天然化學連接法(Native Chemical ligation, NCL) 是被廣泛用作蛋白質化學合成的實用策略，該方法透過 N 端半胱胺酸 (Cysteine,
Cys) 和 C 端硫酯胜肽之間的化學選擇性反應於水相中形成天然肽鍵。儘管被廣泛用於肽鏈連接中，但是對於 N 端半胱胺酸的需求卻限制了此策略之連接位點。為了將此方法擴展到 Xaa–Cys 連接位點之外， 硫醇輔助基 (thiol-containing auxiliary) 的出現成為另一種替代半胱 胺酸的方法。然而，部分輔助基卻於連接反應結束後無法有效率地由 胜肽鏈上移除因而增加了合成難度，因此，本論文欲結合光化學與側鏈輔助連接法之優勢，將容易移除之光解輔助基團建構於穀胺酸(Glutamic acid, Glu) 之側鏈上，開發天然化學連接法之新策略。

Native chemical ligation (NCL) developed by Kent and coworkers is widely used as a practical method for the chemical synthesis of proteins. This method forms a native peptide bond by a chemoselective reaction between a N-terminal cysteine residue and a C-terminal thioester peptide. Despite its extensive use in peptide ligation, the requirement of a N-terminal cysteine has restricted the ligation sites. To extend the approach beyond Xaa–Cys connection, thiol auxiliaries mimicking the cysteine function were developed. However, some of these auxiliaries cannot be efficiently cleaved from the ligation product, while some require harsh conditions to remove, thus increasing the synthetic difficulties. Herein, we introduced a thiol-containing photocleavable auxiliary at the side-chain of glutamic acid to achieve the same function as cysteine. After completion of ligation, mild photo-irradiation was applied to remove the auxiliary to yield the final product. This method allows unprotected peptides to be joined together at cysteine-free ligation sites, expanding the scope of NCL reaction.

摘要 I
Abstract II
目錄 III
圖目錄 VI
表目錄 IX
流程圖目錄 X
縮寫對照表 XI
胺基酸對照表 XIV
第一章 緒論 1
1-1 前言 1
1-2 選擇性化學連接法 2
1-3 天然化學連接法 5
1-4 非半胱胺酸連接位點之天然化學連接法 6
1-4-1 以自由基去除半胱胺酸上之硫醇 6
1-4-2 N 端修飾硫醇輔助基團 9
1-4-3 側鏈輔助連接法 11
1-5 多肽硫酯之合成 14
1-5-1 硫解 safety-catch sulfonamide 以合成胜肽硫酯 14
1-5-2 硫解醯亞胺以合成胜肽硫酯 15
1-5-3 選擇性氧化醯胺或醯肼以合成胜肽硫酯 16
1-5-4 藉分子內 N→S 或 O→S 醯基遷移以合成胜肽硫酯.18
1-6 研究動機與構想 20
第二章 結果與討論 21
2-1 合成具光敏感輔助基團之胜肽 21
2-1-1 具光敏感輔助基團胜肽之逆合成分析 21
2-1-2 光敏感輔助基團之合成 21
2-1-3 合成具光敏感輔助基團之胺基酸建構單元 22
2-2 光解條件之測試 24
2-3 側鏈輔助連接法之模型實驗 26
2-4 糖尿病新藥利拉魯肽之合成 29
2-4-1 利拉魯肽之介紹 29
2-4-2 利拉魯肽合成之模型研究 29
2-5 神經內分泌調節肽之合成 35
2-5-1 神經內分泌調節肽之介紹 35
2-5-2 神經內分泌調節肽-1 之合成 36
2-6 提高分子內醯基遷移效率之嘗試 42
2-6-1 優化遷移效率之分析 42
2-6-2 移除酯鍵上之甲基進行側鏈輔助連接法 43
2-6-3 縮減分子內醯基遷移之環數進行側鏈輔助連接法 45
2-6-4 增加分子內醯基遷移之環數進行側鏈輔助連接法 47
2-6-5 結論 48
2-7 結論與未來展望 50
第三章 實驗部分 53
3-1 Reagents and solvents 53
3-2 Spectrum Notes 53
3-3 High-performance liquid chromatography (HPLC) 54
3-3-1 Analytical HPLC 54
3-3-2 Semi-preparative HPLC 54
3-4 Solid Phase Peptide Synthesis 54
3-4-1 General procedure for manual peptide synthesis 55
3-4-2 General procedure for microwave peptide synthesis 55
3-4-3 Final cleavage from resin 56
3-4-4 Peptide precipitation 56
3-4-5 Peptide purification and analysis 57
3-4-6 General procedure for thioester synthesis 57
3-5 UV-irradiation 58
3-6 Synthetic procedures and characterization 58
第四章 參考文獻 79
附錄 89
附錄目錄 90

1. Dawson, P.; Muir, T.; Clark-Lewis, I.; Kent, S., Synthesis of proteins by native chemical ligation. Science 1994, 266, 776-779.
