Acyclopyrimidine C-nucleosides. Synthesis of acyclopseudoisocytidine and its derivatives

Acyclopseudouridine (IV), acyclopseudoisocytidine (VII), and their 1-methyl derivatives (V and VIII) were synthesized from 5-hydroxymethyluracil (I). Acyclopseudouridine (IV) was conveniently prepared from the condensation of 5-hydroxymethyluracil ( I ) with ethylene glycol under acidic condition. Compound IV also could be prepared from 5-chloromethyluracil, however, this procedure was found to be inferior to the direct condensation method. Methylation of IV with dimethylformamide dimethyl acetal gave 1,3-dimethylacyclopseudouridine (VI) which was subsequently converted to acyclopseudoisocytidine (VII). 1-Methyl derivatives V and VIII were obtained from the selective methylation of IV and VII, respectively. 5-Hydroxymethyluracil also reacted with 2-mercaptoethanol to give the sulfide derivative (IX).     

Azabicyclo chemistry II. Synthesis of 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepines. B-norbenzomorphans

The syntheses of the B-norbenzomorphans, 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepine (1a) and its N-methyl derivative (Ib) were accomplished. Phenylsuccinic anhydride (III) was cyclized to 3-carboxy-1-indanone (IVa), which was converted by the Arndt-Eistert method to the homologous methyl indanone-3-acetate (V). One experiment in the synthesis of V led to the by-products 3-carboxamido-1-indanone (IVd) and 3-(N-methylcarboxamido)-1-indanone (IVe), identified by physical and chemical means. Methyl 1-aminoindan-3-acetate (VII) was prepared by catalytic reduction of methyl indanone-3-acetate oxime (VI). Hydrolysis of VII afforded 1-aminoindan-3-acetic acid (VIII), which was cyclized with dicyclohexylcarbodiimide to 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepin-3-one (IX). Reduction (lithium aluminum hydride) of IX gave amine Ia which was then methylated to Ib. The mass spectral fragmentation patterns of IX and Ia are discussed.     

Synthesis of thia-ellipticine, 5,11-dimethylbenzothieno[2,3-g]isoquinoline

1,4-Dimethyldibenzothiophene (VII) was synthesized and was converted with butyl dichloromethyl ether to the 2-aldehyde (VIII). The structure was confirmed by an independent synthesis of the 2-ester (XI) derived from it. The 2-aldehyde (VIII) with aminoacetaldehyde diethylacetal formed the Schiff′s base (IX), and Pomeranz-Fritsch cyclization with 105% superphosphoric acid then formed thia-ellipticine (II), an isostere of the antitumor alkaloid, ellipticine.     

Synthese des (R)-trans-11-Hydroxy-8-dodecensäure-lactons (Recieifeiolid)

Synthesis of Recifeiolide The synthesis of the mould metabolite recifeiolide (VIII), a 12-membered ring lactone, is described. 1,3-Butandiol was resolved with (?)-camphanic acid via (R)-1-iodo-3-butanol (II) into (R)-3-hydroxybutyl triphenyl phosphonium iodide (III). Wittig condensation of the phosphorane derived from III with methyl 8-oxo-octanoate (V) led to the methyl trans-11-hydroxy-8-dodecenoate (VI). The corresponding hydroxy acid VII was transformed into the S-(2-pyridyl) carbothioate which cyclizes under the influence of silver ion to the lactone VIII. With (?)-(R)-1,3-butandiol (I) as starting material the naturally occurring (+)-(R)-recifeiolide (VIII) is produced in 70% yield from VII.     

Pyrimidines. XIX. Pyrimido[4,5-e]dihydro-1,3-oxazines and related compounds

A number of 2-substituted 4,5-dihydroxy-6-(substituted aminomethyl)pyrimidines (VIII) were prepared from the corresponding 2-substituted 4,5-dihydroxypyrimidines (VII) by a new pyrimidine Mannich reaction. The structure of VIII was proved by an independent synthesis. Further study of this reaction led to the synthesis of a new class of compounds: the pyrimido[4,5-e]dihydro-1,3-oxazines (VI).     

