請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/96329
標題: Concise Synthesis of Stellettoside Glycosides
簡潔合成 Stellettoside 之三醣體醣苷骨架
作者: Yu-Tung Lin
關鍵字: L-阿拉伯糖
lanthanide triflates
orthogonal protecting group
regioselective protection
引用: [1] Peddie, V.; Takada, K.; Okuda, S.; Ise, Y.; Morii, Y.; Yamawaki, N.; Takatani, T.; Arakawa, O.; Okada, S.; Matsunaga, S., Cytotoxic glycosylated fatty acid amides from a Stelletta sp. Marine Sponge. J. Nat. Prod. 2015, 78, 2808–2813. [2] (a) Houseknecht, J. B.; Lowary, T. L., Chemistry and biology of arabinofuranosyl- and galactofuranosyl-containing polysaccharides. Curr. Opin. Chem. Biol, 2001, 5, 677–682. (b) Crich, D.; Pedersen, C. M.; Bowers, A .A.; Wink, D. J., On the use of 3,5-O-benzylidene and 3,5-O-(di-tert-butylsilylene)-2-O-benzylarabinothiofuranosides and Their Sulfoxides as glycosyl donors for the synthesis of β-arabinofuranosides: importance of the activation method. J. Org. Chem. 2007, 72, 1553–1565. (c) Konishi, T.; Ishii, T., The origin and functions of arabinofuranosyl residues in plant cell walls. Trends in Glycoscience and Glycotechnology. 2012, 24, 13–23. (d) Kotake, T.; Yamanashi, Y.; Imaizumi, C, Tsumuraya, Y., Metabolism of L-arabinose in plants. J. Plant. Res. 2016, 129, 781–792. (e) Shinohara, H.;Matsubayashi, Y., Chemical synthesis of Arabidopsis CLV3 glycopeptide reveals the impact of hydroxyproline arabinosylation on peptide conformation and activity. Plant and Cell Physiol. 2013, 54, 369–374. (f) Wu, Y.; Xiong, D.-C.; Chen, S.-C.; Wang, Y.-S.; Ye, X.-S., Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units. Nat. Commun. 2017, 8, 14851. (g) Kinnaert, C.; Daugaard, M.; Nami, F.; Clausen, M. H., Chemical synthesis of oligosaccharides related to the cell walls of plants and algae. Chem. Rev. 2017, 117, 11337–11405. [3] (a) Fusetani, N.; Sata, N.; Asai, N.; Matsunaga S., Isolation and Sstructure elucidation of Erylusamine B, a new class of Marine natural products, which blocked an IL-6 receptor, from the Marine sponge Erylus placenta thielet. Tetrahedron Lett. 1993, 34, 4067–4070. (b) Zheng, D.; Zhou, L.; Guan, Y.; Chen, X.-Z.; Zhou, W.-Q.; Chen, X.-G.; Lei, P.-S., Synthesis of cholestane glycosides bearing OSW-1 disaccharide or its 1→4-linked analogue and their antitumor activities. Bioorg. Med. Chem. Lett. 2010, 20, 5439–5442. (c) Rao, Y.; Buskas, T.; Albert, A.; O'Neill, M. A.; Hahn, M. G.; Boons, G.-J. Synthesis and immunological properties of a tetrasaccharide portion of the B side chain of rhamnogalacturonan II (RG-II). Chem. BioChem. 2008, 9, 381–388. (d) Sun, J.; Han, X.; Yub, B., Synthesis of a typical N-acetylglucosamine-containing saponin, oleanolic acid 3-yl α-L-arabinopyranosyl-(1→2)-β-L-arabinopyranosyl-(1→6)-2-acetamido-2-deoxy-β-D-glucopyranoside. Carbohydr.Res. 2003, 338, 827–833. (e) Mandal, S.; Das, R.; Mukhopadhyay, B., Synthesis of two trisaccharides related to the triterpenoid saponineryloside isolated from the sponge Erylus nobilis. Tetrahedron: Asymm. 2011, 22, 1108–1113. [4] (a) Valiullina, Z. R.; Khasanova, L. S.; Gimalova, F. A.; Selezneva, N. K.; Spirikhin, L. V.; Miftakhov, M. S., Synthesis of vespertilin conjugates with OSW-1 disaccharide blocks. Russ. J. Org. Chem. 2014, 10, 1538–1543. (b) Liu, Q.-C.; Guo, T.-T.; Zhao, C.; Sun, J.; Li, W.-H., synthesis of a trisaccharide related to the cytotoxic triterpenoid saponins isolated from the bark of Albizia procera. Helv. Chim. Acta. 2014, 97, 361–368. [5] (a) Yu, W.