Highly efficient synthesis of novel methyl 13²-methylene mesopyropheophorbide a and its stereoselective Michael addition reaction

Abstract

Treatment of methyl mesopyropheophorbide a with formaldehyde under basic conditions gave a novel 13(2)-methylene derivative in 85% yield; under acidic conditions, the corresponding 20-hydroxymethyl derivative was obtained in 65% yield. The high reactivity of the enone structural motif existed in the former product provides a unique way to construct some novel chlorophyll a derivatives for various applications. Stereoselective Michael reaction of this compound is studied and discussed.

Substituted Methylenation at the 132‐Position of a Chlorophyll‐a Derivative via Mixed Aldol Condensation, Optical Properties of the Synthetic Bacteriochlorophyll‐d Analogs, and Self‐aggregation of Their Zinc Complexes†

“…1C) in methyl pyropheophorbide‐ a (R 3 = vinyl) led to red shifts of the Soret and Qy band because of the direct conjugation of an ethenyl moiety at the 15‐position in a chlorin π‐skeleton (47). Similar bathochromic shifts were found in the related 3‐substituted chlorins: R 3 = Et (24), CH 2 OH (48), and CH(OH)Me (49). To clarify the substitution effect at the methylene terminal on the physical properties, we herein report the synthesis of methyl 3‐hydroxymethyl‐13 2 ‐(substituted methylene)pyropheophorbides‐ a 2 and the optical properties of 2 and their zinc complexes 3 in a solution.…”

“…In addition to the aforementioned Chls possessing vinyl groups, many vinyl‐chlorins have been prepared by chemically modifying natural Chls, and their physical properties have been investigated. In a series of (zinc) methyl pyropheophorbides, a vinyl (or methylene) group was substituted at the 3‐, 7‐, 8‐ (20), 12‐ (21,22), 13 1 ‐ (23), 13 2 ‐ (24), and 20‐positions (25) (see Fig. 1B), and their physical properties were compared with those of the unsubstituted, methylated, and ethylated counterparts.…”

Mitochondrial Targeting Cationic Purpurinimide–Polyoxometalate Supramolecular Complexes for Enhanced Photodynamic Therapy with Reduced Dark Toxicity

“…PDT is a promising non‐invasive and patient‐specific cancer treatment with minimal side effects, which is based on the administration and selective accumulation of a PS in tumour tissue, to generate cytotoxic reactive oxygen species (ROS), especially singlet oxygen ( 1 O 2 ), after photoirradiation. These cytotoxic species inflict direct cellular damage, destroy tumour vascularization, and trigger subsequent inflammatory and immune cell destruction [13–23] . However, the clinical application of PDT is hampered by the need to increase cellular penetration without causing aggregation, light penetration with long wavelength absorption, and prevention of dark toxicity of PSs for enhanced PDT activity with few side effects [15,24–30] …”

Efficient Synthesis of Long‐wavelength Absorbing Cyanochlorophyll a Derivatives via Stereoselective Horner–Wadsworth–Emmons Reaction

“…In particular, chlorins capable of absorbing 650–900 nm radiation, whose wavelength is at the frontier of the biological window, have attracted much synthetic and biological interest . It is well known that structural changes, induced by the peripheral substituents conjugated with the chlorin chromophore, remarkably affect the photophysical properties of these porphyrins, especially their electronic absorptions . Various long‐wavelength absorbing chlorins have been synthesized by introducing electron‐withdrawing groups including nitro, keto, carboxyl, pyridyl, quinolyl and cationic N ‐heteroaromatic groups, most of which are prepared from 3‐formyl chlorins via classical CC bond‐forming reactions such as the Wittig, Knoevenagel, Henry, Grignard, and the aldol and aldol‐like condensation reactions …”