β-L-Arabinokloraloz’un Mono- ve Di-Sülfonat Esterleri; 3-O-Korunmuş-5-Azido ve 5-O-Alkil Türevleri

Yıl 2019, Cilt: 21 Sayı: 62, 659 - 668, 21.05.2019

Nilgün Yenil

https://doi.org/10.21205/deufmd.2019216228

Öz

Bu araştırmada, basit monosakkarit iskeleti üzerinde
di-mesilat (metan sülfonat) ve di-tosilat ester grupları ile primer pozisyonda
azido gruplarının bulunduğu mono-mesilat ve mono-tosilat yapılı organik
türevlerin sentezi hedeflenmiştir. Bu hedef doğrultusunda, β-L-Arabinofuranoz
başlangıç şekeri olarak seçilmiştir. Bu monosakkarit biriminin kloral ile
derişik H₂SO₄ varlığındaki tepkimesi sonrası 1,2-O-(S)-Trikloroetiliden-β-L-arabinofuranoz
elde edilmiştir. Daha sonra, trikloroetiliden asetal halkası ile korunmuş olan
bu şekerin iskelet yapısı üzerinde öncelikle 3,5-Di-O-mesil (di-mesilat)
ve 3,5-di-O-tosil (di-tosilat) gruplarının var olduğu ester türevleri
sentezlenmiştir. Devamında, uygun reaksiyon koşullarında bu di-mesilat ve
di-tosilat ester türevlerinden 5-Azido-3-O-mesil ve 5-azido-3-O-tosil
türevleri elde edilmiştir. Ayrıca, 1,2-O-(S)-Trikloroetiliden-β-L-arabinofuranoz’un
mono-tosilat ester türevi, ilgili 5-O-tosil-3-O-metil türevini
elde etmek için gümüş oksit varlığında metil iyodür ile reaksiyona sokulmuştur.
Elde edilen bu türev uygun reaksiyon koşullarında 5-Azido-3-O-metil
türevine dönüştürülmüştür. İlaveten, 1,2-O-(S)-Trikloroetiliden-β-L-arabinofuranoz
ilgili 5-O-tritil türevi elde etmek için tritil klorür ile reaksiyona
sokulmuştur. 5-O-Tritil türevinin metilleme reaksiyonuyla 5-O-tiritil-3-O-metil
arabinokloraloz sentezlenmiştir. Böylelikle, 5-O-Tosil ve 5-O-tiritil
türevlerinde, karbohidrat iskelet biriminin sekonder hidroksil grubu metil
grubu ile korunmuştur. Sentezlenen tüm yeni moleküller spektroskopik teknikler
(IR, NMR ve Kütle) kullanılarak yapısal olarak karakterize edilmiştir.

Anahtar Kelimeler

Arabinoz, Azit, Furanoz, Kloraloz, Monosakkarit

Mono- and Di-Sulfonate Esters of -L-Arabinochloralose; 3-O-Protected-5-Azido and 5-O-Alkyl Derivatives

Öz

In this research, it was aimed to synthesize the
organic compounds containing di-mesylate (methane sulfonate) and di-tosylate
ester groups on the simple monosaccharide skeleton and mono-mesylate and
mono-tosylate organic derivatives including azido groups in the primer
position. In this target, β-L-arabinofuranose
was chosen as the starting sugar. After the reaction of this monosaccharide
unit with chloral in the presence of concentrated H₂SO₄,
1,2-O-(S)-trichloroethylidene-β-L-arabinofuranose
was firstly obtained. The ester derivatives, 3,5-di-O-mesyl (di-mesylate) and 3,5-di-O-tosyl (di-tosylate), were then synthesized on this sugar skeleton
protected with trichloroethylidene acetal ring. 5-Azido-3-O-mesyl and 5-azido-3-O-tosyl
derivatives of these di-mesylate and di-tosylate ester derivatives were
subsequently obtained under appropriate reaction conditions. Furthermore, the
mono-tosylate ester derivative of 1,2-O-(S)-Trichloroethylidene-β-L-arabinofuranose
was reacted with methyl iodide in the presence of silver oxide to obtain the
corresponding 5-O-tosil-3-O-methyl derivative. This obtained
derivative was converted to the 5-Azido-3-O-methyl
derivative under suitable reaction conditions. In addition, the 1,2-O-(S)-Trichloroethylidene-β-L-arabinofuranose
was reacted with trityl chloride to produce the corresponding 5-O-trityl derivative. The 5-O-Trityl-3-O-methyl arabinochloralose was synthesized by the methylation
reaction of 5-O-trityl derivative.
Thus, the secondary hydroxyl group of the carbohydrate skeleton unit is
protected by methyl group in the 5-O-tosyl
and 5-O-trityl derivatives. All newly
synthesized molecules were structurally characterized by using spectroscopic
techniques (IR, NMR and Mass).

