Halohidrin Birimi İçeren Yeni İsoindol-1,3-dion Türevlerinin Sentezi

Year 2021, Volume: 11 Issue: 3, 2173 - 2183, 01.09.2021

Özlem Gündoğdu

https://doi.org/10.21597/jist.933775

Abstract

Bu çalışmada, 2–(benzil/etil/fenil/metil)-3a,4,7,7a-tetrahidro-1H-isoindol-1,3-(2H)-dion bileşiklerinin m-KPBA (m-kloroperbenzoik asit) ile reaksiyonları incelendi. Epoksidasyon reaksiyonlarından ana ürün olarak syn-epoksitler elde edildi. Daha sonra syn-epoksitlerin HBr ve HCl ile halka açılma reaksiyonları gerçekleştirildi. Epoksit halka açılma reaksiyonlarından halohidrin birimi içeren sekiz farklı isoindol türevi stereokontrollü olarak sentezlendi. Sentezlenen bileşiklerin yapıları spektroskopik yöntemler kullanılarak aydınlatıldı. Böylece kolay ve uygulanabilir yöntemler kullanılarak isoindol-1,3-dion ana iskelet yapısı içeren polifonksiyonel türevlerin sentezi için başlangıç veya öncü bileşikler elde edildi.

Keywords

Epoksitler, halka açılma reaksiyonu, isoindol-1, 3-dion, halohidrin

Thanks

Bu çalışmanın gerçekleşmesine katkı sağlayan Atatürk Üniversitesi Fen Fakültesi Kimya Bölümü’ne ve Kırşehir Ahi Evran Üniversitesi Kaman MYO’na teşekkür ederim.

Synthesis of New Isoindole-1,3-dione Derivatives Containing Halohydrin Unit

Abstract

In this study, the reaction of 2-(benzyl/ethyl/phenyl/methyl)-3a,4,7,7a-tetrahydro-1Hisoindole-1,3-(2H)-dione compounds with m-CPBA (m-chloroperbenzoic acid) has been examined. Syn-epoxides were obtained as the main product from the epoxidation reactions. Then, ring opening reactions of syn-epoxides with HBr and HCl were carried out. Eight different isoindole derivatives containing halohydrin units were synthesized from epoxide ring opening reactions in stereocontrol. The structures of the synthesized compounds were elucidated using spectroscopic methods. Thus, starting or precursor compounds were obtained for the synthesis of polyfunctional derivatives containing isoindole-1,3-dione main skeletal structure using easy and applicable methods.

