5,7-二甲氧基-4-甲基苯酞和5,7-二羟基-4-甲基苯酞的新合成方法

以3,5-二甲氧基苯甲醇为起始原料, 经过五步反应, 合成了5,7-二甲氧基-4-甲基苯酞和5,7-二羟基-4-甲基苯酞这两个用于合成霉酚酸的重要中间体, 产率分别达到80%和72%. 6-氯甲基-2,4-二甲氧基苯甲醛经过亚氯酸钠氧化成酸的同时发生内酯化反应生成5,7-二甲氧基苯酞是最关键的一步.     

2,6-二氨基-3,5-二硝基吡嗪-1-氧化物的合成

研究了2,6-二氨基-3,5-二硝基吡嗪-1-氧化物(LLM-105)的合成新方法. 该方法是以2,6-二氯吡嗪和甲醇钠作为起始原料, 经烷氧基化、硝化、胺化、N-氧化四步反应得到LLM-105, 总收率为50%. 用¹H NMR, ¹³C NMR, IR, MS和元素分析对LLM-105及其中间体结构进行了表征.     

2,6-二氨基-3,5-二硝基吡啶-1-氧化物的合成新方法

研究了2,6-二氨基-3,5-二硝基吡啶-1-氧化物(ANPyO)的合成新方法. 以2,6-二氨基吡啶为起始原料, 经酰基化、N-氧化、硝化三步反应得到ANPyO, 总收率为75%. 测试了ANPyO的爆速、爆压、DSC, 以及电火花感度和落锤感度, 同1,3,5-三氨基-2,4,6-三硝基苯(TATB)的性能进行了对比, 结果表明ANPyO综合性能和TATB基本相当. 用1H NMR, MS和红外光谱对ANPyO及其中间体结构进行了表征.     

1-{8-甲氧基-2,3-二氢苯并[b][1,4]二噁烷-5-基}乙酮的合成

以邻香兰素为起始原料、经氧化裂解、付克反应及环合反应制得PDE-4抑制剂的中间体1-{8-甲氧基-2,3-二氢苯并[b][1,4]二噁烷-5-基}乙酮,总收率58.9%。     

9, 9-二(3-氨基-4-羟基苯基)呫吨的合成

以醋酸酐为溶剂, 将9, 9-二(4-羟基苯基)呫吨与浓硝酸在15 ℃左右发生硝化反应1.5 h, 形成中间体-9, 9-二(3-硝基-4-羟基苯基)呫吨, 产率为88.5%;继而以Pd/C 为催化剂, 80%的水合肼为还原剂, 在乙醇和1, 4-二氧六环混合溶剂中, 于70 ℃将中间体进行还原反应10 h, 得到目标产物9, 9-二(3-氨基-4-羟基苯基)呫吨, 产率为90.8%, 两步反应总收率为80.4%。 中间体与目标化合物经NMR、FTIR和元素分析等确定了它们的结构。     

1,3-二叔丁基-5,5-二硝基嘧啶烷的合成及反应机理研究

1,3-二叔丁基-5,5-二硝基嘧啶烷(3)是混合炸药含能增塑剂1,3,5,5-四硝基-1,3-二氮杂环环己烷的关键硝化前体. 通过研究3的合成反应机理, 目的是为制备1,3,5,5-四硝基-1,3-二氮杂环环己烷的工艺优化提供理论依据. 以2,2-二硝基-1,3-丙二醇(1)、甲醛和叔丁胺为原料, 通过Mannich缩合反应得到1,3-二叔丁基-5,5-二硝基嘧啶烷. 采用同位素示踪技术以及分离关键中间体对反应机理进行推测. 以氘代甲醛、1和叔丁胺缩合得到氘标记的3, ¹H NMR和MS分析结果表明: 在反应过程中1首先解离生成偕二硝基甲烷和甲醛, 小分子碎片随机组合生成了3. 分离出了关键中间体1-叔丁氨基-2,2-二硝基乙烷. 根据所获得的证据, 推断了3的合成反应机理.     

