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Difficultly accessible pyrimidine, thiazolopyrimidine, triazolopyrimidine, and thiazinopyrimidine derivatives containing an oleyl residue were synthesized via alkylation of 6-oleyl-2-thiouracil. The structure of the synthesized compounds was established on the basis of their spectral data, elemental analyses, and chemical behavior. The in vitro cytotoxicity of selected compounds was screened against two human cancer cell lines, MCF-7 breast cancer and HepG2 liver cancer cell lines. 8-[(8Z)-Heptadec-8-en-1-yl)-3-hydroxy-3,4-dihydropyrimido[2,1-b][1,3]thiazin-6(2H)-one turned out to be the most potent with IC50 values of 12.5 and 20 μg/mL against MCF-7 and HepG2 cancer cell lines, respectively. The structure–activity relationship for this compound was interpreted in terms of molecular docking and molecular dynamics studies.

4-Amino-5-(heptadec-8-en-1-yl)-4H-1,2,4-triazole-3-thiol was prepared for the first time and reacted with different reagents to yield new series of 3-olyl-6-substituted [1,2,4]triazolo[3,4-b]thiadiazoles, 3-olyl-6-substituted [1,2,4]triazolo[3,4-b]thiadiazines, and S- or N-substituted 3-mercapto-1,2,4-triazoles. The synthesized compounds have been evaluated for their antimicrobial and antioxidant activities. These studies revealed that some of the screened compounds have promising antimicrobial and antioxidant activities.

A facile, convenient, and high yielding synthesis of a new series of pyrimidine N- and S-glycosides incorporating an oleyl residue from readily available starting materials was developed. The key step of this protocol is the formation of a 2-thioxopyrimidine as aglycon which is coupled with an activated cyclic and acyclic halo sugar in the presence of sodium hydride. In addition, 5-fluorouracil analogues containing an oleyl moiety were prepared. The in vitro anticancer activity of the newly synthesized compounds was evaluated against two human cancer cell lines, namely MCF-7 (breast) and HEPG2 (liver) carcinoma. The compounds exhibited moderate to high activities with IC 50 values of 13.2–34.2 μM for MCF-7 and 16.2–63.8 μM for HEPG-2 cell lines. 5-Fluorouracil derivatives incorporating a fatty residue are therefore potent against both cell lines.

The behavior of 4-azidocoumarin-3-carboxaldehyde ( 1 ) towards certain sulfur reagents such as isothiocyanates ( 2a–c ), thionyl chloride, Lawesson's reagent (LR, 3 ), and phosphorus pentasulfide as well as towards primary amines such as glycine ( 4 ) and towards anthranilic acid ( 5 ) was investigated. The structures of the new products were attested by suitable analytical and spectroscopic measurements.

The reaction of 3-amino-2-phenyl-4(3H)-quinazolinone with oxovinylidenetriphenylphosphorane afforded 5-phenylpyrazolo[1,5-c] quinazoline-2(3H)-one and triphenylphosphine oxide. On the other hand, when quinazolinone reacts with phosphorus ylides, the corresponding phosphorane adducts were obtained. Moreover, quinazolinone reacts with trisdialkylaminophosphines to give the new (dialkylamino)oxophosphonium dipolar products. Possible reaction mechanisms are considered and the structural assignments are based on analytical and spectroscopic results.

Thiohydantoin 1 reacts with 2-oxovinylidenetriphenylphosphorane (2) to give 1-methyl-2-thioxo-6-(triphenyl-λ5-phosphoranylidene)-hexahydro-furo[2,3-d]imidazol-5-one (5). On the other hand, when 1 reacts with phosphorus ylides 3a–d, the respective olefinic adducts 6a, 6b, 8, and the dimeric product 7 were obtained together with triphenyl-phosphine oxide. Moreover, the application of reagent 4 on 1 renders the new product 4-methyl-2,3-diphenyl-2,3,4,6-tetrahydro-1-oxa-1,3,4,6-tetra-azapentalene-5-thione. Mechanisms accounting for the formation of the products are presented based on analytical and spectroscopic data.

A facile, convenient, and high yielding synthesis of a new series of pyrimidine N- and S-glycosides incorporating an oleyl residue from readily available starting materials was developed. The key step of this protocol is the formation of a 2-thioxopyrimidine as aglycon which is coupled with an activated cyclic and acyclic halo sugar in the presence of sodium hydride. In addition, 5-fluorouracil analogues containing an oleyl moiety were prepared. The in vitro anticancer activity of the newly synthesized compounds was evaluated against two human cancer cell lines, namely MCF-7 (breast) and HEPG2 (liver) carcinoma. The compounds exhibited moderate to high activities with IC 50 values of 13.2–34.2 μM for MCF-7 and 16.2–63.8 μM for HEPG-2 cell lines. 5-Fluorouracil derivatives incorporating a fatty residue are therefore potent against both cell lines.

