobial properties. Even so, enzymes’ incorporation into processes has limitations and is regulated by national and international levels.     

Mechanisms Governing Anaphylaxis: Inflammatory Cells,Mediators, Endothelial Gap Junctions and Beyond

Anaphylaxis is a severe, acute, life-threatening multisystem allergic reaction resulting from the release of a plethora of mediators from mast cells culminating in serious respiratory, cardiovascular and mucocutaneous manifestations that can be fatal. Medications, foods, latex, exercise, hormones (progesterone), and clonal mast cell disorders may be responsible. More recently, novel syndromes such as delayed reactions to red meat and hereditary alpha tryptasemia have been described. Anaphylaxis manifests as sudden onset urticaria, pruritus, flushing, erythema, angioedema (lips, tongue, airways, periphery), myocardial dysfunction (hypovolemia, distributive or mixed shock and arrhythmias), rhinitis, wheezing and stridor. Vomiting, diarrhea, scrotal edema, uterine cramps, vaginal bleeding, urinary incontinence, dizziness, seizures, confusion, and syncope may occur. The traditional (or classical) pathway is mediated via T cells, Th2 cytokines (such as IL-4 and 5), B cell production of IgE and subsequent crosslinking of the high affinity IgE receptor (FcεRI) on mast cells and basophils by IgE-antigen complexes, culminating in mast cell and basophil degranulation. Degranulation results in the release of preformed mediators (histamine, heparin, tryptase, chymase, carboxypeptidase, cathepsin G and tumor necrosis factor alpha (TNF-α), and of de novo synthesized ones such as lipid mediators (cysteinyl leukotrienes), platelet activating factor (PAF), cytokines and growth factors such as vascular endothelial growth factor (VEGF). Of these, histamine, tryptase, cathepsin G, TNF-α, LTC₄, PAF and VEGF can increase vascular permeability. Recent data suggest that mast cell-derived histamine and PAF can activate nitric oxide production from endothelium and set into motion a signaling cascade that leads to dilatation of blood vessels and dysfunction of the endothelial barrier. The latter, characterized by the opening of adherens junctions, leads to increased capillary permeability and fluid extravasation. These changes contribute to airway edema, hypovolemia, and distributive shock, with potentially fatal consequences. In this review, besides mechanisms (endotypes) underlying IgE-mediated anaphylaxis, we also provide a brief overview of IgG-, complement-, contact system-, cytokine- and mast cell-mediated reactions that can result in phenotypes resembling IgE-mediated anaphylaxis. Such classifications can lead the way to precision medicine approaches to the management of this complex disease.     

Effects of Extraction Temperature and Preservation Method on Functionality of Soy Protein

The effects of extraction temperature and preservation method on the functional properties of soy protein isolate (SPI) were determined. Four extraction temperatures (25, 40, 60, and 80 °C) were used to produce SPI and yields of solids and protein contents were determined. Three preservation methods were also tested (spray-drying, freeze-drying, and freezing–thawing) and compared to fresh (undried) samples for each extraction temperature. No differences in yields of solids and protein were observed among SPIs extracted at 25, 40, and 60 °C; however, SPI extracted at 80 °C yielded significantly less solids and protein. Extraction temperature significantly affected SPI functionality. As extraction temperature increased, solubility and emulsification capacity decreased; surface hydrophobicities, emulsification activities and stabilities, and dynamic viscosities increased; and foaming properties improved. Preservation method also significantly affected SPI functionality. Drying method did not affect the denaturation enthalpies of SPIs, but spray-dried SPIs had higher solubilities, surface hydrophobicities, and emulsification stabilities, and lower viscosities, emulsification activities and rates of foaming than freeze-dried SPI exhibited. Emulsification and foaming capacities and foaming stabilities were similar for both methods of drying. There was significant interaction between extraction temperature and preservation method for all functional properties except emulsification capacity.     