Anahtar Kelimeler

Arabinoz, Azit, Furanoz, Kloraloz, Monosakkarit, Sülfonat ester

Kaynakça

• Griess, P. 1863-1864. On a New Class of Compounds in Which Nitrogen is Substituted for Hydrogen. Proceedings of the Royal Society of London, Cilt. 13, s. 375-384.
• Scriven, E.F.V. 1984. Azides and Nitrenes: Reactivity and Utility. E-Book, Academic Press. Inc. Orlando and London, 542 pp
• Scheinman, F. 1985. Azides and Nitrenes. Reactivity and utility. Edited by E.F.V Scriven. Book Reviews, Journal of Medicinal Chemistry, Cilt, 28 (5), s. 686. DOI: 10.1021/jm50001a026
• Smith, A.S.; Brown, B.B. 1951. The Synthesis of Heterocyclic Compounds from Aryl Azides. I. Bromo and Nitro Carbazoles. Journal of the American Chemical Society, Cilt, 73 (6), s. 2435-2437. DOI: 10.1021/ja01150a008
• Boyer, J.H.; Canter, F.C. 1954. Alkyl and Aryl Azides. Chemical Reviews, Cilt, 54 (1), s. 1-57. DOI: 10.1021/cr60167a001
• Hassner, A.; Stern, M. 1986. Synthesis of Alkyl Azides with a Polymeric Reagents. Angewandte Chemmie, International Edition, Cilt, 25 (5 ), s. 478-479. DOI: 10.1002/anie.198604781 Scriven, E.F.V.; Turnbull, K. 1988. Azides: Their Preparation and Synthetic Uses. Chemical Reviews, Cilt, 88 (2), s. 297-368. DOI: 10.1021/cr00084a001
• Brase, S.; Banert, K. 2010. Organic Azides: Synthesis and Applications. John Willey&Sons Ltd. Great Britain, 507 pp.
• Binkley, R.W.; Binkley, E.R. 2014. Radical Reactions of Carbohydrates, Vol. II-Radical reactions in Carbohydrate Synthesis. Chapter 15-Azides and Azo Compounds, s. 323-335 http://www.carborad.com/Volume%20II/volumeII.html (Erişim Tarihi: 15.05.2017)
• Yüceer, L. 1978. Galakto ve Glukokloralozlar. Bazı Tosil Türevlerinin Nükleofilik Sübstitüsyon Reaksiyonlarında Sterik ve Polar Etkenler. Doçentlik Tezi, 121 sayfa. İzmir.
• Eric, F.; Scriven, V.; Turnbull, K. 1988. Azides: Their Preparation and Synthetic Uses. Chemical Reviews, Cilt, 88 (2), s. 297-368. DOI: 10.1021/cr00084a001
• Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. 2005. Organic Azides: An Exploding Diversity of a Unique Class of Compounds. Angewandte Chemistry International Edition, Cilt, 44, s. 5188-5240. DOI: 10.1002/anie.200400657
• Joshi, S.M.; Cozar, A.; Gomez-Vallejo, V.; Koziorowski, J.; Llop, J.; Cossio, F. 2015. Synthesis of Radiolabeled Aryl Azide from Diazonium Salts: Experimental and Computational Result Permit the Identification of the Preferred Mechanism. Royal Society of Chemistry, Chemical Communication, Cilt 51, s. 8954-8957. DOI: 10.1039/C5CC01913C
• Singh, B.K.; Yadav, A.K.; Kumar, B.; Gaikwad, A.; Sinha, S.K.; Chatuverdi, V.; Tripathi, R.P. 2008. Preparation and Reactions of Sugar Azides with Alkynes: Synthesis of Sugar Triazoles as Antitubercular Agents. Carbohydrate Research, Cilt, 343, s. 1153-1162. DOI: https://doi.org/10.1016/j.carres.2008.02.013
• Alper, P.B.; Hung, S.C.; Wong, C.H. 1996. Metal Catalyzed Diazo Transfer for the Synthesis of Azides from Amines. Tetrahedron Letters, Cilt, 37 (34), s. 6029-6032. DOI: https://doi.org/10.1016/0040-4039(96)01307-X
