Five-membered 2,3-dioxoheterocycles: XC. Reaction of 4,5-bis(methoxycarbonyl)-1H-pyrrole-2,3-diones with enaminoesters. crystal and molecular structure of 4-methyl 9-ethyl 7-benzyl-3-hydroxy-8-methyl-1-(4-methoxyphenyl)-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-4,9-dicarboxylate

1-Aryl-4,5-bis(methoxycarbonyl)-1H-pyrrole-2,3-diones react with ethyl 3-(benzylamino)but-2-enoate and ethyl 3-(benzylamino)-3-phenylacrylate giving 4-methyl 9-ethyl 1-aryl-7-benzyl-3-hydroxy-8-methyl- and 4-methyl 9-ethyl 1-aryl-7-benzyl-3-hydroxy-8-phenyl-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-4,9-dicarboxylates.     

Synthesis of 4,6-diaryl-1-benzyl-6-hydroxy-5,5-dimethyl-2-oxopiperidine-3-carbonitriles and their analogs via a modified Reformatsky reaction

Organozinc compounds obtained from 1-aryl-2-bromo-2-methylpropanone and zinc react with N-benzyl-3-aryl-2-cyanoacrylamides or N-[6-(2-cyano-1-oxo-3-phenylprop-2-enylamino)hexyl]-2-cyano-3-phenylacrylamide to give 4,6-diaryl-1-benzyl-6-hydroxy-5,5-dimethyl-2-oxopiperidine-3-carbonitriles or 1,6-bis(6-aryl-3-cyano-6-hydroxy-5,5-dimethyl-2-oxo-4-phenylpiperidyl)hexanes as a single isomer with trans-located piperidine hydrogen atoms.     

Regioselective 1,3-Dipolar Cycloaddition Reactions of Unsymmetrical Münchnones (1,3-Oxazolium-5-olates) with 2- and 3-Nitroindoles. A New Synthesis of Pyrrolo[3,4-b]indoles

The unsymmetrical mesoionic münchnones 13 (3-benzyl-2-methyl-4-phenyl-1,3-oxazolium-5-olate) and 14 (3-benzyl-4-methyl-2-phenyl-1,3-oxazolium-5-olate) react with the N-protected 2- and 3-nitroindoles 1 (ethyl 2-nitroindole-1-carboxylate), 6 (3-nitro-1-(phenylsulfonyl)indole), and 17 (ethyl 3-nitroindole-1-carboxylate) in refluxing THF to afford in good to excellent yields the pyrrolo[3,4-b]indoles 15 (2-benzyl-1-methyl-3-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 16 (2-benzyl-3-methyl-1-phenyl-4-carboethoxy-2,4-dihydropyrrolo[3,4-b]indole), 18 (2-benzyl-1-methyl-3-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole), and 19 (2-benzyl-3-methyl-1-phenyl-4-(phenylsulfonyl)-2,4-dihydropyrrolo[3,4-b]indole). In several cases the regiochemistry, which is opposite to that predicted by FMO theory, is very high and leads essentially to a single pyrrolo[3,4-b]indole; e.g., 6+13→19 in 74% yield.     

Synthesis and photochromic and fluorescence properties of 3-(1-benzyl-5-methoxy-2-methylindolyl)-4-thienyl-substituted furan(pyrrole)-2,5-diones

New nonsymmetrical dihetarylethenes, 3-(1-benzyl-5-methoxy-2-methyl-1H-indol-3-yl)-4-(3-thienyl)furan-2,5-dione and 1-alkyl- and (1-aryl)-3-(1-benzyl-5-methoxy-2-methyl-1H-indol-3-yl)-4-(3-thienyl)-1H-pyrrole-2,5-dione, exhibiting photochromic properties in solutions were synthesized. Noncyclic isomers of dihetarylethenes show fluorescence with quantum yields up to 0.13.     

Hydrazinolysis of Compounds Containing Oxazolidine Ring

We have studied hydrazinolysis of (4S,5S)-3-benzyl-4-hydroxymethyl-5-(4-nitrophenyl)oxazolidine, (1R,4S,5S)-1-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3,3,0]octane, and (1R,4S,5S)-1-benzyl-4-(4-nitrophenyl)-1-azonia-3,7-dioxabicyclo[3,3,0]octane. We have shown that neutral compounds are decomposed with opening of the oxazolidine ring, while quaternary ammonium salts react with hydrazine in several directions.     

Reactivity of allenoates toward aziridines: [3+2] and formal [3+2] cycloadditions

The reactivity of buta-2,3-dienoates toward aziridines is reported. Allenoates react as 2π-component in the [3+2] cycloaddition with the azomethine ylide generated from cis-1-benzyl-2-benzoyl-3-phenylaziridine affording 4-methylenepyrrolidines in a site-, regio-, and stereoselective fashion. Under conventional thermolysis, cis- and trans-2-benzoyl-1-cyclohexyl-3-phenylaziridines showed a different reactivity. These aziridines participate in formal [3+2] cycloadditions with allenes via C-N bond cleavage of the three-membered ring leading to functionalized pyrroles.     

