5-甲基-[(2E,6E)-3,7,11-三甲基-9-氧代十二碳二烯]苯醌和氢醌的首次全合成

以2-甲基对苯二酚和香叶基溴为起始原料, 经过酚羟基保护, 溴代, Li₂CuCl₄催化的芳基溴与Grignard试剂的偶联以及Julia偶联等一系列反应, 完成了裸鳃亚动物的代谢产物, 5-甲基-[(2E,6E)-3,7,11-三甲基-9-氧代十二碳二烯]苯醌(1)和氢醌(2)的首次全合成, 将1用NaBH₄还原, 得到(±)-3, (±)-3也是此类天然产物之一.     

保幼激素类似物11-甲氧基-3,7,11-三甲基-2,4-十二碳二烯酸异丙酯的简便全合成

从价廉的丙酮出发,首先经羟醛缩合、脱水、氧化、酯化、溴代反应合成了4-溴-3-甲基-2-丁烯酸异丙酯,继而与亚磷酸三乙酯反应得到了Wittig-Homer试剂,随后与香茅醛发生Wittig-Horner反应,最后在阳离子树脂催化作用下与甲醇醚化,成功地全合成了具有保幼激素活性的昆虫生长调节剂11-甲氧基-3,7,11-三甲基-2,4-十二碳二烯酸异丙酯.所得标题化合物的四种异构体中,具有较高生物活性的(2E,4E)-异构体的含量达66%.各步所合成化合物的结构经1H NMR,IR,MS分析确证.     

光学活性化合物多羟基庚酸乙酯的合成

以不对称环氧化和双羟化反应为构筑手性碳的关键步骤, 首次合成了(＋)-(2R,3S,4S,5S)-6-甲基-4,5-环氧-2,3-二羟基-庚酸乙酯(5)和(－)-(2R,3S,4R,5S)-6-甲基-2,3,4,5-四羟基-庚酸乙酯(11). 找到一条适宜于该类化合物合成的简便有效且立体选择性好的合成路线. 初步生物活性测试表明, 化合物5, 11对HL60细胞具有抑制活性.     

利用工业废弃物中获得的(R)-5-甲基-δ-戊酸内酯为原料合成(2R,6R)-2,6,10-三甲基十一醇

(2R,6R)-2,6,10-三甲基十一醇(1)是维生素E、维生素K和植醇的基本结构单元. 利用从甾体皂甙元氧化降解产生的工业废弃物中所获得的手性化合物(R)-5-甲基-δ-戊酸内酯(6), 先将其转化成为化学性质稳定的(4R)-甲基-5-甲氧甲氧基戊酸甲酯(7), 再经十二步反应, 以14.1%的总收率合成得到了目标化合物(2R,6R)-2,6,10-三甲基十一醇(1).     

(αE,E)-α-(甲氧亚氨基)-2-[1-(芳香醛酮肟氧基)甲基]苯乙酸甲酯的立体选择性合成及生物活性研究

使用邻甲苯基重氮盐与乙醛酸甲酯肟偶联反应高立体选择性合成出 (E)-2-(羟基亚氨基)-2-邻甲基苯乙酸甲酯,经硫酸二甲酯的甲基化反应可得到重要的中间体(E)-2-(甲氧亚氨基)-2-邻甲基苯乙酸甲酯, 再经NBS溴化后与 (E)-芳香醛酮肟进行醚化反应最终得到目标物(αE,E)-α-(甲氧亚氨基)-2-[1-(芳香醛酮肟氧基)甲基]苯乙酸甲酯, 这些化合物多数具有很好的广谱杀菌活性.     

5-(N-2-羟乙基)羟乙酰氨基-N,N'-双(2,3-二羟丙基)-2,4,6-三碘-1,3-苯二甲酰胺的合成

5-氨基-N,N'-双(2,3-二羟丙基)-2,4,6-三碘-1,3-苯二甲酰胺(2)在N,N-二甲基乙酰胺中可直接与乙酰氧基乙酰氯反应, 产物再经碱性水解得5-羟乙酰氨基-N,N'-双(2,3-二羟丙基)-2,4,6-三碘-1,3-苯二甲酰胺(3), 后者再与氯乙醇反应生成5-(N-2-羟乙基)羟乙酰胺基-N,N'-双(2,3-二羟丙基)-2,4,6-三碘-1,3-苯二甲酰胺(1), 经乙二醇甲醚/正丁醇重结晶, 纯度高于99% (HPLC), 反应总收率由39.3% (文献值)提高到55.1%.     

