含半胱氨酸多肽的研究——Ⅲ.牛胰岛素A链带保护基的氨端九肽的合成

本文报告带保护基的牛胰岛素A链氨端九肽酯■和相应的九肽酰肼■与九肽酸■的合成.苄氧羰基甘氨酰-异亮氨酰-缬氨酰-γ-叔丁酯谷氨酸乙酯(III)分别由已知的苄氧羰基缬氨酰-γ-叔丁酯谷氨酸乙酯经催化氢解法脱去N-保护基后与苄氧羰基甘氨酰-异亮氨酰肼(VIII)按迭氮化合物法缩合,以及由已知的苄氧羰基甘氨酰-异亮氨酰-缬氨酸(VIII)与γ-叔丁酯谷氨酸乙酯按碳二亚胺法合成.III经肼解或皂化分别得四肽酰肼■和四肽酸■.苄氧羰基谷氨酰胺酰-S-苄基半胱氨酰-S-苄基半胱氨酰-丙氨酰-O-乙酰丝氨酸甲酯(V)分别由已知的苄氧羰基-S-苄基半胱氨酰-S-苄基半胱氨酰-丙氨酰-丝氨酸甲酯XII_a或苄氧羰基-S-苄基半胱氨酰-S-苄基半胱氨酰-丙氨酰-O-乙酰基丝氨酸甲酯XII以溴化氢-乙酸脱去N-保护基后与苄氧羰基谷氨酰胺对硝基苯酯(XIII)按活化酯法缩合而得.如以溴化氢-三氟乙酸脱去XIIa的N-保护基后与XIII按活化酯法缩合则得Va,合成Va的另一方法是将已知的苄氧羰基谷氨酰胺酰-S-苄基半胱氨酰-S-苄基半胱氨酰肼XIV通过迭氮化物法与丙氨酰-丝氨酸甲酯(X)缩合而得.五肽V经溴化氢-乙酸脱去N-保护基后与四肽酰肼IV或四肽酸IV_a分别通过迭氮化物法和碳二亚胺法缩合得到同一的九肽甲酯(I).化合物I用三氟乙酸脱去叔丁酯后肼解得九肽肼(II).化合物I经皂化得相应的九肽酸IIa.     

α-葡萄糖苷酶抑制剂Radicamine B的合成

以D-阿拉伯糖为原料,依次合成了中间体(2R,3R,4R)-2,3,5-三-O-苄氧基-4-羟基-O-叔丁基二甲基硅基-戊醛肟(3),(2R,3S,4S)-2,3,5-三-O-苄氧基-4-碘-O-叔丁基二甲基硅基-戊醛肟(4)和(2R,3R,4R)-3,4-二-O-苄氧基-2-(苄氧甲基)-3,4-二氢-2H-吡咯-1-醇(5);5与芳基Grignard试剂进行高立体选择性的加成反应制得(2R,3R,4R,5R)-3,4-二-O-苄氧基-2-[4-(苄氧基)苯基)]-5-吡咯-1-醇(6);6经催化氢化合成Radicamine B,总收率18.5%。3和4为新化合物,其结构经1HNMR,MS和元素分析表征。     

2,2'－联吡啶桥连的双－4,4'-联吡啶哑铃型化合物的合成

二甘醇2与对甲苯磺酰氯在CH_2Cl_2中，0 ℃～r.t.及Et_3N存在下反应得2－ （羟乙氧基）乙醇对甲苯磺酸酯（3），收率88％。化合物3与对叔丁基苯甲酰氯在 CH_2Cl_2中0～5 ℃及吡啶存在下反应得2－（对叔丁基苯甲酰氧基乙氧基）乙醇对 甲苯磺酸酯（4），收率96％。4与对羟苯甲醇在乙腈中及CsF/K_2CO_3存在下70 ℃ 反应得2－（对叔丁基苯甲酰氧基乙氧基）乙氧苄醇（5），收率98％。5与NBS及 PPh_3在THF中，室温下反应得化合物2－（对 丁基苯甲酰氧基乙氧基）乙氧苄溴 （6），收率95％。6与4,4'－联吡啶在乙腈中，60 ℃反应1h得N－[2－（对叔丁基 苯甲酰氧基乙氧基）乙氧苄基]－4,4'－联吡啶六氟磷酸盐（7），收率85％。7与 α,α－二（溴甲基）－2,2'－联吡啶在乙腈中，油浴60 ℃反应36h，得到标题化 合物，产率为45％。     

(S)-4-羟基吡咯烷-2-酮的简便合成

(S)-3-羟基-γ-丁内酯开环制得手性3,4-二羟基丁酸甲酯(2);对2的伯羟基进行对甲苯磺酰化、仲羟基进行苄基保护得4-对甲苯磺酰氧基-3-苄氧基丁酸甲酯(5);5在氨甲醇作用下合环、脱苄基保护合成了(S)-4-羟基吡咯烷-2-酮,总收率26%,其结构经1HNMR和HR-MS确认,比旋光值与文献值相符。     