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part 6: synthesis and incorporation into peptides of the first reported 2,3-dihydroxycyclopentanecarboxylic acid

Herein we report the intramolecular alkylation of nitronates of methyl-5-O-benzyl-3,6-deoxy-6-nitro-β-d-glucofuranoside and methyl-5-O-benzyl-3,6-deoxy-6-nitro-α-d-glucofuranoside into the corresponding 2-oxabicyclo[2.2.1]heptane derivatives. Similarly, methyl-3-O-benzyl-5-deoxy-5-nitromethyl-β-d-xylofuranoside and methyl-3-O-benzyl-5-deoxy-5-nitromethyl-α-d-xylofuranoside were cyclized to (1R,3R,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane and (1R,3S,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane, respectively. These 2-oxabicyclo[2.2.1]heptane derivatives were eventually transformed into enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-2,3-dihydroxycyclopentanecarboxylate and this novel β-amino acid was incorporated into peptides.     

Synthesis of New Heterocyclic Systems on the Basis of 7-Benzyl-3-chloro-1-(morpholin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthiridine-4-carbonitrile

Methods have been developed for the synthesis of new 8-amino-3-benzyl-5-(morpholin-4-yl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c][2,7]naphthyridine starting from 7-benzyl-3-chloro-1-(morpholin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carbonitrile. 8-Hydrazinyl-3-benzyl-5-(morpholin-4-yl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c][2,7]naphthyridine has been converted to isomeric pentacyclic structures with a triazole ring fused through the [c] side of the pyrimidine ring, and their Dimroth rearrangement has been accomplished in both acidic and basic media. New heterocyclic systems containing pyrrolo[1,2-a]pyrimidinone and pyrimido[1,2-a]azepinone fragments were obtained on the basis of the thieno-[2,3-c][2,7]naphthyridine derivative.     

New heterocyclic derivatives of trifluoroalanine

A new method of the synthesis of heterocyclic derivatives of trifluoroalanine based on the cyclocondensation of methyl trifluoropyruvate tert-butoxycarbonylimine with C,N- and N,N-binucleophiles, like Nsubstituted ureas, 1-benzyl-6-aminouracil, benzamidine, and 3-aminocrotononitrile, followed by hydrolysis of the resulting Boc-derivatives to 5-amino-5-trifluoromethylimidazolidine-2,4-diones, 5-amino-5-trifluoromethyl-1-benzyl-5,7-dihydropyrrolo[2,3-d]-pyrimidine-2,4,6-3H-trione, 4-amino-2-methyl-5-oxo-4-(trifluoromethyl)-4,5-dihydro-1H-pyrrole-3-carbonitrile, or 5-amino-5-trifluoromethyl-2-phenyl-3,5-dihydroimidazol-4-one, respectively, was developed.     

Reaction of Zinc Enolates of Alkyl Esters of Substituted 4-Bromo-3-Oxoalkanoic Acids with Aldehydes

Zinc enolates formed from ethyl 4-bromo-2,2,4-trimethyl-3-oxopentanoate react under the conditions of one- of two-stage synthesis with aliphatic, unsaturated, or aromatic aldehydes to form 6-R-2,2,4,4-tetramethyl-2,3,5,6-tetrahydropyran-2,4-diones. Zinc enolates obtained from ethyl 4-bromo-2,2-dimethyl-3-oxopentanoate, -hexanoate, and -2,2,5-trimethyl-3-oxohexanoate under the similar conditions react with aliphatic or aromatic aldehydes to give mainly 5-R¹-6-R²-3,3-dimethyl-2,3,5,6-tetrahydropyran-2,4-diones as E or Z isomers or their mixtures. Zinc enolates generated from the ethyl 4-bromo-2,2-diethyl- or 2-benzyl-2-ethyl-3-oxobutanoates react with aromatic aldehydes to give ethyl 5-R-2-R-2-ethyl-3-oxo-4-pentenoates as E isomers.     