Quantum chemical calculations of the redox potential of the Pu(VII)/Pu(VIII) couple

The redox potential of the Pu(VII)/Pu(VIII) couple was studied by density functional theory calculations. The spin-orbit effect was corrected at the CASSCF level. The redox potential (relative to the standard hydrogen potential) of the Pu(VII)/Pu(VIII) couple in alkaline solution was found to vary from 4.36 to 1.06 V depending on the number of Pu-O oxo bonds, coordination numbers, and coordination modes. The redox potential drops substantially as the number of Pu-O oxo bonds increases. Pu(VIII) may be synthesized in strong alkaline solution assuming that both Pu(VII) and Pu(VIII) exist in penta-oxo form, Pu (VII)O 5OH (4-) and Pu (VIII)O 5OH (3-), respectively. The Mulliken population of Pu in Pu(VII) and Pu(VIII) complexes are very similar, suggesting that the spin-orbit effect is rather small in Pu(VII) complexes and that when Pu(VII) is oxidized to Pu(VIII) the electron is stripped mainly from the ligand. Consequently, Pu(VIII) is in an unstable oxidation state and easily reduced back to Pu(VII) by the solvent water molecules. In acidic medium, the Pu(VII)/Pu(VIII) redox potential is too high to get the Pu(VIII) valence state.     

Synthesis of pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5-ones. Cyclization reaction of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid with acetic anhydride

Treatment of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid (X) with acetic anhydride under refluxing conditions afforded 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]-pyrimido[4,5-d]pyrimidin-5-one acetate (IX). The intermediate X was prepared from 4-chloro-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (V). The reaction of V with the sodium salt of 2-amino-3-hydroxypyridine at room temperature gave 4-(2-amino-3-pyridyloxy)-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (VI). Treatment of VI with a hot aqueous sodium hydroxide solution and subsequent acidification gave X. Involvement of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecaroboxylic acid ethyl ester (VIII) (Smiles rearrangement product) as an intermediate in the above alkaline hydrolysis reaction of VI to X was demonstrated by the isolation of VIII and its subsequent conversion into X under alkaline hydrolysis conditions. Acetylation of VIII with acetic anhydride in pyridine solution gave 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester acetate (XI), which afforded IX on fusion at 220°. This alternative synthesis of IX from XI supported the structural assignment of IX. Fusion of VI gave 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]pyrimido]4,5-d]pyrimidin-5-one (VII). The latter was also obtained when VIII was fused at 210°. Acetylation of VII with acetic anhydride afforded IX.     

13C-NMR Spectra of 2- and 3-Phthalimido-3(2)-Benzimidazolylpropanoic Acid and 2- and 3-Phthalimidobenzimidazopyrrolone,Reaction Products of Phthaloylaspartic Anhydride with Ortho-Phenylenediamine

Two pairs of isomers of 3- and 2-phthalimido-3(2)benzimidazolylpropanoic acid (V and VI) and 2- and 3-phthalimidobenzimidazopyrrolone (VII and VIII) were produced from the reaction of phthaloylaspartic anhydride (I) with o-phenylenediamine (II). The ¹³C-NMR spectra of V and VI both showed 11 carbon signals indicating that the structures of their benzimidazole groups were symmetric. Isomers V and VI were easily distinguished from each other by the chemical-shift-differences (Δδ) of the methylene carbon and the methine carbon. Compounds VII and VIII displayed 14 carbon signals and no longer showed the symmetric structure of the benzimidazole moity, The chemical-shift-differences (Δδ) between methylene carbon and methine carbon in pyrrolones of VII and VIII can also be used to distinguish VII from VIII. The Δδ of compound VII is less than that of compound VIII.     