(3S,4S)-4-氨基-3-羟基-6-甲基庚酸的合成

价廉易得的L-亮氨酸先以苄基同时保护氨基及羧基得(S)-2-(二苄胺基)-4-甲基戊酸苄酯,进而在碱性条件下与乙腈发生亲核取代反应得(S)-4-(二苄胺基)-6-甲基-3-氧代庚腈,再经硼氢化钠选择性还原羰基得(3S,4S)-4-(二苄胺基)-3-羟基-6-甲基庚腈,用双氧水氧化得(3S,4S)-4-(二苄胺基)-3-羟基-6-甲基庚酸,最后在Pd(OH)2/C-H2作用下脱掉苄基得到(3S,4S)-4-氨基-3-羟基-6-甲基庚酸,即(3S,4S)-statine。整个合成路线总产率为33.6%。     

阳离子光固化活性单体氧杂环丁烷的合成及表征

以3-乙基-3-羟甲基氧杂环丁烷为原料，与甲基磺酰氯磺酰化，得到3-乙基-3-甲磺酰基甲基氧杂环丁烷；在碱性条件下，以PEG600作相转移催化剂，用3-乙基-3-甲磺酰基甲基氧杂环丁烷与乙二醇醚化得到2-[（3-乙基-3-氧杂环丁基）甲氧基]乙醇；然后与甲基丙烯酸甲酯进行酯交换得到目的产物2-[（3-乙基-3-氧杂环丁烷）甲氧基]甲基丙烯酸乙酯。3-乙基-3-羟甲基氧杂环丁烷与3-溴丙烯反应，生成3-乙基-3-[（2-丙烯-1-基氧基）甲基]氧杂环丁烷，然后在氯铂酸的催化下，与三乙氧基硅烷反应得到3-乙基-3-[[3-（三乙氧基硅）丙氧基]甲基]氧杂环丁烷。产物经红外光谱和核磁共振谱表征得到确证。     

几种碳环糖的合成

以四-O-苄基-葡萄糖酸-1,5-内酯为原料,通过四步反应合成了四-O-苄基-Valiolone(1,总产率40％)；以1 为原料合成了四-O-苄基-Valielone(产率95％)和四-O-苄基-Validone(产率20％),其结构经1H NMR,13C NMR和MS确证.     

可光固化单体2,7-二溴-9,9-双[4’-(3″-乙基-3″-氧杂环丁烷甲氧基己基氧基)苯基]芴的合成

以芴为原料,经溴代和氧化反应制得2,7-二溴芴酮(3);3与苯酚反应合成2,7-二溴-9,9-双(4’-羟基苯基)芴(4);4与3-(6’-溴己氧基甲基)-3-乙基氧杂环丁烷经醚化反应合成了可光固化单体2,7-二溴-9,9-双[4’-(3″-乙基-3″-氧杂环丁烷甲氧基己基氧基)苯基]芴,总收率67%,其结构经1H NMR,13C NMR和元素分析表征。     

(4-苄氧基苄基)-2,3-二-O-苄基-β-D-吡喃葡萄糖苷的合成

为合成酚酸取代的葡萄糖苷类天然产物,以全乙酰溴代葡萄糖为起始物,与4-苄氧基苄醇反应成苷,脱乙酰基后,选择性地在葡萄糖4,6-位形成亚苄基,2,3-位羟基用苄基保护,脱去亚苄基得到裸露葡萄糖4,6-位羟基的化合物(4-苄氧基苄基)-2,3-二-O-苄基-β-D-吡喃葡萄糖苷(7),该化合物可作为合成4,6-位选择性取代的葡萄糖衍生物的有效中间体。     

1-苄氧羰基-3-叔丁氧羰酰氨基氮杂环丁烷的合成工艺改进

以苄胺和环氧氯丙烷为原料,经开环、关环、取代、还原、脱苄等反应合成了1-苄氧羰基-3-叔丁氧羰酰氨基氮杂环丁烷,总收率22.9%.其结构经1H NMR,13C NMR和MS表征.     

Dichroism of absorption and polarization of phosphorescence of molecules of the closed form of nitrobenzospirothiopyran

The spectral-polarization characteristics of absorption and phosphorescence of molecules of the initial form of nitro-substituted indolinospirobenzothiopyran were studied in oriented polyethylene films and in solutions with different polarity. An oscillator model of the electron transitions responsible for the formation of absorption and luminescence spectra was suggested. It was established that the principal differences in the spectral and photophysical properties of the compound studied and its oxygen-containing analog are associated with the fact that the electronegativity of the S atom is lower than that of the O atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1143–1146, June, 1997.     

