Synthesis from L-menthol of optically active macrolides with <Emphasis Type="Italic">N</Emphasis>-containing (azine or hydrazide) groups

Potentially useful 15- and 20-membered macrolides containing azine or hydrazide groups were synthesized from L-menthol via [1+1]-condensation at room temperature of 3R,7-dimethyl-6-oxooctyl-3R,7-dimethyl-6-oxooctanoate, which was obtained from 3R,7-dimethyl-6-oxooctanal via a Tishchenko reaction, with hydrazine hydrate or malonic acid dihydrazide.     

Reaction of 2,6-dibutylaminohepta-2,5-dien-4-one with malononitrile

Malononitrile reacted with the title compound to give 6-amino-5-cyano-2-(3,3-dicyano-2-methylallylidene-4-methyl-2H-pyran (3). Treatment of 3 with hot 80% sulfuric acid yielded 4,7-dimethyl-56-hydroxy-2(1H)quinolone. With concentrated aqueous sodium hydroxide, 3 gave 5-amino-3,6-dicyano-4,7-dimethyl-2(1H)quinolone and 5-amino-6-carbamoyl-3-cyano-4,7-dimethyl-2(1H)quinolone. The reaction of 3 with hydrochloric in acetic acid gave a mixture of 6-amino-3,7-dicyano-2,8-dimethyl-4-quinolizone and 3-cyano-4-methyl-6-(3,3-dicyano-2-methylallyl)-2-pyrone. Compound 3 also reacted with methylamine, butylamine and piperidine to give 8-amino-5-cyano-4-methyl-2-pyridone, 6-bulylamino-5-cyano-4-methyl-2-pyridone and 5-eyano-4-methyl-6-piperidino-2-pyridone respectively.     

13C-enriched end groups of poly(3,7-dimethyl-1-octene) prepared in the presence of isotactic specific catalysts

Polymerizations of (R,S)-3,7-dimethyl-1-octene in the presence of heterogeneous or homogeneous isotactic specific catalysts give very similar products with a homopolymeric isotactic structure. The insertion of (R,S)-3,7-dimethyl-1-octene into the metal-CH₃ bond (both heterogeneous and homogeneous catalysts) is highly stereospecific and stereoselective.     

Synthesis of enantiomerically pure macrolides with hydrazide fragments from tetrahydropyran and l-(+)-tartaric acid derivatives

A synthesis of two potentially useful bicyclic 26- and 33-membered macrolides containing 1,3-dioxolane and hydrazide fragments was developed starting from tetrahydropyran via a [1+1]-condensation of 7′-oxooctyl-7-oxooctanoate and bis(7-oxooctyl)hexanedioate with hydrazide of L-(+)-tartaric acid acetonide derivative.     

Photochemistry synthesis. Part 1: Syntheses of xanthine derivatives by photolysis of 1-(5′-oxohexyl)-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione (pentoxifylline): an ambident chromophore

We investigated the use of photochemistry to make novel derivatives of pentoxifylline. Under conditions that favour singlet excited states, we obtained 1-allyl-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione, (R^∗,R^∗)-(±)-1-{[2-hydroxy-2-methylcyclobutyl]methyl}-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione and 1-(5-hydroxyhexyl)-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione. Naphthalene or molecular oxygen increases the yields and triplet sensitisers (acetophenone, benzophenone and acetone) decrease the yields. Efficient intramolecular triplet energy transfer from the carbonyl to the xanthine moiety allows the carbonyl moiety to react from a singlet excited state only. In solvents with an α-hydroxyalkyl hydrogen under conditions that favour triplet excited states, we obtained 8-substituted pentoxifylline derivatives: 8-(1-hydroxy-1-methylethyl)-3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione in isopropanol, 8-(1-hydroxymethyl)-3,7-dimethyl-1-(5-oxo-hexyl)-3,7-dihydro-1H-purine-2,6-dione in methanol and 8-(1-hydroxyethyl)-3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione in ethanol. The xanthine moiety reacts from a triplet state via a radical mechanism and yields are considerably improved by the addition of catalytic amounts of di-tert-butyl peroxide.     