2. Canne, L. E.; Bark, S. J.; Kent, S. B. H., Extending the Applicability of Native Chemical Ligation. J. Am. Chem. Soc. 1996, 118, 5891-5896.
3. Offer, J.; Boddy, C. N. C.; Dawson, P. E., Extending Synthetic Access to Proteins with a Removable Acyl Transfer Auxiliary. J. Am. Chem. Soc. 2002, 124, 4642- 4646.
4. Matthews, B. W., Structural and genetic analysis of protein stability. Annu. Rev.Biochem. 1993, 62, 139-160.
5. Jeffrey L. Cleland, C. S. C., Protein Engineering: Principles and Practice. Wiley 1996.
6. Nilsson, B. L.; Kiessling, L. L.; Raines, R. T., Staudinger Ligation:  A Peptide from a Thioester and Azide. Org. Lett. 2000, 2, 1939-1941.
7. Saxon, E.; Armstrong, J. I.; Bertozzi, C. R., A “Traceless” Staudinger Ligation for the Chemoselective Synthesis of Amide Bonds. Org. Lett. 2000, 2, 2141-2143.
8. Bode, J. W.; Fox, R. M.; Baucom, K. D., Chemoselective Amide Ligations by Decarboxylative Condensations of N-Alkylhydroxylamines and α-Ketoacids. Angew. Chem. Int. Ed. 2006, 45, 1248-1252.
9. Zhang, Y.; Xu, C.; Lam, H. Y.; Lee, C. L.; Li, X., Protein chemical synthesis by serine and threonine ligation. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 6657-62.
10. Wang, Y.-C.; Peterson, S. E.; Loring, J. F., Protein post-translational modifications and regulation of pluripotency in human stem cells. Cell Res. 2014, 24, 143-160.
11. Merrifield, R. B., Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide.J. Am. Chem. Soc. 1963, 85, 2149-2154.
12. Bodanszky, M., Principles of Peptide Synthesis. Berlin, 1984.
13. N. Seewald, H.-D. J., Peptides:Chemistry and Biology. Weinheim, 2002.
14. Hojo, H.; Matsumoto, Y.; Nakahara, Y.; Ito, E.; Suzuki, Y.; Suzuki, M.; Suzuki, A.; Nakahara, Y., Chemical Synthesis of 23 kDa Glycoprotein by Repetitive Segment Condensation:  A Synthesis of MUC2 Basal Motif Carrying Multiple O-GalNAc Moieties. J. Am. Chem. Soc. 2005, 127, 13720-13725.
15. Hackenberger, C. P. R.; Schwarzer, D., Chemoselective Ligation and Modification Strategies for Peptides and Proteins. Angew. Chem. Int. Ed. 2008, 47, 10030-10074.
16. Agouridas, V.; El Mahdi, O.; Diemer, V.; Cargoët, M.; Monbaliu, J.-C. M.; Melnyk, O., Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations. Chem. Rev. 2019, 119, 7328-7443.
17. Staudinger, H.; Meyer, J., Ü ber neue organische Phosphorverbindungen III. Phosphinmethylenderivate und Phosphinimine. Helv. Chim. Acta 1919, 2, 635-646.
18. Wieland, T. B., E.; Bauer, L.; Lang, H. U.; Lau, H. Über peptidsynthesen. 8. mitteilung bildung von S haltigen peptiden durch intramolekulare wanderung von aminoacylresten. Justus Liebigs Ann. Chem. 1953, 129-148.
19. Nilsson, B. L.; Soellner, M. B.; Raines, R. T., Chemical synthesis of proteins. Annu.Rev. Biophys. 2005, 34, 91-118.
20. Muralidharan, V.; Muir, T. W., Protein ligation: an enabling technology for the biophysical analysis of proteins. Nat. Methods 2006, 3, 429-38.
21. Kent, S. B. H., Total chemical synthesis of proteins. Chem. Soc. Rev. 2009, 38, 338-351.
22. McCaldon, P.; Argos, P., Oligopeptide biases in protein sequences and their use in
predicting protein coding regions in nucleotide sequences. Proteins 1988, 4, 99- 122.
