1-Methylgalanthamine Derivatives

Summary. The syntheses of pharmaceutically interesting galanthamine analogues bearing a methyl group at the C1 position are described.     

Derivatives of 1-aryl-5-methoxyindoles

By fusion with potassium hydroxide, derivatives of 1-aryl-3-ethoxycarbonyl-5-methoxy-2-methylindole are converted into the corresponding indole-3-carboxylic acids. When the indole-3-carboxylic acids are heated to their melting points, they are readily converted into derivatives of 1-arylindoles with unsubstituted -positions. A similar cycle of conversions has been carried out for 3-ethoxycarbonyl-5-methoxy-2-methyl-1-phenylbenzoindole. The reactions of derivatives of 1-aryl-5-methoxy-2-methylindoles with formaldehyde and dimethylamine hydrochloride gives Mannich bases.     

1-羟基-1-甲基-3-氧-异吲哚类衍生物的合成

邻苯二甲酸酐与丙二酸反应合成邻乙酰基苯甲酸(1);1经酰氯化反应得邻乙酰基苯甲酰氯(2);2与伯胺反应合成了3个1-羟基-1-甲基-3-氧-异吲哚化合物,总收率65.0%～76.8%,其结构经1H NMR, 13C NMR, IR和MS表征.     

Derivatives of 1-hydroxytetrazole-5-carboxylic acid

Conclusions We have developed a method for obtaining ethyl 1-hydroxytetrazole-5-carboxylate from ethoxycarbonylchloroaldoxime. Various derivatives of 1-hydroxytetrazole-5-earboxylic acid have been obtained.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2540–2543, November, 1987.     

Synthesis of New 1-Adamantanecarboxylic Acid Derivatives

Reactions of 1-adamantanecarbonyl chloride with functionally substituted alcohols, phenols, amines, thiols, and ketone oximes gave hitherto unknown 1-adamantanecarboxylic acid esters, amides, and thio esters, including those containing a peroxide group.     

Spectroscopic Investigation of Amylose 1-Phenylflavazole Derivatives

Amylose 1-phenylflavazole has been prepared and its ultraviolet absorption spectrum determined in DMSO solution. Five samples of amylose 1-phenylflavazole were prepared in which different times of reaction were used. Although the polymer was hydrolyzed during the reaction, the molar extinction coefficient of each sample was equal to that of maltose 1-phenylflavazole, and so the number-average degree of polymerization of the initial sample of amylose can be determined by extrapolation. This value was in close agreement with that obtained by viscometry.     

1-苯甲酰-2-苯磺酰肼类化合物的合成

以苯磺酰肼为原料,在低温下滴加苯甲酰氯,方便地合成了7个1-苯甲酰-2-苯磺酰肼类化合物,收率40.3%～75.8%。其结构经1H NMR表征。     

Stereoselective Synthesis of 1-Aminocyclopropanecarboxylic Acid Derivatives via Ylide Cyclopropanation of Dehydroamino Acid Derivatives

1‐Aminocyclopropanecarboxylic acid derivatives are synthesized from readily available dehydroamino acid derivatives via sulfur ylide. A range of different ylides are employed and the corresponding aminocyclopropanes are afforded with reasonable diastereoselection in good yields.     

Synthesis of Adamantane Derivatives. XIX. Aluminum Chloride-Catalyzed Reactions of N-Chloro-1-Adamantylamine Derivatives

The chemical behavior of 1-adamantylnitrenium ion seems to be not known much compared to 1-adamantylcarbinyl cation,² though one example of the rearrangement of 1-adamantylnitrenium ion to 4-azahomoacamantyl ion has been reported recently by Kovacic et al in the reaction of 1-M,N-dichloroaminoadamantane with aluminum chloride.³ From our interest in the reactivity and rearrangement aptitude of 1-adamantylnitrenium ion, we investigated the reactions of various N-substituted N-chloro-1-adamantylamine derivatives with aluminum chloride. This communication deals with the preliminary results which indicated that the reactions of 1-adamantylnitrenium ion are much affected by the N-substituents and also by the solvents used.     

Derivatives of 1-azabicyelo[4.3.1]decane

1-Azabicyclo[4.3.1]decan-3-one has been synthesized via Dieckmann condensation and converted to the corresponding hydroxy and chloro derivatives.     

