1β-/3R-芳基硫代糖的区域与立体选择性合成

doi:10.6023/cjoc202307001

摘要/Abstract

硫代糖因具有优良的生物活性在生物医药领域备受关注, 化学合成是得到硫代糖的重要途径. 采用6-膦酸酯- 3,4-碳酸酯半乳烯糖和硫酚为原料, 分别以Pd₂(dba)₃和NiBr₂为催化剂调控了1β-芳基硫代糖和(3R)-芳基硫代糖的区域和立体选择性合成. 目标化合物的结构通过核磁共振、高分辨质谱和单晶X射线衍射进行了表征. 该合成方法对各类官能团取代的硫酚都有良好的兼容性, 可用于活性天然产物的硫糖基化修饰, 为1β-/(3R)-芳基硫代糖化合物库的快速构建和药物发现提供了新方法.

关键词: Pd催化, Ni催化, D-半乳糖, 硫代糖, 合成

Thiosugars have attracted much attention in the field of pharmaceuticals because of their excellent biological activities, and chemical synthesis is an important way to obtain thiosugars. Using 6-O-diphenylphosphoryl-3,4-O-carbonate-D-gala- ctal and thiophenols as starting materials, the regio- and stereo-selective syntheses of 1β-/(3R)-aryl thiosugars were controlled with NiBr₂ and Pd₂(dba)₃ catalysts, respectively. The structures of the target compounds were characterized by nuclear magnetic resonance, high-resolution mass spectrometry and single crystal X-ray diffraction. This method exhibited favourable compatibility with various functional groups substituted thiophenols, which could be used for the structural modification of active natural products. The research work is help for the rapid construction of the compound library of 1β-/(3R)-aryl thiosugars for drug discovery.

Key words: Pd catalysis, Ni catalysis, D-galactal, thiosugar, synthesis

引用此文

邹发凯, 王能中, 姚辉, 王慧, 刘明国, 黄年玉. 1β-/3R-芳基硫代糖的区域与立体选择性合成[J]. 有机化学, 2024, 44(2): 593-604.

Fakai Zou, Nengzhong Wang, Hui Yao, Hui Wang, Mingguo Liu, Nianyu Huang. Regio- and Stereo-selective Synthesis of 1β-/3R-Aryl Thiosugar[J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 593-604.

