糖类化学催化转化为氨基酸（英文）

在著名的1953年米勒实验中,甲烷、氨气、氢气和水在持续电火花的作用下被转换成一系列天然氨基酸混合物,包括甘氨酸、丙氨酸、天冬氨酸和α-氨基丁酸等等.这种化学转化过程奠定了现代人们对地球生命起源的认知基础.氨基酸作为蛋白质的基本组成成分,在生产生活中有广泛的应用,扮演着不可或缺的角色.目前,微生物发酵过程是氨基酸的主要生产途径,其生产受到许多限制.通过高效的催化方法将氨气和丰富的可再生碳资源直接转化成一系列氨基酸的化学路径尚未实现.近日,新加坡国立大学颜宁教授课题组与厦门大学王野教授课题组等数个国内外研究小组合作,开辟了一种用化学方法将木质生物质转化成一系列氨基酸的新路径.转化策略分两步:首先将纤维素、葡萄糖等转化为α-羟基酸,再将α-羟基酸在氨水和氢气作用下制备对应的氨基酸.第二步是核心步骤,可以被看作是一种改进版的米勒实验:即采用特定的木质生物质衍生物替代甲烷作为底物,而负载的钌催化剂则取代电火花实现定向高效转化.该系统已经成功用于6种氨基酸制备,包括丙氨酸、亮氨酸、缬氨酸、天冬氨酸和苯丙氨酸等.将α-羟基酸转化成氨基酸的反应遵循先脱氢再还原胺化途径,其中脱氢是速率控制步骤.在该反应中,碳纳米管上负载的钌催化剂比其他贵金属催化剂表现出显著优异的活性.这主要得益于氨分子对钌纳米颗粒的配位作用增强了钌脱氢反应的活性.基于新开发的催化体系,葡萄糖经由两步化学反应转化成43%丙氨酸,产率与微生物发酵过程相当.文章作者还使用膜蒸馏作为产物分离提纯技术,完成了概念性工艺设计,并用实验加以验证.考虑到氨基酸的高价值,这项报道不仅代表了近年来生物质催化转化的一项重要学术突破,在进一步开发和优化后还具有很好的应用潜力.     

Aminoglycoside microarrays to explore interactions of antibiotics with RNAs and proteins

RNA is an important target for drug discovery efforts. Several clinically used aminoglycoside antibiotics bind to bacterial rRNA and inhibit protein synthesis. Aminoglycosides, however, are losing efficacy due to their inherent toxicity and the increase in antibiotic resistance. Targeting of other RNAs is also becoming more attractive thanks to the discovery of new potential RNA drug targets through genome sequencing and biochemical efforts. Identification of new compounds that target RNA is therefore urgent, and we report here on the development of rapid screening methods to probe binding of low molecular weight ligands to proteins and RNAs. A series of aminoglycosides has been immobilized onto glass microscope slides, and binding to proteins and RNAs has been detected by fluorescence. Construction and analysis of the arrays is completed by standard DNA genechip technology. Binding of immobilized aminoglycosides to proteins that are models for study of aminoglycoside toxicity (DNA polymerase and phospholipase C), small RNA oligonucleotide mimics of aminoglycoside binding sites in the ribosome (rRNA A-site mimics), and a large (approximately 400 nucleotide) group I ribozyme RNA is detected. The ability to screen large RNAs alleviates many complications associated with binding experiments that use isolated truncated regions from larger RNAs. These studies lay the foundation for rapid identification of small organic ligands from combinatorial libraries that exhibit strong and selective RNA binding while displaying decreased affinity to toxicity-causing proteins.     

Aminoglycoside Antibiotics: New Insights into the Biosynthetic Machinery of Old Drugs

2‐Deoxystreptamine (2DOS) is the unique chemically stable aminocyclitol scaffold of clinically important aminoglycoside antibiotics such as neomycin, kanamycin, and gentamicin, which are produced by Actinomycetes. The 2DOS core can be decorated with various deoxyaminosugars to make structurally diverse pseudo‐oligosaccharides. After the discovery of biosynthetic gene clusters for 2DOS‐containing aminoglycoside antibiotics, the function of each biosynthetic enzyme has been extensively elucidated. The common biosynthetic intermediates 2DOS, paromamine and ribostamycin are constructed by conserved enzymes encoded in the gene clusters. The biosynthetic intermediates are then converted to characteristic architectures by unique enzymes encoded in each biosynthetic gene cluster. In this Personal Account, we summarize both common biosynthetic pathways and the pathways used for structural diversification.

     

Chemical transformation of ecdysteroids: Latest advances

In this review the results of chemical transformations of ecdysteroids reported in the literature during 1986–1996 are discussed.Institute of Bioorganic Chemistry of the Belarus Academy of Sciences, 220141, Minsk, Zhodinskaya, 5/2. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 139–160, March–April, 1998.     