1-(2,6-二氯-4-三氟甲基苯基)-3-氰基-5-氨基吡唑及其磺酰胺的合成及晶体结构

2,6-二氯-4-三氟甲基苯胺经重氮化后与2,3-二氰基丙酸酯反应合成了1-(2,6-二氯-4-三氟甲基苯基)-3-氰基-5-氨基吡唑(1), 1与苯磺酰氯、对甲基苯磺酰氯、甲基磺酰氯反应, 得到1的苯磺酰胺2a、对甲基苯磺酰胺2b和双甲基磺酰胺2c. 通过元素分析、红外光谱、核磁共振氢谱、核磁共振碳谱、质谱等手段对其结构进行了表征. 用X射线单晶衍射测定了化合物1, 2a和2c的晶体结构. 1属于正交斜方晶系, Pbca空间群, 晶胞参数 a＝1.61739(7) nm, b＝1.62480(7) nm, c＝3.10857(13) nm, ＝＝＝90, V＝8.1691 nm³, Z＝24, R＝0.1089, wR＝0.2545. 2a属于单斜晶系, C2/c空间群, 晶胞参数 a＝3.35144(18) nm, b＝0.97948(5) nm, c＝2.44717(12) nm, β＝102.460(1), V＝7.8440(7) nm³, Z＝8, R＝0.1831, wR＝0.2600. 2c属于三斜晶系, P-1空间群, 晶胞参数 a＝0.84681(7) nm, b＝0.89652(83) nm, c＝1.43497(12) nm, α＝75.198(2), β＝87.918(1), γ＝65.395(1), V＝0.9546 nm³, Z＝2, R＝0.049, wR＝0.135.     

一个简捷、高效合成松叶蜂性信息素的方法

以从甾体皂甙元降解的废弃物获取的(4R)-甲基-5-溴戊酸甲酯(4)为起始原料, 通过4与正庚基溴化镁选择性的偶联反应, 经关键合成中间体(4S)-甲基溴代十二烷(7)分别以52%和49%的总收率合成了松叶蜂性信息素(2S,3S,7S)-3,7-二甲基十五-2-醇乙酸酯(2)和丙酸酯(3).     

N-{2-氯-5-[3-甲基-2,6-二氧-4-三氟甲基-2,3-二氢嘧啶-1(6H)-基]苯基}酰胺类化合物的合成及除草活性

为了寻找高效、安全的除草活性化合物, 合成了12个全新的N-{2-氯-5-[3-甲基-2,6-二氧-4-三氟甲基-2,3-二氢嘧啶-1(6H)-基]苯基}酰胺类化合物, 其化学结构经IR, ¹H NMR, LC/MS和元素分析确证. 初步生物活性测定结果表明, 该类化合物具有一定的除草活性, 如7a, 7b, 7c, 7g, 7h, 7i, 7k和7l在有效成分75 g/hm²剂量下, 茎叶处理对苘麻(Abutilon theophrasti)、刺苋(Amaranthus spinosus)等阔叶杂草具有良好的除草活性, 其抑制率达100%.     

1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶的合成

报道了1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶方便、高产率的合成方法. 以6-甲基尿嘧啶(1)为起始物, 经硝化、嘧啶N¹,N ³-烷基化、还原及氨基甲基化, 首次高产率合成了1,3-二(乙氧基甲基)-5- N,N -二甲氨基-6-甲基尿嘧啶(5), 并对其化学结构进行了表征.     

Antimicrobial terpenoids from Pterocarpus indicus

A mixture of loliolide 1 (> 85%) and paniculatadiol 2 (< 15%) was obtained from the ethyl acetate leaf extract of Pterocarpus indicus by silica gel chromatography, while the air-dried flowers afforded lupeol 3 and phytol esters 4. The structures of 1-4 were determined by NMR spectroscopy. Antimicrobial tests on a mixture of 1 and 2 indicated that it has moderate activity against Candida albicans and low activity against Pseudomonas aeruginosa, Escherichia coli, and Aspergillus niger. It was found inactive against Staphylococcus aureus, Bacillus subtilis, and Trichophyton mentagrophytes.     