• Malkinson, P.M.; Falconer, A.F.; Toth, I. 2000. Synthesis of C-Terminal Gylcopeptides from Resin via a Modified Staudinger Reaction. Journal of Organic Chemistry, Cilt, 65 (17), s. 5249-5252. DOI: 10.1021/jo000381z
• Matsubara, K.; Mukaiyama, T. 1994. High-yielding Catalytic Synthesis of Gylcosyl Azides from Peracylated Sugars. Chemistry Letters, Cilt, 23 (2), s. 247-250. DOI: http://dx.doi.org/10.1246/cl.1994.247
• Bianci, A.; Bernardi A. 2006. Traceless Staudinger Ligation of Gylcosyl Azides with Triaryl Phosphines: Stereoselective Synthesis of Glycosyl Amides. Journal of Organic Chemistry, Cilt 71 (12), s. 4565-4577. DOI: 10.1021/jo060409s
• Xiao, C.; Zhao, C.; He, P.; Tang, Z.; Chen, X. and Jing, X. 2010. Facile Synthesis of Glycopolypeptides by Combination of Ring-opening Polymerization of an Alkyne-Substituted N-carboxyanhydride and Click “Glycosylation”. Macromolecular Rapid Communications, Cilt, 31, s. 991-997. DOI: 10.1002/marc.200900821
• Moreno-Garcia, M.I.; Diaz-Perez, P.; Benito, M.J.; Mellet, O.C.; Defaye, J.; Fernandez, J.M.G. 2002. One-step Synthesis of Non-Anomeric Sugar Isothiocyanates from Sugar Azides. Carbohydrate Research, Cilt, 337, s. 2329-2323. DOI: https://doi.org/10.1016/S0008-6215(02)00273-2
• Becer, C.R.; 2012. The Gylcopolymer Code: Synthesis of Glycopolymers and Multivalent Carbohydrate-lectin Interaction. Macromolecular Rapid Communications, Cilt, 33, s. 742-752. DOI: 10.1002/marc.201200055
• Sabesan, S.; Neira, S. 1992. Synthesis of Glycosyl Phosphates and Azides. Carbohydrate Research, Cilt, 223, s. 169-185. DOI: https://doi.org/10.1016/0008-6215(92)80015-S
• Yenil, N.; Ay, E.; Ay, K.; Oskay, M.; Maddaluno, J. 2010. Sythesis and Antimicrobial Activities of Two Novel Amino Sugars Derived from Chloraloses. CArbohdrate Research, Cilt, 345 (11), s. 1617-1621. DOI: https://doi.org/10.1016/j.carres.2010.03.043
• Wang, J.; Chang, C.W.T. 2012. Systematic Synthesis of Amino Sugars and Their Stereoselective Glycosylation. Glycobiology and Drug Design, ACS Symposium Series, e-Book, Cilt, 1102, Chapter 10, s. 265-286. DOI: 10.1021/bk-2012-1102.ch010
• Ricci, A. 2008. Amino Group Chemistry: from Synthesis to the Life Science. Willey-VCH Verlag GmbH&Co. s. 257-300, Germany,
• Anıl, H.; Yüceer, L. 1983. Effects of the Trichloromethyl Group in Displacement Reactions of Some 3-O-Tosyl-1,2-O-trichloroethylidene-α-D-galacto- and -Gluco-furanose Derivatives. Carbohydrate Research, Cilt, 123(2), s. 315-319. DOI: https://doi.org/10.1016/0008-6215(83)88486-9
• Yenil, N.; 2009. Furanoz Türevi Aminoşekerlerden Yeni Sülfa İlaçlarının Sentezi ve Antimikrobiyal Aktiviteleri. Tübitak Proje Raporu, 106T410, 185 sayfa. Manisa.
• Kuypens, J.M.H. 1995. A New Photochemical Method for Surface Modification of Medical-grade Polyurethane Biomaterials to Improve Blood Compatibility. University of Limburg, BIOmaterials and Polymer Research Institute, Thesis, 101 pp. Eindhoven.
