丹曲林钠杂质B的合成

以5-对硝基苯胺为原料,与糠醛经重氮化反应制得5-对硝基苯基糠醛(1);1与1-氨基乙内酰脲盐酸盐经缩合、精制得丹曲林(2);2与甲醇钠成盐制得丹曲林钠(3);3在氢氧化钠水溶液中加热条件下,经开环水解制得丹曲林钠杂质B钠盐,再经盐酸酸化、精制合成了丹曲林钠杂质B,总收率16.9%,纯度99.9%,其结构经1H NMR,IR和MS(ESI)确证。     

氘代AZD9291的合成

吲哚和2,4-二氯嘧啶经偶联反应制得3-(2-氯嘧啶-4-基)-1H-吲哚(1); 1与CD₃I 经取代反应制得3-(2-氯嘧啶-4-基)-1-(甲基-d₃)-吲哚(2); 2经两步亲核取代反应制得N′-(2-二甲基氨基乙基)-2-甲氧基-N′-甲基-N-{［4-(1-(甲基-d₃)吲哚-3-基)］嘧啶-2-基}-5-硝基苯-1,4-二胺(4); 4经还原反应后,与氯丙酰氯发生缩合反应合成了氘代AZD9291,总收率8.5%,其结构经¹H NMR, ¹³C NMR和ESI-MS表征。     

盐酸奈法唑酮的合成

盐酸奈法唑酮是一类新型抗抑郁药.先用间氯苯胺与二乙醇胺环化合成1-(3-氯苯基)哌嗪,再与1-溴-3-氯丙烷反应制得1-(3-氯丙基)-4-(3-氯苯基)哌嗪盐酸盐,最后与5-乙基-4-(2-苯氧乙基)-1,2,4-三唑-3-酮反应得到盐酸奈法唑酮.产物结构经IR,MS,1H NMR及13C NMR确证.     

Fluorimetric and mass spectrometric study of the interaction of beta-cyclodextrin and osthole

The inclusion complex of beta-cyclodextrin (beta-CD) and osthole was studied by the electrospray ionization mass spectrometry (ESI-MS) and fluorescence spectrometry. From the mass spectrum, the 1:1 stoichiometric inclusion complex of beta-CD and osthole was observed. The tandem mass spectrum was performed. The fluorescence intensity of osthole increased in the present of beta-CD. According to the 1:1 beta-CD-osthole mode, the dissociation constant (KD) was obtained by ESI-MS and fluorescence spectrometry. The KD of beta-CD-osthole inclusion complex is 6.96 x 10(-3) mol L(-1) obtained by mass spectrometry and that is 8.14 x10 (-3) mol L(-1) obtained by fluorescence spectrometry, which is consistent with each other.     

吡啶基三唑功能化罗丹明化合物的合成

以2-溴甲基吡啶氢溴酸盐和叠氮化钠为原料,合成中间体2-叠氮甲基吡啶（1）;对羟基苯甲醛和溴丙炔经取代反应合成中间体4-（丙-2-炔基丙氧基）苯甲醛（2）; 2与1经点击反应制得关键中间体BPT（3）; 3与罗丹明B酰肼经还原胺化反应得罗丹明类荧光探针,其结构经¹H NMR, IR和元素分析表征。     

两种氮杂环丁烷类药物中间体的合成

1-二苯甲基-3-羟基氮杂环丁烷(1)经过对甲苯磺酰氯取代、叠氮化及还原反应合成了药物中间体--1-二苯甲基-3-氨基氮杂环丁烷(4);1经过氧化、氰基化与还原反应合成了1-二苯甲基-3-羟基-3-氨甲基氮杂环丁烷(8).4和8的结构经1H NMR表征.     

立体选择性合成内型N-Boc-N-去甲托品醇

以托品酮为起始原料,与氯甲酸氯乙酯经脱甲基化反应制得脱甲基托品酮（1）; 1与Boc酸酐反应制得N-Boc-N-去甲托品酮（2）;以三仲丁基硼氢化锂为还原剂,2经还原反应立体选择性合成了内型N-Boc-N-去甲托品醇（内型/外型=6.5/1）,总收率60%,其结构经¹H NMR和ESI-MS确证。     

Effects of the tumor promoter TPA on the induction of DNA synthesis in normal and RSV-transformed rat fibroblasts.

