Pyrolysis of 3-hydroxy-2-arylhydrazonoalkanoic acid derivatives

1,2-Diaza-1,3-butadienes have been obtained from readily available 3-hydroxy-2-arylhydrazonopropanoates under various reaction conditions including pyrolysis, dehydration under Mitsunobu conditions or with acetic anhydride or acetic acid. According to their method of synthesis these 1,2-diaza-1,3-butadienes underwent subsequent reactions to give interesting products, and in the presence of proper dienophiles gave the corresponding cycloaddition products. Also, a new approach to pyrazole-3-carboxylic acid derivatives was discovered during an attempt to dehydrate 3-hydroxy-2-arylhydrazonobutanoic esters.     

A novel synthesis of 3-cyanoindoles and a new route to indole-3-carboxylic acid derivatives

2-Alkyl-3-cyanoindoles are obtained when 1-alkylmethyl-2-chloro-(or 2-phenylsulfonyl)-3-phenylsulfonylindoles are reacted with excess azide ion (90°/DMF). The reaction is considered to occur by a fragmentation recombination process in which the Schiff's base $\text{12}$ is of central importance. This proposal is supported by the formation of 2-substituted indole-3-carboxylates $\text{17}$ from aldehydes and the α-phenylsulfonyl-$\text{o}$-aminophenylacetic acid ester derivative $\text{16}$.     

Syntheses and crystal structures of diorganotin (IV) moieties with 3-hydroxy-2-pyridinecarboxylic acid

A series of new organotin (IV) complexes with 3-hydroxy-2-pyridinecarboxylic acid (3-OH-2-picH) of two types: R₂SnCl(3-OH-2-pic) (I) (R = Me 1, n-Bu 2, Ph 3, PhCH₂4) and R₂ Sn(3-OH-2-pic)₂ (II) (R = Me 5, n-Bu 6, Ph 7, PhCH₂8)have been synthesized by reactions of diorganotin (IV) dichloride with 3-hydroxy-2-pyridinecarboxylic acid in the presence of sodium ethoxide. All complexes are characterized by elemental analyses, IR spectra and NMR spectra analyses. Among them, complexes 1, 5, 6 and 7 are also characterized by X-ray crystallography diffraction analyses. Complex 1 is a 1D polymeric chain with six-coordinate tin atoms and the packing of complex 1 is stabilized by the C-H?Cl intermolecular weak interactions, thus a 2D network of 1 is formed. Complex 5 is also a 1D polymeric chain with seven-coordinate tin atoms. Complex 6 is a zigzag polymeric chain linked by Sn?O intermolecular weak interactions. Complex 7 is a monomeric complex with distorted octahedral geometry.     

Conformationally constrained serine analogues: synthesis of new 2-amino-3-hydroxynorbornanecarboxylic acid derivatives

A synthesis of the new oxazolone 2, functionalized with the ethoxycarbonyloxy group on methylenic carbon, is presented, starting from 4-hydroxymethylenoxazolone 1 and ethyl chlorocarbonate. Oxazolone 2 was reacted with cyclopentadiene in the presence of EtAlCl(2), giving the two diastereoisomeric cycloadducts exo-3 and endo-3 in a 70:30 ratio. Selective hydrolysis of the lactone ring (THF, HCl) gave the corresponding acids 5 and 6 which were transformed into hydroxyacid derivatives 7 and 8, respectively, operating in an ethanolic solution of Me(2)NH. The new 3-hydroxy-2-aminonorbornane-2-carboxylic acids 11 and 12, in which the serine skeleton is included, were obtained by reduction of acids 5 and 6 to derivatives 9 and 10 and a subsequent hydrolysis with HCl.     

A new stereoselective synthesis of 2-amino-4,5-dihydrothiophene-3-carbonitrile derivatives

A new stereoselective method for the synthesis of trans-isomers of 2-amino-4-aryl-5-benzoyl-4,5-dihydrothiophene-3-carbonitriles was proposed. The method involves base-catalyzed reactions of phenacyl thiocyanate with 3-(het)aryl-2-cyanoprop-2-enethioamides. (4R,5S/4S,5R)-2-Amino-5-benzoyl-4-(2-chlorophenyl)-4,5-ihydrothiophene-3-carbonitrile was structurally characterized by X-ray diffraction analysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1379–1383, July, 2007.     

Asymmetric synthesis of 2-amino-3-hydroxynorbornene-2-carboxylic acid derivatives

The enantioselective synthesis of 2-amino-3-hydroxynorbornene-2-carboxylic acid derivatives (5) was studied using the Diels-Alder reaction between cyclopentadiene and different dienophiles, i.e., alkyl 5-oxo-2-phenyloxazol-4-methylenecarbonates (1) or 2-benzoylamino-3-alkoxycarbonyloxy-acrylates (12), operating with different Lewis acids and both with thermal and with ultrasound conditions. The enantioselective synthesis of the exo/endo compounds 5c,d and 5'c,d was achieved starting from the chiral menthyl acrylates 12b,c using Mg(ClO(4))(2) as the catalyst and ultrasound. The cycloadducts were obtained in very good yield, in mild conditions, in short time, and in good diastereomeric excess (exo, 80%; endo, 87%). Finally, the use of alkylidene-oxazolones or acrylates and EtAlCl(2) or Mg(ClO(4))(2) as the catalyst allowed control of the cycloaddition reaction in favor of the exo or endo products.     

New route to N-aryl and N-heteroaryl derivatives of 4-hydroxy-3-quinolinecarboxamides

The synthesis of N-aryl and N-heteroaryl substituted 4-hydroxy-3-quinolinecarboxamides 1 is described. The attack of dianions 12 of N-aryl substituted acetamides on the C-4 carbonyl of 4H-3,1-benzoxazin-4-ones 11 gave rise to ketoamides 13 , which smoothly cyclised in the presence of bases to afford quinolinecarboxamides 1 . By this method, a large number of 2-substituted 4-hydroxyquinolinecarboxamides can be prepared.     

