4-烷硒基4-脱氧4′-去甲表鬼臼毒素衍生物的合成和抗肿瘤活性

4-溴-4-脱氧-4′-去甲表鬼臼毒素与硒脲作用生成假硒脲盐。该化合物在三乙胺作用下转化为类似于硒醇的不稳定中间体;而在氮气保护下,与活泼卤代烃室温反应即可得到相应的硒醚。六个硒取代的化合物均显示良好的体外抑制L1210及KB细胞活性。     

4-巯基-4-脱氧-4′-去甲表鬼臼毒素的立体控制合成

4-巯基-4-脱氧-4′-去甲表鬼臼毒素是合成4位硫取代的4′-去甲表鬼臼毒素的关键中间体,由4′-去甲表鬼臼毒素与硫化氢在BF_3·Et_2O存在下立体控制制备,也可通过以NH_3/CH_3CN选择性地水解4-乙酰硫基-4-脱氧-4′-去甲表鬼臼毒素而制备.     

2－芳胺基－2－硒唑啉－4－酮的简便合成

芳基硒脲与溴乙酸乙酯在乙醇溶液中作用，可合成得到含硒杂环化合物2-芳胺 基-2-硒唑啉-4-酮，反应产率为71%。     

硒催化4-氨基吡啶与硝基芳烃羰基化合成4-吡啶基脲

以非金属硒为催化剂,三乙胺为助催化剂,用CO替代剧毒光气作为羰基化试剂,通过鼓泡方式经硒催化"一锅煮"的4-氨基吡啶与硝基芳烃的氧化还原羰基化反应合成4-吡啶基脲.通过探究反应温度、反应时间、溶剂及碱的种类等因素的影响,获得了反应的优化条件.在优化条件的基础上,以中等到良好的收率制得4-吡啶基脲类化合物,反应底物硝基芳烃的普遍适用性较好;还提出了该反应的可能机理.     

2-硒代咪唑类化合物催化CO与胺的羰基化反应

首次研究了2-硒代咪唑类化合物催化的一氧化碳对胺的羰基化生成对称脲或噁唑啉-2-酮的反应,目标产物收率中等到良好.与传统的单质硒催化的羰基化反应相比,新催化体系有效避免了有恶臭气味的含硒化合物的产生.     

相转移催化条件下N-芳酰基-N′-芳基硒脲衍生物的合成及其晶体结构

硒是人体所必需的14种微量元素之一,硒脲作为有机硒化合物中的重要一类,在抗菌和抗肿瘤方面已显示出了很高的生物活性[1].关于芳酰基硒脲的合成方法虽然早在1937年就有报道[2],但是由于反应复杂且控制条件苛刻,故有关芳酰基硒脲的研究至今仍然很少见报道.我们曾用相转移催化法合成了芳酰基硫脲衍生物[3],鉴于硒、硫有机化合物的相似性,本文将相转移催化法应用到芳酰基硒脲的合成中,在温和条件下,方便、快速、较高产率地合成了一系列N-芳酰基-N′-芳基硒脲(2a~2l).作为超分子化学方面研究的一部分[4,5],合成了化合物2a的单晶,并对其晶体结构…     

硒脲及其衍生物的合成和应用

硒脲及其衍生物具有抗真菌、抗肿瘤、抗癌等生物活性,可作为合成其它化合物的中间体和配体,还可用于增强显影剂的感光度。硒脲及取代硒脲的合成有取代脲法、氨腈法、异硒氰酸酯法等,缩氨基硒脲的合成有硒氰酸盐法和取代硫脲法,酰基硒脲的合成用常规法和相转移催化法。本文对硒脲及其衍生物的上述合成方法和应用作了介绍。     

β-榄香烯烃基硒醚的一锅法合成

常温下将硒用N2H4•H2O还原后与卤代烃反应得到对称二硒醚, 不经分离直接用NaBH4还原, 再与13-氯-β-榄香烯作用得到β-榄香烯烃基硒醚. 此一锅法操作简便、条件温和、反应快速而且产率较高, 是合成不对称硒醚的一种简便实用的方法. 对化合物g的初步生物活性实验表明其具有显著的抗氧化作用.     