4-Substituted 5-nitroisoquinolin-1-ones from intramolecular Pd-catalysed reaction of N-(2-alkenyl)-2-halo-3-nitrobenzamides

4-Methyl- and 4-benzyl-5-aminoisoquinolin-1-ones are close analogues of the water-soluble PARP-1 inhibitor 5-AIQ. Their synthesis was approached through Pd-catalysed cyclisations of N-(2-alkenyl)-2-iodo-3-nitrobenzamides. Reaction of N,N-diallyl-2-iodo-3-nitrobenzamide with Pd(PPh₃)₄ gave a mixture of 2-allyl-4-methyl-5-nitroisoquinolin-1-one and 2-allyl-4-methylene-5-nitro-3,4-dihydroisoquinolin-1-one. N-Benzhydryl-N-cinnamyl-2-iodo-3-nitrobenzamide similarly gave 2-benzhydryl-4-benzyl-5-nitroisoquinolin-1-one and 2-benzhydryl-4-benzylidene-5-nitro-3,4-dihydroisoquinolin-1-one. The isomeric products are not interconvertible. A deuterium-labelling study indicated that the isomers were formed by different pathways: a π-allyl-Pd route and the classical Heck route. The corresponding secondary amides N-allyl-2-iodo-3-nitrobenzamide and N-((substituted)-cinnamyl)-2-iodo-3-nitrobenzamide gave good yields of the required 4-methyl- and 4-((substituted)-benzyl)-5-nitroisoquinolin-1-ones, respectively, under optimised conditions (Pd(PPh₃)₄, Et₃N, Bu₄NCl, 150 °C, rapid heating). Hydrogenation of the nitro groups gave 4-methyl- and 4-benzyl-5-aminoisoquinolin-1-ones, which were potent inhibitors of PARP-1 activity.     

Alkylation of 1,2,4-triazole-3-thiols with haloalkanoic acid esters

Alkylation of 4,5-disubstituted 4H-1,2,4-triazole-3-thiols with methyl chloroformate and ethyl chloroacetate chemoselectively afforded the corresponding S-alkyl derivatives, whereas the alkylation of 5-benzyl-4-phenyl-4H-1,2,4-triazole-3-thiol with methyl 3-bromopropanoate gave an inseparable mixture of S- and N-alkylation products. Hydrazinolysis of S-(5-benzyl-4-phenyl-4H-1,2,4-triazol-3-yl) methyl carbonothioate involved anomalous cleavage with formation of the initial 4,5-disubstituted 1,2,4-triazole and methyl hydrazinecarboxylate.     

Synthesis of (1H-pyrrol-2-ylsulfanyl)alkanoic acids

(1-Benzyl-1H-pyrrol-2-ylsulfanyl)acetic acid, 2- and 3-(1-benzyl-1H-pyrrol-2-ylsulfanyl)propionic acids, 1,1′-[1,4-phenylenebis(methylene)]bis[(1H-pyrrol-2-ylsulfanyl)acetic acid], and 1,1′-(hexane-1,6-diyl)bis-[(1H-pyrrol-2-ylsulfanyl)acetic acid] were synthesized for the first time by reactions of 1-benzyl-1H-pyrrole, 1,1′-[1,4-phenylenebis(methylene)]bis(1H-pyrrole), and 1,1′-(hexane-1,6-diyl)bis(1H-pyrrole) with thiourea, iodine, and the corresponding halogen-substituted alkanoic acids. 1-(4-Nitrophenyl)-1H-pyrrole failed to react with thiourea and iodine.     

First synthesis of 5,6-branched galacto-hexasaccharide,the dimer of the trisaccharide repeating unit of the cell-wall galactans of Bifidobacterium catenulatum YIT 4016

α-d-Galactopyranosyl-(1→6)-[β-d-galactofuranosyl-(1→5)]-β-d-galactofuranosyl-(1→6)-β-d-galactofuranosyl-(1→5)-[α-d-galactopyranosyl-(1→6)]-β-d-galactofuranose, the dimer of the trisaccharide repeating unit of the cell-wall galactans of Bifidobacterium catenulatum YIT 4016, has been synthesized as its dodecyl glycoside 2 by coupling of 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-[6-O-acetyl-2,3,5-tri-O-benzoyl-β-d-galactofuranosyl-(1→5)]-2-O-acetyl-3-O-benzyl-β-d-galactofuranosyl trichloroacetimidate 14 with dodecyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-[2,3,5-tri-O-benzoyl-β-d-galactofuranosyl-(1→5)]-2-O-acetyl-3-O-benzyl-β-d-galactofuranoside 16. The trisaccharide trichloroacetimidate donor 14 and trisaccharide acceptor 16 were regiospecifically prepared by employing 3-O-benzyl-1,2-O-isopropylidene-α-d-galactofuranose 4 as the glycosyl acceptor, and isopropyl 2,3,4,6-tetra-O-benzyl-1-thio-β-d-galactopyranoside 5 and 6-O-acetyl-2,3,5-tri-O-benzoyl-β-d-galactofuranosyl trichloroacetimidate 9 as glycosyl donors.     

