Abstract
Regioselective reactions of methyl pyropheophorbide a (MPPa) with formaldehyde based on hydroxymethylation have been studied. It was found that MPPa can react regioselectively with formaldehyde under different conditions to produce a series of 3-dioxane, 12-, 132- or 20-hydroxymethyl and 12-/132-alkenyl-substituted chlorins via Prins reaction, Blanc chloromethylation and aldol reaction, respectively. The first examples of direct C–C bond formation at 12-position of chlorophyll derivatives were also reported to give a series of 12-vinyl-substituted chlorins. These chlorins showed extend Qy absorptions and efficient singlet oxygen generation property, indicating their potential as photosensitizers for application in photodynamic therapy.
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References
Cui BC, Yoon I, Li JZ, Lee WK, Shim YK (2014) Synthesis and characterization of novel purpurinimides as photosensitizers for photodynamic therapy. Int J Mol Sci 15(5):8091–8105. https://doi.org/10.3390/ijms15058091
Ethirajan M, Chen YH, Joshi P, Pandey RK (2011) The role of porphyrin chemistry in tumor imaging and photodynamic therapy. Chem Soc Rev 40(1):340–362. https://doi.org/10.1039/B915149b
Gao N, Li J-Z, Li Y–L, Wang Z, Wang J–J (2016) A facile synthesis of cyano–chlorins related to chlorophyll from formyl (pyro)–pheophorbide–a by a tandem transformation of the aldehyde into a nitrile group. Chin Chem Lett 27(5):789–794. https://doi.org/10.1016/j.cclet.2016.01.008
Kozyrev AN, Dougherty TJ, Pandey RK (1998) LiOH promoted allomerization of pyropheophorbide a. A convenient synthesis of 132–oxopyropheophorbide a and its unusual enolization. Chem Commun 4:481–482. https://doi.org/10.1039/A707805F
Kozyrev AN, Suresh V, Das S, Senge MO, Shibata M, Dougherty TJ, Pandey RK (2000) Syntheses and spectroscopic studies of novel chlorins with fused quinoxaline or benzimidazole ring systems and the related dimers with extended conjugation. Tetrahedron 56(21):3353–3364. https://doi.org/10.1016/S0040-4020(00)00256-8
Li J-Z, Cui B–C, Wang J–J, Shim Y–K (2011a) Aldol-like carbon–carbon condensation for pyridyl substituted chlorins. B Kor Chem Soc 32(7):2465–2468. https://doi.org/10.5012/bkcs.2011.32.7.2465
Li JZ, Li L, Kim JH, Cui BC, Wang JJ, Shim YK (2011b) Efficient synthesis andin vitrophotodynamic anticancer study of new purpurinimide–hydrazone conjugates. J Porphyr Phthalocya 15(04):264–270. https://doi.org/10.1142/s1088424611003239
Li JZ, Wang JJ, Yoon I, Cui BC, Shim YK (2012) Synthesis of novel long wavelength cationic chlorins via stereoselective aldol–like condensation. Bioorg Med Chem Lett 22(5):1846–1849. https://doi.org/10.1016/j.bmcl.2012.01.088
Li J, Zhang P, Yao N-N, Zhao L–L, Wang J–J, Shim YK (2014) Convenient peripheral aroyloxylation reactions of porphyrins and chlorophyll–a–based chlorins with benzoyl peroxide. Tetrahedron Lett 55(5):1086–1089. https://doi.org/10.1016/j.tetlet.2013.12.093
Li J, Liu Y, Xu X-S, Li Y–L, Zhang S–G, Yoon I, Shim YK, Wang J–J, Yin J–G (2015a) Highly efficient synthesis of novel methyl 132–methylene mesopyropheophorbide a and its stereoselective Michael addition reaction. Org Biomol Chem 13(7):1992–1995. https://doi.org/10.1039/C4OB02491E
Li J, Zhang X, Liu Y, Yoon I, Kim D-K, Yin J–G, Wang J–J, Shim YK (2015b) Synthesis, optical properties and preliminary in vitro photodynamic effect of pyridyl and quinoxalyl substituted chlorins. Bioorg Med Chem 23(8):1684–1690. https://doi.org/10.1016/j.bmc.2015.03.021
Li Y, Sasaki S–i, Tamiaki H, Liu C–L, Song J, Tian W, Zheng E, Wei Y, Chen G, Fu X, Wang X–F (2015c) Zinc chlorophyll aggregates as hole transporters for biocompatible, natural–photosynthesis–inspired solar cells. J Power Sources 297:519–524. https://doi.org/10.1016/j.jpowsour.2015.08.045
Li J, He N, Liu Y, Zhang Z, Zhang X, Han X, Gai Y, Liu Y, Yin J, Wang J (2017) Synthesis and photophysical properties of novel pyridine fused chlorophyll a derivatives. Dyes Pigment 146:189–198. https://doi.org/10.1016/j.dyepig.2017.07.005