来源于Alcaligenes A-6的D-氨基酰化酶基因的合成与融合表达

将来源于Alcaligenes A-6的D-氨基酰化酶基因用大肠杆菌中的丰沛密码子替换, 利用化学和基于聚合酶链反应(PCR)技术的酶促方法进行基因全合成, 利用pET-32a构建重组表达载体pET-dan, 转化进E.coil BL21(DE3)中进行融合表达. 经SDS-PAGE电泳、 Western-blot检测和活性测定发现, D-ANase可在大肠杆菌中高效表达, 目的蛋白可达到菌体总蛋白的69.2%, 密码子优化后基因构建的工程菌发酵活性为96 U/mL, 重组蛋白经超声细胞破碎及Ni²⁺柱亲和层析纯化, 比活可达1692.3 U/mg, 纯度可达95%以上.     

Peculiarities of the chemical properties of vicinally disubstituted veratrole and synthesis of 1-methyl-4,5-dimethoxybenzimidazole derivatives

Various paths for the synthesis of 4-methylamino-3-aminoveratrole (I) from 4-amino-3-nitroveratrole (II) were investigated, and it was found that I can be obtained in a high overall yield of 65% through the tosyl derivative of II. 1-Methyl-4,5-dimethoxybenzimidazolone, 1-methyl-4,5-dimethoxybenzimidazole and its 2-phenyl-, 2-chloro-, and 2-dimethylamino derivatives were synthesized on the basis of I in order to investigate their biological activity. It was established that the chemical properties of vicinally disubstituted veratrole, particularly the increased basicity of II, are determined to a significant degree by steric strains caused by bulky substituents. It is shown that 85% formic acid can be successfully used in place of 98–100% formic acid for the N-formylation of aromatic amines with a mixture of formic acid and acetic anhydride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1387–1392, October, 1970.     

Atropisomeric myristinins: selective COX-2 inhibitors and antifungal agents from Myristica cinnamomea

The first naturally occurring atropisomeric flavans, myristinins B (2), C (2a), E (4), and F (4a), together with their corresponding trans-isomers, myristinins A (1) and D (3), were isolated from the CH(2)Cl(2) extract of Myristica cinnamomea fruits. Compounds 1, the mixture of 2 and 2a, and the mixture of 4 and 4a, exhibited antifungal activity against Candida albicans with IC(50) values ranging from 5.9 to 8.8 microg/mL, and they selectively inhibited the enzyme cyclooxygenase-2 (COX-2).     

Regio - and stereospecific halogenation of 7alogenoalkenes in liquid hydrogen fluoride

The products of bromo and chlorofluorination of E and Z-1,2-dichloroethylenes, 1, 3-dichloro-1-propenes, 1, 1-dichloro- ethylene and 1, 3-dichloro-2-fluoro-1-propene by N-bromosuccinimide and hexachloromelamine in anhydrous hydrogen fluoride have been studied. It was found that the reaction was in all cases 100% regio and 93–100% trans-stereospecific with the exception of E-1, 2-dichloro-ethylene, its trans-stereospecificity being 85%.Threo and erithro-1-bromo-1, 2-dichloro-2-fluoroethanes, 2-bromo-1, 3-dichloro-1-fluoropropanes and 1, 2, 3-trichloro-1-fluoro-propanes as well 1, 1, 2-trichloro-2-fluoroethane, 1-bromo-2, 2-dichloro-2-fluoroethane, 1, 2, 2-trichloro-2 fluoroethane, 1-bromo-1, 3-dichloro-2, 2-difluoropropane, and 1, 1, 3-trichloro-2,2-difluoropropane were obtained in 50–70% yield.The bromination of E and Z-1, 3-dichloro-1-propenes with molecular bromine in carbon tetrachloride in the dark is non-stereospecific and gives a mixture of erithro and threo-1, 2-dibromo-1, 3-dichloropropanes in the ratio about 1:1. However, the bromination reaction in anhydrous hydrogen fluoride solution proceeds with a high degree of stereospecificity (94–95%) and gives threo-1, 2-dibromo-1, 3-dichloropropane from Z and erithro-1, 2-dibromo-1, 3-dichloropropane from E-1, 3-dichloro-1-propene.The data obtained are considered in terms of an electrophilic mechanism of halogenoalkene halogenation in anhydrous hydrogen fluoride and a free-radical mechanism in carbon tetrachloride.     