松香基表面活性剂研究进展

松香是一类产量丰富、价格低廉的可再生林产资源,被广泛地应用于食品、农业、橡胶、油墨、涂料等领域。松香的三环二萜结构具有超强的疏水性,通过催化异构、Diels-Alder加成等手段引入亲水基团可制备高附加值、易生物降解的绿色表面活性剂。本文从阴离子、阳离子、非离子和两性离子表面活性剂4个大类对松香基表面活性剂应用的文献及专利进行综述,重点分析了羧酸盐、磺酸盐、硫酸盐和磷酸盐4种阴离子型表面活性剂和季铵盐阳离子型表面活性剂,多元醇型和聚氧乙烯型非离子表面活性剂,以及甜菜碱型和氧化胺型两性离子表面活性剂。剖析松香基表面活性剂产业化开发的新技术及新产品概况,提出松香基表面活性剂替代传统表面活性剂的潜在应用领域。同时,对松香基表面活性剂的研究发展与产业化发展进行了评价与展望。     

中低温煤焦油蒸馏过程中金属元素的迁移规律

以中低温煤焦油轻油和重油为实验原料,采用常压蒸馏获得170~200℃、200~240℃、240~270℃、270~300℃、300~320℃、320~340℃、340~360℃和360~390℃煤焦油馏分油;利用配有油品加氧制冷进样系统的ICP-OES测定了21种微量元素在馏分油中的含量,考察了不同馏分油中元素的分布情况。研究表明：在原煤焦油中,未发现Ag、Mg、Mo、Na、Ni、Fe、Mn、Cr及Ti元素,含量较高的元素有Sn、P、Al、Pb、Si,其中Sn元素在轻油和重油中的含量分别为11.78μg/g和14.04μg/g;在所有馏分油中,未发现Al、Mo、Fe、Mn、Cr及Ti元素,含量比较高的元素有Si、Sn、Na、Zn、Pb,特别是Si、Na、Sn、Zn、Ni、Pb及B元素可以有效富集于馏分油中。可能的原因是Ca、Fe、Mg、Al等金属以不同的盐类形态存在,在煤焦油脱水及<170℃蒸馏过程中,这些金属盐类会被部分带出,导致其在馏分油中的含量未富集或未检出;通过关联金属元素在馏分油中的分布与其组成的关系,馏分油中元素的分布可能与酚类化合物、杂环化合物和蒸馏温度等相关。酚类化合物及杂环化合物可能与Ag、B、Cu、Mo、Sn、Na、Zn、Ca、Pb等金属形成络合物或卟啉配合物,蒸馏温度一方面可以破坏Sn、Cd、Pb、Zn、Cu、Ca、Pb等元素在馏分油中的结合力,另一方面也可以促进这些元素与馏分油中的含氧、含氮等化合物更好地发生化合反应,进而影响金属元素在馏分油中的含量分布。     

Recent Progress in Biopolymer-Based Hydrogel Materials for Biomedical Applications

Hydrogels from biopolymers are readily synthesized, can possess various characteristics for different applications, and have been widely used in biomedicine to help with patient treatments and outcomes. Polysaccharides, polypeptides, and nucleic acids can be produced into hydrogels, each for unique purposes depending on their qualities. Examples of polypeptide hydrogels include collagen, gelatin, and elastin, and polysaccharide hydrogels include alginate, cellulose, and glycosaminoglycan. Many different theories have been formulated to research hydrogels, which include Flory-Rehner theory, Rubber Elasticity Theory, and the calculation of porosity and pore size. All these theories take into consideration enthalpy, entropy, and other thermodynamic variables so that the structure and pore sizes of hydrogels can be formulated. Hydrogels can be fabricated in a straightforward process using a homogeneous mixture of different chemicals, depending on the intended purpose of the gel. Different types of hydrogels exist which include pH-sensitive gels, thermogels, electro-sensitive gels, and light-sensitive gels and each has its unique biomedical applications including structural capabilities, regenerative repair, or drug delivery. Major biopolymer-based hydrogels used for cell delivery include encapsulated skeletal muscle cells, osteochondral muscle cells, and stem cells being delivered to desired locations for tissue regeneration. Some examples of hydrogels used for drug and biomolecule delivery include insulin encapsulated hydrogels and hydrogels that encompass cancer drugs for desired controlled release. This review summarizes these newly developed biopolymer-based hydrogel materials that have been mainly made since 2015 and have shown to work and present more avenues for advanced medical applications.     