Novel cembranolides (Coralloidolide D and E) and a 3,7-Cyclized cembranolide (Coralloidolide C) from the mediterranean coral Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium (= Parerytkropodium) coralhides (PALLAS, 1766) is shown to contain three novel diterpenes which are of biogenetic significance: the 3,7-cyclized cembranoid Coralloidolide C ( = (+)-(6R*, 7R*, 11S*, 12aS* 3aE)-7,8-epoxy-3,5,6,7,8,9,10,11,12,12a-decahydro-12a-hydroxy-11-isopropenyl-1,4-dimethyl-3-oxocyciopentacydoundecene-8,6-carbolactone; (?)- 3 ), the O-bridged diketonic cembranolide Coralloidolide D (= (+)-(1R*, 2S*, 3R*, 5R*, 12S*, 8Z)-2,5-epoxy-1-hydroxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetradeca-8-ene-1,3-carbolactone; (+)- 4 ), and the diketonic epoxycembranolide coralloidolide E (=(+)-(1R*, 2R*, 3R*, 12S*, 5Z, 8Z)-1,2-epoxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetra-deca-5,8-diene-1,3-carbolactone; (+)- 5 ), The latter in pyridine at r. t. undergoes a double bond shift from C(4) = C(5) to C(4) = C(18) to give the isomer (?)- 7 . Structural assignments are mainly based on ID and 2D NMR and MS spectral data. Either corailoidolide A ((?)- 1 ) or the hypothetic unsaturated 1,4-diketone 9 can be envisaged as the precursors of all coralloidolides.     

Skeletal rearrangements of <Emphasis Type="Italic">cis</Emphasis>-(-)-7,8-epoxycarveol derivatives promoted by triethylsilyl trifluoromethanesulfonate

Diastereoisomeric couples of (1R,5R,6RS)-2,6-dimethyl-7-oxabicyclo[3.2.1]oct-2-en-6-ylmethanols and their epoxide precursors, (5R,2′RS)-2-methyl-5-(2-methyloxiran-2-yl)cyclohex-2-en-1-ols, in the presence of triethylsilyl trifluoromethanesulfonate underwent [3.2.1]→[3.3.1] skeletal rearrangement with formation of scalemic mixtures of (1R,5R,6R)- and (1R,5R,6S)-2,6-dimethyl-6-triethylsiloxy-8-oxabicyclo[3.3.1]non-2-enes; the (6R)-stereoisomer was isolated as individual substance.     

7-Substituted 8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones and their broncholytic activity

Summary Alkylation of 8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (1) with alkyl halides inDMF in the presence of potassium carbonate, or alternatively, alkylation of its sodium salt (2) with alkyl iodide or hydroxyalkyl iodide afforded the 7-alkyl- or 7-(-hydroxyalkyl)-8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones3. 2-Substituted oxiranes reacted with1 catalyzed by2 or Triton B to yield 7-(2-hydroxyalkyl)-8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-diones4. Compounds3 and4 were tested for broncholytic activity. The most effective derivatives were3c and4b.

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7-Substituierte 8-Vinyl-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dione und ihre broncholytische Wirkung

Zusammenfassung Alkylierung von 8-Vinyl-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dion (1) mit Halogenalkanen in Gegenwart von Kaliumkarbonat inDMF oder Alkylierung seines Natrium-Salzes (2) mit Iodalkanen beziehungsweise Iodalkanolen führte zu den 7-Alkyl- bzw. 7-(-Hydroxyalkyl)-8-vinyl-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dionen3. 2-Substituierte Oxirane reagierten mit Verbindung1 unter Katalyse durch2 oder Triton B zu den entsprechenden 7-(2-Hydroxyalkyl)-derivaten4. Die Substanzen3 und4 wurden auf ihre broncholytische Wirkung geprüft. Die höchste Aktivität wurde bei den Derivaten3c und4b festgestellt.

     

[f]-Fused purine-2,6-diones: Synthesis of new [1,3,5]- and [1,3,6]-thiadiazepino-[3,2-f]-purine ring systems

Summary 6-Phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,8,9-hexahydro-[1,3,5]-thiadiazepino-[3,2-f]-purine (5) was obtained by a three-step synthesis from 8-mercapto-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (1) and 2-(benzoylamino)-ethyl chloride (2)via 8-(benzoylaminoethylthio)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (3) and its chloromido derivative4. The analogous 9-phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,6,7-hexahydro-[1,3,6]-thiadiazepino-[3,2-f]-purine (7) was synthesized either from compound1 and N-(2-chloroethyl)-benzimido chloridevia N-(chloroethyl)-S-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-7H-purin-8-yl)-benzothioimide (6), or alternatively from 7-(2-benzoylaminoethyl)-8-bromo-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (9), its 8-mercapto derivative10 and the corresponding chloroimido compound11 being the intermediates.Part of this paper was presented as a preliminary report at the Congress of Czech and Slovak Chemical Societies, Olomouc, Czech Republic, September 13–16, 1993     

Studies on ketene and its derivatives. CXI . Photoreaction of diketene with 2(1H)-quinolone derivatives

