焦脱镁叶绿酸的区域和立体选择性的芳(芳酰)亚甲基化及其叶绿素类二氢卟吩衍生物的合成

doi:10.6023/cjoc202109052

摘要/Abstract

以焦脱镁叶绿酸-a甲酯为起始原料, 利用其外接环酮的空气氧化反应, 在大环色基N²¹-N²³轴的水溶性端向的不同位置上构建了甲酰基和邻位二酮结构. 通过交叉羟醛缩合反应, 在焦脱镁叶绿酸的外接环和12-位上区域和立体选择性地完成了芳(芳酰)亚甲基化, 合成出一系列未见报道的具有芳(芳酰)烯酮结构单元的叶绿素类二氢卟吩衍生物, 同时, 讨论了芳(芳酰)亚甲基化二氢卟吩的形成机理、立体异构以及紫外-可见光谱性质. 所有新合成化合物的结构均经UV-Vis、¹H NMR、MS以及元素分析予以证实.

关键词: 叶绿素, 二氢卟吩, 区域和立体选择性, 交叉羟醛缩合反应, 芳(芳酰)亚甲基化

Using the pyropheophorbide-a methyl ester as the starting material, the formyl group and α-diketone moiety were introduced into the water-soluble end of the N²¹-N²³ axis of the macrocyclic chromophore at different positions by the allomerization on the exocyclic ring ketone. Based on the cross-aldol condensation, the regio- and stereoselective aryl(aroyl)methylenations of pyropheophorbide-a were accomplished on the exocyclic ring and at C12-position. A series of unreported chlorin derivatives that contain the aryl(aroyl)ketene unit were synthesized. In addition, the formation mechanism, stereoisomerism and the optical properties of the aryl(aroyl)methylenated products were discussed. The chemical structures of all newly synthesized compounds were characterized by elemental analysis, MS, UV-Vis and ¹H NMR spectra.

Key words: chlorophyll, chlorin, regio- and stereoselectities, cross-aldol reaction, aryl(aroyl)methylenenation

引用此文

高娜, 初晓辉, 刘洋, 李家柱, 王进军. 焦脱镁叶绿酸的区域和立体选择性的芳(芳酰)亚甲基化及其叶绿素类二氢卟吩衍生物的合成[J]. 有机化学, 2022, 42(4): 1111-1122.

Na Gao, Xiaohui Chu, Yang Liu, Jiazhu Li, Jinjun Wang. Regio- and Stereoselective Aryl(aroyl)methylenenation of Pyropheophorbide and Syntheses of Chlorophyllous Chlorin Derivatives[J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1111-1122.

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图/表 8

Scheme 1. Synthesis of (aryl)methylenated chlorins 2~3 from 1a by cross-aldol reaction

Scheme 2. Synthesis of (aryl)methylenated chlorins 4~8 from chlorins 1a~3a by cross-aldol reaction Reaction conditions: (a) ArCHO, Sar, toluene, reflux; (b) CH2O, NaOMe, THF, r.t., N2; (c) ArCHO, NaOMe, THF, r.t., N2; (d) C6H5CHO, NaOMe, THF, r.t., N2; (e) C6H5CHO, Sar, toluene, reflux

Scheme 3. Synthesis of aroyl(aryl)methylenated chlorins 9~12 from chlorins 1b~1d by cross-aldol reaction Reaction conditions: (a) LiOH/O2/MeOH/H2O; (b) CH2N2/Et2O/THF/r.t; (c) PhAc/NaOMe/MeOH/THF; (d) PhAc/Diox/BF3•Et2O; (e) 4-MePyr/ AcOH/Ac2O; (f) 4-NO2CHO/Diox/BF3•Et2O; (g) 4-NO2CHO/NaOMe/THF/r.t./N2

Figure 1. Region-selectivities of the cross-aldol reaction of 1a with aromatic aldehyde under different conditions

Figure 2. Stereoselectivity based on Lewis acid catalyzed cross-aldol reaction of MPPa 1a with aromatic aldehyde

Figure 3. Comparison of the 1H NMR spectra (CDCl3, 400 MHz) in the region of δ 3.5~9.7 for chlorins 1a, 4a, and 5a

Figure 4. NOE interactions between the C17-H and C132b-H observed in 2D/NOESY 1H NMR spectra of 4a and 5a

Figure 5. UV-Vis spectra of 1a, arylmethylenated chlorins 3a, 4a and diarylmethylenated chlorin 8 in CH2Cl2

