The Synthesis of possible di- and trihydroxylated chlorpromazine metabolites

The syntheses of di- and trihydroxychlorpromazines, I, II, III, and V, and of dioxo derivatives, IV and VI, are described.     

Synthesis of possible metabolites of chlorpromazine. I. 7-hydroxy derivatives of chlorpromazine,nor1-chlorpromazine and nor2-chlorpromazine

The title compounds and various derivatives have been prepared as analytical standards for the identification of chlorpromazine metabolites in biological materials. Additional evidence is presented for the existence of a halogen-induced Smiles rearrangement in the phenothiazine series.     

Synthesis of ± 8- and 9-HETEs

We describe the first total syntheses of ±8 and ±9 HETEs using the addition of diazoketones to furan followed by electrocyclic ring opening to provide the necessary cis-trans diene system.     

微波辐射下4-(4-羟基-3-甲氧基)苯基-3,3,6,6-四甲基-1,8-二氧代1,2,3,4,5,6,7,8,9,10-十氢吖啶的合成和晶体结构

标题化合物C24H29NO4?1/2C2H5OH稨2O)由香兰素、5,5-二甲基-1,3-环己二酮、醋酸铵在微波辐射下干反应并经95%乙醇重结晶而得C24H29NO4穀2(C2H5OH稨2O)晶体。结构通过单晶X-射线衍射法确定,其晶体属单斜晶系,空间群P21/n, a = 9.810(2), b = 14.516(3), c = 17.008(3) ? b = 101.03(2), V = 2377.2(8) ?, Z = 4, Mr = 427.52, Dc = 1.195 g/cm3 , m(MoKa) = 0.082 mm-1, F(000) = 920。晶体结构用直接法解出,经全矩阵最小二乘法对原子参数进行修正,最终的偏离因子为R = 0.0406, wR = 0.0892。X-射线衍射分析结果表明,吡啶环和与之稠合的2个六员环均为信封式构象。     

Synthesis of possible metabolites of menazon

A product of the peracetic acid oxidation of 2,4-diamino-6-methylthiomethyl-1,3,5-triazine is identical with a major urinary metabolite of the aphicide, menazon, in the rat. This product has been shown to be the S-oxide 2,4-diamino-6-methylsulphinyl-methyl-1, 3, 5-triazine and not the N-oxide.     

Synthesis of 3-Chloro-2-hydroxyimipramine and 3-chloro-8-hydroxyimipramine,Hypothetical metabolites of clomipramin

Fremy salt oxidation of 3-chloroiminodibenzyl yields a mixture of two isomeric iminequinones, which can be separated and reduced to aminophenols and the phenolic group protected with addition of dihydropyran. Introduction of the N,N-dimethylaminopropyl side chain and removal of the protective group provided the two chlorohydroxyimipramines, which can serve as standards for the identification of possible biotransformation products of the parent drug, clomipramine.     

1-(取代硅基甲硫基)甲基-2,8,9-三氧杂-5-氮杂-1-硅杂双环[3.3.3]十一烷的合成与生物活性

2,8,9一三氧杂一5一氮杂司一硅杂双环［3．3．3」十一烷（Silatrane）衍生物是一类具有广泛生物活性的五配位有机硅化合物,自6O年代发现以来一直引起人们浓厚的兴趣,随着其1位硅原子上所连基团的变化,该类化合物可表现出通然不同的生物活性［’j．为寻找新的生物活性物质,本文在Silatranel位引入一类含硅甲硫醚基团,合成了11种新的Silatrane衍生物,并初步测定了其在农药、医药方面的生物活性;同时,在其质谱中发现存在罕见的重排裂解过程．合成方法如下：回实验部分1．l仪器与试剂BrukerAC－PZOO型NMR仪,CDCI。为溶剂,TM…     

Synthesis of nitrolipids. All four possible diastereomers of nitrooleic acids: (E)- and (Z)-, 9- and 10-nitro-octadec-9-enoic acids

Unsaturated fatty acids are nitrated endogenously to produce nitrated lipids. Recent studies have shown that these nitrated lipids have high chemical reactivity and profound biological implications. We report an efficient, scalable synthesis which is regiospecific and stereoselective for all possible isomers of nitrated oleic acid: (E)- and (Z)-, 9- and 10-octadec-9-enoic acids.     