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[1]	Hu, J.; Lu, K.; Gu, C.; Heng, X.; Shan, F. J.; Chen, G. J. Biomacromolecule. 2022, 23, 1075. doi: 10.1021/acs.biomac.1c01409
[2]	Tyrikos-Ergas, T.; Fittolani, G.; Seeberger, P. H.; Delbinco, M. Biomacromolecule. 2019, 21, 18. doi: 10.1021/acs.biomac.9b01090
[3]	Ng, J. Y.; Tan, K. Y. F.; Ee, P. L. R. Biomacromolecule. 2022, 23, 2803. doi: 10.1021/acs.biomac.2c00176
[4]	Li, G. F.; Jing, J.; Luo, Z. Y.; Mo, J.; Xiong, D. C.; Ye, X. S. Chin. J. Org. Chem. 2023, 43, 1991 (in Chinese). doi: 10.6023/cjoc202211024
	(李格非, 荆杰, 罗振扬, 默娟, 熊德彩, 叶新山, 有机化学, 2023, 43, 1991.)
[5]	Morrone-Pozzuto, P.; Uhrig, M. L.; Agusti, R. J. Org. Chem. 2022, 87, 13455. doi: 10.1021/acs.joc.2c01059 pmid: 35775947
[6]	Wang, Q. Y.; Lai, M. N.; Luo, H. J.; Ren, K. K.; Wang, J. R.; Huang, N. Y.; Deng, Z. S.; Zou, K.; Yao, H. Org. Lett. 2022, 24, 1587. doi: 10.1021/acs.orglett.1c04378
[7]	Hou, M. Y.; Xiang, Y. M.; Gao, J. Y.; Zhang, J. Y.; Wang, N. Z.; Shi, H. L.; Huang, N. Y.; Yao, H. Org. Lett. 2023, 25, 832. doi: 10.1021/acs.orglett.2c04379
[8]	Qin, K.; Zhang, H.; Zhao, Z.; Chen, X. J. Am. Chem. Soc. 2020, 142, 9382. doi: 10.1021/jacs.0c02110 pmid: 32339456
[9]	Xiong, T.; Xie, R.; Huang, C.; Lan, X.; Huang, N. Y.; Yao, H. J. Carbohydr. Chem. 2021, 40, 401. doi: 10.1080/07328303.2022.2027433
[10]	Li, G.; Dao, Y.; Mo, J.; Dong, S. W.; Shoda, S.; Ye, X. S. CCS Chem. 2022, 4, 1930. doi: 10.31635/ccschem.021.202101115
[11]	Castaneda, F.; Burse, A.; Boland, W.; Kinne, R. K. Int. J. Med. Sci. 2007, 4, 131.
[12]	Zhang, J. J.; Cao, W.; Xi, P.; Li, L.; Qiao, S. T.; Luo, H. W.; Zhang, J. Y.; Liu, X. Y.; Du, N. S. J. Agric. Food Chem. 2021, 69, 12974. doi: 10.1021/acs.jafc.1c04725
[13]	Ding, X. L.; Kong, F. Z. Chin. J. Org. Chem. 2000, 20, 319 (in Chinese).
	(丁香兰, 孔繁祚, 有机化学, 2000, 20, 319.)
[14]	Liu, H.; Zhi, F.; Liu, H.; Liao, J.; Zhong, L.; Tu, Y.; Zhang, Q.; Xiong, B.; Sun, J. J. Am. Chem. Soc. 2023, 145, 3682. doi: 10.1021/jacs.2c13018
[15]	Marzo, T.; Cirri, D.; Gabbiani, C.; Gamberi, T.; Magherini, F.; Pratesi, A.; Guerri, A.; Biver, T.; Binacchi, F.; Stefanini, M.; Arcangeli, A.; Messori, L. ACS Med. Chem. Lett. 2017, 8, 997. doi: 10.1021/acsmedchemlett.7b00162
[16]	Epstein, T. D.; Wu, B.; Moulton K. D. Yan, M.; Dube, D. H. ACS Infect. Dis. 2019, 5, 1682. doi: 10.1021/acsinfecdis.9b00251 pmid: 31487153
[17]	Escrig, J. I.; Hahn, H. J.; Debnath, A. ACS Chem. Neurosci. 2020, 11, 2464. doi: 10.1021/acschemneuro.0c00165
[18]	Chevolleau, S.; Debrauwer, L.; Boyer, G.; Tulliez, J. J. Agric. Food Chem. 2002, 50, 5185. doi: 10.1021/jf020125i
[19]	Agneta, R.; Rivelli, A. R.; Ventrella, E.; Leario, F.; Sarli, G.; Bufo, S. A. J. Agric. Food Chem. 2012, 60, 7474. doi: 10.1021/jf301294h
[20]	Sun, J.; Kou, L.; Geng, P.; Huang, H.; Yang, T.; Luo, Y.; Chen, P. J. Agric. Food Chem. 2015, 63, 1863. doi: 10.1021/jf504710r
[21]	Birkenmeyer, R. D.; Kroll, S. J.; Lewis, C.; Stern, K. F.; Zurenko, G. E. J. Med. Chem. 1984, 27, 216. pmid: 6363698
[22]	Ding, C.; Bremer, N. M.; Smith, T. D.; Seitz, P. K.; Anastasio, N. C.; Cunningham, K. A.; Zhou, J. ACS Chem. Neurosci. 2012, 3, 538. doi: 10.1021/cn300020x
[23]	Guo, Z.; Bai, J.; Liu, M.; Xiong, D.; Ye, X. Chin. J. Org. Chem. 2020, 40, 3094 (in Chinese). doi: 10.6023/cjoc202006005
	(郭真言, 柏金和, 刘苗, 熊德彩, 叶新山, 有机化学, 2020, 40, 3094.)
[24]	Ji, P.; Zhang, Y.; Gao, F.; Bi, F.; Wang, W. Chem. Sci. 2020, 11, 13079. doi: 10.1039/D0SC04136J
[25]	Liu, J.; Zhang, G. Chin. J. Org. Chem. 2009, 29, 1890 (in Chinese).
	(刘青锋, 张贵生, 有机化学, 2009, 29, 1890.)
[26]	Sarkar, B.; Pramanik, T.; Jayaraman, N. J. Org. Chem. 2023, 88, 607.
[27]	Li, X.; Zhu, J. Eur. J. Org. Chem. 2016, 2016, 4724. doi: 10.1002/ejoc.v2016.28
[28]	Wan, Y.; Deng, L.; Tu, Y.; Liu, H.; Sun, J.; Zhang, Q. Chin. J. Chem. Eng. 2023, 41, 2837.
[29]	Zhang, G.; Gadi, M.; Cui, X.; Liu, D.; Zhang, J.; Saikam, V.; Gibbons, C.; Wang, P.; Li, L. Green Chem. 2021, 23, 2907. doi: 10.1039/D1GC00098E
[30]	Wang, Y.; Cao, Z.; Wang, N.; Liu, M.; Zhou, H.; Wang, L.; Huang, N. Adv. Synth. Catal. 2023, 365, 1699. doi: 10.1002/adsc.v365.10
[31]	Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596. doi: 10.1021/cr100347k pmid: 21391564
[32]	Li, J.; Wang, M.; Jiang, X. Org. Lett. 2021, 23, 9053. doi: 10.1021/acs.orglett.1c03302
[33]	Liu, Y.; Jiao, Y.; Luo, H. J.; Huang, N. Y.; Lai, M. N.; Zou, K.; Yao, H. ACS Catal. 2021, 11, 5287. doi: 10.1021/acscatal.1c00225
[34]	Jiao, Y.; Zhang, J.; Wang, S.; Yao H. ; Liu, M.; Huang, N. Chin. J. Struct. Chem. 2021, 40, 1238.
[35]	Yao, H.; Zhang, S.; Leng, W. L.; Leow, M. L.; Xiang, S. H.; He, J. X.; Liao, H. Z.; Hoang, K. L. M.; Liu, X. W. ACS Catal. 2017, 7, 5456. doi: 10.1021/acscatal.7b01630
[36]	Hua, M.; Sun, Y. X.; Zhang, X. Q.; Huang, N. Y.; Yao, H. Chin. J. Org. Chem. 2022, 42, 2140 (in Chinese). doi: 10.6023/cjoc202202021
	(华敏, 孙阳星, 张雪晴, 黄年玉, 姚辉, 有机化学, 2022, 42, 2140.)
[37]	Guerrero, G.; Mutin, P. H.; Vioux, A. Chem. Mater. 2001, 13, 4367. doi: 10.1021/cm001253u
[38]	Hoogenband, A.; Lange, J. H. M.; Bronger, R. P. J.; Stoit, A. R.; Terpstra, J. Tetrahedron Lett. W. 2010, 51, 6877. doi: 10.1016/j.tetlet.2010.10.125
[39]	You, X.; Cai, Y.; Xiao, C.; Ma, L.; Wei, Y.; Xie, T.; Chen, L.; Yao, H. Molecule. 2022, 27, 7979. doi: 10.3390/molecules27227979
[40]	Shang, W.; Shi, R.; Niu, D. Chin. J. Chem. 2023, 17, 2217.
[41]	Liu, X.; Lin, Y.; Liu, A.; Sun, Q.; Sun, H.; Xu, P.; Li, G.; Song, Y.; Xie, W.; Sun, H.; Yu, B.; Li, W. Chin. J. Chem. 2022, 40, 443. doi: 10.1002/cjoc.v40.4