A nitro sugar mediated synthesis of 6-amino-1,5,6-trideoxy-1,5-imino-d-glucitol (6-amino-1,6-dideoxynojirimycin)

6-Benzoylamino-3-O-benzyl-1,5,6-trideoxy-N-(1,1-diphenylmethyl)-1,5-imino-d-glucitol 12a and its epimer 6-benzoylamino-3-O-benzyl-1,5,6-trideoxy-N-(1,1-diphenylmethyl)-1,5-imino-l-iditol 12b, the protected forms of 6-amino-1,6-dideoxynojirimycin 4 and its C-5 epimer 5, respectively, were easily prepared from diacetone-d-glucose via 6-O-benzoyl-3-O-benzyl-1,2-O-isopropylidene-5-C-nitromethyl-α-d-glucofuranose 7a or 6-O-benzoyl-3-O-benzyl-1,2-O-isopropylidene-5-C-nitromethyl-β-l-idofuranose 7b. 6-Amino-1,6-dideoxynojirimycin 4 (an important precursor of a wide range of glycosidase inhibitors) was easily prepared from 1,5-imino-d-glucitol 12a.     

Reaction of benzoyl and trichloroacetyl isocyanates with Schiff bases

Conclusions Benzalbenzylamine and p-substituted benzalbenzylamines react with benzoyl and trichloroacetyl isocyanates by the type of 1,4-addition, with the formation of 2,6-diphenyl-3-benzyl-3,4-dihydro-2H-1-oxa-3, 5-diazin-4-one and 2-phenyl-3-benzyl-6-trichloromethyl3,4-dihydro-2H-1-oxa-3,5-diazin-4-one derivatives.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 617–621, March, 1970.     

Reactions of N-substituted pyridinium carbamoylmethylenides with ethyl arylidenecyanoacetates

Condensation of pyridinium N-alkyl-, N-cycloalkyl-, N-benzyl-, and N-phenethylcarb-amoylmethylenides with ethyl arylidenecyanoacetates stereoselectively gives 4,5-trans-1-alkyl-, 4,5-trans-l-cycloalkyl-, 4,5- trans-1-benzyl-, and 4,5-trans-1-phenethyl-4-aryl-3-cyano-6-oxo-5-(3-R-1-pyridinio)-1,4,5,6-tetrahydropyridin-2-olates. However, pyridinium N-arylcarb-amoylmethylenides react with the same esters without ring closure, yielding Michael adducts, viz., ethyl 3-aryl-4-(N-arylcarbamoyl)-2-cyano-4-(1-pyridinio)butyrates.     

Ab initio calculations of effect of (thio)xanthenyl and dibenzosuberenyl substituents on dehydrogenation of N-Benzylanilines

Higher values of the energies of the highest occupied molecular orbitals for N-benzyl-4-[9-(thio)-xanthenyl]aniline, N-benzyl-4-(5-dibenzosuberenyl)aniline molecules and their zwitterions and the electron density increase on the reaction center (carbon atom in the CH₂-group) for the latter were obtained in the quantum-chemical calculations by RHF/6-31G(d) method. This explains the possibility and the ease of dehydrogenation of N-benzyl-4-[9-(thio)xanthenyl]aniline with imines in trifluoroacetic acid due to effect of the substituents. The calculated data suggest the same possibility for N-benzyl-4-(5-dibenzosuberenyl)aniline: it is dehydrogenated already in the synthesis from N-benzylaniline and dibenzosuberenol in acetic acid.     

An orthogonal protection strategy for the synthesis of 2-substituted piperazines

Tetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-ones are readily prepared from the bis-carbamate protected piperazine-2-carboxylic acids and serve as orthogonally protected piperazines from which a variety of 2-substituted piperazines can be prepared. Sodium benzylate and sodium phenoxides react at the C-5 carbon of the oxazolidinone to yield 2-(benzyloxymethyl)piperazines and 2-(phenoxymethyl)piperazines, respectively. The tetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-ones also provide convenient scaffolds from which 2-benzyl- and 2-phenethylpiperazines are prepared.     

Synthesis of the dibenzo[f,h]phthalazine and dibenzo[f,h]cinnoline skeleton via a ‘Suzuki-Pd-catalyzed intramolecular arylation’ and a ‘Suzuki-Pschorr’ approach

Palladium-catalyzed intramolecular arylation of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2H)-one yielded hitherto unknown 2-benzyldibenzo[f,h]phthalazin-1(2H)-one. The synthesis of this new tetracyclic pyridazinone from 2-benzyl-5-(2-aminophenyl)-4-phenylpyridazin-3(2H)-one via a Pschorr type reaction was also investigated. Similarly, the construction of 2-methyldibenzo[f,h]cinnolin-3(2H)-one from 2-methyl-5-(2-bromophenyl)-6-phenylpyridazin-3(2H)-one and 2-methyl-5-(2-aminophenyl)-6-phenylpyridazin-3(2H)-one is also reported. Removal of the N-benzyl protective group of 2-benzyl-dibenzo[f,h]phthalazin-1(2H)-one with AlCl₃ yielded unsubstituted dibenzo[f,h]phthalazin-1(2H)-one.