A cyclopropenone route to new pyrrolizidine derivatives

New pyrrolizidine derivatives 6 and 7 were prepared from the 1, 5-dihydro-2H-pyrrol-2-one 3a via an acidic intramolecular aldol condensation in 16% and 42% yields, respectively. Compound 6 was obtained by dehydration of 7 with p-toluenessulfonic acid in 67% yield.     

A new route to 7-deazaguanine derivatives

The Synthesis of 2-amino-4,6-dichloro-5-(2,2-diethoxyethyl) pyrimidine $\text{7}$ has been performed in four steps starting from guanidine and diethylallylmalonate. $\text{7}$ is a new key intermediate for the synthesis of 7-alkyl-2-amino-3,4-dihydro-7H-pyrrolo [2,3-d] pyrimidin-4-ones.     

Efficient syntheses of naturally occurring 3,4-dihydroxyprolines: Electrophile-mediated lactonization of 2-amino-3-hydroxy-4-pentenoic acid derivatives

Stereospecific conversion of β-hydroxyallylglycine derivatives into (2$\text{S}$, 3$\text{R}$, 4$\text{R}$) 1 and (2$\text{S}$, 3$\text{S}$, 4$\text{S}$) 2 $\text{via}$ halo- or mercuri-lactonization has been described.     

Pyrazoline derivatives: A convenient synthetic route to new pyrazolo-benzothia-(oxa) or diazepinone derivatives

New pyrazolo-[3,4-b]-[1,5]-benzoazepinone derivatives are reported. One pot reactions of 5-chloro-4-carboxy-1-phenyl (3-substituted) pyrazole derivatives with o-thioaminophenol, o-phenylenediamine, and o-aminophenol derivatives were realized. The influences of the polarizability of the heteroatoms on the reaction rates and chemical yields are discussed. © John Wiley & Sons, Inc.     

Evaluation of 2-methyl-3-hydroxy-4-pyridinecarboxylic acid as a possible chelating agent for iron and aluminium

In view of a possible application to Fe and Al chelation therapy, 2-methyl-3-hydroxy-4-pyridinecarboxylic acid (DT2) was synthesised, and its complex formation, electrochemical and cytotoxic properties were studied. The complexing properties of DT2 towards Fe(III) and Al(III) were investigated in aqueous 0.6 m (Na)Cl at 25 degrees C by means of potentiometric titrations, UV-vis spectrophotometry, and 1H NMR spectroscopy. DT2 is a triprotic acid (H3L+) having pKa1 = 0.47, pKa2 = 5.64 and pKa3 = 11.18. The metal-ligand complexes observed in solution and their corresponding stability constants (log beta values) are the following: FeLH (19.38), FeL (16.01), FeLH(-1) (12.28), FeL2H2 (37.29), FeL3H3 (53.41), FeL3H2 (47.99), FeL3H (41.21) and FeL3 (34.1); AlLH (17.43), AlL2H2 (33.74), AlL2H (27.6), AlL3H3 (48.72), AlL3H2 (42.67), AlL3H (35.8) and AlL3 (27.92). The complex formation between DT2 and Fe(II) was studied by UV-vis: the weak complex FeLH (log beta = 15.8) was detected. DT2 shows a lower complexation efficiency with Fe(III) and Al(III) than that of other available chelators, but higher than that of its non-methylated analogue 3-hydroxy-4-pyridinecarboxylic acid (DT0). The electrochemical behaviour of DT2 was investigated by means of cyclic voltammetry, indicating that the oxidation of the ligand proceeds through a two electron process with a CECE mechanism. Voltammetric curves suggest that the oxidation or the reduction of DT2 in vivo is unlikely. According to the thermodynamic data, also the Fe(III)-DT2 complexes do not undergo redox cycling at physiological pH. Amperometric titrations of solutions containing Fe(III) and DT2 at pH = 5 indicated the same Fe(III) : ligand stoichiometric ratio as calculated from potentiometric data. The toxicity of DT2 and of other simple hydroxypyridinecarboxylic acids was investigated in vitro and no cytotoxic activity was observed (IC50 > 0.1 mM) on cancer cell lines and also on primary human cells, following a three day exposure.     

A new route to fullerene substituted phenylalanine derivatives

A series of fullerene substituted phenylalanine derivatives have been prepared by the condensation of 1,2-(4'-oxocyclohexano)fullerene with ester or Boc protected (4-amino)phenylalanine, H(2)NC(6)H(4)CH(2)CH(COR(1))(NHCOR(2))(where R(1) = OMe, R(2) = Me; R(1) = OH, R(2) = Me, O(t)Bu). Conversion of the imine to the corresponding amine is achieved by di-acid catalyzed hydroboration. Reaction of the N-Ac amino ester with BBr(3) led to the formation of the parent amino acid, while the Boc-protected derivative readily undergoes coupling with NH(2)-Gly-OEt. The reduction of the imine is not accompanied by hydroboration of the fullerene cage.     

Asymmetric synthesis of 3-amino-2-hydroxy-4-phenylbutanoate

Asymmetric synthesis of 3-amino-2-hydroxy-4-phenylbutanoate, a key component of the natural product bestatin and HIV protease inhibitors of KNI-272 and R-87366, has been achieved from the stereoselective aldimine coupling reaction between 3-phenyl-2-aminopropanenitrile and (Z)-α-methoxy trimethylsilyl ketene acetal in the presence of Lewis acids.