Induction of DNA synthesis by the tumor promoter tetradecanoyl phorbol acetate (TPA) was studied in a line of cultured rat fibroblasts (Rat-1) and their Rous sarcoma virus-transformed derivative (Rat-1 (RSV)). Following serum deprivation for 54 h to achieve quiescence, semiconservative DNA replication was measured by incubation of cells in BrdUrd and FdUrd after serum stimulation in the presence or absence of TPA. Optimal concentrations of TPA (0.1--0.5 microgram/ml) in serum-free medium induced a small increase (10--15%) in the amount of DNA made over a 30-h period in both Rat-1 and Rat-1 (RSV) cells. When Rat-1 cells were stimulated by a 4-h serum pulse, 30% of the DNA was replicated by 30 h. If the serum pulse was followed by TPA addition, 70% DNA replication was observed. If the serum pulse was preceded by TPA addition, the onset of DNA synthesis was delayed by several houses, but stimulation of DNA synthesis occurred. In contrast, the Rat-1 (RSV) cells did not show an increased in DNA synthesis induced by TPA in similar protocols, but the serum-induced onset of DNA synthesis was delayed by several hours in the presence of TPA. Therefore, TPA acts as a co-inducer of DNA synthesis in the Rat-1 but not in the Rat-1 (RSV) cells. The parent alcohol, phorbol, was inactive in Rat-1 cells, but delayed the onset of DNA synthesis in the Rat-1 (RSV) cells. We conclude that the co-inducing and delaying activities of TPA on DNA synthesis appear to be distinct and to act a different points in the G1 phase of the cell cycle.     

1,1,3,3-四(全氟己基乙基)二锡氧烷二聚体在环氧化合物开环反应中的催化作用

采用氟碳-有机溶剂两相催化体系,考察了1,1,3,3-四(全氟己基乙基)二锡氧烷二聚体(1)在环氧化合物开环反应中的催化作用.结果表明,催化剂(1)在氟碳-有机溶剂两相体系中使环氧苯乙烯和甲醇的开环反应产率高达95%,¹³CNMR谱表明,开环反应的区域选择性为100%.在氟碳-有机溶剂两相催化体系中以一锅法制备了3-苯基丙酸2-甲氧基-2-苯乙醇酯,收率高,方法简便,催化剂几乎可以定量回收循环使用.     

An efficient preparation of isosteric phosphonate analogues of sphingolipids by opening of oxirane and cyclic sulfamidate intermediates with alpha-lithiated alkylphosphonic esters

D-erythro-(2S,3R,4E)-Sphingosine-1-phosphonate (1), the isosteric phosphonate analogue of naturally occurring sphingosine 1-phosphate (1a), and D-ribo-phytosphingosine 1-phosphonate (2), the isosteric phosphonate analogue of D-ribo-phytosphingosine-1-phosphate (2a), were synthesized starting with methyl 2,3-O-isopropylidene-d-glycerate (4) and D-ribo-phytosphingosine (3), respectively. Oxirane 12 was formed in eight steps from 4, and cyclic sulfamidate 22 was formed in five steps from 3. The phosphonate group was introduced via regioselective ring-opening reactions of oxirane 12 and cyclic sulfamidate 22 with lithium dialkyl methylphosphonate, affording 13 and 23, respectively. The synthesis of 1 was completed by S(N)2 displacement of chloromesylate intermediate 14b with azide ion, followed by conversion of the resulting azido group to a NHBoc group and deprotection. The synthesis of 2 was completed by cleavage of the acetal, N-benzyl, and alkyl phosphonate ester groups.     

二苯并[b,f][1,5]二氮杂芳辛四烯衍生物的合成及拆分

以邻氨基二苯甲酮为原料,经自身缩合环化合成了3种二苯并[1,5]二氮杂芳辛四烯衍生物(1a~1c);以邻苯二甲酸酐和溴苯为原料经傅-克反应制得中间体2-(4-溴苯甲酰溴)苯甲酸(M1);M1经叠氮化后自缩合制得6,12-二(4-溴苯基)二苯并[b,f][1,5]二氮杂环辛四烯(1d);以邻氨基苯甲酸甲酯为原料,经自身缩合环化制得中间体二苯并[b,f][1,5]二氮杂环辛四烯-6,12(5H,11H)-二酮(M2);M2经氯化合成6,12-二氯二苯并[b,f][1,5]二氮杂环辛四烯(1e),化合物1a~1e的结构经~1H NMR,~(13)C NMR和ESI-MS表征,其中化合物1c为新化合物。利用超临界色谱(SFC)技术对化合物1a~1e实现了手性拆分,获得5对具有高旋光度的光学活性异构体(ee99%)。     