An allyltitanium derived from acrolein 1,2-dicyclohexylethylene acetal and (eta(2)-propene)Ti(O-i-Pr)(2) as a chiral propionaldehyde homoenolate equivalent that reacts with imines with excellent stereoselectivity. An efficient and practical access to optically active gamma-amino carbonyl compounds

A chiral allyltitanium compound 2, prepared in situ by the reaction of optically active acrolein 1,2-dicyclohexylethylene acetal (3) with (eta(2)-propene)Ti(O-i-Pr)(2) (1), reacts with a variety of acyclic and cyclic imines 4 in a regiospecific way to afford alpha-addition products 5 as a mixture of the E- and Z-isomers in good combined yield, where the former is predominant in a ratio of 92:8 to >95:5. The mixture of (E)- and (Z)-5 and pure (E)-5 which could be isolated in several cases were respectively converted to the corresponding beta-amino ester 6 to confirm the absolute configuration and enantiomeric purity. The ee of the newly formed asymmetric center of 5 is more than 78% for the mixture of (E)- and (Z)-5 and more than 96% for pure (E)-5. By taking advantage of the versatility of the vinyl ether moiety in 5, optically active gamma-amino aldehydes 8, gamma-amino aldehyde acetals 7 and 10, gamma-amino acids 9, beta-amino esters 6, and pyrrolidinoisoquinolines 12 were readily prepared. In the reaction of 2 with optically active alpha-silyloxyimine 4n, remarkable double stereodifferentiation was observed; thus, the reaction of 2 derived from (S,S)- or (R,R)-3 provided syn- and anti-5n in a ratio of 55:45 or 0:100, respectively. Meanwhile, the stereochemistry of the product in the reaction of 2 with beta-silyloxyimine 4o was controlled mainly by 2. Thus, the reaction of beta-silyloxyimine 14 with 2 derived from 1 and (R,R)-3 afforded gamma-silyloxyimine 15 with 92% diastereoselectivity, from which 4-amino-6-hydroxypentadecanal dimethyl acetal (13), a key intermediate for the synthesis of batzelladine D, was synthesized.     

A total synthesis of milbemycin G: approaches to the C1-C10-fragment and completion of the synthesis

A synthesis of the hydroxybutenolide (-)-6 required for synthesis of alpha-milbemycins and the completion of a total synthesis of milbemycin G 7 is reported. Following preliminary studies, an optimised synthesis of the hydroxybutenolide (-)-6 from the hydroxyketone 38 was developed which involved the resolution of 38 by separation of the 3-(O-chloroacetyl)-(S)-mandelates 80 and 83. Ester 80, which corresponded to the required enantiomer of the hydroxyketone 38, crystallized from the mixture of the diastereoisomeric esters 80 and 83 giving the (-)-hydroxyketone (-)-38 in an overall yield of 47%(based on racemic 38) after ethanolysis. Hydroxyketone (-)-38 was oxidised to the enolic diketone (-)-39 and phenylselenation and stereoselective reduction gave the trihydroxycyclohexyl selenide (-)-43. The regioselective introduction of the non-conjugated double-bond into the six-membered ring was then achieved by esterification of the 4-hydroxyl group using trichloroacetic acid to give the trichloroacetate (-)-69. Oxidative elimination from the trichloroacetate using tert-butyl hydroperoxide was highly regioselective and gave the endo- and exocyclic alkenes (-)-44 and (-)-46 in a ratio of 95 : 5 after ethanolysis of the trichloroacetates. Selective O-methylation of the 4-hydroxyl group via the cyclic stannylene 55 and protection of the 3-hydroxyl group as its 2-trimethylsilylethoxymethyl (SEM) ether gave the ester (-)-57. Following saponification of the ethyl ester, re-esterification using 2-trimethylsilylethanol and oxidation of the 2-trimethylsilylfuryl fragment using singlet oxygen gave the required hydroxybutenolide (-)-6.The Wittig reaction between the phosphonium salt 2 and the hydroxybutenolide (-)-6 gave a ca. 2 : 1 mixture of the (4Z)- and (4E)-isomers of the ester 84 which on treatment with a catalytic amount of iodine was converted into the (4E)-isomer (4E)-84. Deprotection gave the seco-acid 85 but attempts to macrocyclise this were unsuccessful, the elimination product 86 being the only product isolated. The Wittig product 84 was taken through to the butenolide (2'E)-91 by removal of the SEM group, cyclisation to form the butenolide ring and diene isomerization, but this could not be converted into the corresponding seco-acid 92. However, removal of the SEM group from the seco-acid 85 gave the trihydroxy-acid 93 which was cyclized under modified Yamaguchi conditions to give the macrolide 94 together with a small amount of the macrocyclic butenolide 95. Reduction of this mixture using diisobutylaluminium hydride gave (6R)-6-hydroxymilbemycin E 96 which was converted to milbemycin G 7 by cyclisation of the primary chloride 97. The synthetic milbemycin G 7 was identical to a sample prepared by methylation of a commercial sample of milbemycin D 98, 7-O-methylmilbemycin G 99 being a side-product of this methylation.     