参考文献 22

[1]	(a) Mori, H.; Tanaka, T.; Osuka, A. J. Mater. Chem. C 2013, 1, 2500. doi: 10.1039/c3tc00932g pmid: 27258218
	(b) Ono, N.; Yamada, H.; Okujima, T. InHandbook of Porphyrin Science, Vol.2, Eds.: Kadish, K. M.; Smith, K. M.; Guilard, R., World Scientific Publishing Company, Singapore, 2012. p. 1-102. pmid: 27258218
	(c) Stępień, M.; Gońka, E.; Żyła, M.; Sprutta, N. Chem. Rev. 2017, 117, 3479. doi: 10.1021/acs.chemrev.6b00076 pmid: 27258218
[2]	(a) Wang, J.-J. Chin. J. Org. Chem. 2005, 25, 1353. (in Chinese)
	( 王进军, 有机化学, 2005, 25, 1353.)
	(b) Ethirajan, M.; Joshi, P.; William, W. H.; Ohkubo, K.; Fukuzumi, S.; Pandey, R. K. Org. Lett. 2011, 8, 1956.
	(c) Bellnier, D. A.; Greco, W. R.; Loewen, G. M.; Nava, H.; Oseroff, A. R.; Pandey, R. K.; Tsuchida, T.; Dougherty, T. J. Cancer. Res. 2003, 63, 1806;
[3]	(a) Ethirajan, M.; Chen, P.; Ohulchanskyy, T. Y.; Goswami, L. N.; Gupta, A.; Srivatsan, A.; Dobhal, M. P.; Missert, J. R.; Prasad, P. N.; Kadish, K. M. Chem.-Eur. J. 2013, 19, 6670. doi: 10.1002/chem.201203867
	(b) Pandey, R. K.; Goswami, L. N.; Chen, Y.; Gryshuk, A.; Missert, J. R.; Oseroff, A.; Dougherty, T. J. Lasers Surg. Med. 2006, 467, 445.
	(c) Tamiaki, H.; Wada, A.; Matsubara, S. J. Photochem. Photobiol., A 2018, 353, 581.
[4]	(a) Pandey, S. K.; Zheng, X.; Morgan, J.; Missert, J. R.; Liu, T.-H.; Shibata, M.; Bellnier, D. A.; Oseroff, A. R.; Henderson, B. W.; Dougherty, T. J.; Pandey, R. K. Mol. Pharmaceutics 2007, 4, 448. doi: 10.1021/mp060135x
	(b) Kozyrey, A. N.; Chen, Y.-H.; Goswami, L. N.; Tabaczynaki, W. A.; Pandey, R. K. J. Org. Chem. 2006, 71, 1949. doi: 10.1021/jo052334i
	(c) Duan, S.; Dall’Agnese, C.; Chen, G.; Wang, X.-F.; Tamiaki, H.; Yamamoto, Y.; Ikeuchi, T.; Sasaki, S. ACS Energy Lett. 2018, 3, 1708. doi: 10.1021/acsenergylett.8b00797
[5]	(a)Ding Y.; Zhu, W.-H.; Xie, Y. Chem. Rev. 2017, 117, 2203. doi: 10.1021/acs.chemrev.6b00021
	(b) Li, M.; Wei, P.; Ishida, M.; Li, X.; Savage, M.; Guo, R. Angew. Chem., Int. Ed. 2016, 55, 3063. doi: 10.1002/anie.201510879
	(c) Ding, Y.; Tang, Y.; Zhu, W.; Xie, Y. Chem. Soc. Rev. 2015, 44, 1101. doi: 10.1039/C4CS00436A
	(d) Xie, Y.; Tang, Y.; Wu, W.; Wang, Y.; Liu, J.; Li, X. J. Am. Chem. Soc. 2015, 137, 14055. doi: 10.1021/jacs.5b09665
[6]	Senge, M. J. Photochem. Photobiol. B 1992, 16, 3. doi: 10.1016/1011-1344(92)85150-S
[7]	(a) Zhang, S.-G.; Li, J.-Z.; Zhang, P.; Qi, C.-X.; Wang, J.-J. Chin. J. Org. Chem. 2015, 35, 1060. (in Chinese) doi: 10.6023/cjoc201408009
