M. Stud

Heterocyclic N-glycosides—V : Synthesis of unsaturated N-glycosides from 6-chloropurine and derivatives of d-xylal and l-arabinal. A conformational NMR study

Abstract The acid-catalyzed reaction of 6-chloropurine with 3,4-di-O-acetyl- d -xylal yielded four compounds. The main products were shown to be the corresponding 6-chloro-9-(4′-O-acetyl-2′,3′-dideoxy-α and β- d -glycero-pent-2′-enosyl)purine, and 1,2,3-trideoxy-4-O-acetyl-3-(6′-chloro-9′-purinyl) d -threo- pent-1-enopyranose. On the other hand reaction of 6-chloropurine with 3,4-di-O-acetyl- l -arabinal yielded, in addition to the enantiomers of the above compounds, 6-chloro-9-(3′,4′-di-O-acetyl-2′-deoxy- α- and β- l -erythro-pentopyranosyl)purine. A NMR study of these compounds showed that the previous reported assignations for 6-chloro-9-(3′,4′-di-O-acetyl-2′-deoxy-α- and β- d -erythro-pentopyranosyl) purine are in error. The conformations of all compounds obtained, as determined from their NMR parameters, are discussed.

Reactivity of 1,1-disubstituted indazol-3-ylio oxides: synthesis of some substituted indazolols and indazolinones

Some aspects of the reactivity of 1,1-disubstituted indazol-3-ylio oxides (indazolol-derived aminimides) have been studied. Treatment of these compounds with hydrochloric acid gave the corresponding indazolium salts which, through elimination of an alkyl chloride, afforded 1-substituted indazol3-ols. Treatment with alkoxides yielded N′,N′-disubstituted 2-alkoxybenzohydrazides or 1-substituted indazolols (aryl or alkyl ether elimination products, respectively). The thermal rearrangements of indazolylio oxides gave 1-substituted indazolols. 1,2-disubstituted indazolinones and 3-alkoxy-1alkylindazoles depending on the substituents. The direct cyclization of N′,N′-disubstituted 2-chloro5-nitrobenzohydrazides to indazole derivatives as well as the reactivity of some of the above mentioned compounds are also reported.

New routes for the synthesis of pyrrolo-[3,2-d]- and -[2,3-d]-pyrimidine systems starting from a common pyrrole derivative

New routes for the synthesis of pyrrolo-[3,2-d]- and -[2,3-d]-pyrimidines from a common 2,3-dicarboxypyrrole derivative are described. The common starting material, 3-ethoxycarbonyl-2-carboxy-4-methylpyrrole (1) is conveniently functionalized to give 2- or 3-azidocarbonylpyrroles (4), (17), and (22) which on Curtius rearrangement followed by treatment with ammonia or amines give the pyrrolylurea (6a) or its derivatives (6b–d), or (23). These, in basic medium cyclise to 7-methylpyrrolo[3,2-d]pyrimidine-2,4-diones (7a), its 3-substituted derivatives (7b–d), or to 5-methylpyrrolo[2,3-d]pyrimidine-2,4-diones (19).

Heterocyclic N-glycosyl derivatives—XIII: Reaction of 6-chloropurine and benzotriazoles with acetylated glycals

Abstract Acid-catalysed reactions of tri-O-acetyl- D -glucal with benzotriazole, 5,6-dimethylbenzotriazole, 5,6-dichlorobenzotriazole and 6-chloropurine have been found to give anomeric mixtures of the corresponding 2′,3′-unsaturated N-glycosyl derivatives with the α-anomers preponderating. When tri-O-acetyl- D -galactal was used the 3′,4′,6′-tri-O-acetyl-α- and β- D -lyxo-hexopyranosyl nucleoside analogs were obtained. The conformation and anomeric configuration of all the N-glycosyl compounds obtained were assigned by NMR studies.

