N-hetaryl-2-cyanoacetamides in the synthesis of substituted (E)-N-hetaryl-2-cyanoacrylamides, (E)-N-alkyl-N-hetaryl-2-cyanoacrylamides, and 6-amino-2-oxo-4-phenyl-1-(pyridin-2-yl)-1,2-dihydropyridine-3,5-dicarbonitriles

Knoevenagel condensation of N-hetaryl-substituted cyanoacetamides with aldehydes gave the corresponding (E)-N-hetaryl-2-cyanoacrylamides which were converted into (E)-N-alkyl-N-hetaryl-2-cyanoacrylamides and 6-amino-2-oxo-4-phenyl-1-(pyridin-2-yl)-1,2-dihydropyridine-3,5-dicarbonitriles. The structure of (E)-N-(pyridin-2-yl)-2-cyano-3-phenylprop-2-enamide was determined by X-ray analysis. Original Russian Text ? I.V. Dyachenko, V.D. Dyachenko, E.B. Rusanov, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 1, pp. 81–86.     

Synthesis of (1′S*,2R*,3R*)- and (1′S*,2R*,3S*)-N-arylsulfonyl-2-(1′-halogenethyl)-3-methylindolines and their selective toxicity against SH-SY5Y cell line

N-tosyl-2- and N-tosyl-4-halogen-substituted derivatives of 2-(1-methylbut-2-en-1-yl)aniline were synthesized and their molecular iodine-mediated cyclization was investigated. The cyclization upon interaction of N-tosyl-6-methyl-2-(1-methylbut-2-en-1-yl)aniline with molecular iodine in methyl tert-butyl ether or acetonitrile was studied, as well as the interaction of this sulfonamide with N-bromosucinimide in dichloromethane. Synthesized (2R*,3R*)- and (2R*,3S*)-N-arylsulfonyl-2-(1-halogenoethyl)-3-methylindoline derivatives showed cytotoxic activity against HEK293 cells, SH-SY5Y, Jurkat, and HepG2 cell lines. The compounds (2R*,3S*)-N-arylsulfonyl-7-bromo-2-(1-halogenoethyl)-3-methylindoline cis- 4a , stereoisomeric (2R*,3R*)-trans- 4h and (2R*,3S*)-N-tosyl-7-chloro-2-(1-halogenoethyl)-3-methylindoline cis- 4h demonstrated selective toxicity against SH-SY5Y cell line (IC₅₀ ≈ 3 ÷ 5 μM), and did not affect HEK293, Jurkat, and HepG2 cells.     

Asymmetric syntheses with BINOL-based imidoyl azide

Thermal decomposition of 2,4,6-trimethylphenyl and (+)-2′-methoxy-1,1′-binaphthalen-2-yl (4-methylphenylsulfonyl)azidimidocarbonates in the presence of norbornene, methyl acrylate, and camphene was studied. (+)-2′-Methoxy-1,1′-binaphthalen-2-yl (4-methylphenylsulfonyl)azidimidocarbonate reacted with norbornene to give (+)-exo-2′-methoxy-1,1′-binaphthalen-2-yl N-(4-methylphenylsulfonyl)-3-azatricyclo-[3.2.1.0^2,4]octane-3-carboximidoate, while in the reaction with methyl acrylate a mixture of stereoisomeric methyl 1-[(2′-methoxy-1,1′-binaphthalen-2-yloxy)(4-methylphenylsulfonylimino)methyl]aziridine-2-carboxylates was obtained. The reaction of 2,4,6-trimethylphenyl (4-methylphenylsulfonyl)azidimidocarbonate with (−)-camphene involved insertion of intermediate nitrene into the exocyclic double bond with formation of 2,4,6-trimethylphenyl N-(3,3-dimethylbicyclo[2.2.1]heptan-2-ylidenemethyl)-N′-(4-methylphenylsulfonyl)-imidocarbamate as a 3: 1 mixture of E,E and E,Z diastereoisomers in good yield. Published in Russian in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 10, pp. 1495–1500. The text was submitted by the authors in English.     