新型1,5-二芳基四氢吡咯烷衍生物的合成

以芳基取代环丙烷为原料,与1,3,5-三嗪烷衍生物进行[3+2]环加成反应,高效合成了一系列1,5-二芳基四氢吡咯烷衍生物（3a~3h,其中化合物3f, 3g, 3h为新化合物）,收率70%~97%,其结构经¹H NMR, ¹³C NMR和HR-MS(ESI)表征。     

A Facile Synthesis of N-Protected 1-Aminoalkylphosphonamidate Derivatives

N-protected 1-amino-alkylphosphonamidates were synthesized using one-pot reactions of benzyl carbamate, aldehydes and alkoxyphosphine dichlorides and then with amines in the presence of triethylamine.     

手性1-芳基四氢异喹啉类衍生物的合成新方法

以1,2,3,4-四氢异喹啉为原料,先依次与二碳酸二叔丁酯、亚氯酸钠反应得到N-Boc-1,2,3,4-四氢-1-异喹啉酮,再和芳基格氏试剂反应得到分子内不对称还原胺化反应的底物,最后以ax-Josiphos为手性配体,[Ir(COD)Cl]₂为金属前体,在Ti(OⁱPr)₄和40%HBr溶液组成的催化体系中合成了8个手性1-芳基四氢异喹啉类化合物,其结构经¹H NMR和¹³C NMR表征。该路线提供了一种以廉价1,2,3,4-四氢异喹啉为原料高效合成手性1-芳基四氢异喹啉类衍生物的新方法,为索利那新等药物的合成提供了新路径。      

Novel Disulfiram Derivatives as ALDH1a1-Selective Inhibitors

Aldehyde dehydrogenase-1a1 (ALDH1a1), the enzyme responsible for the oxidation of retinal into retinoic acid, represents a key therapeutic target for the treatment of debilitating disorders such as cancer, obesity, and inflammation. Drugs that can inhibit ALDH1a1 include disulfiram, an FDA-approved drug to treat chronic alcoholism. Disulfiram, by carbamylation of the catalytic cysteines, irreversibly inhibits ALDH1a1 and ALDH2. The latter is the isozyme responsible for important physiological processes such as the second stage of alcohol metabolism. Given the fact that ALDH1a1 has a larger substrate tunnel than that in ALDH2, replacing disulfiram ethyl groups with larger motifs will yield selective ALDH1a1 inhibitors. We report herein the synthesis of new inhibitors of ALDH1a1 where (hetero)aromatic rings were introduced into the structure of disulfiram. Most of the developed compounds retained the anti-ALDH1a1 activity of disulfiram; however, they were completely devoid of inhibitory activity against ALDH2.     

Synthesis and Properties of Aminomethoxy Derivatives of 1-Hexylthioheptane

A series of new aminomethoxy derivatives of 1-hexylthioheptane have been synthesized via the Mannich reaction based on 1-hexylthioheptan-2-ol, secondary aliphatic and cyclic amines. Antimicrobial activity of the synthesized compounds has been studied in relation to gram-negative (E. coli and Pseudomonas aeruginosa), gram-positive (Staphylococcus aureus), sporogenous (anthracoid) bacteria, and yeast-like Candida fungi.

     

1-磺酰基-3,5-二氨基-1H-吡唑-4-腈的合成及其生物活性

除草剂;1-磺酰基-3;5-二氨基-1H-吡唑-4-腈的合成及其生物活性     

Functiaonalization of 2-(1-Cyclohexen-1-yl)aniline Derivatives

The reaction of 2-(1-cyclohexen-1-yl)aniline and -6-methylaniline with phthalic anhydride has afforded 2-(2-cyclohex-1-en-1-ylphenyl)- and 2-(2-cyclohex-1-en-1-ylphenyl)-6-methylphenyl)-1H-isoindole-1,3(2H)-diones. The reaction of the obtained isoindole-1,3-diones with bromine in dichloromethane in the presence of sodium bicarbonate has led to the formation of the product of pseudo-allylic halogenation. Replacement of the halogen atom by methoxy group has been performed by keeping 2-[2-(6-bromocyclohex-1-en-1-ylphenyl)-6-methylphenyl)]-1H-isoindole-1,3(2H)-dione in a methanolic solution in the presence of NaHCO₃. The reaction of 2-(2-cyclohex-1-en-1-yl-6-methylphenyl)-1H-isoindole-1,3(2H)-dione with molecular bromine in the presence of methanol has given a co-halogenation product, whereas the dibromination product has been obtained in the presence of octyl alcohol.