除草剂磺草酮的合成方法

磺草酮是捷利康公司80年代开发的新颖玉米田苗后除草剂。现已在美国、欧洲等许多国家获得广泛应用。由于磺黄酮的特殊作用机制,使得它对玉米田的阔叶杂草和禾本科杂草都有良好的防除效果。它对玉米有极好的安全性,对下茬作物亦同样安全。     

氟酮磺隆的合成研究

以硫氢酸钠及氯甲酸甲酯为起始原料,经5步反应合成得到新型磺酰脲类除草剂氟酮磺隆,产品纯度达99%,工艺路线步骤相对较少,成本较低,适宜于工业化生产。     

双环磺草酮的合成研究

双环磺草酮是由史迪士生物科学株式会社开发的三酮类对羟基丙酮酸双氧化酶(HPPD)除草剂.笔者以2-氯-4-甲磺酰基苯甲酸为起始原料,经5步反应合成了双环磺草酮,目标化合物的结构经1HNMR和MS确证.同时,笔者对双环磺草酮关键步骤的反应参数进行了系统优化,并对烯醇酯中间体的重排机理进行了探讨.     

磺酰三唑酮的合成及工艺研究

以2,4-二氯苯胺为原料,经NaNO2重氮化后,用SnCl2还原制得2,4-二氯苯肼,和乙醛、NaOCN环合制备4,5-二氢-3-甲基-1-(2,4-二氯苯基)-1,2,4-三唑-5(1H)酮(三唑啉酮),在常温下和CHClF2反应制得4,5-二氢-3-甲基-1-(2,4-氯-5-氨基-苯基)4-二氟甲基-1,2,4-三唑-5(1H)酮(4-取代三唑啉酮),再经混酸硝化、铁粉还原后得4,5-二氢-3-甲基-1-(2,4-二氯-5-氨基-苯基)-4-二氟甲基-1,2,4-三唑-5(1H)酮,最后和甲基磺酰氯反应后制得N-(2,4-二氯-5-(4-二氟甲基-4,5-二氢-3-甲基-5-氧代-1H-1,2,4-三唑-1-基)苯基)甲磺酰胺(磺酰三唑酮),并对该工艺中关键的环合步骤进行了工艺优化,实验表明,最佳的醇类溶剂为叔丁醇,环合反应温度10～15℃时产率高,催化环合反应时使用的最佳有机质子酸为乙酸,在此条件下,环合反应的产率达到89.3％.     

甲基磺酰胺合成工艺研究

以甲基磺酰氯为原料，通过氨解反应合成了甲基磺酰胺，探讨了合成反应的工艺条件。实验表明，当原料用量与溶剂的体积比为1：5时，反应温度控制在35－40℃之间，用环己烷作为反应的溶剂，并以乙醇作萃取分离剂，可使产品的收率达87％－89％。     

环丙羧酸中试合成工艺研究

介绍以氰氯苯乙酮为起始原料,经缩合、酯化、胺化、闭环和水解、中和等6个反应步骤的环丙羧酸中试合成工艺。     

过氧化尿素在苯唑草酮和环磺酮合成中的应用

[目的]探索过氧化尿素将苯唑草酮中间体4-甲硫基-2,3-二甲基溴苯氧化成4-甲磺酰基-2,3-二甲基溴苯的新方法,并将其拓展至除草剂环磺酮中间体和杂质的合成中。[方法]建立了过氧化尿素/甲酸的氧化体系,将4-甲硫基-2,3-二甲基溴苯氧化成4-甲磺酰基-2,3-二甲基溴苯,并确定了反应条件,发现氧化经历亚砜的过程。将该过氧化尿素/甲酸氧化体系应用于除草剂环磺酮的中间体2-氯-3-甲基-4-甲磺酰基苯乙酮及杂质2-氯-6-甲磺酰基甲苯的合成中,同样获得了理想的效果。[结果]苯唑草酮中间体4-甲硫基-2,3-二甲基溴苯氧化为亚砜的转化率达99.97%,亚砜收率99.76%,亚砜氧化为砜的收率为96.39%。环磺酮中间体2-氯-3-甲基-4-甲磺酰基苯乙酮的收率为97.56%,杂质2-氯-6-甲磺酰基甲苯的收率为97.95%。[结论]过氧化尿素作为高效的氧化剂适用于苯唑草酮中间体及环磺酮中间体和杂质的氧化,同时也为其他农药中间体合成提供了新思路。     