	( 张善国, 李家柱, 张朋, 祁彩霞, 王进军, 有机化学, 2015, 35, 1060.)
	(b) Zhang, Z.; Xu, X.-S.; Li, Y.-L.; Li, J.-Z.; Wang, J.-J. Chin. J. Org. Chem. 2018, 38, 2993. (in Chinese) doi: 10.6023/cjoc201804048
	( 张珠, 徐希森, 李彦龙, 李家柱, 王进军, 有机化学, 2018, 38, 2993.)
	(c) Wang, J.-J.; Li, J.-Z.; Li, Y.-W.; Jakus, J.; Shim, Y. K. J. Porphyrins Phthalocyanines 2010, 14, 860.
[8]	(a) Takahashi, T.; Ogasawara, S.; Shinozaki, Y.; Tamiaki, H. Bull. Chem. Soc. Jpn. 2020, 93, 467. doi: 10.1246/bcsj.20190367
	(b) Kozyrev, A. N.; Suresh, V.; Das, S.; Senge, M. O.; Shibata, M.; Doughertya, T. J.; Pandeya, R. K. Tetrahedron 2000, 56, 3353. doi: 10.1016/S0040-4020(00)00256-8
	(c) Chen, Y.; Sajjad, M.; Wang, Y..; Batt, C.; Nabi, H. A.; Pandey, R. K. ACS Med. Chem. Lett. 2011, 2, 136. doi: 10.1021/ml100211g
[9]	(a) Zhang, Z.; Li, J.-Z.; Wang, X.-Y.; Ma, J.-H.; Wang, X.; Wang, J.-J. Chin. J. Org. Chem. 2020, 40, 2895. (in Chinese) doi: 10.6023/cjoc202004054
	( 张珠, 李家柱, 王欣悦, 马计划, 王旭, 王进军, 有机化学, 2020, 40, 2895.)
	(b) Zhang, Z.; Zhao, Y.; Wang, X.-Y.; Li, J.-Z.; Wang, J.-J. Chin. J. Org. Chem. 2021, 41, 1177. (in Chinese) doi: 10.6023/cjoc202006080
	( 张珠, 赵雨, 王欣悦, 李家柱, 王进军, 有机化学, 2021, 41, 1177.)
	(c) Jiang, Q.-Y.; Zhang, Z.; Liu, Y.; Yao, N.-N.; Wang, J-J. Chin. J. Org. Chem. 2017, 37, 1814. (in Chinese) doi: 10.6023/cjoc201610045
	( 姜齐永, 张珠, 刘洋, 姚楠楠, 王进军, 有机化学, 2017, 37, 1814.)
[10]	(a) Wang, L.-M.; Wang, Z.; Yang, Z.; Jin, Y.-X.; Wang, J.-J. Chin. J. Org. Chem. 2012, 32, 2154. (in Chinese) doi: 10.6023/cjoc1201202
	( 王鲁敏, 王振, 杨泽, 金英学, 王进军, 有机化学, 2012, 32, 2154.)
	(b) Liu, Y.; Xu, X.-S.; Li, J.-Z.; Yin, J.-G.; Qi, C.-X.; Wang, J.-J. Chin. J. Org. Chem. 2014, 34, 552. (in Chinese) doi: 10.6023/cjoc201310002
	( 刘洋, 徐希森, 李家柱, 殷军港, 祁彩霞, 王进军, 有机化学, 2014, 34, 552.)
	(c) Gao, N.; Li, J.-Z.; Li, Y.-L.; Wang, Z.; Wang, J.-J. Chin. Chem. Lett. 2016, 27, 789. doi: 10.1016/j.cclet.2016.01.008
	(d) Wu, H.-Q.; Wang, X.-M.; Liu, Y.; Zhao, Y.; Shim, Y.-K.; Yoon, I.; Xu, X.-M.; Li, J.-Z. Bull. Korean Chem. Soc. 2020, 41, 504. doi: 10.1002/bkcs.11998
[11]	(a) Wang, L.-M.; Wang, P.; Liu, C.; Jin, Y.-X.; Wang, J.-J. Chin. J. Org. Chem. 2012, 32, 1700. (in Chinese) doi: 10.6023/cjoc1202055
	( 王鲁敏, 王朋, 刘超, 金英学, 王进军, 有机化学, 2012, 32, 1700.)
	(b) Ji, J.-Y.; Yin, J.-G.; Zhang, Q.; Liu, C.; Qi, C.-X.; Wang, J.-J. Chin. J. Org. Chem. 2014, 34, 2047. (in Chinese) doi: 10.6023/cjoc201402041
	( 纪建业, 殷军港, 张千, 刘超, 祁彩霞, 王进军, 有机化学, 2014, 34, 2047.)
	(c) Shoji, S.; Nomura, Y.; Tamiaki, H. Tetrahedron 2020, 76, 131130. doi: 10.1016/j.tet.2020.131130