Entry	Catalyst	Ligand	Solvent	Yield^c/%
1	PdCl₂	Xantphos	CH₂Cl₂	N.R.
2	Pd(PPh₃)₄	Xantphos	CH₂Cl₂	N.R.
3	Pd(OAc)₂	Xantphos	CH₂Cl₂	Trace
4	Pd(dba)₂	Xantphos	CH₂Cl₂	5
5	Pd(acac)₂	Xantphos	CH₂Cl₂	24
6	Pd₂(dba)₃	Xantphos	CH₂Cl₂	68
7	Pd₂(dba)₃	DPPB	CH₂Cl₂	57
8	Pd₂(dba)₃	DPPE	CH₂Cl₂	Trace
9	Pd₂(dba)₃	PPh₃	CH₂Cl₂	Trace
10	Pd₂(dba)₃	DPPF	CH₂Cl₂	46
11	Pd₂(dba)₃	DPEPhos	CH₂Cl₂	35
12	Pd₂(dba)₃	Xantphos	THF	23
13	Pd₂(dba)₃	Xantphos	Toluene	Trace
14	Pd₂(dba)₃	Xantphos	DMF	N.R.
15	Pd₂(dba)₃	Xantphos	CH₃CN	Trace
16^b	Pd₂(dba)₃	Xantphos	CH₂Cl₂	30