Organophosphorus compounds—XVI: The reaction of phosphite esters with vicinal triketone monohydrates

Trialkyl phosphites react with the monohydrates of 1,2,3-indantrione (ninhydrin) (VII) and 1,3-diphenylpropanetrione (VIII) to give the corresponding phosphate derivatives XIa–c and XVIIIa–c. The same compounds are obtained upon reacting VII and/or VIII with the proper dialkyl hydrogen phosphite. The trialkyl phosphites cause the quantitative reduction of perinaphthindantrione (IX) and/or its monohydrate (X) producing dihydroxy-peri-naphthindenone (XXI). On the other hand, dialkyl hydrogen phosphites add to IX (or X), yielding compounds XXIIa–c.     

Studies on the syntheses of heteroeyelie compounds. Part DVI . Synthesis of oxynilidine and nitidine

A benzyne type reaction of 1-bromo-3,4-dimethoxybenzene (V) with 3,4-dihydro-6,7-methylenedioxy-I(2H)naphthalenone (VI) gave the tetralone derivative VII, which was converted into the amine IX via the oxime VIII. A Mannich reaction of IX afforded the benzo[c]phen-anthridine II which was then transformed into oxynitidine (I) and nitidine (IV).     

Reaction of thioxanthylium perchlorate with diazomethane

The reaction of thioxanthylium perchlorate with diazomethane was investigated. Depending on the reaction conditions, seven compounds (II, III, V, VI, VIII, IX, and X) are formed which were identified on the basis of spectral data (mainly mass spectra) and chemical reactions. A synthesis was worked out (reaction of compound VII with boron trifluoride) in which dibenzo[b,f]thiepine (VIII) is formed as major product (55%).     

Pheromones of insects and their analogs. XX. Methyl-branched pheromones based on 4-methyltetrahydropyran.

A synthesis is proposed of 4,8-dimethyldecanal (VIII) — a pheromone of the flour beetlesTribolium confusum andT. castaneum. By heating 71.2 g of 4-methyltetrahydropyran (I), 83.2 g of AcBr and 1.57 g of ZnCl₂ (45°C), then 120°C, 2 h), 1-acetoxy-5-bromo-3-methylpentane (II) was obtained. The hydrolysis of 19.8 g of (II) (MeOH-H₂O, TsOH, 20°C, 15 h) gave 5-bromo-3-methylpentan-1-ol (III). From 18.1 g of (III) and 38.9 ml of 2,3-dihydropyran (Et₂O, TsOH, 20°C, 20 h) was obtained the 2-THPL ester of (III), (IV), which was converted into 3-methyloct-7-en-1-ol (V) by the treatment of the corresponding Grignard reagent with allyl bromide (THF, CuI-bi-2-pyridyl, 2°C, 4 h, Ar). The interaction of 1.42 g of (V) with Et₃Al (hexane, 20°C, Cp₂ZrCl₂, Ar) gave 3,7-dimethylnonan-1-ol (VI), boiling which with 48% HBr in the presence of concentrated H₂SO₄ gave 1-bromo-3,7-dimethylnonane (VII) which was then converted into the desired (VIII) by the reaction of the corresponding Grignard reagent with DMFA (0–2°C, 1 h; 20°C, 2 h; Ar). The characteristics of the compounds — yield (%), n_D (°C): (I), 79, 1.4340 (22); (III) 89, 1.4660 (23); (IV), 82, 1.4739 (23); (V), 85, —; (VI), 90, 1.4483 (20); (VII), 88, 1.4409 (22); (VIII), 88, 1.4589 (22). Details of the IR and PMR spectra of compounds (II)–(VII) are given.Institute of Chemistry, Bashkir Scientific Center, Urals Branch, USSR Academy of Sciences, Ufa. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 272–276, March–April, 1989.     