Chemical trans-glycosylation of bioactive glycolinkage: synthesis of an α-lycotetraosyl cholesterol

The aim of this study was to verify the antitumor role of the β-d-glucopyranosyl-(1→2)-O-[β-d-xylopyranosyl-(1→3)]-O-β-d-glucopyranosyl-(1→4)-d-galactopyranosyl (lycotetraosyl) moiety present in steroidal glycosides from Solanaceous plants. We explored a new chemical trans-glycosylation method using an endoglycosidase called tomatinase that is produced by the tomato pathogen, Fusarium oxysporum f. sp. lycopersici. The lycotetraose, which was prepared by enzymatic hydrolysis of α-tomatine with tomatinase, was converted to glycosyl donors such as trichloroacetimidate, fluoride, and thioglycoside. All obtained glycosyl donors were glycosylated with cholesterol to form α-lycotetraosyl cholesterols in a stereoselective manner. The obtained lycotetraosyl derivatives together with typical natural lycotetraosyl glycosides were examined for their antiproliferative activity.     

Chemoenzymatic Synthesis of a Multivalent Aminoglycoside

A polymeric aminoglycoside was prepared by a facile chemoenzymatic reaction. Boc‐protected aminoglycoside, amikacin, was chemoselectively esterified with divinyl sebacate at a hydroxyl group in the C6″ position by protease from Bacillus subtilis. The resulting 3,6′,3″,4?‐tetra‐N‐Boc‐6″‐O‐vinyl sebacate was copolymerized with maltitol 6‐vinyl sebacate to yield a polymeric amikacin. The polymeric amikacin showed a modest inhibitory effect on in vitro protein synthesis, and a little antibiotic activity in minimum inhibitory concentration (MIC) assay in the presence of protease.

The synthesis of Boc‐protected amikacin ester by an enzyme‐catalyzed (protease) esterification.     

Regioselective transformation of octaethylporphyrin into a phytoporphyrin analogue

An octaethylporphyrin derivative, 1, possessing an exo-five-membered ring fused at the 13- and 15-positions was oxidized by osmium tetroxide to give two isomeric chlorins, 3 and 5, possessing beta,beta'-dihydroxy groups at the A- and C-rings, respectively. Single dehydration of 2,3-dihydroxychlorin 3 gave a mixture of 2- and 3-(1-hydroxyethyl)porphyrins 7, while that of 12,13-dihydroxychlorin 5 resulted in the sole formation of 131-hydroxyporphyrin 9. The latter was modified smoothly to the phytoporphyrin analogue 2, whose molecular skeleton was similar to that of naturally occurring chlorophylls possessing a 131-oxo group fixed on an exo-five-membered ring.     

Chemical composition of bioactive pressurized extracts of Romanian aromatic plants

In this contribution, pressurized liquid extraction (PLE) has been employed to isolate bioactive compounds from three native Romanian plants, oregano (Origanum vulgare), tarragon (Artemisia dracunculus) and wild thyme (Thymus serpyllum). Different PLE conditions have been tested including extraction with water, ethanol and their mixtures in a wide range of extraction temperatures (50-200°C), and the antioxidant capacity of the extracts was measured using different assays (DPPH radical scavenging, TEAC assay and Folin-Ciocalteau assay to measure total phenols). Moreover, a complete chemical characterization by using LC-MS/MS was carried out to be able to correlate the bioactivity with the particular chemical composition of each extract and plant. The use of PLE with water as a solvent at the highest temperature tested (200°C) always provided the highest extraction yields for the three studied plants, being maximum for oregano (>60%). Besides, oregano's pressurized water extracts at lower temperatures (50°C) presented the highest content on total phenols (184.9 mg gallic acid/g extract) and the best antioxidant activities (EC(50) 6.98 μg/ml). In general, oregano extracts were the most active, followed by wild thyme extracts. The antioxidant capacity measured by DPPH assay was highly correlated with the amount of total phenols. Moreover, the use of a LC-MS/MS method allowed the identification of 30 different phenolic compounds in the different extracts, including phenolic acids, flavones, flavanones and flavonols, which have an important influence on the total antioxidant capacity of the different extracts.     

Thermal transformation of a chiral,non-racemic epoxide into a conglomerate

Formation of conglomerates is of general interest because they offer the possibility of enantiomeric separation by preferential crystallization. A surprising result was obtained for the chiral epoxide 1a, 2, 7, 7a-tetrahydro-3-methoxynaphth-(2,3b)-oxirene, for which we have shown that the racemate crystals of a non racemic mixture can be easily transformed into a conglomerate by gentle heating and cooling within a defined temperature range. This transformation is not possible with the pure racemic mixture. Thus the enantiomeric excess seems to be the driving force for the conglomerate formation. Experiments have been carried out on analytical and preparative scale. Non racemic mixtures have been characterized by high pressure liquid chromatography on chiral stationary phase and crystal transformation has been monitored with differential scanning calorimetry (DSC) and infrared spectroscopy (IR).     

Incorporation of the bioactive moiety of leinamycin into thymidine

A simple synthesis of 1,2-dithiolan-3-ones from α,β-unsaturated thiophenyl esters has been elaborated. With the aim of introducing the biologically active 1,2-dithiolan-3-one-1-oxide moiety of leinamycin into a nucleoside, the method was successfully applied to thymidine-5^′-aldehyde.