Pandey RK, Goswami LN, Chen Y, Gryshuk A, Missert JR, Oseroff A, Dougherty TJ (2006) Nature: a rich source for developing multifunctional agents. Tumor-Imaging and photodynamic therapy. Laser Surg Med 467:445–467. https://doi.org/10.1002/lsm.20352
Pandey SK, Zheng X, Morgan J, Missert JR, Liu TH, Shibata M, Bellnier DA, Oseroff AR, Henderson BW, Dougherty TJ, Pandey RK (2007) Purpurinimide carbohydrate conjugates: effect of the position of the carbohydrate moiety in photosensitizing efficacy. Mol Pharm 4(3):448–464. https://doi.org/10.1021/Mp060135x
Smith KM, Goff DA, Simpson DJ (1985) Meso substitution of chlorophyll derivatives: direct route for transformation of bacteriopheophorbides d into bacteriopheophorbides c. J Am Chem Soc 107:4946–4954. https://doi.org/10.1021/ja00303a021
Takanami T, Matsumoto J, Kumagai Y, Sawaizumi A, Suda K (2009) A facile one–pot preparation of meso–hydroxymethylporphyrins via a sequential SNAr reaction with (2–pyridyldimethylsilyl)methyllithium followed by hydrolysis and aerobic oxidation. Tetrahedron Lett 50(1):68–70. https://doi.org/10.1016/j.tetlet.2008.10.087
Tamiaki H, Kunieda M (2012) Handbook of porphyrin science. In: Kadish KM, Smith KM, Guilard R (eds) 51 Photochemistry of chlorophylls and their synthetic analogs. World Scientific Publishing Company, Singapore, pp 223–290. https://doi.org/10.1142/9789814322386_0003
Tamiaki H, Machida S, Mizutani K (2012) Modification of 3–substituents in (bacterio)chlorophyll derivatives to prepare 3–ethylated, methylated and unsubstituted (nickel) pyropheophorbides and their optical properties. J Org Chem 77(10):4751–4758. https://doi.org/10.1021/jo300442t
Tamiaki H, Tsuji K, Kim K, Miyatake T (2016) Preparation of mono–vinylated and formylated chlorophyll derivatives and their optical properties. Tetrahedron 72(29):4368–4376. https://doi.org/10.1016/j.tet.2016.06.001
Tokuji S, Awane H, Yorimitsu H, Osuka A (2012) Direct arylation of meso–formyl porphyrin. Chem Eur J 19(1):64–68. https://doi.org/10.1002/chem.201203742
Wang XF, Kitao O (2012) Natural chlorophyll–related porphyrins and chlorins for dye–sensitized solar cells. Molecules 17(4):4484–4497. https://doi.org/10.3390/molecules17044484
Wang J-J, Wang P, Li J–Z, Jakus J, Shim Y–K (2011) Synthesis of novel C12–nonmethylated chlorophyll derivatives from methyl pyropheophorbide-a by allomerization and functionalization. B Kor Chem Soc 32(9):3473–3476. https://doi.org/10.5012/bkcs.2011.32.9.3473
Wang K, Poon CT, Choi CY, Wong W-K, Kwong DWJ, Yu FQ, Zhang H, Li ZY (2012) Synthesis, circular dichroism, DNA cleavage and singlet oxygen photogeneration of 4–amidinophenyl porphyrins. J Porphyr Phthalocya 16(01):85–92. https://doi.org/10.1142/S108842461100435X
Yao Z, Bhaumik J, Dhanalekshmi S, Ptaszek M, Rodriguez PA, Lindsey JS (2007) Synthesis of porphyrins bearing 1–4 hydroxymethyl groups and other one–carbon oxygenic substituents in distinct patterns. Tetrahedron 63(43):10657–10670. https://doi.org/10.1016/j.tet.2007.07.108
Zhang Z, Jiang Q, Li J, Wang J (2017) Rearrangement reactions of chlorophyllous tetrapyrrole macrocyclic molecules. Prog Chem 29(02):262–284. https://doi.org/10.7536/PC160805
Acknowledgements
This study was supported by research Grants from the Natural Science Foundation of Shandong Province of China (No. ZR2015BQ012), National Natural Science Foundation of China (No. 51472212), the Project of Shandong University Science and Technology Plan (J15LC51) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (to J. Li).
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Liu, Y., Wu, H., Zhang, X. et al. Regioselective reactions of methyl pyropheophorbide a with formaldehyde based on hydroxymethylation. Chem. Pap. 72, 1389–1398 (2018). https://doi.org/10.1007/s11696-017-0376-4
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DOI: https://doi.org/10.1007/s11696-017-0376-4