17α,21-二羟基孕甾-4-烯-3,20-二酮-17-戊酸酯的合成

以雄烯二酮为起始原料,经加成、硅醚化、环加成-质子脱硅基化及置换等7步反应合成了氢化可的松的中间体——17α,21-二羟基孕甾-4-烯-3,20-二酮-17-戊酸酯,总收率75%,纯度96%,其结构经1H NMR和ESI-MS确证。     

2,5-二溴-4-硝基咪唑的合成

以咪唑为原料,经硝化和溴化反应合成了抗炎药物中间体——2,5-二溴-4-硝基咪唑,总收率80.3%,其结构经1H NMR和IR确认。     

新化合物A-失碳-△~(3(5),9(10))-雌甾二烯-2,17-二酮的合成

报道了一个可以合成甾体新药的前体:A-失碳-△~(3(5),9(10))-雌甾二烯-2.17-二酮的合成.以炔诺酮的中间体,3β-羟基-5α-6β,19-环氧-雄甾-17-酮为原料,通过氧化开环、脱羧合环、锌粉还原性破开环氧、去羟甲基和去乙酰氧基,五步反应成功地合成了标题化合物,五步总收率25%.     

2-取代-5,5-二硝基嘧啶-4,6-二酮的合成和反应

研究了2-取代嘧啶-4,6-二酮的硝化反应, 产物为2-取代-5,5-二硝基嘧啶-4,6-二酮(3), 收率＞80%, 3与亲核试剂反应形成开环产物. 2-位取代基为烷基时, 嘧啶环5-位和侧链的α-位都发生反应, 当取代基为甲基时, 硝化产物为2-(二硝基亚甲基)-5,5-二硝基嘧啶-4,6-二酮(1), 1的水解产物为1,1-二氨基-2,2-硝基乙烯 (FOX-7) 和二硝基甲烷(2). 2-位取代基为羟基时, 硝化产物为5,5-二硝基巴比妥酸(7b), 7b水解可制得偕二硝基乙酰基脲(9b), 9b与KOH作用生成偕二硝基乙酰基脲钾盐(10b)和二硝基甲烷钾盐(11). 2-位取代基为氨基时, 硝化开环生成偕二硝基乙酰基胍(9a), 9a与KOH作用生成偕二硝基乙酰基胍钾盐(10a)和11. 当2-位无取代基时, 硝化产物无法分离, 结构推测为7c. 考察了亲核试剂对FOX-7收率的影响并对FOX-7的三种合成方法进行了评价, 对反应机理进行了探讨.     

Synthetic Studies of Didemnaketals Analogue-Construction of the Intermediate (3S,5S,6R)-3,7-Dimethyl-5,6,7-trihydroxy-octanal

TheDidemnaketalsAandBhavebeenreportedtobesignificantinhibitorstoHlV-protease'.Inconnectionwiththetotalsynthesisofthiskindofcompounds,ourrecentresearchinterestisfocusedontheirsyntheticstudiesaswellassynthesisofananaloguel,whichincorPoratedthekeyspiroketalmoietyofthedidemnaketalsAandB.Basedontheretrosyntheticconsideration(Schemcl),thelinearintermediate2wouIdbeconstructedfrom3and4.Furthermore,4wouldbesynthesizedfrom( )-PuIegone5.Wehereinreportedastereoselectivesyntheticprocedureforthe(3S,5S…     

Total synthesis of (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A and (-)-(6S,7S,8S,9R,10S)- membrenone-B and structural assignment of membrenone-C

[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products.     

光学纯的(4S, 8R)-和(4S, 8S)-1- 烯-8, 9-二醇的改进合成法

本文提出了一个改进的合成两个光学异构纯的94S)-1- 烯-8, 9-二醇的方法,其优点是简便、有效, 适于克量级制备。     

(7R,10S)-Boivinianin B的不对称合成

报道了一种基于Dehydro-α-curcumene(4)为关键中间体, 以Sharpless不对称双羟化反应和碘催化的分子内环化成醚反应为关键步骤, 构建2,2,5位三取代的四氢呋喃骨架的方法, 完成了(7R,10S)-Boivinianin B(1)的不对称合成. 合成路线简捷, 对此类化合物的合成有一定的借鉴意义.     

Synthesis of 5S,12S - diHETE (LTBx)

The total synthesis of 5S, 12S-diHETE (LTB_x) was completed. The Wittig reaction of phosphorane 8 and chiral aldehyde 9 provided the key step to from the C-20 chain.     