Entry	Catalyst	Ligand	Solvent	Yield^c/%
1	PdCl₂	Xantphos	CH₂Cl₂	N.R.
2	Pd(PPh₃)₄	Xantphos	CH₂Cl₂	N.R.
3	Pd(OAc)₂	Xantphos	CH₂Cl₂	Trace
4	Pd(dba)₂	Xantphos	CH₂Cl₂	5
5	Pd(acac)₂	Xantphos	CH₂Cl₂	24
6	Pd₂(dba)₃	Xantphos	CH₂Cl₂	68
7	Pd₂(dba)₃	DPPB	CH₂Cl₂	57
8	Pd₂(dba)₃	DPPE	CH₂Cl₂	Trace
9	Pd₂(dba)₃	PPh₃	CH₂Cl₂	Trace
10	Pd₂(dba)₃	DPPF	CH₂Cl₂	46
11	Pd₂(dba)₃	DPEPhos	CH₂Cl₂	35
12	Pd₂(dba)₃	Xantphos	THF	23
13	Pd₂(dba)₃	Xantphos	Toluene	Trace
14	Pd₂(dba)₃	Xantphos	DMF	N.R.
15	Pd₂(dba)₃	Xantphos	CH₃CN	Trace
16^b	Pd₂(dba)₃	Xantphos	CH₂Cl₂	30

Entry	Catalyst	Ligand	Solvent	Yield^c/%
1	Ni(DPPE)Cl₂	Xantphos	CH₃CN	N.R.
2	Ni(cod)₂	Xantphos	CH₃CN	21
3	Ni(PPh₃)₂Cl₂	Xantphos	CH₃CN	Trace
4	Ni[P(Cy)₃]₂Cl₂	Xantphos	CH₃CN	18
5	NiCl₂	Xantphos	CH₃CN	50
6	NiBr₂	Xantphos	CH₃CN	63
7	NiBr₂	DPPB	CH₃CN	N.D.
8	NiBr₂	DPPE	CH₃CN	N.R.
9	NiBr₂	PPh₃	CH₃CN	N.R.
10	NiBr₂	DPPF	CH₃CN	N.D.
11	NiBr₂	DPEPhos	CH₃CN	35
12	NiBr₂	Xantphos	THF	N.R.
13	NiBr₂	Xantphos	Toluene	N.R.
14	NiBr₂	Xantphos	DMF	N.R.
15^b	NiBr₂	Xantphos	CH₃CN	21

Entry	Catalyst	Ligand	Solvent	Yield^c/%
1	Ni(DPPE)Cl₂	Xantphos	CH₃CN	N.R.
2	Ni(cod)₂	Xantphos	CH₃CN	21
3	Ni(PPh₃)₂Cl₂	Xantphos	CH₃CN	Trace
4	Ni[P(Cy)₃]₂Cl₂	Xantphos	CH₃CN	18
5	NiCl₂	Xantphos	CH₃CN	50
6	NiBr₂	Xantphos	CH₃CN	63
7	NiBr₂	DPPB	CH₃CN	N.D.
8	NiBr₂	DPPE	CH₃CN	N.R.
9	NiBr₂	PPh₃	CH₃CN	N.R.
10	NiBr₂	DPPF	CH₃CN	N.D.
11	NiBr₂	DPEPhos	CH₃CN	35
12	NiBr₂	Xantphos	THF	N.R.
13	NiBr₂	Xantphos	Toluene	N.R.
14	NiBr₂	Xantphos	DMF	N.R.
15^b	NiBr₂	Xantphos	CH₃CN	21