2-乙氧羰基-3-甲基-4,5-四亚甲基吡咯的合成

以乙酰乙酸乙酯(1)为原料,在醋酸中与亚硝酸钠通过肟化反应制得N-羟基亚胺乙酰乙酸乙酯(2);2在醋酸缓冲溶液中经锌粉还原后与环己酮加成环化合成了2-乙氧羰基-3-甲基-4,5-四亚甲基吡咯(3),其结构经1H NMR,IR和元素分析表征。较适宜的反应条件为:1100 mmol,n(Zn)∶n(1)=2.9∶1.0,在醋酸中回流反应,总收率39%;以多步反应的最佳反应条件进行"一锅煮"合成3,收率50%。     

The interplay of iron(II) spin transition and polymorphism

The mononuclear compound (1) [Fe(II)(L)(2)](BF(4))(2) (L = 4-ethynyl-2,6-bis(pyrazol-1-yl)pyridine) was prepared and structurally as well as magnetically characterised. The crystallisation revealed the formation of two polymorphs--the orthorhombic 1A and the tetragonal form 1B. A third, intermediate phase 1C was found exhibiting a different orthorhombic space group. Reversibility of the phase transition between 1A and 1C was studied by variable-temperature single-crystal and powder X-ray diffraction studies, while an irreversible phase transition was observed for the transition of 1B→1C. The magnetic studies show that the 1A?1C transition is accompanied by a very abrupt spin transition (ST) with 8 K hysteresis width (T(1/2)(↓) = 337 K, T(1/2)(↑) = 345 K). The ST was confirmed by M?ssbauer spectroscopy as well as by DSC studies. In contrast, the 1B polymorph remained low-spin up to 420 K. In conclusion, a full cycle of intertwined phase- and spin-conversions of three polymorphs could be proven following the general scheme 1B→1C?1A.     

Kinetics and mechanism of the oxidation of amaranth with hypochlorite

The reaction mechanism of the oxidation of Amaranth dye (2-hydroxy-1-(4-sulfonato-1-naphthylazo) naphthalene-3,6-disulfonate) with hypochlorite under varied pH conditions was elucidated by a kinetic approach. Under excess concentration of oxidant, the reaction followed pseudo-first-order kinetics with respect to Amaranth, and the oxidation was found to occur through two competitive reactions, initiated by hypochlorite and hypochlorous acid. The reaction order with respect to both OCl(-) ion and HOCl was unity. While the latter reaction was fast, the significance of the oxidation paths depended on the relative concentration of the two oxidizing species, which was dictated by the reaction pH. The role of the H(+) ion in the reaction was established. For the hypochlorite ion and hypochlorous acid facilitated reactions, the second-order rate coefficients were 1.9 and 23.2 M(-1) s(-1), respectively. The energy parameters were E(a) = 33.7 kJ mol(-1), ΔH(?) = 31.2 kJ mol(-1) and ΔS(?) = -190.6 J K(-1) mol(-1) for the OCl(-) ion-driven oxidation, and E(a) = 26.9 kJ mol(-1), ΔH(?) = 24.3 kJ mol(-1) and ΔS(?) = -222.8 J K(-1) mol(-1) for the reaction with HOCl-initiated oxidation. The major oxidation products for both the pathways were 3,4-dihydroxy naphthalene-2,7-disulfonic sodium salt (P(1)), dichloro-1,4-naphthoquione (P(2)) and naphtha(2,3)oxirene-2, 3-dione (P(3)). On the basis of the primary salt effect and other kinetic data, the rate law for the overall reaction and probable reaction mechanism was elucidated. The proposed mechanism was validated by simulations using Simkine-2.     

Characterization of a chiral enolate aggregate and observation of 6Li-1H scalar coupling

A chiral enolate aggregate 1 containing a lithium enolate and a chiral lithium amide was systematically investigated by various NMR techniques. (1)H and (13)C DOSY at 25 and -78 degrees C provide its solution structure, aggregation number, and formula weight. Multiple 2D (6)Li NMR techniques, such as (6)Li-(6)Li EXSY, (6)Li-(1)H HOESY, were utilized to investigate its stereochemical structure. The configuration of the enolate in complex 1 was confirmed by (6)Li-(1)H HOESY and trapping with TMS-Cl. A unique (6)Li-(1)H coupling through the Li-N-C-H network was observed. This scalar coupling was corroborated by (6)Li-(1)H HMQC, deuterium labeling experiments, and selective (1)H decoupling (6)Li NMR. The stereostructure of 1 provides a model for the origin of enantioselectivity of chiral lithium amide-induced enolate addition reactions.     