QUENCHING OF SINGLET MOLECULAR OXYGEN BY PHTHALOCYANINES AND NAPHTHALOCYANINES

Using the direct measurement of the photosensitized luminescence of singlet molecular oxygen (1O2) the rate constants (kq) have been determined for 1O2 quenching by the monomeric molecules of the following phthalocyanines and naphthalocyanines in chloroform: tetra-(4-tert-butyl) phthalocyanine (I); octa-(3,6-butoxy) phthalocyanine (II), tetra-(6-tert-butyl)-2,3 naphthalocyanine (III), aluminium tetra-(1-tert-phenyl)-2,3 naphthalocyanine (IV), tri-(n-hexyl-siloxy) derivatives of silicon- (V), tin- (VI), aluminium- (VII) and gallium- (VIII) 2,3 naphthalocyanine. The following kq values were obtained (kq x 10(-8) M-1 s-1): 2.9 (I), 59 (II), 100 (III), 20 (IV), 3.9 (V), 53 (VI), 33 (VII), 110 (VIII). As most of the quenchers have the low-lying triplet levels, a contribution of the quenching mechanism based on the energy transfer from 1O2 to these levels has been analysed. A formula is proposed describing the relation between kq values caused by this mechanism, and photophysical constants of the quencher triplet state. This formula was applied to phthalocyanines, naphthalocyanines, beta-carotene and bacterochlorophyll a. The data suggest that the energy transfer can fully explain the activity of V and strongly contributes into the activities of II, III and VI-VIII. A charge transfer interaction might be an additional mechanism involved in 1O2 quenching by compounds studied. As some phthalocyanines and naphthalocyanines are strong physical quenchers of singlet oxygen they can be used as efficient inhibitors for photodestructive processes in photochemical systems.     

Dibenzo[b,f]oxepin‐10(11H)‐one and dibenzo[b,f]thiepin‐10(11H)‐one as useful synthons in the synthesis of various dibenzo[e,h]azulenes

The present review focuses on dibenzo[b,f]oxepin‐10(11H)‐one ( I , X = O) and dibenzo[b,f]thiepin‐10(11H)‐one ( I , X = S) as common synthons in the efficient synthesis of various dibenzoxepino[4,5‐ and dibenzothiepino[4,5]‐fused five‐membered heterocycles: [2,3] fused thiophene ( II ), [3,4] fused thiophene ( III ), furan ( IV ), pyrrole ( V ), imidazole ( VI ), pyrazole ( VII ), oxazole ( VIII ), and thiazole ( IX ). The potential of I to be converted into reactive intermediates that readily undergo heteroaromatic annulation reactions by cyclocondensation with proper binucleophiles allows formation of a range of enumerated functionalized dibenzo[e,h]azulene [4] structures ( II , III , IV , V , VI , VII , VIII , IX ). Dibenzo[e,h]azulenes as heterotetracyclic scaffold can be exploited in further modifications to obtain compounds with altered physicochemical and biological profile. J. Heterocyclic Chem., (2012).     

Syntheses of derivatives of oestrane and 19-norsteroids from 6-methoxytetralone and 6-hydroxytetralone

The corresponding derivatives of Δ^{1,3,5(10),9,(11)}-8,14-seco- -homo-oestratetraen-3-ol-14,17a-dione(VII, VIII, IX) have been obtained by the condensation of 3-methoxy-, 3-hydroxy-, and 3-tetrahydropyranyloxy-1-vinyltetralols (IV, V, VI) with methyldihydroresorcinol. The diketones VIII and IX cyclize to form Δ^{1,3,5(10),8,14}- -homo-oestrapentaen-3-ol-17a-one (XIII), and the diketone (VII) may be converted, according to conditions, into 3-methoxy-Δ^{1,3,5(10),8,14}- -homo-oestrapentaen-17a-one (X), 3-methoxy-Δ_{1,3,5(10),9,(11)}- -homo-oestratetraen-14-ol-17a-one (XIV), and -homoequilenin (XI). Hydrogenation of the ketones X and XIII leads to the dihydroketones XV and XVI with a trans junction of the C and D rings. Reduction or hydrogen of XV gives the methyl ethers of -homo-oestrone and 8-iso- -homo-oestrone XIX and XVII which have been converted into the methyl ethers of (±)-oestrone and 8-iso-oestrone (XX and XXI). 19-Nor- -homotestosterone (XXV) and its methyl and ethyl analogues, which possess anabolic activity, have been obtained by a series of reactions from the ketones X and XV.     