Stable azomethine imines having a 3,4-dihydroisoquinoline fragment and their cycloaddition to <Emphasis Type="Italic">N</Emphasis>-arylmaleimides

Aroylation of 5,6,8,8a,13,14,16,16a-octahydro[1,2,4,5]tetrazino[6,1-a:3,4-a′]diisoquinoline or 1,3,4,8b-tetrahydro[1,2]diazireno[3,1-a]isoquinoline, as well as reactions of 2-(2-bromoethyl)benzaldehyde with aroylhydrazines followed by treatment with triethylamine, led to the formation of stable azomethine imines, aroyl(3,4-dihydroisoquinolinium-2-yl)azanides. 1,3-Dipolar cycloaddition of the latter to N-mesitylmaleimide was stereoselective: the ratio of the trans- and cis-adducts was ∼(3–7): 1, the former prevailing. The reactions with N-arylmaleimides having no ortho-substituents in the aryl group gave the corresponding cis-adducts as the major products [trans/cis ratio ∼1: (2.5–10)].     

Studies on the synthesis of heterocyclic compounds. Part VI. The action of methyl salicylate on some 5-aminopyrazoles

Some 1-phenyl-3-R-5-aminopyrazoles reacted with methyl salicylate to give N-(1-phenyl-3-R-pyrazol-5-yl)-2-methoxybenzamides ( 3a,b,c ), 1-phenyl-2-methyl-3-R-salicyloilimino-3-pyrazolines ( 4a,b,c ) together with 1-phenyl-3-R-5-methylamino pyrazoles ( 5a,b,c ). The structures of the new compounds 3 and 4 were determined on the basis of analytical and spectroscopic data as well as on the acid hydrolysis products.     

Synthesis of optically active hydridocarbonyl triosmium clusters with terpene derivatives as ligands. Molecular structure and absolute configuration of a cluster with a bridging dihydroimidazole ligand

Reactions of the triosmium clusters Os₃(CO)₁₁(NCMe) (1) and Os₃(CO)₁₀(NCMe)₂ (2) with terpene derivatives,viz., (1S,3S,4R,6R)-3-(N,N-dimethylamino)-4-amino-3,7,7-trimethylbicyclo [4.1.0]heptane (3). (3bR,4aR)-(3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa [3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid (4a), and (3bR,4aR)-3-(3,4,4-trimethyl-3b, 4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)propionic acid (4b), were studied. A complex with the terminally coordinated ligand is formed in the first step of the reaction of diamine3 with cluster1. Heating of the resulting complex is accompanied by activation of one of the methyl groups of the ligand to form diastereomers with the bridging tricyclic dihydroimidazole ligand. One of these diastereomers was studied by X-ray diffraction analysis and its absolute configuration was established. Pyrazolycarboxylic acids react with cluster2 as simple organic acids and are coordinated as a bridge at the Os—Os bond through the carboxyl group. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1447–1454, August, 2000.     

A selector/selectand molecular complex for the study of enantiodiscriminative processes

The structure of the molecular complex between the chiral selector (+)1-(3-allylpropyl)-(5R,8S,10R)-N,N-diethyl-N′-[6-methyl ergolin-8-yl]urea, C₂₃H₃₃N₄O, (allyl-terguride) and the HPLC more retained (S)-enantiomer of dansyl-tryptophan, C₂₃H₂₃N₃O₄S, has been determined. It is a part of the study on the chiral recognition mechanism of ergot alkaloids, when used in chiral stationary phases (CSPs) for the separation of racemic mixture of organic acids by liquid chromatographic methods. At the pH of crystallization conditions, which mimic those corresponding to the best enantiodiscriminative activity, each molecule of (S)-dansyl-tryptophan is locked to a molecule of allyl-terguride by hydrogen bonds and by C–H···π edge-to-face interactions.     

A new ceramide from the root of <Emphasis Type="Italic">Isatis Indigotica</Emphasis> and its cytotoxic activity

In addition to two ceramides 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2'-hydroxyhexadecanoyl)-octadeca-4E,8Esphingenine (2) and (2S,3S,4R)-N-(2'-hydroxytetracosanoyl)-octadecasphingenine (3), which separated for the first time, a new ceramide 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2'-hydroxyhexacosanoyl)octadecasphingenine (1) was isolated from the traditional Chinese medicinal herb Isatis indigotica. Their cytotoxic effects were evaluated by the MTT method.     