23. Yan, L. Z.; Dawson, P. E., Synthesis of Peptides and Proteins without Cysteine Residues by Native Chemical Ligation Combined with Desulfurization. J. Am. Chem. Soc. 2001, 123, 526-533.
24. S. He, D. B., J. S. Davis, A. Loyola, K. Nishioka, J. L.; Gronlund, D. R., F. Meng, N. Kelleher, D. G. McCafferty, Proc. Natl. Acad. Sci. U.S.A 2003, 100, 12033- 12038.
25. Wan, Q.; Danishefsky, S. J., Free-radical-based, specific desulfurization of cysteine: a powerful advance in the synthesis of polypeptides and glycopolypeptides. Angew. Chem. Int. Ed. 2007, 46, 9248-52.
26. Crich, D.; Banerjee, A., Native Chemical Ligation at Phenylalanine. J. Am. Chem. Soc. 2007, 129, 10064-10065.
27. Haase, C.; Rohde, H.; Seitz, O., Native chemical ligation at valine. Angew. Chem. Int. Ed. 2008, 47, 6807-10.
28. Tan, Z.; Shang, S.; Danishefsky, S. J., Insights into the finer issues of native chemical ligation: an approach to cascade ligations. Angew. Chem. Int. Ed. 2010, 49, 9500-3.
29. Thompson, R. E.; Chan, B.; Radom, L.; Jolliffe, K. A.; Payne, R. J., Chemoselective peptide ligation-desulfurization at aspartate. Angew. Chem. Int. Ed. 2013, 52, 9723-7.
30. Malins, L. R.; Cergol, K. M.; Payne, R. J., Peptide Ligation–Desulfurization Chemistry at Arginine. Chembiochem 2013, 14, 559-563.
31. Yang, R.; Pasunooti, K. K.; Li, F.; Liu, X. W.; Liu, C. F., Dual native chemical ligation at lysine. J. Am. Chem. Soc. 2009, 131, 13592-3.
32. Chen, J.; Wang, P.; Zhu, J.; Wan, Q.; Danishefsky, S. J., A program for ligation at threonine sites: application to the controlled total synthesis of glycopeptides.
Tetrahedron 2010, 66, 2277-2283.
33. Siman, P.; Karthikeyan, S. V.; Brik, A., Native Chemical Ligation at Glutamine. Org. Lett. 2012, 14, 1520-1523.
34. Cergol, K. M.; Thompson, R. E.; Malins, L. R.; Turner, P.; Payne, R. J., One-Pot Peptide Ligation–Desulfurization at Glutamate. Org. Lett. 2014, 16, 290-293.
35. Ajish Kumar, K. S.; Haj-Yahya, M.; Olschewski, D.; Lashuel, H. A.; Brik, A., Highly efficient and chemoselective peptide ubiquitylation. Angew. Chem. Int. Ed. 2009, 48, 8090-4.
36. Shang, S.; Tan, Z.; Dong, S.; Danishefsky, S. J., An Advance in Proline Ligation. J. Am. Chem. Soc. 2011, 133, 10784-10786.
37. Malins, L. R.; Cergol, K. M.; Payne, R. J., Chemoselective sulfenylation and peptide ligation at tryptophan. Chem. Sci. 2014, 5, 260-266.
38. Botti, P.; Carrasco, M. R.; Kent, S. B. H., Native chemical ligation using removable Nα-(1-phenyl-2-mercaptoethyl) auxiliaries. Tetrahedron Lett. 2001, 42, 1831-1833.
39. Kawakami, T. A., S., A photoremovable ligation auxiliary for use in polypeptide synthesis. Tetrahedron Lett. 2003, 44, 6059-61.
40. Marinzi, C.; Offer, J.; Longhi, R.; Dawson, P. E., An o-nitrobenzyl scaffold for peptide ligation: synthesis and applications. Bioorg Med Chem 2004, 12, 2749-57.
41. Nadler, C.; Nadler, A.; Hansen, C.; Diederichsen, U., A Photocleavable Auxiliary for Extended Native Chemical Ligation. Eur. J. Org. Chem. 2015, 2015, 3095- 3102.
42. Brik, A.; Yang, Y.-Y.; Ficht, S.; Wong, C.-H., Sugar-Assisted Glycopeptide Ligation. J. Am. Chem. Soc. 2006, 128, 5626-5627.