外消旋螺环二酮的合成工艺条件研究

详细研究了以己二酸、溴代丁酸乙酯为原料，采用简便高效的方法制备外消旋螺环二酮的最佳条件和有关工艺。     

除草剂环磺酮应用研究与开发进展

环磺酮(tembotrione)是拜耳公司开发的HPPD抑制剂类除草剂。自2007年上市以来,其全球销售额总体上保持高速增长态势。环磺酮2015年全球销售额为2.3亿美元,2016年全球销售额为2.1亿美元,2010—2015年复合年增长率为19.3%。本文概述了环磺酮的理化性质、合成路线与专利状况等,并重点介绍其发展历程、应用及市场概况。     

甲基磺酰胺合成工艺改进

介绍了硫酸二甲酯和硫代硫酸钠合成工艺的改进方法,采用水－二氯乙烷介质,不经精制直接胺化,得到甲基磺酰胺。总收率（以硫代硫酸钠计）为66％。产品纯度大于98％。     

除草剂Tembotrione的合成研究

Tembotrione为HPPD抑制剂类除草剂,具有三酮结构。以3-氯-2-甲基苯胺为起始原料,经由重氮化、傅克酰基化、氧化、卤仿、酯化、溴代、缩合、水解、酰氯化以及缩合、重排反应合成目标化合物tembotrione。该工艺总收率达到60%,目标产物质量分数在95%以上。工艺条件温和,原料易得,适合工业化大生产。     

稳定同位素标记的Y101及其代谢产物的合成

以氘代甲苯为原料,经高锰酸钾氧化反应生成氘代苯甲酸,再经缩合、烷基化、水解等反应,合成了N-(N-苯甲酰基-O-二甲氨基乙基-L-酪氨酰基)-L-苯丙氨醇及其代谢产物M-8、M-9的稳定同位素标记化合物。所得化合物均经核磁(NMR)、质谱(ESI-MS)进行结构确证。样品可作为生物内标,用于高效液相色谱/质谱联用法对目标化合物及其代谢产物在体内的定量分析,同时开展了该化合物的体内代谢研究。     

Synthesis of Homochiral Side-chain Precursors for Modified Vitamin D3 Metabolites

Homochiral 3-alkylated (2R,3R)- and (2R,3S)-2,3-dihydroxyalkyl p-toluenesulfonates ( 9 and 10 ) are essential building blocks for vitamin D₃ metabolites with a modified side chain. Nine of these compounds have been prepared starting from (R)-2,3-O-cyclohexylideneglyceraldehyde ( 1 ) by addition of alkylmagnesium halides, Jones oxidation of the obtained diastereomeric alcohols 2 and 3 to the corresponding ketones 4 , and a second addition of alkylmagnesium halides, followed by hydrolytic removal of the cyclohexylidene group and selective tosylation. The opposite diastereoselectivity of the two Grignard reactions is discussed.     

Synthesis of Fatty Acid Amides of Catechol Metabolites that Exhibit Antiobesity Properties

A series of fatty acid amides of 3,4‐methylenedioxymethamphetamine (MDMA) catechol metabolites were synthesized in order to evaluate their biological activities. Upon administration, all synthesized compounds resulted in negative modulation of food intake in rats. The most active compounds have affinity for the CB₁ receptor and/or PPAR‐α; part of their biological activity may be caused by these double interactions.     

