酸催化噁唑烷酮稠合吖環丙烷進行開環反應之合成研究

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姓名

蔡宗倫(Tsung-Lun Tsai) 查詢紙本館藏

畢業系所

化學學系

論文名稱

酸催化噁唑烷酮稠合吖環丙烷進行開環反應之合成研究

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至系統瀏覽論文 (2027-9-1以後開放)

摘要(中)

第一部分: KRN7000 肌醇類似物之合成研究
以 1,4-戊二烯-3-醇為起始物，利用夏普萊斯不對稱環氧化反應 (Sharpless epoxidation) 生成兩個立體中心，接著以高效率微波加熱的方式進行立體選擇性分子內吖環丙烷化 (stereoselective intramolecular aziridination) 以具有非鏡像選擇性的反應建立第三個立體中心，而最關鍵的步驟則是利用肌醇衍生物對吖環丙烷進行開環反應生成碳-氧鍵，最後經數步反應即可獲得具有五種不同長度醯基鏈的 KRN7000 肌醇類似物。
第二部分: 酸催化醇對噁唑烷酮稠合吖環丙烷進行開環反應
對單至三取代的噁唑烷酮稠合吖環丙烷以一至三級醇，進行酸催化開環反應的研究。此方法大幅縮短了反應時間，並且在室溫下就能進行反應，得到有立體選擇性的單一非鏡像的化合物。

摘要(英)

Part 1. Research on the Synthesis of KRN7000 Inositol Analogs
Using 1,4-pentadiene-3-ol as the starting material and utilizing Sharpless asymmetric epoxidation, two stereocenters were generated selectively. Subsequently, stereoselective intramolecular aziridination was carried out with high efficiency using microwave heating to establish the third stereocenter with high diastereoselectivity. The ring-opening of the aziridine by inositol derivatives to form a carbon-oxygen bond was critical. Further chemical transformations, five target KRN7000 inositol analogs with different lengths of acyl chains were obtained.
Part 2. Acid-Catalyzed Ring-Opening of Oxazolidinone Fused Aziridines by Alcohols
This study investigated acid-catalyzed ring-opening reactions of mono-, di and tri-substituted oxazolidinone-fused aziridines with primary, secondary and tertiary alcohols. This method significantly shortened the reaction time and allowed the reaction acurred at room temperature to yield the products with high stereoselectivity.

關鍵字(中)

★ 唑烷酮稠合吖環丙烷
★ 酸催化開環

關鍵字(英)

★ KRN7000
★ Oxazolidinone Fused Aziridines
★ acid-catalyzed ring-opening

論文目次

目錄
中文摘要 i
Abstract iii
目錄 v
圖目錄 vii
表目錄 viii
流程圖目錄 ix
式圖目錄 x
附圖目錄 xi
第一章緒論 2
1-1 研究動機 2
1-2 KRN7000 及其類似物的介紹 2
1-3 KRN7000半乳糖類似物之合成研究 6
1-4 本實驗室對 KRN7000 類似物的相關研究 9
1-5 目標產物設計 11
第二章結果與討論 12
2-1 KRN7000 肌醇類似物之逆合成分析 12
2-2 起始物吖環丙烷 9 的合成 13
2-3 去氧肌醇類似物的合成 15
2-4 羥基對噁唑烷酮稠合吖環丙烷進行開環反應 17
2-5 合成最終產物 KRN7000 肌醇類似物 22a-e 19
第三章結論 23
第四章緒論 26
4-1 研究動機 26
4-2 藉由氮烯與烯烴生成吖環丙烷 26
4-3 吖環丙烷開環反應之介紹 32
4-4 吖環丙烷在酸性條件下進行羥基開環反應之文獻 33
4-5 本實驗室對噁唑烷酮稠合吖環丙烷進行醇開環反應之研究 36
第五章結果與討論 39
5-1 合成化合物 39
5-2 合成三取代噁唑烷酮稠合吖環丙烷 39
5-3 合成三取代噁唑烷酮稠合吖環丙烷 41
5-4 醇對單取代噁唑烷酮稠合吖環丙烷進行開環反應 42
5-5 醇對二取代噁唑烷酮稠合吖環丙烷進行開環反應 44
5-6 醇對三取代噁唑烷酮稠合吖環丙烷進行開環反應 45
第六章結論 50
第七章實驗部分 51
7-1 實驗藥品及試藥 51
7-2 實驗器材與儀器 52
7-3 實驗步驟與光譜資訊 53
第八章參考資料 99