Isolation,structural determination and cytotoxic activity of two new ceramides from the root of <Emphasis Type="Italic">Isatis indigotica</Emphasis>

Two new ceramides were isolated from the 95% EtOH extract of traditional Chinese medicinal plant Isatis indigotica. Their structures were elucidated as 1-O-β-D-glucopyranosyl-(2S, 3R)-N-(2′-hydroxype-ntacosanoyl)-octadeca-11E-sphingenine (1) and 1-O-β-D-glucopyranosyl-(2S,3R)-N-(2′-hydroxyhe xacosanoyl)-octadeca-11E-sphingenine (2) on the basis of spectroscopic data. Their cytotoxic effects were evaluated by using MTT method.     

A new method for the synthesis of [1,4]diazepino[6,5-b]indole derivatives

Reactions of 3-[(N-aryl-N-chloroacetyl)amino]-2-formylindoles with substituted anilines gave 1,4-diaryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indol-4-ium chlorides and those with 4-aminopyridine yielded 4-amino-1-(1-aryl-2-oxo-2,5-dihydro-1H-pyrido[3,2-b]indol-3-yl)pyridinium chlorides. Reduction of 1,2,3,6-tetrahydrodiazepinoindol-4-ium chlorides afforded the corresponding hexahydro derivatives. An alternative synthesis of 1-(4-nitrophenyl)-3-oxo-4-phenyl-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole from 3-[N-(4-nitrophenyl)amino]-2-[(phenylimino)methyl]indole was developed. The method involves the following sequence of transformations: reduction, chloroacetylation, and intramolecular alkylation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2193–2199, December, 2006.     

Immobilization of porphyrins in poly(hydroxymethylsiloxane)

Three tetracationic porphyrins differing in the position of charged nitrogen atoms on the peripheral substituents — 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin (TMPyP4), 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin (TMPyP2), 5,10,15,20-tetrakis(4-trimethylammoniophenyl) porphyrin (TMAPP), and hydrophobic 5,10,15,20-tetraphenylporphyrin (TPP), were immobilized by adsorption and encapsulation in poly(hydroxymethylsiloxane) (PHOMS). The so prepared porphyrin-PHOMS composites were characterized by porosimetry, scanning electron microscopy, fluorescence and diffuse reflectance UV-VIS spectroscopy. It was found that porphyrins are immobilized in the PHOMS matrix in the free base monomer form Their irradiation produced singlet oxygen O₂(¹Δ_g) with the lifetime of 10–30 μs.     

Crystallographic study and molecular modeling on the oxidation product of <Emphasis Type="Italic">N</Emphasis>-[(8<Emphasis Type="Italic">R</Emphasis>)-2-methoxy-5,6,7,8,9,10-hexahydro-6,9-methanocyclohepta[<Emphasis Type="Italic">b</Emphasis>]indol-8-yl]acetamide

Crystallization of N-[(8R)-2-methoxy-5,6,7,8,9,10-hexahydro-6,9-methanocyclohepta[b]indol-8-yl]acetamide was accompanied by oxidation at the C^5a–C^10a bond with formation of N-[(5S)-10-methoxy-2,8-dioxo-1,2,3,4,5,6,7,8-octahydro-3,6-methano-1-benzazecin-5-yl]acetamide whose structure was determined by X-ray analysis. Docking of this compound into melatonin-binding pocket of MT_1A receptor was simulated by computer-assisted molecular modeling.     

Sesquiterpenoids of the Sponge Dysidea fragilis of the North-Brittany Sea

The title sponge is shown to contain eight new sesquiterpenoids for which a common, unusual biogenetic origin is postulated. The compounds are shown to be: (–)-(1R*,4R*)-3-(3′-furyl)methyl-2-p-menthen-7-yl acetate ((–)- 8b ); two diols separated as the monoacetates (–)-(1S*,4R*)-3-(3′-furyl)methyl-l-hydroxy-2-p-menthen-7-yl acetate ((–)- 13a ) and the (–)-(1R*,4R*)-epimer (–)- 13b , the two C(4)-epimeric 4-ethoxy-3-(1′(7′),2′-p-menthadien-3′-yl)methyl-2-buten-4-olides ((+)- 14a and (–)- 14b ), (–)-3-(3′-furyl)methyl-7-nor-2-p-menthen-l-one ((–)- 11 ), (–)-(3Z)-1-(3′-furyl)-4,8-dimethylnona-3, 7-dien-2-yl acetate ((–)- 17 ), and (+)-3-(5′,7′-seco-2′(10′)-pinen-7′-yl)methylfuran ((+)- 15 ).     