Photoreaction of diketene with 4-methyl-2(1H)-quinolone and 1,4-dimethyl-2(1H)-quinolone gave 2R*,2aR*,SbR*- and 2R*,2aS*8bS*-8b-methyl-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline-2-spiro-2′-(oxetan)-4′-one ( 6a and 6b ), and their 4-methyl derivatives 7a and 7b , respectively. Thermolysis of compounds 6 and 7 afforded 2aR*,8bS*-8b-methyl-2-methylene-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline ( 8 ) and its 4-methyl derivatives 9 , respectively. Similarly, photolysis of diketene and 4-acetoxy-2(1H)-quinolone gave 1R*,2aS*,8bS*- and 1R*,2aR*,8bR*-8b-acetoxy-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]-quinoline ( 11a and 11b ). Alcoholysis of compounds 11a and 11b with hydrogen chloride in methanol gave 1-hydroxy-1-(methoxycarbonyl)methylcyclobuta[c]quinoline derivative 12 and 13 which were transformed to 4-acetyl-3-methyl-2(1H)-quinolone ( 15 ) by further alcoholysis. Photoreaction of diketene with 2(1H)-quinolone derivatives gave the corresponding cyclobuta[c]quinoline spirooxetanone derivatives 18 and 23 , which, by thermolysis, were transformed to 2-methylenecyclobuta[c]quinoline 23 and 25 , respectively.     

Synthesis of (4R)-Methylnonan-1-ol and (4R,8RS)-Dimethyldecanal from (S)-(+)-3,7-Dimethyl-1,6-octadiene

Optically active (4R,8RS)-dimethyldecanal, an analog of the aggregation pheromone of the flour beetles Tribolium confusum and T. Castaneum, and (4R)-methylnonan-1-ol, the sex pheromone of the yellow mealworm Tenebrio molitor L., are synthesized using ozonolytic transformation of (6R,10)-dimethyl-9-undecen-2-one to (6R)-methyl-9-hydroxynonan-2-one in the key step. The starting compound is available as enantiomerically enriched (ee ~50%) (S)-(+)-3,7-dimethyl-1,6-octadiene.     

Electron Ionization Mass Spectra of Organophosphorus Compounds Part I: The Mass Fragmentation Pathways of Cyclic α-Aminophosphonates Monoester Containing 1,2,4-Triazinone Moiety

Abstract

The electron impact induced fragmentation reactions of 3-(4-chlorophenyl)-3,4- dihydro-2-ethoxy-2-oxido-7-methyl-2H,6H-[1,2,4]triazino[4,3-e][1,4,5,2]thiadiazaphosphin in-6-one (1), 3,7-dimethyl-2-ethoxy-2-oxido-1,2,3,4-tetrahydro-6H-[1,2,4]triazino[4,3-b][1,2,4,5]triazaphosphinin-6-one (2), and 9-amino-3,7-dimethyl-4-ethoxy-4-oxido-2,3,4,9-tetrahydro-8H-[1,2,4]triazino[3,2-c][1,2,4,5]triazaphosphinin-8-one (3) are presented and compared. The 1,2,4-triazine rings have almost identical fragmentation routes. The 1,2,4-triazine rings are rather stable relative to the phosphorus rings. Therefore, fragmentation of the phosphorus rings is more favorable for the compounds than the stable 1,2,4-triazine rings.     

2,5-dimethyl-4-phenylpyridine in the synthesis of substituted indolizines and indeno [2,1-f]indo lizines

The previously unknown 1-acyl-2-aryl(alkyl)-6-methyl-3,7-diphenylindolizines, 2,3-diphenyl-1-acetyl-6-oxo-6H-indeno[2,l-f ]indolizine and 2-methyl-3,6-diphenyl-1-acetyl-6-hydroxy-6H-indeno[2,1-f] indolizine were obtained from 2,5-dimethyl-4-phenylpyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1220–1223, September, 1972.     

Synthesis and transformations of (±)-trans-4aβ(H), saα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one

Hydrogenation of 4,7-dimethylcoumarin ( 1 ) in alkaline medium has been shown to furnish a mixture of (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one ( 2 ), (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 3 ) and (±)-cis-4aα(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 4 ) in 40:25:35:ratio, respectively. The stereochemistry of the major hydrogenation product 2 , has been established by transforming it to p-menthane derivatives e.g. (±)-2 (R)-[2′(R)hydroxy-4′(R) methylcyclohex-(1′S)-yl]propan-1-ol ( 20 ) and (±)-trans-3α,6β-dimethyl-3aβ(H),7aα(H)-octahydrobenzofuran ( 12 ). Starting from a mixture of lactones 2, 3 and 4 , lactone 3 has been obtained in pure state employing a sequence of reactions.     