(2S,3S,4R)-2-正戊基-3,4-二叠氮基四氢噻吩的合成

以（＋）－4，10－二氧杂三环[5.2.1.O^2,6]－癸－8－烯－3－醇为原料。经8步反应，对映选择性地合成出去氧维生素H的重要中间体：（2S，3S，4R）－2－正戊基－3，4－二叠氮基四氢噻吩。为对映选择性合成手性四氢噻吩类化合物提供了新的方法。     

An asymmetric synthesis of (2S,5S)-5-substituted azepane-2-carboxylate derivatives

To facilitate a drug discovery project, we needed to develop a robust asymmetric synthesis of (2S,5S)-5-substituted-azepane-2-carboxylate derivatives. Two key requirements for the synthesis were flexibility for elaboration at C5 and suitability for large scale preparation. To this end we have successfully developed a scalable asymmetric synthesis of these derivatives that starts with known hydroxy-ketone 8. The key step features an oxidative cleavage of aza-bicyclo[3.2.2]nonene 14, which simultaneously generates the C2 and C5 substituents in a stereoselective manner.     

Impact of coated calcium carbonate nanofillers and annealing treatments on the microstructure and gas barrier properties of poly(lactide) based nanocomposite films

Amorphous poly(lactide) (PLA) and nanocomposite films were prepared from melt‐blending with precipitated calcium carbonate nanofillers (PCC). Nanocomposites based on uncoated PCC (PCC‐UT), stearic acid coated PCC (PCC‐S), and poly(ε‐caprolactone) coated PCC (PCC‐P) were investigated for an inorganic content fixed to 8 wt %. Using coated nanofillers allowed preserving both PLA average molar mass and thermal stability while enhancing the nanofiller dispersion state. Poly(ε‐caprolactone) was identified as the best coating for optimized morphology and thermal properties. Maxwell law accurately described the increase in oxygen barrier properties observed for the nanocomposites based on PCC‐S. A modified Maxwell law was proposed to take account of the additional increase in barrier properties evidenced for the PLA/PCC‐P nanocomposites and assigned to the particularly strong compatibility between PCL and PLA. Different annealing conditions were investigated to respectively study the impact of physical ageing and PLA crystallization on gas permeability. Different extents of physical ageing did not significantly modify the oxygen transport properties. However, a high permeability decrease was observed for the semicrystalline nanocomposites with respect to the amorphous reference PLA film. Finally, the gain in barrier properties was shown to result from both contribution of the nanofillers and the crystalline phase. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 649–658     

Cu_7S_4纳米管的生物分子辅助水热合成与光学性质(英文)

使用生物分子DL-甲硫氨酸辅助水热方法合成Cu7S4纳米管,产物的形貌与晶型可通过改变实验参数进行调控.研究表明,硝酸铜和DL-甲硫氨酸在反应开始时的配位比为1∶2,而且当反应物的摩尔比为1∶2和反应温度为200℃时可合成直径为100-600nm、长度达40-100μm的多晶Cu7S4纳米管.使用D-或L-甲硫氨酸均能得到类似Cu7S4纳米管.Cu7S4纳米管的禁带宽度为2.88eV,与Cu7S4的块体材料相比有明显蓝移.基于实验研究结果,讨论了甲硫氨酸分子中的官能团与反应产物之间的联系并提出了Cu7S4纳米管的自牺牲模板法形成机理.     

Total synthesis of an immunosuppressive glycolipid, (2S,3S,4R)-1-O- (alpha-d-galactosyl)-2- tetracosanoylamino-1,3,4-nonanetriol

[reaction: see text] A practical and efficient total synthesis of (2S,3S,4R)-1-O-(alpha-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonanetriol, OCH 1b, a potential therapeutic candidate for Th1-mediated autoimmune diseases, is described. The synthesis incorporates direct alkylation onto epoxide 5 and stereospecific halide ion catalyzed alpha-glycosidation reaction. A key intermediate 10 was obtained in only eight steps and 37% overall yield from commercially available d-arabitol 2, and the total synthesis of 1b was accomplished in 12 steps and 19% overall yield. This method will enable the synthesis of a variety of phytosphingolipids, especially that with the shorter sphingosine side chain than 1a, in a highly stereoselective manner.