New Acyclic Dimers of Cholic Acid with Oxamide and Hydrazide Spacers

Summary. Three new acyclic dimers of cholic acid with oxamide and isomeric hydrazide (N,N′-diacylhydrazine) spacers were obtained. The oxamide spacers bind two identical steroidal subunits through position 3 (head-to-head dimer) or position 23 (tail-to-tail dimer). In the case of a third dimer the hydrazine moiety binds two molecules of cholic acid through position 24 (tail-to-tail dimer).     

Efficient Synthesis of Functionalized 2H-Thiopyrans via Hetero-Diels-Alder Reactions of an Enaminothione with Electrophilic Olefins

Summary.  The hetero-Diels-Alder reaction of 3-dimethylamino-1-(2-thienyl)-2-propene-1-thione (diene) with substituted β-nitrostyrenes, as well as maleic and fumaric acids (dienophiles) yielded 3,4-dihydro-2H-thiopyran derivatives. The treatment of some of those cycloadducts with acetic acid caused elimination of dimethylamine, affording stable 2H-thiopyrans. A reaction of the diene with maleic anhydride furnished a cycloadduct which underwent spontaneous rearrangement to form an N,N-dimethylamide derivative. Cycloadditions of the diene to maleimide, N-phenylmaleimide, maleic acid monoanilide, diethyl maleate, fumarate, and butenolide carried out in the presence of acetic anhydride were followed by elimination of dimethylamine under formation of stable 2H-thiopyran derivatives. Received February 19, 2001. Accepted (revised) March 12, 2001     

吲哚-2-甲酸和(S)-吲哚啉-2-甲酸的合成和相互转化研究进展

吲哚-2-甲酸和(S)-吲哚啉-2-甲酸均是具有生物活性的天然产物和众多降压药的特征结构片段,报道了它们的合成及其相互转化研究进展.吲哚啉-2-甲酸可由吲哚-2-甲酸还原制得,其中(S)-吲哚啉-2-甲酸可由外消旋体拆分或通过不对称合成法制备,其中"手性源法"作为一种新出现的方法具有较好的前景.吲哚-2-甲酸可由Fischer吲哚合成法制备,或通过取代苯胺或苯甲醛制备,也可通过吲哚啉衍生物氧化脱氢制备,其中Fischer合成法仍具有较强的竞争力.     

Synthesis and Hemolytic Properties of Glycyrrhetic Acid Glycosides

Summary.  The synthesis of monodesmosidic glycyrrhetic acid disaccharides via its diphenylmethyl ester is described. Their hemolytic activity is lower as compared to the corresponding oleanolic aciddisaccharides. The influence of the structure of the aglycon on the hemolytic activity is discussed. Received November 18, 1999. Accepted November 30, 1999     

新型2-取代嘧啶酮-5-甲酰苄胺的合成及抗肿瘤生物活性试验

以丙二酸单甲酯单甲酰氯、苄胺为起始原料,经与DMF-DMA反应后形成的关键中间体分别与胍或脒缩合关环,合成了2-取代嘧啶酮-5-甲酰苄胺化合物6和7。产物经1HNMR、13CNMR、MS、HRMS进行了结构表征。初步的生物活性试验显示化合物6和7具有抗肿瘤活性。     

On The Chemistry of Cinnoline IV [1]. Synthesis and Reactions of (4-Aminocinnolin-3-yl)-aryl-methanones

Summary.  The synthesis of a series of disubstituted (4-aminocinnolin-3-yl)-aryl-methanones from aryl-hydrazonomalononitrile in a one-step procedure is described. Cyclocondensation of (4-amino-6,8-dimethyl-cinnolin-3-yl)-phenyl-methanone with malononitrile, diethylmalonate, and dimethylacetamide-dimethylacetal gave the corresponding pyrido[3,2-c]cinnoline derivatives. Treatment of (4-amino-6,8-dimethyl-cinnolin-3-yl)-phenyl-methanone with triethyl-orthoacetate under reflux readily afforded the corresponding imidoester which underwent cyclization to a pyrido[3,2-c]cinnoline derivative. This starting compound could also be annelated to the corresponding 1,2-dihydro-4-aryl-2-oxo-pyrido[3,2-c]cinnoline derivatives via the (4-acetamidocinnolin-3-yl)-aryl-methanones. Chemical and spectroscopic evidences for the structures of the new compounds are presented. The effect of three of the compounds against sixty cancer types was tested. Received November 27, 2000. Accepted December 4, 2000     