參考文獻

(1) Morita, M.; Motoki, K.; Akimoto, K.; Natori, T.; Sakai, T.; Sawa, E.; Yamaji, K.; Koezuka, Y.; Kobayashi, E.; Fukushima, H. Structure-Activity Relationship of .alpha.-Galactosylceramides against B16-Bearing Mice. J. Med. Chem. 1995, 38 (12), 2176-2187.
(2) Natori, T.; Morita, M.; Akimoto, K.; Koezuka, Y. Agelasphins, novel antitumor and immunostimulatory cerebrosides from the marine sponge Agelas mauritianus. Tetrahedron 1994, 50 (9), 2771-2784.
(3) Hayakawa, Y.; Rovero, S.; Forni, G.; Smyth, M. J. α-Galactosylceramide (KRN7000) suppression of chemical-and oncogene-dependent carcinogenesis. Proc. Nat. Acad. Sci. 2003, 100 (16), 9464-9469.
(4) Natori, T.; Akimoto, K.; Motoki, K.; Koezuka, Y.; Higa, T. Development of KRN7000, derived from agelasphin produced by Okinawan sponge. Folia Pharmacol Jpn. 1997, 110, 63-68.
(5) Taniguchi, M.; Harada, M.; Kojo, S.; Nakayama, T.; Wakao, H. The regulatory role of Vα14 NKT cells in innate and acquired immune response. Annu. Rev. Immunol. 2003, 21 (1), 483-513.
(6) Satoh, M.; Iwabuchi, K. Immunomodulatory Functions of α-GalCer and a Derivative, α-Carba-GalCer. Methods Mol. Biol. 2023, 1-11.
(7) Kawano, T.; Cui, J.; Koezuka, Y.; Toura, I.; Kaneko, Y.; Motoki, K.; Ueno, H.; Nakagawa, R.; Sato, H.; Kondo, E. CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 1997, 278 (5343), 1626-1629.
(8) Tashiro, T.; Nakagawa, R.; Hirokawa, T.; Inoue, S.; Watarai, H.; Taniguchi, M.; Mori, K. RCAI-56, a carbocyclic analogue of KRN7000: its synthesis and potent activity for natural killer (NK) T cells to preferentially produce interferon-γ. Tetrahedron Lett. 2007, 48 (19), 3343-3347.
(9) Yang, G.; Schmieg, J.; Tsuji, M.; Franck, R. W. The C-Glycoside Analogue of the Immunostimulant α-Galactosylceramide (KRN7000): Synthesis and Striking Enhancement of Activity. Angew. Chem., Int. Ed. Engl. 2004, 43 (29), 3818-3822.
(10) Tashiro, T.; Nakagawa, R.; Hirokawa, T.; Inoue, S.; Watarai, H.; Taniguchi, M.; Mori, K. RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000: Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines. Bioorg. Med. Chem. 2009, 17 (17), 6360-6373.
(11) Harrak, Y.; Barra, C. M.; Bedia, C.; Delgado, A.; Castaño, A. R.; Llebaria, A. Aminocyclitol-Substituted Phytoceramides and their Effects on iNKT Cell Stimulation. ChemMedChem. 2009, 4 (10), 1608-1613.
(12) Park, J.-J.; Lee, J. H.; Ghosh, S. C.; Bricard, G.; Venkataswamy, M. M.; Porcelli, S. A.; Chung, S.-K. Synthesis of all stereoisomers of KRN7000, the CD1d-binding NKT cell ligand. Bioorg. Med. Chem. Lett. 2008, 18 (14), 3906-3909.
(13) Banchet-Cadeddu, A.; Hénon, E.; Dauchez, M.; Renault, J.-H.; Monneaux, F.; Haudrechy, A. The stimulating adventure of KRN 7000. Org. Biomol. Chem. 2011, 9 (9), 3080-3104.
(14) Laurent, X.; Bertin, B.; Renault, N.; Farce, A.; Speca, S.; Milhomme, O.; Millet, R.; Desreumaux, P.; Hénon, E.; Chavatte, P. Switching Invariant Natural Killer T (iNKT) Cell Response from Anticancerous to Anti-Inflammatory Effect: Molecular Bases. J. Med. Chem. 2014, 57 (13), 5489-5508.
(15) Wu, T.-N.; Lin, K.-H.; Wu, Y.-T.; Huang, J.-R.; Hung, J.-T.; Wu, J.-C.; Chen, C.-Y.; Chu, K.-C.; Lin, N.-H.; Yu, A. L. Phenyl glycolipids with different glycosyl groups exhibit marked differences in murine and human iNKT cell activation. ACS. Chem. Biol. 2016, 11 (12), 3431-3441.