[12]	(a) Li, J.-Z.; Zhang, P.; Yao, N.-N.; Zhao, L.-L.; Wang, J.-J.; Shim, Y.-K. Tetrahedron Lett. 2014, 55, 1086. doi: 10.1016/j.tetlet.2013.12.093
	(b) Wang, J.-J.; Li, J.-Z.; Jakus., J.; Shim, Y. K. J. Porphyrins Phthalocyanines 2012, 16, 122. doi: 10.1142/S1088424611004403
	(c) Takahashi, T.; Ogasawara, S.; Shinozaki, Y.; Tamiaki, H. Bull. Chem. Soc. Jpn. 2020, 93, 467. doi: 10.1246/bcsj.20190367
[13]	(a) Li, J.; He, N.; Liu, Y.; Zhang, Z.; Zhang, X.; Han, X.; Gai, Y.; Liu, Y.; Yin, J.; Wang, J. Dyes Pigm. 2017, 146, 189. doi: 10.1016/j.dyepig.2017.07.005
	(b) Nyman, E. S.; Hynninen, P. H. J. Photochem. Photobiol. B 2004, 73, 1. doi: 10.1016/j.jphotobiol.2003.10.002
[14]	(a) Wang, P. M.S. Thesis, Yantai University, Yantai, 2009. (in Chinese)
	( 王朋, 硕士论文, 烟台大学, 烟台, 2009.)
	(b) Yang, X.-Y.; Yin, J.-G.; Jin, Y.-X.; Qi, C.-X.; Wang, J.-J. Chin. J. Org. Chem. 2014, 34, 2279. (in Chinese) doi: 10.6023/cjoc201403067
	( 杨晓英, 殷军港, 金英学, 祁彩霞, 王进军, 有机化学, 2014, 34, 2279.)
	(c) Zhang, Z.; jiang, Q.-Y.; Zhang, Q.; Wu, J.; Wang, J.-J. Chin. J. Org. Chem. 2015, 35, 1929. (in Chinese) doi: 10.6023/cjoc201503050
	( 张珠, 姜齐永, 张千, 武进, 王进军, 有机化学, 2015, 35, 1929.)
	(d) Li, Y. -L.; Li, J. Z.; Zhang, S.-G, Wang, J.-J. Simpson, D. J. J. Chin. J. Org. Chem. 2016, 36, 562. (in Chinese) doi: 10.6023/cjoc201508032
	( 李彦龙, 李家柱, 张善国, 王进军, 有机化学, 2016, 36, 562.)
[15]	Smith, K. M.; Gogg, D. A.; Simpson, D. J. J. Am. Chem. Soc. 1985, 107, 4946. doi: 10.1021/ja00303a021
[16]	Wang, J.-J.; Zhang, P.; Wang, P.; Chen, G.-L.; Li, F.-G. Chin. J. Org. Chem. 2010, 30, 1192. (in Chinese) doi: 10.1002/cjoc.201290014
	( 王进军, 张朋, 王朋, 陈冠龙, 有机化学, 2010, 30, 1192.)
[17]	Wang, J.-J.; Wang, P.; Li, J.-Z.; Jakus, J.; Shin, Y.-K. Bull. Korean Chem. Soc. 2011, 32, 3473. doi: 10.5012/bkcs.2011.32.9.3473
[18]	Liu, C. M.S. Thesis, Yantai University, Yantai, 2010. (in Chinese)
	( 刘超, 硕士论文, 烟台大学, 烟台, 2010.)
[19]	Mysliwiec, D.; Donnio, B.; Chmielewski, P. J.; Heinrich, B.; Stepien, M. J. Am. Chem. Soc. 2012, 134, 4822. doi: 10.1021/ja210991f
[20]	Tokuji. S.; Takahashi. Y.; Shinmori. H.; Shinokubo. H.; Osuka. A. Chem. Commun. 2009, 1028.
[21]	(a) Akita, M.; Hiroto, S.; Shinokubo, H. Angew. Chem., Int. Ed. 2012, 51, 2894. doi: 10.1002/anie.201108037
	(b) Chen, Y.-H.; Li, L.-G.; Pankey, R.-K. Curr. Org. Chem. 2004, 8, 1107
[22]	Li, J. Z.; Liu, Y.; Xu, X.-S.; Li, Y.-L.; Zhang, S.-G.; Toon, I.; Shim, Y. K.; Wang, J.-J.; Yin, J.-G. Org. Biomol. Chem. 2015, 13, 1992. doi: 10.1039/C4OB02491E