Keywords

Epoxides, ring opening reaction, isoindol-1, 3-dione, halohydrin

References

• Aral T, 2010. Organokatalitik Asimetrik Epoksit Halka Açılma Reaksiyonları, Dicle Üniversitesi Fen Bilimleri Enstitüsü, Doktora Tezi (Basılmış).
• Aydın K, 2010. Reactions of salicylaldehyte derivatives with epoxides. Ege Üniversitesi Fen Bilimleri Enstitüsü, Yüksek Lisans Tezi (Basılmış).
• Bonollo S, Lanari D and Vaccaro L, 2011. Ring-Opening of Epoxides in Water. European Journal of Organic Chemistry, 2587–2598.
• Brana MF, Dominguez G, Saez B, Romerdahl C, Robinson S, Barlozzari T, 2001. Synthesis of Antitumor Dendritic Imides. Bioorgaanic Medicinal Chemical Letters, 11, 3027-3029.
• Chakraborti AK, Rudrawar S, Kondaskar A, 2004. An efficient synthesis of 2-amino alcohols by silicagel catalysed opening of epoxide rings by amines. Organic Biomolecules Chemistry, 2, 1277-1280.
• Ciganek E, Square K, 1993. Hydroisoindolines and Hydroisoquinolines as Psychotropi. United States Patent, 5, 216, 018.
• Cope AC, Herrick EC, 1950. Cis-Δ 4 -Tetrahydrophthalic Anhydride. Organic Syntheses Collective, 4, 890, 30, 93.
• Ecer K, Salamci E, 2014. Efficient and shortcut syntheses of some novel eight-membered ring cyclitols starting from cycloocta-1,3-diene. Tetrahedron, 70, 8389-8396.
• Kiss L, Forro E, Fulop F, 2012. Selective syntheses of novel highly functionalized beta-aminocyclohexanecarboxylic acids. Tetrahedron, 68, 23, 4438-4443.
• Köse A, Bal Y, Kishali NH, Sanli-Mohamed G, Kara Y, 2017. Synthesis and anticancer activity evaluation of new isoindole analogues. Medicinal Chemistry Research, 26 (4), 779-786.
• Köse A, Kaya M, Kishali NH, Akdemir A, Şahin E, Kara Y, Şanlı-Mohamed G, 2020. Synthesis and biological evaluation of New Chloro/Acetoxy Substituted Isoindole Analogues as new tyrosine kinase inhibitors. Bioorganic Chemistry, 94, 103421.
• Kushwahaa N, Kaushik D, 2016. Recent Advances and Future Prospects of Phthalimide Derivatives. Journal of Applied Pharmaceutical Science, 6 (3), 159-171.
• Lacy MQ, McCurdy AR, 2013. Pomalidomide. Blood, 122, 14, 2305-2309.
• Li D, Wang J, Yu S, Ye S, Zou W, Zhang H and Chen J, 2012. Highly regioselective ring-opening of epoxides with amines: A metal- and solvent-free protocol for the synthesis of β-amino alcohols. Chemical Communications, 00, 1-3. doi: 10.1039/C9CC09048G.
• Li M, Sun W, Yang Y, Xu B, Yi W, Ma Y, Li Z, Cui J, 2009. In vitro anticancer property of a novel thalidomide analogue through inhibition of NF-KappaB activation in HL-60 cells. Acta Pharmaceutica Sinica, 30, 134-140.
• Lima LM, Castro P, Machado AL, Fraga CA, Lugnier C, De Moraes VL, Barreiro EJ, 2002. Synthesis and anti-inflammatory activity of phthalimide derivatives, designed as new thalidomide analogues. Bioorganic & Medicinal Chemistry, 10, 3067-3073.
• Marca-Contelles J, Molina MT, Anjum S, 2004. Naturally occuring cyclohexene epoxides: Sources, Biyological Activites and Synthesis. Chemical Reviews, 104, 2857-2899.
• McCluskey A, Ackland SP, Bowyer MC, Baldwin ML, Garner J, Walkom CC and Sakoff AJ, 2003. Cantharidin analogues: synthesis and evaluation of growth inhibition in a panel of selected tumour cell lines. Bioorganic Chemistry. 31, 68–79.
• Mehta, G, Roy, S. 2004. Enantioselective Total Synthesis of (+)-Eupenoxide and (+)-Phomoxide:  Revision of Structures and Assignment of Absolute Configuration. Organic Letters, 6(14), 2389-2392.
• Moschona F, Savvopoulou I, Tsitopoulou M, Tataraki D and Rassias G, 2020. Epoxide Syntheses and Ring-Opening Reactions in Drug Development. Catalysts, 10, 1117.
• Neumann H, Strübink D, Lalk M, Klaus S, Hübner S, Spannenberg A, Lindequist U, Beller M, 2006. Synthesis and antimicrobial activity of N-analogous corollosporines. Organic and Biomolecular Chemistry, 4, 1365-1375.
• Polat İ, 2017. 6-aminosiklooktantriol, 2-amino-6-halosiklooktandiol, 3,4-dihidroksisiklooktan karboksilikasit ve türevlerinin sentezi. Atatürk Üniversitesi, Fen Bilimleri Enstitüsü, Yüksek lisans tezi, (Basılmış).
• Rickards RW, Duke RK, 1984. Stereospecific total synthesis of the cyclohexane oxide antibiotic eupenoxide. Journal of organic Chemistry, 49, 1898.
• Sabastiyan A, Suvaikin MY, 2012. Synthesis, characterization and antimicrobial activity of 2-(dimethylaminomethyl) isoindoline-1,3-dione and its cobalt(II) and nickel(II) complexes. Advances in Applied Science Research, 3, 45-50.
• Saddique FA, Zahoor AF, Faiz S, Naqvi SAR, Usman M and Ahmad M, 2016. Recent trends in ring opening of epoxides by amines as nucleophiles. Synthetic Communications, 46, 10, 831-868.
• Singh J, Singha T, Naskar A, Kundu M, Harwansh RK, Mondal A, Ghosh T, Maity TK, 2011. Synthesis and anti-proliferative activity of some isoindoline-1,3-dione derivatives against ehrlich’s ascites carcinoma bearing mice model, Pharmacologyonline, 2, 976-987.
• Süloğlu AK, Selmanoglu G, Gündoğdu Ö, Kishalı NH, Girgin G, Palabıyık S, Tan A, Kara Y, Baydar T, 2020. Evaluation of isoindole derivatives: Antioxidant potential and cytotoxicity in the HT‐29 colon cancer Cells. Archiv der Pharmazie, 353, 11.
• Tan A, Kazancıoglu MZ, Aktas D, Gundogdu O, Sahın E, Horasan Kıshalı N, Kara Y, 2014. Convenient Synthesis of New Polysubstituted İsoindole-1,3-Dione Analogues. Turkish Journal of Chemistry, 38, 629-637.
• Tan A, Koc B, Kishalı NH, Sahin E, Kara Y, 2016. Synthesis of New Norcantharimide Derivatives from 2-Methyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3-(2H)-dione. Turkish Journal of Chemistry, 40 (5), 830-840.
• Tan A, Koc B, Sahin E, Kishali NH, Kara Y, 2011. Synthesis of new cantharimide analogues derived from 3-sulfolene. Synthesis, 7, 1079-1084.
• Tan A, Yaglioglu AS, Kishali NH, Sahin E, Kara Y, 2018. Evaluation of Cytotoxic Potentials of Some Isoindole-1, 3-Dione Derivatives on HeLa, C6 and A549 Cancer Cell Lines. Medicinal Chemistry, 2020, 16, 69-77.
• Tan A, Yağlıoğlu AŞ, Kishalı NH, Şahin E, Kara Y, 2020. Evaluation of Cytotoxic Potentials of Some Isoindole-1, 3-Dione Derivatives on HeLa, C6 and A549 Cancer Cell Lines. Medicinal Chemistry, 69-77.
• Uyanık A, Şen N, Kurbanlı S, Kar Y, 2010. Bazı Aromatik Aminoalkollerin Sentezi ve Yapılarının Aydınlatılması. Selçuk Üniversitesi Fen Fakültesi Fen Dergisi, 35, 33-42.
• Zentz F, Valla A, Le Guillou R, Labia R, Mathot A, Sirot D, 2002. Synthesis and Antimicrobial Activities of N-Substitued Imides. IL Farmaco, 57, 421-42.
• Zhao XZ, Maddali K, Marchand C, Pommier Y, Burke JTR, 2009. Diketoacid-genre HIV-1 integrase inhibitors containing enantiomeric arylamide functionality. Bioorganic Medicinal Chemistry, 7, 15, 5318-5324.
• Zhao XZ, Semenova EA, Vu BC, Maddali K, Marchand C, Hughes SH, Pommier Y, Burke Jr TR, 2008. 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one-based HIV-1 integrase inhibitors. Journal of Medicinal Chemistry, 2008, 51, 251.