Synthesis and reactions of 1-benzylide neaminoimidazo[1,2-a]imidazoles

The method of synthesizing condensed imidazo-heterocyclic systems has been extended to the production of N-benzylideneaminoimidazo[1,2-a]imidazoles (VI, VII), the successive hydrolysis and treatment with nitrous acid of which has enabled N-substituted imidazo[1,2-a]imidazoles to be obtained. A by-product of the synthesis is 1,2-dibenzylideneamino-4-phenyl-5-n-propylimidazole (VIII), the condensation of the reduction product of which with isatin leads to a tetracyclic system.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1190–1193, September, 1973.     

Electrooxidation of alken-1-ylarenes in aqueous alcohol solutions

In the initial stages of the electrooxidation of alken-1-ylarenes-propenyl-benzene (Ia) and 4-propenylanisole (Ib)- in aqueous alcohol solutions, 1,2-dialkoxypropyl- (II), 1-hydroxy-2-alkoxypropyl- (VII), and 1,2-dihydroxy-propyl arenes (VIII) are formed. Subsequent rupture of the C-C benzyl bond converts the ethers (II) into benzaldehyde acetals (III) and benzaldehydes (IV), and compounds (VII) and (VIII) into (IV). Benzaldehydes (IV) are also formed from (II) by hydrolysis of the acetals (III)- partly for (IIIa) and completely for (IIIb). Electrolysis of (Ia and Ib) in aqueous alcohol solution leads mainly to their conversion into benzaldehydes (IV).Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2356–2361, October, 1991.     

Syntheses of polyethylenimine containing asymmetric nucleic acid base derivatives as grafted pendants

Preparations of new model polymers of polynucleotides with linear polyethylenimine (PEI) backbones and optically active nucleic acid base derivatives as pending side chains are described. (±)-2-(Thymin-1-yl)propionic acid (II) and (±)-2-(adenin-9-yl)propionic acid (IV) were synthesized. These carboxylic acid derivatives were grafted onto PEI at the imino nitrogen by the p-nitrophenyl active ester method. The enantiomeric pairs of II were optically resolved with quinine to yield (?) and (+)-2-(thymin-1-yl)propionic acid (VII and VIII). VII and VIII were grafted onto PEI through amide bond by direct coupling with diethylphosphoryl cyanide to give optically active graft polymers. The related monomer and dimer model compounds were also prepared by the same method from diethylamine and dimethylethylene diamine, respectively.     

Synthesis of N-substituted C-normorphinans and their pharmacological properties.

Several N-substituted C-normorphinans (VIII and IX) were synthesized and tested for their analgetic and narcotic antagonist activities and physical dependence capacity. Treatment of N-formyl- octahydro-2-pyrindine (IIIc) with polyphosphoric acid readily gave N-formyl-C-normorphinan (IV). The N-nor bases (V and VII) obtained from IV were converted to VIII and IX. The N-methyl derivative (I), which was previously reported to be inactive by Haffner's method, exhibited potent analgetic activity by the hot plate method and the AcOH-induced writhing test. Compounds VIII and IX showed pharmacological properties similar to those of N-substituted morphinans and exhibited agonist (analgetic) and/or narcotic antagonist activities. The C-nor analogue (IXa) of cyclorphan (IIc) exhibited potent analgetic and antagonist activities with no physical dependence capacity in the single-dose suppression tests both in rats and monkeys.     

Studies on the Alkaloids of Formosan Lauraceous Plants XVIII Alkaloids of Neolitsea Buisanensis Yamamoto Et Kamikoti and Neolitsea Aurata (Hay.) Koidz

Two alkaloids, laurolitsine (V) and litsericine (VII), were isolated from the woods of Neolitsea buisanersis. Six alkaloids were isolated from the woods of Neolitsea aurata and five of them were laurolitsine (V), litsericine (VII), N–methyllitsericine (VIII), (+)–anonaine (IX), and (–)-roemerine (X) (Table I).