Regio- and Stereoselective Aryl(aroyl)methylenenation of Pyropheophorbide and Syntheses of Chlorophyllous Chlorin Derivatives

doi:10.6023/cjoc202109052

Abstract

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

Cite this article

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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Fig. & Tab. 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

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