Spectroscopic Study of the Conformation of 2-Anilino-2-ethoxy-3-oxothiobutyric Acid Anilides

Summary.  An NMR study of the equilibriummixture of two conformers of 2-anilino-2-ethoxy-3-oxothiobutyric acid anilides 3 allows to estimate their population ratio in solvents of increasing polarity. X-Ray analysis as well as IR spectroscopy confirmed that the conformer present in the solid state is stabilized by two hydrogen bonds. The structural basis of the second conformer observed in solution is the 1,4-type S⋯O interaction between the sulfur of the thioanilide moiety and the oxygen of the ethoxy group with a distance of 2.878 ?. Received May 29, 2000. Accepted (revised) July 14, 2000     

Synthesis and Hemolytic Properties of Lactosides of Glycyrrhetic Acid Derivatives

Summary.  The partial synthesis of lactosides of glycyrrhetic acid, its 11-deoxo and 18α-derivatives, and their methyl esters is described. The influence of the aglycon structure on the hemolytic properties of the title compounds is discussed and compared with those of oleanolic acid derivatives. Furthermore, we describe an optimized preparation of 18α-glycyrrhetic acid. Received August 20, 2001. Accepted September 3, 2001     

On Condensation Reactions of Aceanthrene Quinone: Novel Heterocycles

Summary.  It was found that aceanthrene quinone can be condensed with ethylenediamine, 1,2-diaminobenzene, 4-nitro-1,2-diaminobenzene, 1,2-diaminoanthrene quinone, and 4,5,6-triaminopyrimidine derivatives to give aceanthryleno[1,2-b]pyrazine and aceanthryleno[1,2-g]pteridine derivatives. Condensation of aceanthrene quinone with 2-aminoguanidine, semicarbazide, and thiosemicarbazide yielded aceanthryleno[1,2-e]triazines, condensation with 6-hydrazinopyrimidine derivatives gave 3,4-aceanthrylenopyrimido[4,5-c]pyridazines. Reaction of aceanthrene quinone with 2-cyanoethanoic acid hydrazide afforded 10,11-dihydro-10-oxo-aceanthryleno[1,2-c]pyridazine-9-carbonitrile. Treatment of aceanthrene quinone with malononitrile and hydrazine hydrate resulted in 10-aminoaceanthryleno[1,2-c]pyridazine-9-carbonitrile. The antibacterial effects of the prepared compounds were tested. Three of the compounds were tested against 60 cancer types. Received May 6, 2001. Accepted June 5, 2001     

Regioselectivity in the Reactions of Bis-hydrazonoyl Halides with Pyrimidine-2-thiones

Summary.  Bis-hydrazonoyl chlorides react regioselectively with pyrimidine-2-thiones, which contain a masked thiourea residue, to give the hitherto unknown annelated 2,3-bis-arylhydrazono-thiazoles and 3,3′-bis-1,2,4-triazoles. Reaction of bis-hydrazonoyl chlorides with 2-methylthio derivatives gave only 3,3′-bis-1,2,4-triazoles. Received October 4, 2000. Accepted (revised) December 20, 2000     

Sulfuric Acid: A Mild Catalyst for the Regioselective Synthesis of 2-Substituted [1,2,4]Triazolo[5,1-b][1,3]thiazin-7-ones

Summary.  A facile and regioselective synthesis of 2-substituted [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by action of sulfuric acid on (4H-[1,2,4]triazol-3-ylsulfanyl)-acrylic acids is described. Received January 23, 2001. Accepted (revised) May 7, 2001     

2-Phenyl-4-quinolinone Alkaloids from Casimiroa edulis Llave et Lex (Rutaceae)

Summary.  Three new 4-quinolinone alkaloids (5,6-dimethoxy-2-(3-methoxyphenyl)-1H-quinolin-4-one, 5,6-dimethoxy-2-(3,4-dimethoxyphenyl)-1H-quinolin-4-one, 5,6-dimethoxy-2-(2,5,6-trimethoxyphenyl)-1H-quinolin-4-one) were isolated from the leaves of Casimiroa edulis Llave et Lex (Rutaceae) cultivated in Egypt. Their structures were determined by UV/Vis, IR, ¹H and ¹³C NMR, and EI mass spectroscopy. The alkaloids were also detected in the kernels of the seeds. Received May 28, 2001. Accepted (revised) July 24, 2001     

Synthesis of C-8 Deuterated Glycosides of 3-Deoxy-D-manno-oct-2-ulosonic Acid (Kdo) Related to Chlamydial Lipopolysaccharides