Heterocyclic N-glycosyl derivatives—XI: Synthesis and NMR conformational study of N-glycosyl benzotriazoles from acetylated glycals

Abstract Acid-catalyzed reaction of benzotriazole, 5,6-dimethylbenzotriazole and 5,6-dichlorobenzotriazole with di-O-acetyl- d -xylal in ethyl acetate afforded 1-(4′-O-acetyl-2′,3′-dideoxy- d - glycero -pent-2′-enopyranosyl)benzotriazole derivatives and small amounts of 1,2,3-trideoxy-4-O-acetyl-3-(benzotriazolyl)- d - threo -pent-1-enopyranose derivatives. The reactions using di-O-acetyl- l -arabinal led to the formation of the corresponding 1- and 2-(3′,4′-di-O-acetyl-2′-deoxy- l - erythro -pentopyranosyl)benzotriazole derivatives. In addition the enantiomers of the above 2′, 3′-unsaturated N-glycosyl compounds were also obtained. The configurations and conformations of the products obtained were determined by NMR spectroscopy.

Prediction of Drug Half‐life Values of Antihistamines Based on the CODES/Neural Network Model

The CODES/neural network model has been successfully applied to the prediction of pharmacokinetic properties of therapeutical compounds. The output of CODES, a graphical module based on the Gestalt isomorphism, is proved to be a valuable tool in the design of a neural network model able to predict the half-life values of antihistamines. Additionally, the generated models are able to classify these drugs in their corresponding therapeutic category (H1 or H2 receptor antagonists).

Stable indazol-3-ylio oxides by intramolecular cyclization of N',N'-disubstituted 2-halobenzohydrazides

Abstract The cyclization of N′,N′-disubstituted 2-halobenzohydrazides to indazol-3-ylio oxides has been explored. Some typical reactions of these previously unknown betaines are also reported.

Reactivity of malononitrile towards sulphamide and N-substituted sulphamides: synthesis and hydrolysis reactions of 3,5-diamino-1,2,6-thiadiazine 1,1-dioxides

The reaction of sulphamide and N-substituted sulphamides with malononitrile under acid catalysis gave respectively 3,5-diamino- 4H- or 2H-1,2,6-thiadiazine 1,1-dioxides (1) and (3a–d). Mild acid hydrolysis of the latter afforded 5-amino-2H-1,2,6-thiadiazin-3(4H)-one 1,1-dioxides (5a–d) in excellent yield. No convenient methods for the preparation of all these compounds had previously been reported.

Synthesis and intramolecular cyclization of bisthiadiazinylmethane derivatives

Abstract Bisthiadiazinylmethane derivatives obtained from 1,2,6-thiadiazine 1,1-dioxides and formaldehyde, undergo unusual intramolecular cyclizations to thiadiazino [4,3-g] [2,1,3] benzothiadiazine tetraoxides. The structures of the newly synthesized compounds are discussed on the basis of 1H and 13C-NMR data and X-ray analysis.

APPROACHES TO 1,1-DISUBSTITUTED CINNOLIN-3-YLIO OXIDES: SYNTHESIS AND REACTIVITY OF A NEW CLASS OF HETEROCYCLIC BETAINES

The cinnolin-3-ylio oxides 6, a new class of heterocyclic aminimide, can be prepared by intramolecular cyclization of the N′,N′-disubstituted (2-fluorophenyl)acetohydrazides 5. Attempts to prepare these betaines by an alternative route, namely cyclization of the nitrenes expected from the thermal decomposition of (2-dialkylaminophenyl)acetyl azides 11, failed, Curtius rearrangement-derived compounds being the main products isolated from these processes. Hydrochlorides of the cinnolin-3-ylio oxides 6 undergo alkyl halide elimination to yield the 1-(ω-chloroalkyl)cinnolin-3-ols 19a,b or 1-methylcinnolin-3-ol 21. Oxidation of the latter to the 3-hydroxycinnolin-4-one 22, its methylation to the corresponding N 1 ,O- 23 and N 1 ,N 2 -dimethyl 24 derivatives as well as the cyclization of 1-(5-chloropentyl)cinnolin-3-ol 19a to the diazepino[1,2-a]cinnolinone 20 are also reported.