Reaction sites of <Emphasis Type="Italic">N,N′</Emphasis>-substituted <Emphasis Type="Italic">p</Emphasis>-phenylenediamine antioxidants

The geometries of N,N′-diphenylbenzene-1,4-diamine (DPPD), N-phenyl-N′-(1-phenylethyl)benzene-1,4-diamine (SPPD), N-(4-methylpentan-2-yl)-N′-phenylbenzene-1,4-diamine (6PPD), N-propan-2-yl-N′-phenylbenzene-1,4-diamine (IPPD), N-(2-methoxybenzyl)-N′-phenylbenzene-1,4-diamine (MBPPD), and N-phenyl-N′-(2-phenylpropan-2-yl)benzene-1,4-diamine (CPPD) as well as of their dehydrogenation products were optimized by the semiempirical AM1 method. The results support the idea of stable N_B=C_X structures formation during the consecutive dehydrogenation of SPPD, 6PPD, IPPD, and MBPPD antioxidants. The biradicals formed during the second step of dehydrogenation of substituted phenylenediamines might be important for their antioxidant effectiveness. Dedicated to Professor Vladimír Kvasnička, DrSc., in honour of his 65th birthday     

Enantiomerically pure 7-oxabicylo[2.2.1]hept-5-en-zyl derivatives as synthetic intermediates. Part III. Total synthesis of D- and L-ribose derivatives

Enantiomerically pure methyl 5-bromo-5-deoxy-2,3-O- isopropylidene-β-D - (D - 5b ) and -β-l-ribofuranoside (l- 5b ) have been derived from (?)-(1R,2S,4R)-2-exo-cyano-7-oxabicylo[2.2.1]hept-5-en-endo,-yl (1′S)-camphanate ( 1 ) and (+)-(1S,2R,4S)-2-exo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl(1′R)-camphanate ( 2 ), respectively, in 5 synthetic steps and 28% overall yield. Hydrolysis of D-5b and L - 5b afforded methyl 2,3-O isopropylidene-β-D -ribofuranoside (D -5a) and methyl 2,3-O-isopropylidene β-L-ribofuranoside (L-5a), respectively. The intermediate (+)-(1R,4R,5R,6R) 5-exo,6-exo-(isopropylidenedioxy)- 7 -oxabicyclo[2.2.1]heptan-2-one ((+)- 7 ) and its enantiomer(–)-7 were also obtained enantiomerically pure by resolution of (=)- 7 by the Johnson-Zeller method. In bothe approaches, the chiral auxiliaries ((–)- and (+)-camphanic acids, or (+)-(S)-N,S-dimethyl-S-phenylsulfoximide) were recovered at an early stage of the synthesis.     

Sarcodictyin A and Sarcodictyin B,Novel Diterpenoidic Alcohols Esterified by (E)-N(1)-Methylurocanic Acid. Isolation from the Mediterranean Stolonifer Sarcodictyon roseum

The Mediterranean stolonifer Sarcodictyon roseum (= Rolandia rosea) (Cnidaria, Anthozoa, Alcyonaria, Stolonifera, Clavulariidae) is shown to contain two novel diterpenoidic alcohols esterified by (E)-N(1)-methyl-urocanic acid (= E)-3-(l-methyl-lH-imidazol-4-yl)acrylic acid). They are sarcodictyin A ( = (?)-(4R,4a,R, 7R,10S,11S,12aR,lZ,5E,8Z)-7,10-epoxy-3,4,4a,7,10,11,12,12a-octahydro-7-hydroxy-6-(methoxycarbonyl)-1,10-dimethyl-4-(1-methylethyl)benzocyclodecen-11-yl (E)-3-(1-methyl-lH-imidazol-4-yl)acrylate; (?)- 1 ) and sarco-dictyin B (the 6-(ethoxycarbonyl analogue; (?)- 2 ). The assignment of the structures is mainly based on 1D- and 2D-NMR data, as well as on chemical transformations of (?)- 1 , such as transesterification with MeONa/MeOH giving methyl (E)-N(1)-methylurocanate ( 3 ) and the free alcohol (+)- 4 and reduction with LiAlH₄ followed by benzoylation giving dibenzoate 7. Absolute configurations are based on Horeau's method of esterification of (+)- 4 .     