Natural product chemistry. Part 160. Synthesis of 8-, 9-, 10- and 11-methylacronycines to improve the cytostatic activity of acronycine

With the help of drug design, 8-, 9-, 10- and 11-methylacronycines 24, 25, 26 and 27 have been selected and synthesised to improve the cytostatic potency of acronycine ( 31 ). The condensation of phloroglucinol with 6-methylanthranilic acid gave 7-hydroxy-1,9-dimethyldibenzo[b,j][1,7]phenanthroline-8,14(5H,13H)-dione ( 32 ) as the main product.     

Synthesis of Drim-9(11)-en-8α- and -8β-ols from Drimenol

Drim-9(11)-en-8α-ol and drim-9(11)-en-8β-ol were synthesized in six steps from drimenol. Drimenol was oxidized by P₂O₅ and DMSO to drimenal, which isomerized with p-TsOH into isodrimenal. Isodrimenal was reduced by NaBH₄ into isodrimenol, epoxidation of which by m-CPBA gave a mixture (3.4:1) of α- and β-epoxyisodrimenols. These reacted with tosyl chloride in Py to give a mixture of α- and β-epoxyisodrimenol tosylates. Treatment of the tosylate mixture with KI and then Ph₃P produced a mixture of drim-9(11)-en-8α- and -8β-ols that was separated chromatographically. The overall yield was ∼26%.__________Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 152–155, March–April, 2005.     

Synthesis and metallochromic properties of some hydrazones of 2-, 3- and 8-hydrazinoquinoline

Twenty-two new hydrazones were synthesized for evaluation as possible calorimetric reagents for trace determinations of iron, cobalt, nickel, copper and zinc. Spectrophotometric studies revealed that several show promise as sensitive reagents, with possible utility for simultaneous determinations of two or more of the metals. Conclusions regarding geometric structures of some of the hydrazones and chelates were deduced from mole-ratio studies.     

3-(9-芴甲氧羰基)四氢噻唑-2-硫酮的合成及其晶体结构

在吡啶存在下, 由9-芴甲氧羰酰氯与四氢噻唑-2-硫酮反应得到3-(9-芴甲氧羰基)四氢噻唑-2-硫酮, 产率为78.0%。用X射线衍射法测定晶体结构, 属正交晶系, Pca21空间群, 晶体学参数:a=0.9654(2), b=2.8032(1), c=0.6069(2)nm, Z=4。分子中的C=O与C=S基团处在C(3)-N-C(4)键的同侧, 为顺式结构。用PM3分子轨道方法研究该化合物的电子结构、电荷和键序分布、前线轨道性质。     

Synthesis of potential metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-Iodophenyl)-8-alkyl-8-azabicyclo[3.2.1]octane-2-carboxylate

The synthesis of potential hydroxy metabolites of the brain imaging agents methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate and methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-(3-fluoropropyl)-8-azabicyclo[3.2.1]octane-2-carboxylate are reported. The nitration of iodophenyltropanes 1 or 2 with nitronium tetrafluoroborate afforded the nitro compounds 3 or 4 which were reduced with iron powder to the corresponding amino compounds 5 and 6 . The final hydroxylated products 7 and 8 were obtained via a modified Sandmeyer reaction.     

Synthesis and potent cytotoxic activity of 8- and 9-anilinophenanthridine-7,10-diones

A series of 8-anilino and 9-anilinophenanthridine-7,10-diones was prepared and screened against various cancer cell lines to measure anti-proliferative activity. The compounds tested display potent cytotoxic activity in the micromolar and sub-micromolar range. These compounds are promising new leads for developing anticancer compounds.