Synthesis of Adducts of PAH Diol Epoxide Metabolites in p53 Tumor Suppressor Gene Sites

The synthesis, structures, and mutagenic properties of benzo[a]pyrene-deoxyadenosine adducts in a sequence context related to the p53 gene are described.     

A Tandem Photochemical Approach for the Synthesis of Biologically Important Metabolites of Benzo[b]fluoranthene

A new photochemical approach for the synthesis of various metabolites of benzo[b]fluoranthene has been investigated, involving an oxidative photocyclization reaction of substituted cis-stilbenes to form the phenanthrene moiety, and an intramolecular photoarylation to generate the five-membered ring system. This methodology allowed a highly convergent synthesis of various benzo[b]-fluoranthene metabolites including those with an additional phenol group in the peninsular ring.     

Nanoporous Gold Catalyst for the Oxidative N-Dealkylation of Drug Molecules: A Method for Synthesis of N-Dealkylated Metabolites

A novel method for the selective catalytic N-dealkylation of drug molecules on a nanoporous gold (NPG) catalyst producing valuable N-dealkylated metabolites and intermediates is described. Drug metabolites are important chemical entities at every stage of drug discovery and development, from exploratory discovery to clinical development, providing the safety profiles and the ADME (adsorption, distribution, metabolism, and elimination) of new drug candidates. Synthesis was carried out in aqueous solution at 80 °C using air (oxygen source) as oxidant, in single step with good isolated yields. Different examples examined in this study showed that aerobic catalytic N-dealkylation of drug molecules on NPG has a broad scope supporting N-deethylation, N-deisopropylation and N-demethylation, converting either 3° amines to 2° amines, or 2° amines to 1° amines.     

Synthesis and in vitro and in vivo Antifungal Activity of the Hydroxy Metabolites of Saperconazole

Herein we describe the scalable diastereoselective and enantioselective syntheses of eight enantiomers of hydroxy metabolites of saperconazole. The in vitro antifungal activity of the eight stereoisomers (compounds 1 – 8 ) was compared against a broad panel of Candida spp. (n=93), Aspergillus spp. (n=10), Cryptococcus spp. (n=19), and dermatophytes (n=27). The four 2S isomers 1 – 4 of the new agent were generally slightly more active than the four 2R isomers 5 – 8 . All eight isomers were tested in a model of experimental A. fumigatus infection in guinea pigs by intravenous inoculation of the fungal conidia. Treatment doses were 1.25 mg kg^?1 and 2.5 mg kg^?1 per day. Infection severity was measured in terms of mean survival time (MST) after infection and mean tissue burdens in brain, liver, spleen, and kidney at postmortem examination. Among the eight isomers, the 2S diastereomers 1 – 4 showed a generally higher level of activity than the 2R diastereomers 5 – 8 , revealing compounds 1 and 4 as the most potent overall in eradicating tissue burden and MST. Compared with reference compounds itraconazole and saperconazole, the hydroxy isomers 1 – 8 are less potent inhibitors of the growth of A. fumigatus in vitro and of ergosterol biosynthesis in both A. fumigatus and C. albicans.     

枝状枝孢菌次级代谢产物的研究

目的 :研究枝状枝孢菌大米固体发酵后产生的次级代谢产物。方法 :采用硅胶柱色谱、凝胶柱色谱、高效液相色谱等方法进行分离纯化,以及NMR、MS等现代波谱手段进行结构鉴定。结果 :分离得到6个单体化合物,分别鉴定为:6,8-二羟基-3-甲基-1H-异铬-1-酮、6-甲氧基-8-羟基-3-甲基异香豆素、豆甾-4-烯-3-酮、3β-羟基-5α,8α-过氧化麦角甾-6,22-二烯、腺嘌呤核苷、甘露醇。结论 :化合物1～3为首次从该植物内生真菌中分离得到。