Syntheses of the title ring systems are described starting with benzothiazol-2-ylacetohydrazide (1). Thus, 1 was reacted with carbon disulfide to afford the 2-methyl heteroaryl derivative 2, which on reaction with hydrazine hydrate yielded the corresponding triazole compound 3. Also, 1 can undergo a reaction with an isothiocyanate to give the N-thiocarbonyl adduct 4 that can then be cyclized to produce a 2-methyl heteroaryl analog 5 or 6. Compounds 8 or 9 could be obtained by the reaction of 1 with an aryl aldehyde followed by malononitrile or via its self-cyclization, respectively. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 177–182, 1999

The reaction of 2,4-bis-(4-methoxyphenyl)-1,3,2,4-dithiaphosphetane-2,4-disulfide (Lawesson's reagent. LR, 1) with ylidenemalononitriles (5a-f) was studied. Partial hydrolysis of 5a-f followed by thi-ation with LR yields the respective thioamides 7a-f. Nucleophilic attack by the monomeric form la of LR on 5, on the other hand, affords the respective 1,2-thiaphosphole-2-sulfides (cf. 9). Compatible elementary and spectroscopic measurements were gained for the new products (7a-f and 9a-d).

The reactions of the entitled compounds ( 4a ) and ( 4b ) with some phosphonium ylides ( 5a–d ) have been studied in considerable detail. By applying the Wittig reagents ( 5a,b ) on the thiazolidinones ( 4a,b ) in refluxing ethyl acetate and in the presence of triethylamine, conjugated dihydro-furo[2,3- d ]thiazol-2( 3H )-ones ( 7a–d ) were obtained while carrying out the reaction in refluxing toluene and also in the presence of triethylamine led to the formation of the pyrone derivatives ( 8 ). Reaction of 4a,b with oxoylide ( 5c ), afforded the pyranderivatives ( 10 ). On the contrary, the reaction of 4a,b with 5d underwent 1,2-addition reaction to yield the new ylides ( 12a,b ) as a sole reaction product. Except the last reaction of 4a,b with 5d , other reactions afforded, in each instance, the olefinated products ( 9a–d ) and ( 11a,b ) in 11–18% yield.

Quinone methide (1) reacts with excess carbmethoxymethylenetriphenylphosphorane (2a) to afford the new product 3a–6 whereas, with carbethoxymethylenetriphenylphosphorane (2b) yielded 3b, 4b, 13 and 14. It was also found that the polarity of the solvent has a limited role in the course of the reaction and in the yield of the condensation products of 1 and ylides 2. Mechanistic studies suggest that 10-methyleneanthrone (1) can react as a Diels-Alder diene and function as a dienophile in the same reaction. When the Wittig reaction was carried out on the new ylides 5 and 6 using benzaldehyde, the new olefins 16 and 17 were isolated.

Wittig-Horner reagents (2a-c) react with 5-(4-pyridyl)-2-thiono-1,3,4-oxadiazole (1) yielding the new adducts (3a-c). Structural reasoning for compounds 3 was based on compatible analytical and spectral data. The mechanism that accounts for the formation of 3 is discussed.

In contrast to the behaviour of the entitled disulfide (1) toward Wittig reagents (2a, b) , which undergoes direct and simple nucleophilic displacement reactions giving 7a, b, 8 and 9 as the final products, an extensive decomposition occurred when the same disulfide was treated with ylides 2c, d , furnishing the adducts 7c, d, 8 and 12 or 14 , respectively. The given structures were based upon analytical, chemical and spectroscopic results. Organic disulfides; tetramethylthiuram disulfide, Wittig reaction, thiaphosphirans.

In contrast to the behaviour of the entitled disulfide (1) toward Wittig reagents (2a, b) , which undergoes direct and simple nucleophilic displacement reactions giving 7a, b, 8 and 9 as the final products, an extensive decomposition occurred when the same disulfide was treated with ylides 2c, d , furnishing the adducts 7c, d, 8 and 12 or 14 , respectively. The given structures were based upon analytical, chemical and spectroscopic results. Organic disulfides; tetramethylthiuram disulfide, Wittig reaction, thiaphosphirans.

The reactions of the entitled compounds ( 4a ) and ( 4b ) with some phosphonium ylides ( 5a–d ) have been studied in considerable detail. By applying the Wittig reagents ( 5a,b ) on the thiazolidinones ( 4a,b ) in refluxing ethyl acetate and in the presence of triethylamine, conjugated dihydro-furo[2,3- d ]thiazol-2( 3H )-ones ( 7a–d ) were obtained while carrying out the reaction in refluxing toluene and also in the presence of triethylamine led to the formation of the pyrone derivatives ( 8 ). Reaction of 4a,b with oxoylide ( 5c ), afforded the pyranderivatives ( 10 ). On the contrary, the reaction of 4a,b with 5d underwent 1,2-addition reaction to yield the new ylides ( 12a,b ) as a sole reaction product. Except the last reaction of 4a,b with 5d , other reactions afforded, in each instance, the olefinated products ( 9a–d ) and ( 11a,b ) in 11–18% yield.

Syntheses of the title ring systems are described starting with benzothiazol-2-ylacetohydrazide (1). Thus, 1 was reacted with carbon disulfide to afford the 2-methyl heteroaryl derivative 2, which on reaction with hydrazine hydrate yielded the corresponding triazole compound 3. Also, 1 can undergo a reaction with an isothiocyanate to give the N-thiocarbonyl adduct 4 that can then be cyclized to produce a 2-methyl heteroaryl analog 5 or 6. Compounds 8 or 9 could be obtained by the reaction of 1 with an aryl aldehyde followed by malononitrile or via its self-cyclization, respectively. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 177–182, 1999