The reactivity of N,N-dialkyl-N-(3-phenylsulfinyltetrahydrofuran-2-ylidene)ammonium bromide

trans-Stereoselective electrophilic cyclization of (2R*,SS*)-N, N-diisopropyl-2-phenylsulfinylpent-4-enamide under the action of bromine afforded (3R*,5S*, SS*)-N-(5-bromomethyl-3-phenylsulfinyltetrahydrofuran-2-ylidene)-N,N-diisopropylammonium bromide. Its transformations under the conditions of hydrolysis, dehydrobromination, and hydride reduction were studied. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1485–1490, August, 2007.     

Reactions of 1,2,4-triazole derivatives with a “model” thiirane

Reactions of 3-mono- and 3,5-disubstituted 1,2,4-triazoles with a “model” thiirane, 8-bromo-1,3-dimethyl-7-(thiiran-2-ylmethyl)-3,7-dihydro-1H-purine-2,6-diones proceed at the positions N¹ and N² of the triazole ring and yield 7-(5-R-3-R′-1,2,4-triazol-1-yl)methyl- and/or 7-(5-R′-3-R-1,2,4-triazol-1-yl)methyl-1,3-dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]-purine-2,4-(1H,3H)-diones. 3-Methylsulfonyl-1,2,4-triazole reacted regiospecifically at the position N¹ forming 1,3-dimethyl-7-[(3-methyl-sulfonyl-1,2,4-triazole-1-yl)-methyl]-6,7-dihydro[1,3]thiazolo-[2,3-f]purine-2,4(1H,3H)-dione.     

Povarov Reaction of Glyoxylate Imines Derived from 12-Aminodehydroabietic Acid

Glyoxylate and arylglyoxal imines based on 12-aminodehydroabietic acid undergo hetero-Diels—Alder (Povarov) reaction with ethyl vinyl ether, cyclopentadiene, and indene to give, respectively, methyl (8aR,9R,12aS)-3-aroyl-5-isopropyl–9,12a-dimethyl–7,8,8a,9,10,11,12,12a-octahydronaphtho[1,2-f]quinoline-9-carboxylates, methyl (7R,10aS,10dR,13aS)-1-aroyl–3-isopropyl–7,10a-dimethyl–2,5,6,6a,7,8,9,10,10a,10d,13,13a-dodecahydro-1H-naphtho[1,2-f]cyclopenta[c]quinoline-7-carboxylates, and methyl (6aS,11bS,11eS,15R,15aR)-6-aroyl–4-isopropyl–11e,15-dimethyl–2,5,6,6a,7,11b,11e,12,13,14,15,15a-1H-dodecahydroindeno[2,1-c]-naphtho[1,2-f]quinoline-15-carboxylates.     

Synthesis and structures of 5(3H)-oxotetrahydro-1H-imidazo[4,5-c][1,2,5]thiadiazole 2,2-dioxides

The reactions of sulfamides with 4,5-dihydroxyimidazolidin-2-ones were studied at ambient and high pressure. The previously unknown derivatives of 5(3H)-oxotetrahydro-1H-imidazo-[4,5-c][1,2,5]thiadiazole 2,2-dioxide, viz., sulfo analogs of tetrahydroimidazo[4,5-d]imidazole-2,5-(1H,3H) diones (glycolurils), were synthesized. The structures of some of these compounds were established by X-ray diffraction. The high-pressure reactions performed under conditions of solvent phase transitions afforded also N-(1,3-diethyl-5-hydroxy-2-oxoimidazolidin-4-yl)-N,N′-dialkylsulfamides. Among these compounds, a new conglomerate was found. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1711–1719, May, 2008.