(16) Chang, Y.-J.; Hsuan, Y.-C.; Lai, A. C.-Y.; Han, Y.-C.; Hou, D.-R. Synthesis of α-C-Galactosylceramide via Diastereoselective Aziridination: The New Immunostimulant 4′-epi-C-Glycoside of KRN7000. Org. Lett. 2016, 18 (4), 808-811.
(17) Katsuki, T.; Sharpless, K. B. The first practical method for asymmetric epoxidation. J. Am. Chem. Soc. 1980, 102 (18), 5974-5976.
(18) Schreiber, S. L.; Schreiber, T. S.; Smith, D. B. Reactions that proceed with a combination of enantiotopic group and diastereotopic face selectivity can deliver products with very high enantiomeric excess: experimental support of a mathematical model. J. Am. Chem. Soc. 1987, 109, 1525-1529.
(19) ATSUUMI, S.; NAKANO, M.; KOIKE, Y.; TANAKA, S.; FUNABASHI, H.; HASHIMOTO, J.; MORISHIMA, H. A New Approach to the Stereospecific Synthesis of a Dihydroxyehylene Isostere. Chem. Pharm. Bull. 1990, 38 (12), 3460-3462.
(20) Yu, J.; Spencer, J. B. Stereoselective Deoxygenation of myo-Inositol Monotosylates with Lithium Triethylborohydride. J. Org. Chem. 1996, 61 (10), 3234-3235.
(21) Bergmeier, S. C.; Stanchina, D. M. A directed amidohalogenation reaction an unusual reaction of azidoformates. Tetrahedron Lett. 1995, 36 (26), 4533-4536.
(22) Posner, G. H.; Rogers, D. Z. Organic reactions at alumina surfaces. Mild and selective opening of epoxides by alcohols, thiols, benzeneselenol, amines, and acetic acid. J. Am. Chem. Soc. 1977, 99 (25), 8208-8214.
(23) Deng, Q.-H.; Wang, J.-C.; Xu, Z.-J.; Zhou, C. Y.; Che, C. M. Metal-Free Intramolecular Aziridination of Allylic Carbamates Mediated by Hypervalent Iodine Compounds. Synthesis 2011, 2011, 2959-2967.
(24) Tanner, D. Chiral Aziridines—Their Synthesis and Use in Stereoselective Transformations. Angew. Chem. Int. Ed. 1994, 33 (6), 599-619.
(25) Akhtar, R.; Naqvi, S. A. R.; Zahoor, A. F.; Saleem, S. Nucleophilic ring opening reactions of aziridines. Mol. Divers. 2018, 22, 447 - 501.
(26) Sweeney, J. B. Aziridines: epoxides’ ugly cousins? Chem. Soc. Rev. 2002, 31 (5), 247-258.
(27) Hu, X. E. Nucleophilic ring opening of aziridines. Tetrahedron 2004, 60 (12), 2701-2743.
(28) Bergmeier, S. C.; Stanchina, D. M. Synthesis of Vicinal Amino Alcohols via a Tandem Acylnitrene Aziridination−Aziridine Ring Opening. J. Org. Chem. 1997, 62 (13), 4449-4456.
(29) Prasad, B. B.; Sanghi, R.; Singh, V. K. Studies on ring cleavage of aziridines with hydroxyl compounds. Tetrahedron 2002, 58 (36), 7355-7363.
(30) Ghorai, M. K.; Das, K.; Shukla, D. Lewis Acid-Mediated Highly Regioselective SN2-Type Ring-Opening of 2-Aryl-N-tosylazetidines and Aziridines by Alcohols. J. Org. Chem. 2007, 72 (15), 5859-5862.
(31) Jiang, H.; Lang, K.; Lu, H.; Wojtas, L.; Zhang, X. P. Asymmetric Radical Bicyclization of Allyl Azidoformates via Cobalt(II)-Based Metalloradical Catalysis. J. Am. Chem. Soc. 2017, 139 (27), 9164-9167.
(32) Liu, C.-Y.; Angamuthu, V.; Chen, W.-C.; Hou, D.-R. Synthesis of Methyl l-Kijanosides by Regio- and Stereoselective Ring Opening of 2-Oxazolidinone-Fused Aziridines. Org. Lett. 2020, 22 (6), 2246-2250.
(33) Mansilla, H.; Afonso, M. M. Iron (III) Tosylate in the Preparation of Dimethyl and Diethyl Acetals from Ketones and β-Keto Enol Ethers from Cyclic β-Diketones. Synth. Commun. 2008, 38 (15), 2607-2618.

指導教授

侯敦仁(Duen-Ren Hou)

審核日期

2024-8-14

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