四(3,4-二甲基苯基)卟啉钴的合成及其光学性质

采用“两步法”,以吡咯和3,4-二甲基苯甲醛为原料,合成了四(3,4-二甲基苯基)卟啉(TDMPP, 1); 1与四水醋酸钴经络合反应合成四(3,4-二甲基苯基)卟啉钴(TDMPPCo, 2),其结构经¹H NMR, IR和荧光光谱确证。考察了金属盐的预处理、反应物浓度、浓缩比和投料比对合成2的收率影响。实验结果表明：在最佳反应条件［γ=n(1)：n(四水乙酸钴)=1 ：7, c（1）为22.95 mmol·L^-1,回流（150 ℃）反应4 h,浓缩比η为75%］下,收率可达82%。     

富马酸奈拉西坦的合成工艺改进

报道了一种合成富马酸奈拉西坦(7)的新工艺。以衣康酸二甲酯和苄胺为起始原料,经Michael加成和分子内环合反应制得1-苄基-5-氧代吡咯烷-3-羧酸甲酯(3); 3经NaBH₄还原得1-苄基-4-羟甲基-吡咯烷-2-酮(4); 4经甲磺酰化反应得1-苄基-5-氧代吡咯烷-3-羧酸甲磺酸酯(5); 5经氨解得奈拉西坦(6); 6与富马酸经成盐反应合成7,总收率78.4%,其结构经¹H NMR确证。     

Phosphorylation of phospholipase D1 and the modulation of its interaction with RhoA by cAMP-dependent protein kinase

Agents that elevate cellular cAMP are known to inhibit the activation of phospholipase D (PLD). We investigated whether PLD can be phosphorylated by cAMP-dependent protein kinase (PKA) and PKA-mediated phosphorylation affects the interaction between PLD and RhoA, a membrane regulator of PLD. PLD1, but not PLD2 was found to be phosphorylated in vivo by the treatment of dibutyryl cAMP (dbcAMP) and in vitro by PKA. PKA inhibitor (KT5720) abolished the dbcAMP-induced phosphorylation of PLD1, but dibutyryl cGMP (dbcGMP) failed to phosphorylate PLD1. The association between PLD1 and Val14RhoA in an immunoprecipitation assay was abolished by both dbcAMP and dbcGMP. Moreover, RhoA but not PLD1 was dissociated from the membrane to the cytosolic fraction in dbcAMP-treated cells. These results suggest that both PLD1 and RhoA are phosphorylated by PKA and the interaction between PLD1 and RhoA is inhibited by the phosphorylation of RhoA rather than by the phosphorylation of PLD1.     

Excited-state dynamics of acetylene excited to individual rotational level of the V04K01 subband

Dynamics of the IR emission induced by excitation of the acetylene molecule using the (3(2)K(a) (0,1,2),A (1)A(u)<--4(1)l(a) (1),X (1)Sigma(g) (+)) transition was investigated. The observed IR emission was assigned to transitions between the ground-state vibrational levels. Acetylene fluorescence quenching induced by external electric and magnetic fields acting upon the system prepared using the (3(4)K(a) (1),A (1)A(u)<--0(0)l(a) (0),X (1)Sigma(g) (+)) excitation was also studied. External electric field creates an additional radiationless pathway to the ground-state levels, coupling levels of the A (1)A(u) excited state to the quasiresonant levels of the X (1)Sigma(g) (+) ground state. The level density of the ground state in the vicinity of the excited state is very high, thus the electric-field-induced transition is irreversible, with the rate constant described by the Fermi rule. Magnetic field alters the decay profile without changing the fluorescence quantum yield in collisionless conditions. IR emission from the CCH transient was detected, and was also affected by the external electric and magnetic fields. Acetylene predissociation was demonstrated to proceed by the direct S(1)-->S(0) mechanism. The results were explained using the previously developed theoretical approach, yielding values of the relevant model parameters.     

5-羟基-3,4-二氢异喹啉-1-酮的合成

以异喹啉为起始原料,经成盐、磺化得异喹啉-5-磺酸(3),3与熔融的氢氧化钠和氢氧化钾反应得1,5-二羟基异喹啉(4),以5%Pd-C为催化剂还原4得5-羟基-3,4-二氢异喹啉-1-酮(1),总收率47.6%。1的结构经1H NMR和MS确证。