Organokines in Rheumatoid Arthritis: A Critical Review

Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects the joints. Organokines can produce beneficial or harmful effects in this condition. Among RA patients, organokines have been associated with increased inflammation and cartilage degradation due to augmented cytokines and metalloproteinases production, respectively. This study aimed to perform a review to investigate the role of adipokines, osteokines, myokines, and hepatokines on RA progression. PubMed, Embase, Google Scholar, and Cochrane were searched, and 18 studies were selected, comprising more than 17,000 RA patients. Changes in the pattern of organokines secretion were identified, and these could directly or indirectly contribute to aggravating RA, promoting articular alterations, and predicting the disease activity. In addition, organokines have been implicated in higher radiographic damage, immune dysregulation, and angiogenesis. These can also act as RA potent regulators of cells proliferation, differentiation, and apoptosis, controlling osteoclasts, chondrocytes, and fibroblasts as well as immune cells chemotaxis to RA sites. Although much is already known, much more is still unknown, principally about the roles of organokines in the occurrence of RA extra-articular manifestations.     

Role of Douglas fir (Pseudotsuga menziesii) carbohydrates in resistance to budworm (Choristoneura occidentalis)

The current year's growth of Douglas fir contains galactose, unusual in that this carbohydrate makes up 78.7% of the total carbohydrate fraction. An agar diet study was undertaken to determine the effects of galactose, other carbohydrates, and terpenes on western spruce budworm larval mortality, growth rate, and adult biomas production. All concentrations of the carbohydrates and terpenes tested, as well as other mineral elements not tested, were typical of the current year's foliage of Douglas fir. In experiment I, the diet containing 5.61% total carbohydrate did not significantly affect larval mortality when compared to the control diet. However, diets containing 9.45% and 15% total carbohydrate concentrations significantly increased larval mortality 64% and 96.1%, respectively, when compared to the control. Also in experiment I, terpenes alone (78.9% morality) and terpenes in combination with 9.45% and 15% total carbohydrates significantly increased larval mortality (97.2% and 100%, respectively) when compared to mortality on the control diet (44%). To determine which carbohydrate was causing the adverse effect, 6% glucose, 6% fructose, and 6% galactose were placed individually and in combination with terpenes in diets in experiment II. The 6% galactose diet significantly increased larval mortality and reduced growth rate when compared to the control, glucose, and fructose diets. Glucose resulted in 16% less larval mortality, significantly enhanced female larval growth rate and pupal weight, but did not affect male larval growth rate and pupal weight, when compared to the control. Fructose resulted in a significant decrease in larval mortality and a general trend of enhanced female and male larval growth rate and pupal weight. Larval mortality on terpenes alone was not significantly different from the control, but terpenes with 6% galactose increased larval mortality and decreased female and male growth rate and pupal weight significantly when compared to glucose-terpene and fructose-terpene diets. No significant interactions were found between carbohydrates and terpenes in either experiment.     

Laccases and Tyrosinases in Organic Synthesis

Laccases (Lac) and tyrosinases (TYR) are mild oxidants with a great potential in research and industry. In this work, we review recent advances in their use in organic synthesis. We summarize recent examples of Lac-catalyzed oxidation, homocoupling and heterocoupling, and TYR-catalyzed ortho-hydroxylation of phenols. We highlight the combination of Lac and TYR with other enzymes or chemical catalysts. We also point out the biological and pharmaceutical potential of the products, such as dimers of piceid, lignols, isorhamnetin, rutin, caffeic acid, 4-hydroxychalcones, thiols, hybrid antibiotics, benzimidazoles, benzothiazoles, pyrimidine derivatives, hydroxytyrosols, alkylcatechols, halocatechols, or dihydrocaffeoyl esters, etc. These products include radical scavengers; antibacterial, antiviral, and antitumor compounds; and building blocks for bioactive compounds and drugs. We summarize the available enzyme sources and discuss the scalability of their use in organic synthesis. In conclusion, we assume that the intensive use of laccases and tyrosinases in organic synthesis will yield new bioactive compounds and, in the long-term, reduce the environmental impact of industrial organic chemistry.