非那雄胺合成工艺改进

非那雄胺能抑制5α-还原酶的活性,明显降低二氢睾酮水平,是一种治疗良性前列腺增生的有效药品。该合成工艺以甾烯酮酸为原料,将其与氯化亚砜反应,无须分离即与叔丁胺反应得17β-酰胺化合物,再氧化开环,环合,氢化,脱氢合成了非那雄胺。经元素分析、IR、1HNMR、13CNMR、MS分析表征了其结构。该法无须使用昂贵的2,2-二吡啶二硫化物和剧毒药品苯亚硒酸酐,且以乙酸铵代替氨气,降低了对设备的要求和腐蚀,更适用于工业生产。     

Synthesis of phenolic components of Grains of Paradise

Two vanilloids, (5E)-8-(4-hydroxy-3-methoxyphenyl)oct-5-en-4-one (1) and 4-[3-hydroxydecyl]-2-methoxyphenol (2), isolated from the dried seeds of Grains of Paradise (Aframomum melegueta), were synthesized; the latter compound was made as the S-enantiomer and the material derived from the seeds was found to be a 1:1.7 mixture of the R and S isomers. The synthetic route used should allow the preparation of analogs having extended alkyl chains and consequently different lipophilicity, and 3, a homolog of 2, was also prepared.     

Acid hydrolysis of carboxymethylcellulose of low degree of substitution

Cotton cellulose was swollen in a sodium hydroxide solution and carboxymethylated by a two-bath method for different periods of time for each process. The kinetics of acid hydrolysis and the crystallinity of the swollen and carboxymethylated samples were measured. The proportion of broken bonds, rate constants for hydrolysis, and permeability of cellulose to hydrolyzing agents were calculated. The susceptibility of glycosidic linkages to acid hydrolysis was improved by carboxymethylation more than by swelling in alkali. The increased accessibility of carboxymethylcellulose to acid was regarded as a consequence of increased intra-and intercrystalline swelling and of the glycosidic bonds' weakness caused by the electron-attracting carboxymethyl group on the C-6 position.     

Study of hydration of two cements of different strengths

Main hydration products of two cement pastes, i.e. CSH-gel, portlandite (P) (and specific surface S) were studied by static heating, and by SEM, TEM and XRD, as a function of cement strength (C-33 and C-43) hydration time (th) and subsequent hydration in water vapour.Total change in mass on hydration and air drying, M_o, increased with strength of cement paste and with hydration time. Content of water escaping at 110 to 220°C, defined as water bound with low energy, mainly interlayer and hydrate water, was independent on cement strength but its content increased with (th). Content of chemically bound (zeolitic) water in CSH-gel, escaping at 220-400°C, was slightly dependent on strength and increased with (th). It was possibly derived from the dehydroxylation of CSH-gel and AFm phase. Portlandite water, escaping at 400-500°C, was independent on cement strength and was higher on longer hydration. Large P crystals were formed in the weaker cement paste C-33. Smaller crystals were formed in C-43 but they increased with (th). Carbonate formated on contact with air (calcite, vaterite and aragonite), decomposed in cement at 600-700^oC. It was high in pastes C-33(1 month) and C-43(1 month), i.e. 5.7 and 3.3%, respectively; it was less than 1% after 6 hydration months (low sensitivity to carbonation) in agreement with the XRD study showing carbonates in the air dry paste (1month), and its absence on prolonged hydration (6 months) and on acetone treatment. Water vapour treatment of (6 months) pastes or wetting-drying increased this sensitivity.Nanosized P-crystals, detected by TEM, could contribute to the cement strength; carbonate was observed on the rims of gel clusters.This revised version was published online in November 2005 with corrections to the Cover Date.     

恶臭嗅辨实验室建设探讨

针对恶臭测试的环境影响问题,提出了解决的实例方案,并对方案的要点及优缺点进行讨论,此方案在实际操作中具有较好的效果。     

Estimation of Kinetic Parameters of Thermal Oxidation of Ilmenite

The aim of the presented work was the investigation of thermal oxidation of ilmenite in static air atmosphere. The investigations were carried out by use of a derivatograph (MOM, Hungary). The changes of crystallographic structure of investigated samples were identified by X-ray diffractometry on Philips PW-1710 diffractometer. In temperature above 500°C appears structure of hematite Fe₂O₃. On the basis of the thermogravimetric measurements, the contracting area and contracting volume models were found as the best fitting experimental data. This revised version was published online in August 2006 with corrections to the Cover Date.     

Mechanism of action of base-catalyzed oxygenation of phenol derivatives

Cyclopropyl derivative of 2,6-di-tert-butylphenol is synthesized as a probe to investigate the mechanism of base-catalyzed autooxidation of phenol derivatives. Our study indicates that one electron reduction of molecular oxygen from phenolate gives phenoxyl radical 3, a key intermediate of autooxidation. The coupling of phenoxyl radical and superoxide radical gives peroxylate anion 4 and produces the final epoxy alcohol adduct 6.     

氯氧化镁生成热的研究

用氧化镁氯化镁水溶液制备了8水合氯氧化镁[nMg(OH)2·MgCl2·8H2O], 并测定了其在盐酸中的溶解热, 实验结果表明, 氯氧化镁溶解热与n值呈线性关系, 根据溶解热求出5Mg(OH)2·MgCl2·8H2O和3Mg(OH)2·MgCl2·8H2O的生成热分别为-7727.1和5888.1kJ·mol^1^-。