-S.; Jin, Z.-D., A new strategy for the stereoselective introduction of steroid side chain via α-alkoxy vinyl cuprates: total synthesis of a highly potent antitumor natural product OSW-1. J. Am. Chem. Soc. 2001, 123, 3369–3370. (b) Xue, J.; Liu, P.; Pan, Y.-B.; Guo, Z.-W., A total synthesis of OSW-1. J. Org. Chem. 2008, 73, 157–161. (c) Rao, Y.; Boons, G.-J., A highly convergent chemical synthesis of conformational epitopes of rhamnogalacturonan II. Angew. Chem. Int. Ed. 2007, 46, 6148–6151. (d) Khasanova, L. S.; Gimalova, F. A.; Valiullina, Z. R.; Selezneva, N. K.; Ganieva, R. M.; Spirikhin, L. V.; Miftakhov, M. S., New disaccharide blocks for OSW-1 and its analogs. Russ. J. Org. Chem. 2012, 48, 1238–1244. (e) Kongkathip, B.; Kongkathip, N.; Rujirawanich, J., New srategy for synthesis of the disaccaride moiety of the highly Potent anticancer natural product OSW-1. Synth. Commun. 2014, 44, 2248–2255. (f) Mancini, R. S.; McClary, C. A.; Anthonipillai, S.; Taylor, M. S., Organoboron-promoted regioselective glycosylations in the synthesis of a saponin-derived pentasaccharide from Spergularia ramose. J. Org. Chem. 2015, 80, 8501–8510. [6] (a) Wang, P.; Li, C.-X.; Zang, J.; Song, N.; Zhang, X.; Li, Y.-X., Synthesis of two bidesmosidic ursolic acid saponins bearing a 2,3-branched trisaccharide residue. Carbohydr. Res. 2005, 340, 2086–2096. (b) Wang, P.; Li, C.-X.; Wang, G.-F.; Li, Y.-X., Synthesis of an ursolic acid saponin with N-acetylglucosamine-containing trisaccharide Residue. Chin. J. Chem. 2006, 24, 1421–1426. [7] Miljkovic, M., Carbohydrides: synthesis, mechanisms, and stereoelectronic effects; Springer Science + Business Media, LLC, 2009. [8] 顏翊凌 《利用三價鑭系金屬催化醣類分子正交性保護基之設計》,2017 年。(國立中興大學化學研究所,碩士學位論文) [9] Yan, Y.-L.; Guo, J.-R.; Liang, C.-F., Sequential Dy(OTf)3-catalyzed solvent-free per-O-acetylation and regioselective anomer de-O-acetylation of carbohydrates. Chem. Asian. J. 2017, 12, 2471–2479. [10] Mukhopadhyay, B.; Kartha, K. P. R.; Russel, D. A.; Field, R. A., Streamlined synthesis of per-O-acetylated sugar, glycosyl iodides, or thio glycosides from unprotected reducing sugars. J. Org. Chem. 2004, 69, 7758 –7760. [11] (a) Khan, K. M.; Hayat, S.; Zia-Ullah; Atta-ur-Rahman; Choudhary, M. I.; Mafarvi, G. M.; Bayer, E., An alternative method for the synthesis of γ-lactones by using cesium fluoride-celite/acetonitrile combination. Synth. Commun. 2003, 33, 3435–3453. (b) Hughes, T. V.; Emanuel, S. L.; Grady, H. R. O'; Connolly, P. J.; Rugg, C.; Fuentes-Pesquera, A. R.; Karnachi, P.; Alexander, R.; Middleton, S. A., 7-[1H-Indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase inhibitors: design, synthesis, and biological activity. Bioorg. Med. Chem. Lett. 2008, 18, 5130–5133. (c) Malwal, S. R.; Chakrapani, H., Benzosulfones as photochemically activated sulfur dioxide (SO2) donors. Org. Biomol. Chem. 2015, 13, 2399–2406. [12] McNulty, J.; Keskar, K., Phthalide: a direct building-block toward P,O and P,N hemilabile ligands. Application in the palladium-catalysed Suzuki-Miyaura cross-coupling of aryl chlorides. Org. Biomol. Chem. 2013, 11, 2404–2407. [13] Daskiewicz, J.-B.; Depeint, F.; Viornery, L.; Bayet, C.; Comte-Sarrazin, G.; Comte, G.; Gee, J. M.; Johnson, I. T.; Ndjoko, K.; Hostettmann, K.; Barron, D., Effects of flavonoids on cell proliferation and caspase activation in a human colonic cell line HT29: an SAR study. J. Med. Chem. 2005, 48, 2790–2804. [14] Huang, H.