高硒情况下维生素E对老龄大鼠血清中抗氧化作用的影响

研究了高Se或高维生素E下，老龄大鼠体内抗氧化活性的变化以及高Se下维生素E对其体内抗氧化水平的影响。将十二月龄Wistar大鼠32只随机分成4组：（1）正常饲料组；（2）高Se饲料组；（3）高维生素E饲料组；（4）高Se高维生素E饲料组。饲至十周末，处死大鼠，按试剂盒要求取其血液制成血清测GSH－Px,SOD活性，MDA含量。结果表明，高Se或高维生素E下饲养下的大鼠与对照组比较，血清中GSH－Px活性升高（P＜0．05）。SOD活性未见改变，MDA含量分别减少50％和56％，有显著差异（P＜0．01）；维生素E与高Se合用与高Se组比较能进一步同GSH－Px,SOD活性（P＜0．01）。结论：高Se会升高老龄大鼠的抗氧化活性，而与维生素E合用更加升高老龄大鼠血液中抗氧化活性。     

Diels-Alder reactions of 3-substituted coumarins in water and under high-pressure condition. An uncatalyzed route to tetrahydro-6H-benzo[c]chromen-6-ones

[reaction: see text] Diels-Alder reactions of 3-substituted coumarins 1a-g with methyl-1,3-butadienes 2a-c carried out in water alone and in CH2Cl2 under 9 kbar pressure are reported. In aqueous medium satisfactory results were obtained by operating at 150 degrees C, whereas under high pressure the cycloadditions were complete at 60-70 degrees C with excellent yields (85-95%). The reactions with isoprene (2b) always resulted in the exclusive formation of para cycloadducts, whereas with (E)-piperylene (2c) only ortho products were detected. The cycloaddition of 3-phenylsulfonylcoumarin (1a) with (E)-piperylene (2c) allowed the endo adduct to be obtained exclusively, whereas 3-carboxycoumarin (1b) reacted with 2c to give a mixture of the corresponding endo/exo adducts in a 58:42 ratio in water and in a 45:55 ratio under high-pressure condition.     

Cyclobutanones through SNi' ring closure, a mechanistic study

Mechanistic studies on the intramolecular nucleophilic substitution with allylic rearrangement (SNi' reaction) and a new stereoselective access to substituted cyclobutanones are reported. 4,4-Dialkyl-5-oxohex-2E-en-1-yl methanesulfonates 4 were converted to 2,2-dialkyl-3-vinylcyclobutanones 6 by SNi' ring closure. The stereochemical analysis of the reaction was achieved through ring closure of (6S)-6-chloro-3,3-diethylhept-4E-en-2-one (S)-17, defined by the absolute configuration of C(6), leading to (3S)-2,2-diethyl-3-(prop-1E-en-1-yl)cyclobutanone (S)-(E)-18 and (3R)-2,2-diethyl-3-(prop-1Z-en-1-yl)cyclobutanone (R)-(Z)-18, in a ratio of 85:15, with almost complete transfer of chirality (>97%). The absolute configuration of (S)-17 was determined by X-ray diffraction analysis of the camphanoate derivative 16. The absolute configuration of the cyclobutanone products (S)-(E)-18 and (R)-(Z)-18 was determined by Raman optical activity spectroscopy. Comparison of the absolute configuration of (S)-17 and the resulting (E)- and (Z)-cyclobutanones 18 allowed the conclusion that the SNi' reaction proceeds with syn geometry relative to the leaving group.