N-(1-异丙基-2-羧基-4-甲基二环[2.2.2]-5-辛烯-3-羰基)-N''''-芳基(硫)脲的合成

在无溶剂绿色化学条件下,将α-萜品烯-马来酸酐加成物(1)与取代苯(硫)脲发生N-酰化反应,合成了4个N-(1-异丙基-2-羧基-4-甲基二环[2.2.2]-5-辛烯-3-羰基)-N'-芳基(硫)脲化合物(3a～3d),并由IR、UV-Vis、MS、1H NMR、13C NMR和元素分析确认了目标产物的结构.生物活性测试表明,其中3个化合物(3a、3b和3c)具有植物激素作用.     

硒杂环化合物(4,5-苯并苤硒脑)在金表面上的自组装

为了寻求新的自组装单分子膜体系,构建新的功能膜,研究了具备平面型的大环共轭硒杂环化合物-- 4,5-苯并苤硒脑(苯并[c]硒二唑,简称苤硒脑)在金表面的自组装单分子膜.通过X射线光电子能谱(XPS)和电化学手段对其进行表征.XPS研究结果表明,自组装形成单分子膜后,苤硒脑分子中Se3d结合能从57.4 eV下降到57.1 eV;表明硒杂环化合物是通过金硒键固定在金表面上的;电化学循环伏安法实验表明,金电极表面上自组装该有机硒后, Fe(CN)63-/4-的氧化还原峰几乎完全消失;以四硼酸钠为底液,测得该化合物自组装在金表面上时,其还原电位在-0.66 V,与在溶液中用裸金电极测得的还原峰电位基本一致.     

Simple and convenient synthesis of a fluorinated GM4 analogue

A series of fluorinated galactosides, dodecyl 2-deoxy-2-fluoro-β-d-galactopyranoside (2F Gal), dodecyl 4-deoxy-4-fluoro-β-d-galactopyranoside (4F Gal) and dodecyl 6-deoxy-6-fluoro-β-d-galactopyranoside (6F Gal), was chemically synthesized and introduced to B16 cells to serve as scaffolds for cellular enzyme glycosylation. Results showed that the presence of fluorine exercised significant effects on cell viability. Among the fluorinated galactosides used, 2F Gal was glycosylated to afford a GM4 analogue.     

Synthesis of 4-deoxy-4-nitrosialic acid

The synthesis of 4-deoxy-4-nitrosialic acid (3,4,5-trideoxy-4-nitro-D-glycero-beta-D-galacto-non-2-ulopyranosonic acid, 5), was completed in seven steps starting from D-arabinose. Coupling of the 6-carbon fragment, 2-acetamido-1,2-dideoxy-1-nitro-D-mannitol (6) with ethyl alpha-(bromomethyl)acrylate afforded a 2 : 1 mixture of ethyl 5-acetamido-2,3,4,5-tetradeoxy-2-methylene-4-nitro-D-glycero-D-galacto-nononate (9a-S) and ethyl 5-acetamido-2,3,4,5-tetradeoxy-2-methylene-4-nitro-D-glycero-D-talo-nononate (9a-R). This mixture of enones was subjected to ozonolysis, and following reduction of the ozonide, the resultant products cyclised to the pyranosides. The target compound, ethyl 4-deoxy-4-nitrosialate (11a) was isolated by fractional crystallisation. Hydrolysis of the ethyl ester proved problematic; thus, the synthesis was modified by using tert-butyl alpha-(bromomethyl)acrylate. Following ozonolysis of the corresponding tert-butyl enoate esters and diastereomer separation, the tert-butyl ester of 4-nitrosialic acid (11b) could be deprotected under acidic conditions to afford . The target compound is a useful intermediate for synthesis of a variety of C-4 substituted sialic acid derivatives, and it is synthesised by a modular route.     

Synthesis of A Novel Fulleroaziridine Carrying 4-Deoxy-4′-demethylepipodophyllotoxin

A novel fulleroaziridine 2 with a closed 6,6-ring junction was synthesized from [60]fullerene and 4-azido-4-deoxy-4′-demethylepipodophyllotoxin 1 in 1, 2-dichlorobenzene at 110℃ for 45 h, in a yield of 39.3 % based on consumed C60. The structure of the product was characterized by NMR and MS.     