43. Brik, A.; Ficht, S.; Yang, Y. Y.; Bennett, C. S.; Wong, C. H., Sugar-assisted ligation of N-linked glycopeptides with broad sequence tolerance at the ligation junction.
J. Am. Chem. Soc. 2006, 128, 15026-33.
44. Lutsky, M. Y.; Nepomniaschiy, N.; Brik, A., Peptide ligation via side-chain auxiliary. ChemComm 2008, 1229-31.
45. Kumar, K. S.; Harpaz, Z.; Haj-Yahya, M.; Brik, A., Side-chain assisted ligation in protein synthesis. Bioorg Med Chem Lett 2009, 19, 3870-4.
46. Payne, R. J.; Ficht, S.; Tang, S.; Brik, A.; Yang, Y.-Y.; Case, D. A.; Wong, C.-H., Extended Sugar-Assisted Glycopeptide Ligations:  Development, Scope, and Applications. J. Am. Chem. Soc. 2007, 129, 13527-13536.
47. Li, X.; Kawakami, T.; Aimoto, S., Direct preparation of peptide thioesters using an Fmoc solid-phase method. Tetrahedron Lett. 1998, 39, 8669-8672.
48. Clippingdale, A. B.; Barrow, C. J.; Wade, J. D., Peptide thioester preparation by Fmoc solid phase peptide synthesis for use in native chemical ligation. Journal of Peptide Science 2000, 6, 225-234.
49. Raz, R.; Rademann, J., Fmoc-Based Synthesis of Peptide Thioesters for Native Chemical Ligation Employing a tert-Butyl Thiol Linker. Org. Lett. 2011, 13, 1606- 1609.
50. Shin, Y.; Winans, K. A.; Backes, B. J.; Kent, S. B. H.; Ellman, J. A.; Bertozzi, C. R., Fmoc-Based Synthesis of Peptide-αThioesters:  Application to the Total Chemical Synthesis of a Glycoprotein by Native Chemical Ligation. J. Am. Chem. Soc. 1999, 121, 11684-11689.
51. Ingenito, R.; Bianchi, E.; Fattori, D.; Pessi, A., Solid Phase Synthesis of Peptide C-Terminal Thioesters by Fmoc/t-Bu Chemistry. J. Am. Chem. Soc. 1999, 121, 11369-11374.
52. Kenner, G. W.; McDermott, J. R.; Sheppard, R. C., The safety catch principle in solid phase peptide synthesis. J. Chem. Soc. D 1971, 636-637.
53. Backes, B. J.; Ellman, J. A., An Alkanesulfonamide “Safety-Catch” Linker for
Solid-Phase Synthesis. J. Org. Chem. 1999, 64, 2322-2330.
54. Heidler, P.; Link, A., N-acyl-N-alkyl-sulfonamide anchors derived from Kenner's safety-catch linker: powerful tools in bioorganic and medicinal chemistry. Bioorg Med Chem 2005, 13, 585-99.
55. Wieland, T. H., H. J., Aminosäure-Sulfimide. Chem. Ber. 1960, 93, 1236−1246.
56. Mezzato, S.; Schaffrath, M.; Unverzagt, C., An orthogonal double-linker resin facilitates the efficient solid-phase synthesis of complex-type N-glycopeptide thioesters suitable for native chemical ligation. Angew. Chem. Int. Ed. 2005, 44, 1650-4.
57. Blanco-Canosa, J. B.; Dawson, P. E., An efficient Fmoc-SPPS approach for the generation of thioester peptide precursors for use in native chemical ligation. Angew. Chem. Int. Ed. 2008, 47, 6851-5.
58. Weidmann, J.; Dimitrijević, E.; Hoheisel, J. D.; Dawson, P. E., Boc-SPPS: Compatible Linker for the Synthesis of Peptide o-Aminoanilides. Org. Lett. 2016, 18, 164-167.
59. Mahto, S. K.; Howard, C. J.; Shimko, J. C.; Ottesen, J. J., A reversible protection strategy to improve Fmoc-SPPS of peptide thioesters by the N-Acylurea approach. Chembiochem 2011, 12, 2488-94.
60. Fang, G.-M.; Li, Y.-M.; Shen, F.; Huang, Y.-C.; Li, J.-B.; Lin, Y.; Cui, H.-K.; Liu, L., Protein Chemical Synthesis by Ligation of Peptide Hydrazides. Angew. Chem. Int. Ed. 2011, 50, 7645-7649.
61. Vinogradov, A. A.; Simon, M. D.; Pentelute, B. L., C-Terminal Modification of Fully Unprotected Peptide Hydrazides via in Situ Generation of Isocyanates. Org. Lett. 2016, 18, 1222-1225.
