الفهرس 
Five membered heterocycles with oneOnly 14 pages are availabe for public view
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Abstract
This invistigation deals with the utility of fatty wastes (produced as by-products of Egypt for Oils and Soap Company, Zagazig, Egypt) in the synthesis of new heterocycles linked to fatty acid residue which could be of potential biological and industrial applications this work is summarized in the following :
First: Facile synthesis of 6-heptadec-8-enyl thiopyrimidines incorporating glycosyl moiety and their antitumor activity.
The synthesis of 6-oleyl pyrimidine derivatives incorporating cyclic and acyclic sugar residue through S- or N-bond formation. In addition, 5-fluorouracil (5 FU) analogues containing oleyl moiety have been achieved. The new synthesized compounds were evaluated as antitumor agent.
Coupling of the aglycon (thio pyrimidine) 1 with sodium hydride in dry N, N-dimethylformamide followed by the addition of ((2,3,4,6-tetra-O-acetyl)-α-D-gluco- (or glacto) pyranosyl bromide) gave the corresponding thioglycoside derivatives 2a,b . Additionally, the reaction of 1 with β-chloroethoxyethanol and β-chloro diethylether in the presence of ethanolic KOH afforded thiopyrimidine derivatives 3a and 3b, respectively. (cf. Scheme1)
The oxidation of thiopyrimidine 1 by boiling in 10% chloroacetic acid gave uracil derivative 4 in a good yield. (cf. Scheme1)
The alkylation of thiopyrimidine 1 with methyl iodide, in the presence of potassium hydroxide, yielded 2- methyl thiopyrimidine derivative (5) which was subjected to react with 2,3,4,6-tetra-O-acetyl-α-D-gluco pyranosyl bromide in the presence of NaH in dry DMF to give the N1-6 nucleoside. (cf. Scheme 2)
Moreover, When compound 5 was reacted with the selected N-nucleophiles (pyrrolidine, morpholine, piperidine, or piperazine ) as a nitrogen base at fused temperature, the substituted pyrimidines 7a-d were obtained in good yield.
Also, the coupling of the aglycon 7a-d with 2,3,4,6-tetra-O-acetyl-α-D-gluco pyranosyl bromide in the presence of NaH in dry DMF gave the corresponding β-glycoside derivatives 8a-d in a good yield. (cf. Scheme 2)
Finally, the reaction of compounds 1, 4, or 7d with lithium fluoride was performed through catalytic substitution reaction using cerium(IV) ammonium nitrate (CAN) to afford the products 9a, 9b, and 10, respectively.(cf. Scheme3)
The structures of newly synthesized compounds were confirmed on the basis of their elemental analysis and spectral data results (EIMS, IR, 1H and 13C NMR).
Second: Synthesis and charcterization of novel fused pyrimidine derivatives.
The preparation of novel heterocyclic derivatives from the thiopyrimidine 1 that have not been reported hitherto.
Thus, the reaction of thiopyrimidine 1 with epichlorohydrin in the presence of sodium bicarbonate gave 2-((3-Chloro-2-hyroxypropyl)thio)-6-(heptadec-8-en-1-yl)pyrimidine-4(1H)-one 11 in a moderate yield. (cf. Scheme 4)
The intermolecular cyclization of compound 11 by stirring in sodium ethoxide solution yielded compound 12 which could be obtained, directly, through reaction of 1 with epichlorohydrin in the presence of NaOEt in a very good yield.
Additionally, the ammination of compound 11 by piperidine or piperazine gave compounds 13a,b.
Finally, the acetylation of compound 12 with acetic anhydride yeilded 8-(heptadec-8-en-1-yl)-6-oxo-2,3,4,6-tetrahydropyrimido[2,1-b]thiazine-3-ylacetate 14. (cf. Schem 4)
On the other hand, the reaction of thiopyrimidine 1 with appropriate hydrazonoyl chlorides in dioxane in the presence of triethylamine under reflux gave thiazolopyrimidine derivatives 15a,b and triazolopyrimidine derivatives 16a-d.
