2-metilfuran-3-karbohidrazid türevlerinin sentezi ve yapılarının aydınlatılması
Synthesis and structure identification of 2-methylfuran-3-carbohydrazide derivatives
Yazar: MERVE TANSUYU
Danışman: PROF. DR. ZAFER CESUR
İstanbul Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmasötik Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2010
Konu: Eczacılık ve Farmakoloji = Pharmacy and Pharmacology
Dizin: 2-metilfuran-3-karbohidrazid = 2-methylfuran-3-carbohydrazide ; Spektrum analizi = Spectrum analysis ; Tiyazolidinon = Thiazolidinone ; İlaçlar-araştırma safhasında = Drugs-investigational ; İnfluenza = Influenza ; İnfluenza virüs = Influenza virus

Özet:
Bu çalışmada, 2-metilfuran-3-karboksamid artığı taşıyan altı yeni spiroheterosiklik bileşik, N-(2-metil-3-okso-1-tiya-4-azaspiro[4.5]des-4-il)-2-metilfuran-3-karboksamid (3a), N-(2,8-dimetil-3-okso-1-tiya-4-azaspiro[4.5]des-4-il)-2-metilfuran-3-karboksamid (3b), N-(8-etil-2-metil-3-okso-1-tiya-4-azaspiro[4.5]des-4-il)-2-metilfuran-3-karboksamid (3c), N-(2-metil-3-okso-8-propil-1-tiya-4-azaspiro[4.5]des-4-il)-2-metilfuran-3-karboksamid (3d), N-(8-ter-bütil-2-metil-3-okso-1-tiya-4-azaspiro[4.5]des-4-il)-2-metilfuran-3-karboksamid (3e) ve N-(8-fenil-2-metil-3-okso-1-tiya-4-azaspiro[4.5]des-4-il)-2-metilfuran-3-karboksamid (3f) sentez edildi. Bunun için, metil 2-metilfuran-3-karboksilat (1) ve hidrazin hidratın reaksiyonundan elde edilen 2-metilfuran-3-karbohidrazid (2), 4-(nonsübstitüe/alkil/aril)siklohekzanonlar ile Dean-Stark su ayıracında N'-[4-(nonsübstitüe/alkil/aril)siklohekziliden]-2-metilfuran-3-karbohidrazid ara ürünlerini oluşturmak üzere reaksiyona sokuldu. Daha sonra siklokondensasyon reaksiyonu, istenen N-{8-(nonsübstitüteü/alkil/aril)-2-metil-3-okso-1-tiya-4-azaspiro[4.5]des-4-il}-2-metilfuran-3-karboksamidleri (3a-f) vermek üzere 2-merkaptopropanoik asit ilavesi ile tamamlandı. Ürünlerin oluşumları ile ilgili mekanizmalar tartışıldı ve bileşiklerin yapıları elemental analiz ve UV, IR, 1H-NMR, HMBC, HSQC, DEPT ve kütle spektrumlarından sağlanan veriler aracılığı ile doğrulandı. Bileşik 3a-f anti-influenza aktivite açısından değerlendirilmiştir. 3b, 3c ve 3d'nin influenza A/H3N2 virus'e karşı aktif oldukları saptanmıştır.Anahtar Kelimeler: Metil 2-metilfuran-3-karboksilat, 2-metilfuran-3-karbohidrazid, tiyazolidinon, spiro, anti-influenza aktivite.

Abstract:
In this study, six new spiroheterocyclic compounds bearing a 2-methylfuran-3-carboxamide moiety; N-(2-methyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2-methylfuran-3-carboxamide (3a), N-(2,8-dimethyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2-methylfuran-3-carboxamide (3b), N-(8-ethyl-2-methyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2-methylfuran-3-carboxamide (3c), N-(2-methyl-3-oxo-8-propyl-1-thia-4-azaspiro[4.5]dec-4-yl)-2-methylfuran-3-carboxamide (3d), N-(8-tert-butyl-2-methyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2-methylfuran-3-carboxamide (3e) and N-(2-methyl-3-oxo-8-phenyl-1-thia-4-azaspiro[4.5]dec-4-yl)-2-methylfuran-3-carboxamide (3f) were synthesized. Thus 2-methylfuran-3-carbohydrazide (2) obtained from the reaction of methyl 2-methylfuran-3-carboxylate (1) and hydrazine hydrate were reacted with 4-(nonsubstituted/alkyl/aryl)cyclohexanones to give N?-[4-(nonsubstituted/alkyl/aryl) cyclohexylidene]-2-methylfuran-3-carbohydrazides as intermediate compounds, using a Dean-Stark water separator. Then the cyclocondensation reaction were completed by the addition of 2-mercaptopropanoic acid to afford the desired N-{8-(nonsubstituted/alkyl/aryl)-2-methyl-3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl}-2-methylfuran-3-carboxamides (3a-f). The reaction mechanisms involved in the formation of the products were discussed and the structures of the compounds were confirmed by means of elemental analysis and the data obtained from UV, IR, 1H-NMR, HMBC, HSQC, DEPT and mass spectra. Compounds 3a-f were evaluated for anti-influenza activity. 3b, 3c and 3d were found to be active against influenza A/H3N2 virus.Key Words: Methyl 2-methylfuran-3-carboxylate, 2-methylfuran-3-carbohydrazide, thiazolidinone, spiro, anti-influenza activity.