62. Wang, J. X.; Fang, G. M.; He, Y.; Qu, D. L.; Yu, M.; Hong, Z. Y.; Liu, L., Peptide o-aminoanilides as crypto-thioesters for protein chemical synthesis. Angew. Chem.
Int. Ed. 2015, 54, 2194-8.
63. Kang, J.; Richardson, J. P.; Macmillan, D., 3-Mercaptopropionic acid-mediated synthesis of peptide and protein thioesters. ChemComm 2009, 407-409.
64. Erlich, L. A.; Kumar, K. S. A.; Haj-Yahya, M.; Dawson, P. E.; Brik, A., N- Methylcysteine-mediated total chemical synthesis of ubiquitin thioester. Org Biomol Chem 2010, 8, 2392-2396.
65. Hojo, H.; Onuma, Y.; Akimoto, Y.; Nakahara, Y.; Nakahara, Y., N-Alkyl cysteine- assisted thioesterification of peptides. Tetrahedron Lett. 2007, 48, 25-28.
66. Dheur, J.; Ollivier, N.; Vallin, A.; Melnyk, O., Synthesis of Peptide Alkylthioesters Using the Intramolecular N,S-Acyl Shift Properties of Bis(2-sulfanylethyl)amido Peptides. J. Org. Chem. 2011, 76, 3194-3202.
67. Taichi, M.; Hemu, X.; Qiu, Y.; Tam, J. P., A Thioethylalkylamido (TEA) Thioester Surrogate in the Synthesis of a Cyclic Peptide via a Tandem Acyl Shift. Org. Lett. 2013, 15, 2620-2623.
68. Nagaike, F.; Onuma, Y.; Kanazawa, C.; Hojo, H.; Ueki, A.; Nakahara, Y.; Nakahara, Y., Efficient microwave-assisted tandem N- to S-acyl transfer and thioester exchange for the preparation of a glycosylated peptide thioester. Org Lett 2006, 8, 4465-8.
69. Sharma, R. K.; Tam, J. P., Tandem Thiol Switch Synthesis of Peptide Thioesters via N–S Acyl Shift on Thiazolidine. Org. Lett. 2011, 13, 5176-5179.
70. Ken’ichiroh, N.; Megumi, S.; Toru, K.; Thomas, V.; Saburo, A., Generation of an S-Peptide via an N–S Acyl Shift Reaction in a TFA Solution. Bull. Chem. Soc. Jpn. 2006, 79, 1773-1780.
71. Shelton, P. M.; Weller, C. E.; Chatterjee, C., A Facile N- Mercaptoethoxyglycinamide (MEGA) Linker Approach to Peptide Thioesterification and Cyclization. J. Am. Chem. Soc. 2017, 139, 3946-3949.
72. Tsuda, S.; Shigenaga, A.; Bando, K.; Otaka, A., N→S Acyl-Transfer-Mediated Synthesis of Peptide Thioesters Using Anilide Derivatives. Org. Lett. 2009, 11, 823-826.
73. Eto, M.; Naruse, N.; Morimoto, K.; Yamaoka, K.; Sato, K.; Tsuji, K.; Inokuma, T.; Shigenaga, A.; Otaka, A., Development of an Anilide-Type Scaffold for the Thioester Precursor N-Sulfanylethylcoumarinyl Amide. Org. Lett. 2016, 18, 4416- 4419.
74. Ollivier, N.; Dheur, J.; Mhidia, R.; Blanpain, A.; Melnyk, O., Bis(2- sulfanylethyl)amino Native Peptide Ligation. Org. Lett. 2010, 12, 5238-5241.
75. Cargoët, M.; Diemer, V.; Snella, B.; Desmet, R.; Blanpain, A.; Drobecq, H.; Agouridas, V.; Melnyk, O., Catalysis of Thiol-Thioester Exchange by Water- Soluble Alkyldiselenols Applied to the Synthesis of Peptide Thioesters and SEA- Mediated Ligation. J. Org. Chem. 2018, 83, 12584-12594.
76. Zheng, J.-S.; Xi, W.-X.; Wang, F.-L.; Li, J.; Guo, Q.-X., Fmoc-SPPS chemistry compatible approach for the generation of (glyco)peptide aryl thioesters. Tetrahedron Lett. 2011, 52, 2655-2660.
77. Eom, K. D.; Tam, J. P., Acid-Catalyzed Tandem Thiol Switch for Preparing Peptide Thioesters from Mercaptoethyl Esters. Org. Lett. 2011, 13, 2610-2613.
