Reaction of methylpheophorbides d and b with amines

Abstract

A series of formyl analogs of chlorin e 6 13-amides were synthesized in high yields by reaction under mild conditions of primary and secondary amines with methylpheophorides b and d. In contrast with the secondary 13-amides, tertiary 13-amides were found as two isomers differing in the orientation of the amide plane relative to the plane of the chlorin ring. Methylpheophorbides b and d were more reactive toward the amines than methylpheophorbide a.Keywords: methylpheophorbides b and d, amides, rhodin g 7 13-amides, formyl analogs of chlorin e 6 13-amides, atropoisomerism.Porphyrins are a promising platform for synthesizing antitumor drugs with various mechanisms of action [1-3]. Because the chlorin molecule contains an aldehyde and the possibilities of its further chemical transformations are greatly expanded by the additional reaction center, it seemed interesting to study chemical transformations of chlorophylls b and d and their derivatives.The known method for synthesizing chlorin e 6 13-amides consists of the reaction of methylpheophorbide a (1) with primary and secondary amines [4][5][6][7]. We used the reaction of primary and secondary amines with formyl analogs of 1, methylpheophorbides b (2) and d (3), in order to synthesize previously unreported formyl analogs of chlorin e 6 amides.

Novel pH-Independent Amphiphilic Chlorophyll a Derivatives with Oligoethyleneglycol Substituents as a Hydrophilic Part: Synthesis and Hydrophilicity Estimation

“…[22][23][24][25][26] In the IR spectra of chlorin e 6 derivatives 22-32 the 13(1)-keto group absorption band about 1700 cm -1 is absent and absorption bands of amide groups ("amide-I» in the region of 1640-1650 cm -1 and «amide-II» in the region 1530-1550 cm -1 ) are present. The singlet of the proton in position 13(2) at 6.25-6.35 ppm is absent and the signals of protons of the methylene group which is formed by opening exocycle (AB multiplet system at 5-6 ppm region) as well as the methylamide group proton signals (broad quartet or unresolved multiplet of NH proton and doublet of the methyl moiety) are observed in the 1 Н NMR spectra of compounds 22-32.…”

“…The same activating agent was also used by us to synthesize 13(2) ethers and methylpheophorbides 6-10 with the di-, tri-, tetra-, penta-and hexaethylene glycol fragments: it is known that the ester group exocycle methylpheophorbide has a relatively high chemical activity and, therefore, can undergo a trans-esterification reaction. [33][34][35][36] Synthesis of chlorin e 6 derivatives with oligoethylene glycol substituents at position 15 (22)(23)(24)(25)(26) was carried out by the action of methylamine on phorbin derivatives 6-10. Chlorin e 6 derivatives with oligoethylene glycol substituents at position 17 (27)(28)(29) were obtained by the same way (the phorbin derivatives 11-13 exo ring recovering by the action of methylamine).…”

“…[15][16][17][18] And the influence of the structure of these compounds on the hydrophilicity was not studied systematically. Here we report the synthesis of several phorbines (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and chlorins (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) with di-, tri-, tetra-, penta-and hexaethylene glycol substituents using methyl pheophorbide a (1) and its derivatives (2)(3)(4)(5) as an initial material (Scheme 1). The influence of the oligoethylene glycol chain length, its position at the macrocycle periphery and the structure of macrocycle on the hydrophilicity of compounds obtained was estimated using their mobility on the reverse phase HPLC data.…”

Catalytic Effect of Thioles in Oxidation of the Vinyl Group to Aldehyde in Chlorophyll a Derivatives

“…To carry out the oxidation in solution the air was bubbled (flow rate 4-5 l/h) through the solution of chlorophyll a derivative (30-40 mg) and 5-7 mol % hexanethiol in THF (40-50 ml) at r.t. After the reaction complete THF was evaporated, the residue after evaporation was recrystallized from a mixture of chloroform and methanol or methylene chloride and hexane to obtain the powder mass. Final purification of formylchlorin was performed by column chromatography on silica gel as in [29,30] . The spectral characteristics [31] of the obtained formylchlorins (6-10) are identical to described earlier.…”

“…The spectral characteristics [31] of the obtained formylchlorins (6-10) are identical to described earlier. [29,30] ¶ Methylpheophorbide d (6). (1Н, I-NH), -2.18 brs (1Н, III-NH …”