Synthesis and kinetic evaluation of 4-deoxy-4-phosphonomethyl-d-erythronate, the first hydrolytically stable and potent competitive inhibitor of ribose-5-phosphate isomerase

4-deoxy-4-Phosphonomethyl-d-erythronate, an isosteric and hydrolytically stable analogue of the known ribose-5-phosphate isomerase inhibitor 4-deoxy-4-phospho-d-erythronate, was obtained by a 14-step synthesis from d-arabinose through an highly improved synthesis of the precursor 5-deoxy-5-phosphonomethyl-d-arabinose. The title compound appears as the first stable and potent competitive inhibitor of the enzyme catalyzed isomerization of ribose-5-phosphate to d-ribulose-5-phosphate (K_i=74 μM, K_m/K_i=100), exhibiting only a 3-fold weaker inhibitory activity than its phosphate analogue.     

High-performance liquid chromatographic identification of disaccharides generated from heparan sulphate isomers using heparitinases

Specific heparan sulphate-lyases, heparitinases I and II, were used to identify unsaturated disaccharide constituents generated from heterogeneous heparan sulphate isomers. All determinations were made using high-performance liquid chromatography with a column containing a sulphonized styrene-divinylbenzene copolymer. Unsaturated disaccharides generated from variously sulphated heparan sulphate isomers after simultaneous digestion with heparitinases I and II facilitated separation of the individual disaccharides, based on sulphate groups at the specific position of the uronic acid and glucosamine residues. The simultaneous digestion with heparitinases I and II produces unsaturated disaccharides from heparan sulphate isomers with the structure of 4-deoxy-2-O-alpha-L-threo-hex-4-enepyranosyluronic acid (1----4)-2-amino-deoxy-D-glucose, 4-deoxy-2-O-alpha-L-threo-hex-4-enepyranosyluronic acid (1----4)-2-deoxy-2-sulphamido-D-glucose, 4-deoxy-2-O-alpha-L-threo-hex-4-enepyranosyluronic acid (1----4)-2-aminodeoxy-6-O-sulpho-D-glucose, 4-deoxy-2-O-alpha-L-threo-hex-4-enepyranosyluronic acid (1----4)-2-deoxy-2-sulphamido-6-O-sulpho-D-glucose, 4-deoxy-2-O-sulpho-alpha-L-threo-hex-4-enepyranosyluronic acid (1----4)-2-amino-2-deoxy-6-O-sulpho-D-glucose and 4-deoxy-2-O-sulpho-alpha-L-threo-hex-4-enepyranosyluronic acid (1----4)-2-deoxy-2-sulphamido-6-O-sulpho-D-glucose.     

Diastereodivergent Hydroxyfluorination of Cyclic and Acyclic Allylic Amines: Synthesis of 4-Deoxy-4-fluorophytosphingosines

A diastereodivergent hydroxyfluorination protocol enabling the direct conversion of some conformationally biased allylic amines to the corresponding diastereoisomeric amino fluorohydrins has been developed. Sequential treatment of a conformationally biased allylic amine with 2 equiv of HBF(4)·OEt(2) followed by m-CPBA promotes epoxidation of the olefin on the face proximal to the amino group under hydrogen-bonded direction from the in situ formed ammonium ion. Regioselective and stereospecific epoxide ring-opening by transfer of fluoride from a BF(4)(-) ion (an S(N)2-type process at the carbon atom distal to the ammonium moiety) then occurs in situ to give the corresponding amino fluorohydrin. Alternatively, an analogous reaction using 20 equiv of HBF(4)·OEt(2) results in preferential epoxidation of the opposite face of the olefin, which is followed by regioselective and stereospecific epoxide ring-opening by transfer of fluoride from a BF(4)(-) ion (an S(N)2-type process at the carbon atom distal to the ammonium moiety). The synthetic utility of this methodology is demonstrated via its application to a synthesis of 4-deoxy-4-fluoro-l-xylo-phytosphingosine and 4-deoxy-4-fluoro-l-lyxo-phytosphingosine, each in five steps from Garner's aldehyde.     