78. Liu, F.; Mayer, J. P., An Fmoc Compatible, O to S Shift-Mediated Procedure for the Preparation of C-Terminal Thioester Peptides. J. Org. Chem. 2013, 78, 9848- 9856.
79. Szychowski, J.; Mahdavi, A.; Hodas, J. J. L.; Bagert, J. D.; Ngo, J. T.; Landgraf, P.; Dieterich, D. C.; Schuman, E. M.; Tirrell, D. A., Cleavable Biotin Probes for Labeling of Biomolecules via Azide−Alkyne Cycloaddition. J. Am. Chem. Soc. 2010, 132, 18351-18360.
80. 林芝蘭, 光解基團修飾天門冬胺酸進行側鏈輔助天然化學連接法. 國立清華大學, 新竹市, 2017.
81. 許為綸, 以光敏感輔助基團修飾之賴胺酸進行天然化學連接法探討大鼠抗微生物肽(rCRAMP)合成. 國立清華大學, 新竹市, 2019.
82. Estiarte, M. A.; Diez, A.; Rubiralta, M.; Jackson, R. F. W., Synthesis of a 3- aminopiperidin-2,5-dione as a conformationally constrained surrogate of the Ala- Gly dipeptide. Tetrahedron 2001, 57, 157-161.
83. Jackson, S. H.; Martin, T. S.; Jones, J. D.; Seal, D.; Emanuel, F., Liraglutide (victoza): the first once-daily incretin mimetic injection for type-2 diabetes. Pharm. Ther 2010, 35, 498-529.
84. Selvaraj, A.; Chen, H.-T.; Ya-Ting Huang, A.; Kao, C.-L., Expedient on-resin modification of a peptide C-terminus through a benzotriazole linker. Chem Sci 2017, 9, 345-349.
85. Toshinai, K.; Nakazato, M., Neuroendocrine regulatory peptide-1 and −2: Novel bioactive peptides processed from VGF. Cell. Mol. Life Sci. 2009, 66, 1939-1945.
86. Yamaguchi, H.; Sasaki, K.; Satomi, Y.; Shimbara, T.; Kageyama, H.; Mondal, M. S.; Toshinai, K.; Date, Y.; González, L. J.; Shioda, S.; Takao, T.; Nakazato, M.; Minamino, N., Peptidomic identification and biological validation of neuroendocrine regulatory peptide-1 and -2. The Journal of biological chemistry 2007, 282, 26354-60.
87. 王瑋皜, 以天然化學連接法合成不具有半胱胺酸單元之胜肽. 國立清華大學, 新竹市, 2015.
88. Schäfer, P. M.; McKeown, P.; Fuchs, M.; Rittinghaus, R. D.; Hermann, A.; Henkel, J.; Seidel, S.; Roitzheim, C.; Ksiazkiewicz, A. N.; Hoffmann, A.; Pich, A.; Jones,
M. D.; Herres-Pawlis, S., Tuning a robust system: N,O zinc guanidine catalysts for the ROP of lactide. Dalton Trans. 2019, 48, 6071-6082.
89. Wakselman, Z. L., Eur. J. Med. Chem. 1983, 18, 307-314.
90. Jarrige, L.; Merad, J.; Zaied, S.; Blanchard, F.; Masson, G., Easy Access to Quinolin-2(1H)-ones via a One-Pot Tandem Oxa-Michael–Aldol Sequence. Synlett 2017, 28, 1724-1728.
91. Suizu, M.; Muroya, Y.; Kakuta, H.; Kagechika, H.; Tanatani, A.; Nagasawa, K.; Hashimoto, Y., Cyclooxygenase Inhibitors Derived from Thalidomide. Chem. Pharm. Bull. 2003, 51, 1098-1102.
92. Atcher, J.; Solà, J.; Alfonso, I., Pseudopeptidic compounds for the generation of dynamic combinatorial libraries of chemically diverse macrocycles in aqueous media. Org Biomol Chem 2017, 15, 213-219.
93. Selvaraj, A.; Chen, H.-T.; Ya-Ting Huang, A.; Kao, C.-L., Expedient on-resin modification of a peptide C-terminus through a benzotriazole linker. Chem Sci 2018, 9, 345-349.
94. 顧皓, 在天門冬醯胺或穀氨醯胺側鏈建構光解輔助基團以進行天然化學連接
法合成胜肽, 國立清華大學, 新竹市, 2019.