Chiral cyclohexene block from <Emphasis Type="Italic">R</Emphasis>-(−)-carvone

The oxidation with SeO₂ of a methyl group linked to an sp²-hybridized carbon in the product of the intramolecular iodoetherification of cis-carveol afforded (1R,5R,7S)-7-iodomethyl-7-methyl-6-oxabicyclo[3.2.1]-oct-3-en-4-carbaldehyde and [(1R,5R,7S)-7-iodomethyl-7-methyl-6-oxabicyclo[3.2.1]oct-3-en-4-yl]methanol that were oxidized to methyl (1R,5R,7S)-7-iodomethyl-7-methyl-6-oxabicyclo[3.2.1]oct-3-en-4-carboxylate. The latter by the Zn-promoted opening of the γ-oxide ring was converted into the target chiral block, methyl (4R,6R)-6-hydroxy-4-(prop-1-en-2-yl)cyclohex-1-encarboxylate.     

Pyrimidine derivatives. IX . Synthesis of bromosubstituted 5-nitro-2,4(1H,3H)-pyrimidinedione derivatives

The following 5-nitro-2,4(1H,3H)-pyrimidinediones possessing bromo substituted side chains at the 1- and 6-positions were prepared by bromination of 3,6-dimethyl-1-(ω-hydroxyalkyl)-5-nitro-2,4(1H,3H)-pyrimidinediones 4a and 4b and its nitrates 2a and 2b . The three of mono-bromo derivatives are: 1-(ω-acetoxyalkyl and ω-hydroxyalkyl)-6-bromomethyl-3-methyl. 6a, 6b, 7a and 7b and 1-(ω-bromoalkyl)-3,6-dimethyl-2,4(1H,3H)- pyrimidinediones 8a and 8b . The one type dibromo derivatives are: 1-(ω-bromoalkyl)-6-bromomethyl-3-methyl-2,4(1H,3H)-pyrimidinediones 5a and 5b .     

A study of the Claisen—Eschenmoser reaction for hydroxymethylbenzofurans and-indoles

N,N-Dimethylacetamide dimethyl acetal reacted with 5(7)-substituted 2-(hydroxy-methyl)benzofurans to give N,N-dimethyl-2-(2-methylbenzofuran-3-yl)acetamides. Analogous reactions with 3-(hydroxymethyl)indole and 1-hydroxy-6-methyl-1,2,3,4-tetrahydro-carbazole afforded N,N-dimethyl-3-(3-indolyl)propionamide and N, N-dimethyl-2-(6-methyl-1,2,3,4-tetrahydrocarbazol-1-yl)acetamide, respectively. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 314–318, February, 2007.     

Synthesis of 3,3′-(1,6-hexanediyl)bis-pyrimidine derivatives and 3,4-dithia[6.6](1.3)pyrimidinophane

Several 3,3′-(1,6-hexanediyl)bis[6-methyl-2,4(1H,3H)-pyrimidinedione] derivatives ( 4a, 4b , and 4c ) were synthesized from 1,6-(hexanediyl)bis[6-methyl-2H-1,3-oxazine-2,4(3H)-dione] (3) . Compound 4c was converted to 6, which reacted with thiourea giving thiuronium salt 7 . 3,3′-(1,6-Hexanediyl)bis [1-(2-mercaptoethyl)-6-methyl-2,4(1H,3H)-pyrimidinedione] (9) was obtained by the hydrolysis of 7 , and then 9 was oxidized to 12,22-dimethyl-3,4-dithia[6.6] (1.3)-1,2,3,4-tetrahydro-2,4-dioxopyrimidinophane (10) .     

Synthesis and molecular structure of 7<Emphasis Type="Italic">H</Emphasis>-12-oxa-3,7-diazapleiadene-substituted 1,3-tropolones

An acid-catalyzed reaction of substituted 2-methyl-7H-12-oxa-3,7-diazapleiadenes with 1,2-benzoquinones leads to 7H-12-oxa-3,7-diazapleiadene-substituted 1,3-tropolones. Molecular structure of 5,7-di(tert-butyl)-2-[9,11-di(tert-butyl)-4-methyl-7H-12-oxa-3,7-diazapleiaden-2-yl]-4-nitro-1,3-tropolone was established by X-ray crystallography. Energy and structural characteristics of isomeric 5,7-di(tert-butyl)-2-[9,11-di(tert-butyl)-4-methyl-7H-12-oxa-3,7-diazapleiaden-2-yl]-4-nitro-1,3-tropolones in the gaseous phase and a polar solution were studied by the PBE0/6-31G** method.     

Oxidation of (1<Emphasis Type="Italic">S</Emphasis>,5<Emphasis Type="Italic">R</Emphasis>,7<Emphasis Type="Italic">R,S</Emphasis>)-(4,7-dimethyl-6-oxabicyclo[3.2.1]oct-3-en-7-yl) methanol with pyridinium chlorochromate

The oxidation of (1S,5R,7R,S)-(4,7-dimethyl-6-oxabicyclo[3.2.1]oct-3-en-7-yl)methanol epimeric at the C⁷ atom resulted in scalemic (5R)-5-acetyl-2-methylcyclohex-2-en-1-one.