Also, condensation reaction of compounds 16c,d with hydrazine hydrate 99% in absolute ethanol under reflux produced the hydrazide derivatives 17c,d, respectively. (cf. schem 5)
Furthermore, using alkyl halides (such as phenacyl bromide, ethyl bromo acetae and chloro acetonitril) in the presence of ethanolic potassium hydroxide solution, the alkylation reactions of 1 gave compounds, 19, 20 and 21, respectively. (cf. Scheme 6)
The structures of newly synthesized compounds were confirmed on the basis of their elemental analysis and spectral data results (EIMS, IR, 1H and 13C NMR).
Third: Chemical Behavior of 4- amino-5-(heptadec-8-en-1-yl)-4-H-1,2,4-triazole-3-thiol and pharmacological studies with the products.
The synthesis of a series of fused 1,2,4-triazoles with oleyl moiety by utilizing oleic acid and screened them for their antimicrobial and antioxidant activities.
The interaction of oleic acid 22 with thiocarbohydrazide at fused temperature afforded 4- amino-5-(heptadec-8-en-1-yl)-4-H-1,2,4-triazole-3-thiol 23 in a very good yield. (cf. Scheme6)
The resulted triazole 23 further converted to compound 24 and 25 by boiling in acetic anhydride. (cf. Scheme 7)
Also, Cyclocondensation of the SH and NH2 function groups of 23 with various substituted carboxylic acids in the presence of phosphorus oxychloride afforded a series of 3-(Heptadec-8-en-1-yl)-6-substituted [1, 2, 4] triazolo [3, 4-b] thiadiazoles ( 26a-e) in a fairly good yeild. (cf. Scheme 7)
Additionally, When compound 23 was reacted with acetyl amygdaline in absolute ethanol in the presence of triethylamine yielded compound 27 in a good yield.
Moreover, the reaction of the triazole 23 with phenacyl bromide derivatives in the same reaction condition, led to the formation of 28a,b.(cf. Scheme 7).
Reaction of the triazole derivative 23 with ethyl bromoacetate in absolute ethanol and in the presence of triethylamine afordded compound 29 which was converted to the corresponding acid 30 by hydrolysis in ethanolic sodium hydroxide.(cf. Scheme 8)
Compound 31 and 32 were successfully achived on treatment of 29 with an excess of hydrazine hydrate and ammonium hydroxide, respectively.(cf. Scheme 8)
On the other hand, the triazole 23 reacts with the appropriate 2-chloro-N-aryl actamides in dry acetone containing anhydrous K2CO3, as a catalyst, to yield the S-alkylated compounds 33 a-g in a good yield.( cf. Scheme 8)
Finally, when compound 23 was treated with som aromatic aldehydes namely, 4- chloro benzaldehyde, 4-fluoro benzaldehyde, 4-methoxy benzaldehyde and 3,4,5-trimethoxy benzaldehyde in dimethyl formamide gave 4-[(4-arylidine) amino]-5-(heptadec-8-en-1-yl) -4H-1,2,4-triazole-3-thiol 34a-d.(cf. Scheme 8)
The structures of newly synthesized compounds were confirmed on the basis of their elemental analysis and spectral data results (EIMS, IR, 1H and 13C NMR).
Some of the new synthesized compounds were screened for their antitumor, antimicrobial and antioxidant activities. It was found that the oleyl moiety containing analogues of 5-fluorouracil (compounds 9a and 10) were potent for both the two carcinoma cell lines MCF-7 and HEPG-2. Compound 30 is the most effective against BaciILus aureus(G-) and Staphylococcus aureus(G+)and compound 33e has high antifungal effect on Aspergillus niger which is higher than standard antifungal agent (fluconazole). Also, the study showed that the most of these compounds have significant activities as antioxidant agents.