• Gritsan, N.P.; Koshkin, A.A.; Denisov, A.Y.; Markushin, Y.Y, Cherepanov, E.V.; Lebedev, A.V. 1997. Azidoethidium Derivatives as Photoaffinity Labels: Study of the Photochemistry of the Monoazidoethidium Derivatives in Water. Journal of Photochemistry and Photobiology B: Biology. Cilt, 37, s. 40-51. DOI: https://doi.org/10.1016/S1011-1344(96)07341-1
• Nilov, D.I. 2011. Photoaffinity Labeling Strategies Using Purine Nucleic Acid Bases. Bowling Green State University, PhD Thesis, 113 pp. USA.
• Drake, R.R.; Evans, R.K.; Wolf, M.J.; Haley, B.E. 1989. Synthesis and Properties of 5-Azido-UDP-Glucose. Development of Photoaffinity Probes for Nucleotide Diphosphate Sugar Binding Sites. Journal of Biological Chemistry, Cilt, 264 (20), s. 11928-11933.
• Bulut, A. The Synthesis of Some Stable Photosensitizers and their Photochemical Analysis. 1998, Ege University, Graduate School of Natural and Applied Sciences, PhD Thesis, 102 pp. İzmir.
• Sun, K.M.; Freiser-Reid, B. 1982. Annulated Sugars: The 1,2-O-Isopropylidene Ring as a Stereo-, Regio-, and Chemo-controlling Agent. Journal of American Chemical Society, Cilt, 104(1), s. 367-369. DOI: 10.1021/ja00365a100
• Özgener, H.; Yüceer, L. 2002. 2-Dichloromethyl-1,3-dioxolan-2-yl-ortho-esters. A Potential Protecting Group for Sugar Derivatives. Journal of Carbohydrate Chemistry, Cilt, 21(6), s. 559-567. DOI: http://dx.doi.org/10.1081/CAR-120016854
• Vatéle, J.M.; Hannesian, S. 1996. Design and Reactivity of Organic Functional Groups-preparation and Nucleophilic Displacement Reactions of Imidazole-1-sulfonates (Imidazylates). Tetrahedron, Cilt, 52(32), s. 10557-10568. DOI: https://doi.org/10.1016/0040-4020(96)00586-8
• Nadkami, S.; Williams, N.R. 1965. Displacement Reactions of Galactose 6-Sulphonate Derivatives. Journal of Chemical Society, s. 3496-3498
• Forsen, S. 1965. Trichloroethylidene Derivatives of D-Glucose. Acta Chemica Scandinavica, Cilt (19), s. 359-369.
• Seçen, S. Amino Şeker Türevlerinin Sentezi. 2005, Celal Bayar Üniversitesi, Fen Bilimleri Enstitüsü, Yüksek Lisans Tezi, 44 sayfa, Manisa. (5,6-Diazido-5,6-dideoksi-1,2-O-izopropiliden-α-D-glukofuranoz; 5,6-O-Ditosil-1,2-O-izopropiliden-α-D-glukofuranoz’un (2 g, 0.00536 mol) kuru DMF (30 ml) içindeki çözeltisine NaN3 (1.043 g, 0.16 mol) eklenir. Reaksiyon karışımı 90 0C de 3 saat karıştırıldıktan sonra sonlandırılır. DMF evapore edilerek konsantre reaksiyon çözeltisi buz-su karışımına dökülür. Organik madde CH2Cl2 ile ekstre edilir, Na2SO4 ile kurutulur ve CH2Cl2: Aseton (10:1) çözgen sistemi ile kolon kromatografisine tabi tutularak metanolden kristallendirilir (0.98 g; %76). Erime noktası: 109-110 0C. IR cm-1 (KBr): 3454 -OH, 2995-2932 alifatik C-H bağları, 2129 ve 2112 -N3; 1H-NMR (CDCl3 δ ppm): 5.92 (d, 1H, J1,2=3.6, H-1), 4.51 (d, 1H, J2,3=0, H-2), 4.34 (d, 1H, H-3) 4.13 ( ddd, 1H, J5,6a=6.3, H-5), 4.02 (dd, 1H, J3,4=2.8, H-4), 3.61 (dd, 1H, J5,6b=6.8, H-6a), 3.54 (dd, 1H, J6a,6b=12.8, H-6b), 1.48 (s, 3H, CH3), 1.32 (s, 3H, CH3))
• Koth, D.; Fiedler, A.; Scholz, S.; Gooschaldt, M. 2007. Synthesis of Different 3,5-Diazidofuranoses: A New and General Synthesis Pathway. Journal of Carbohydrate Chemistry, Cilt 26(5-6), s. 267-278. DOI: 10.1080/07328300701540175