Efficient Synthesis of 4-Amino-4-deoxy-L-arabinose and Spacer-equipped 4-Amino-4-deoxy-L-arabinopyranosides by Transglycosylation Reactions

Methyl 4-azido-4-deoxy-β-L-arabinopyranoside has been synthesized in five steps starting from methyl β-D-xylopyranoside in a multigram scale without chromatographic purification in 78% overall yield. The transformation relied on selective tosylation/nosylation at O-4 followed by acylation, S(N)2 displacement with sodium azide and subsequent deprotection. The methyl 4-azido-4-deoxy-arabinoside was then converted into allyl, propenyl, ω-bromohexyl and chlorethoxyethyl spacer glycosides by transglycosylation with the respective alcohols in good yields and fair anomeric selectivity. Reduction of the azido group and further transformations of the aglycon afforded ω-thiol-containing spacer derivatives. Coupling to maleimide-activated BSA provided a potent immunogen which was used to generate murine and rabbit polyclonal sera binding to LPS-core epitopes containing 4-amino-4-deoxy-arabinose residues.     

Synthesis of a 4-Deoxy-4-C-Methylene Analog of Glucosylceramide

Abstract

D-Glucose was transformed into 2,3:5,6-di-O-isopropylidene dithioacetal 1; its oxidation to ketone 2 and subsequent Wittig reaction afforded 4-deoxy-4-C-methylene derivative 3. Hydrolytic removal of the protective groups, then O-acetylation, selective anomeric O-deacetylation, and base catalyzed trichloroacetonitrile addition furnished 4-deoxy-4-C-methylene substituted glycopyranosyl donor 7 as an anomeric mixture. Reaction of 7 with azidosphingosine derivative 8 under BF₃-OEt₂ catalysis gave β-glycopy-ranoside 9. Azido group reduction with triphenylphospnine in the presence of palmitic anhydride and water afforded directly O-acyl protected glycosphingolipid derivative 10 which yielded after Zemplen O-deacylation target molecule 11     

Straightforward synthesis of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes via 2′,3′-O-orthoester group elimination: a simple route to 3′,4′-didehydronucleosides

Straightforward, high-yielding syntheses of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes and 3′-deoxy-3′,4′-didehydronucleosides starting from 2′,3′-O-orthoester derivatives of ribonucleosides are described.     

Biosynthesis of 1-deoxy-1-imino-D-erythrose 4-phosphate: a defining metabolite in the aminoshikimate pathway.

With respect to the source of the nitrogen atom incorporated into the aminoshikimate pathway, d-erythrose 4-phosphate has been proposed to undergo a transamination reaction resulting in formation of 1-deoxy-1-imino-d-erythrose 4-phosphate. Condensation of this metabolite with phosphoenolpyruvate catalyzed by aminoDAHP synthase would then hypothetically form the 4-amino-3,4-dideoxy-d-arabino-heptulosonic acid 7-phosphate (aminoDAHP), which is the first committed intermediate of the aminoshikimate pathway. However, in vitro formation of aminoDAHP has not been observed. In this account, the possibility is examined that 3-amino-3-deoxy-d-fructose 6-phosphate is the source of the nitrogen atom of the aminoshikimate pathway. Transketolase-catalyzed ketol transfer from 3-amino-3-deoxy-d-fructose 6-phosphate to d-ribose 5-phosphate would hypothetically release 1-deoxy-1-imino-d-erythrose 4-phosphate. Along these lines, a chemoenzymatic synthesis of 3-amino-3-deoxy-d-fructose 6-phosphate was elaborated. Incubation of 3-amino-3-deoxy-d-fructose 6-phosphate in Amycolatopsis mediterranei crude cell lysate with d-ribose 5-phosphate and phosphoenolpyruvate resulted in the formation of aminoDAHP and 3-amino-5-hydroxybenzoic acid. 3-[15N]-Amino-3-deoxy-d-6,6-[2H2]-fructose 6-phosphate was also synthesized and similarly incubated in A. mediterranei crude cell lysate. Retention of both 15N and 2H2 labeling in product aminoDAHP indicates that 3-amino-3-deoxy-d-fructose 6-phosphate is serving as a sequestered form of 1-deoxy-1-imino-d-erythrose 4-phosphate.