Summary.  Methyl glycosides of Kdo and a (2→8)-linked Kdo disaccharide were prepared which contain a deuterium label at C-8 of the reducing unit. The label was introduced in fair diastereoselectivity upon reduction of an aldehyde group using a chiral borane complex derived from N-benzyloxycarbonyl-(S)-proline which produced the 8-(S)-deuterated derivative as the major isomer. Further coupling with a Kdo bromide gave the α-(2→8)-linked disaccharide in good yield. The deprotected disaccharide serves as a model for NMR spectroscopic studies on the side chain conformation of a carbohydrate epitope from the bacterial pathogen Chlamydia. Received September 17, 2001. Accepted October 17, 2001     

Asymmetric Synthesis of a Structurally Simplified Analogue of the Antibiotic Heptelidic Acid

Summary.  A structurally simplified analogue of the antibiotic (+)-heptelidic acid was synthesized in ten steps with an overall yield of 9%. Key step was a conjugate addition of a silyl protected vinylcuprate to an asymmetrically shielded enoate, which gave an adduct as a single diastereomer. Transesterification in the presence of triethylamine allowed a selective cleavage of the chiral auxiliary and afforded an enantiomerically pure methyl ester. This easily enolizable β-ketoester was transformed to the trans configurated methylene derivative using a four-step reaction sequence. Finally, the desired epoxylactone was accessible from the methylene derivative by lactone ring formation and successive oxidation in four steps. Received July 13, 2001. Accepted August 16, 2001     

Invited Review Chemoenzymatic Synthesis of Lipidated Peptides

Summary.  This review highlights the use of enzymatic protecting group techniques in the synthesis of lipidated peptides. Lipidated proteins play key roles in signal transduction processes. Moreover, structurally well-defined peptides containing the characteristic linkage region of the peptide backbone with the lipid can provide valuable tools for the study of biological phenomena associated with these protein conjugates. The multifunctionality and pronounced lability towards acids and bases of such compounds render their synthesis a formidable challenge. However, the recent development of enzymatic protection groups provides an efficient access to these sensitive and biologically relevant peptide conjugates under particular mild conditions and with high selectivity. Received December 12, 1999. Accepted January 26, 2000     

含2-三氟甲基苯并咪唑杂环化合物的合成

以2-三氟甲基苯并咪唑-1-乙酰肼为原料,在不同条件下合成了一系列新的1,3,4-(丰刀女)二唑啉及均三唑并噻二唑衍生物,所得化合物的结构经元素分析,IR,¹HNMR和MS确证,并对其波谱性质进行了讨论.     

Synthesis and Structure of O-silylated 2-Polyfluoroacyl-cycloalkanones

Summary.  2-Acyl-cycloalkanones containing polyfluoroalkyl groups react with dichlorodimethylsilane to form the corresponding heterocyclic bis-enol derivatives. The reaction of 2-polyfluoroacyl-cycloalkanones with chlorotrimethylsilane leads to mixtures of the corresponding (Z)-configured O-silylethers. The silatropy process in this case is slow on the NMR time scale. Received February 26, 2001. Accepted (revised) March 27, 2001     

Synthesis of the Racemates of the b-Carboline Alkaloid Chrysotricine and its Diastereomer

Summary.  The racemates of the rubiacea alkaloid Chrysotricine (1) and its diastereomer are synthesized from the isomeric mixture of linalyl oxides 3 and tryptamine in six steps, followed by separation of the diastereomers. Received November 11, 1999. Accepted November 25, 1999     

Formation of Peracetic Acid upon Aging of Perborate in Acetic Acid. Kinetics of the Oxidation of S-Phenylmercaptoacetic Acids

Summary.  Upon aging, perborate in glacial acetic acid generates peracetic acid and thus oxidizes S-phenylmercaptoacetic acid rapidly. Perborate dissolved in ethylene glycol, however, does not show the aging effect, and the corresponding oxidation proceeds smoothly. The oxidation is of second order and not acid catalyzed. Boric acid and borate do not influence the oxidation. In the smooth oxidation, is the reactive species. The oxidation of some para-substituted S-phenylmercaptoacetic acids conforms to the Exner relationship, indicating operation of a common mechanism. Also, the oxidation obeys the Hammett equation with a negative reaction constant. However, the oxidation of p-nitro-S-phenylmercaptoacetic acid follows a different kinetic pathway. Received March 15, 2000. Accepted (revised) May 3, 2000