-Y.; Liang, C.-F., Sequential Ytterbium(III) triflate catalyzed one-pot three-component thia-michael addition. Asian J. Org. Chem. 2018, 7, 955–963. [15] 郭峻榕 《利用三價鑭系金屬催化醣類分子正交性保護基之設計》,2017 年。(國立中興大學化學研究所,碩士學位論文) [16] Codée, J. D. C.; Litjens, R. E. J. N.; Bos, L. J. V. D.; Overkleeft, H. S.; Marel, G. A. V. D. Thiglycosides in sequential glycosylation strategies. Chem. Soc. Rev. 2005, 34, 769–782. [17] (a) Timmons, S. C.; Jakeman, D. L., Stereospecific synthesis of sugar-1-phosphates and their conversion to sugar nucleotides. Carbohy. Res. 2008, 343, 865–874. (b) Zhang, J.-B.; Zhou, J.-F.; Li, J.; Shi, C.-J.; Huang, T.; Wang, Z.-F.; Tang, J., H2SO4-SiO2: Highly efficient and reusable catalyst for per-O-acetylation of carbohydrates under solvent-free conditions. J. Carbohydr. Chem. 2011, 30, 165–177. [18] Morotii, A. L. M.; Lang, K. L.; Carvalho, I.; Schenkel, E. P.; Bemardes. L. S. C., Semi-synthesis of new glycosidic triazole derivatives of dihydrocucurbitacin B. Tetrahedron Lett. 2015, 56, 303–307. [19] Murakami, T.; Matsuda, H.; Inadzuki, M.; Hirano, K.; Yoshikawa, M., Medicinal Foodstuffs. XVI. Sugar Beet. (3): Absolute Stereostructures of Betavulgarosides II and IV, Hypoglycemic Saponins Having a Unique Substituent, from the Roots of Beta vulgaris L. Chem. Pharm. Bull. 1999, 47, 1717–1721. [20] Liu, C.; Wang, A.-P.; Jin, L.-L.; Guo, Y.-S.; Li, Y.; Zhao, Z.-H.; Lei, P.-S., Synthesis, conformational analysis and SAR research of OSW-1 analogues. Tetrahedron 2016, 72, 4091–4102.
摘要: We report a highly efficient strategy to synthesize the building blocks of stellettosides B, of use for biological and medicinal structure activity studies. The synthesis of Stellettoside glycosides is a challenge due to the need of multiple synthetic steps including regioselective protection and deprotection, which is used for the keeping peracetylated sugar unit of the non-reducing end after complete deprotection. By our retrosynthetic strategy, compound 1 served as a glycosyl donor starting from L-arabinose was synthesized by our recent report,9 We developed two methods for regioselective installation of orthogonal protecting group, namely ASMB, to prepare the building blocks of 10 and 11 served as glycosyl acceptors for glycosylation. We used lanthanide triflates as catalyst to get the compound 10, and used sodium thiosulfate as catalyst to get the compound 11. Model study of glycosylation between thioglycoside 5a and PMBOH was successfully achieved to obtain the desired product. Based on our experimental results, the installation of PMB group on anomeric center can be prevented the occurrence of aglycone transfer in glycosylation. Consequently, this work is still under process.
由於 Stellettoside B1-B4 混合物對於子宮頸癌的海拉細胞 (HeLa cells) 表現出中等的細胞毒殺活性 (cytotoxic activity),其 IC50 值為 9 μM,然而文獻報導並沒有分別針對這四種化合物進行活性測試,所以並不知道這四種化合物對於海拉細胞是否具有甚麼樣的生物活性,而此化合物目前也尚未成功合成。因此,為了合成非還原端之全乙醯基醣體 Stellettoside 的三醣體骨架,本篇論文將說明我們如何利用本實驗室開發之正交性保護基策略應用在以L-阿拉伯糖為起始物來合成建構組元,與解決在合成過程中前人所沒有說明的問題,進而去合成 Stellettoside 三醣體。   在合成醣體建構組元的部分,其合成策略面臨的挑戰是如何選擇性在三號或四號位置上保護和探討選擇去保護後將非還原端之乙醯基保留下來的方法開發。本論文中,我們開發出兩種不同方法,一種是在鑭系金屬催化下選擇性在三號位置引入 ASMB 保護基,而另一種是在硫代硫酸鈉的催化下選擇性在四號位置引入 ASMB 保護基。而在其醣基化反應的部分,則是目前利用 NIS 和鑭系金屬的催化下經由醣基化反應將 PMB 成功接於醣苷予體,我們期望未來也可將其應用於建構組元與三醣體的醣基化反應。
URI: http://hdl.handle.net/11455/96329
文章公開時間: 2021-07-26

檔案 大小格式 
nchu-107-7105051049-1.pdf13.48 MBAdobe PDF 請求副本

在 DSpace 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。