Title

Chlorin e6 131:152-anhydride: A key intermediate in conjugation reactions of chlorin e6

Document Type

Article

Publication Date

6-1-2015

Abstract

Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Since the patent for the photodynamic therapy agent Talaporfin (mono-L-aspartylchlorin e6) was issued in 1987, confusion has existed regarding which of the three carboxylic acid groups in the chlorophyll degradation product, chlorin e6 (1), is modified in standard amino acid type conjugations (using DCC or EDC and an organic base) with amino acids and other biomolecules. Here it is shown that the site of conjugation is the central 152-carboxylic acid, such reactions proceeding in numerous examples via a 131:152-anhydride for which a high resolution X-ray structure is reported. Conjugation with eight oxygen and nitrogen nucleophiles, in every case, afforded the 152-conjugate, reinforcing the earlier conclusion that Talaporfin is the 152-aspartyl conjugate of chlorin e6 and suggesting that reports of 173-conjugation of chlorin e6 using stoichiometric peptide coupling procedures should be subjected to further scrutiny. Standard stoichiometric peptide-type conjugations of chlorin e6 with eight oxygen and nitrogen nucleophiles proceed via the title 152,131-anhydride to give the corresponding 152-conjugate. The intermediate anhydride is definitively identified and an X-ray structure of it is reported.

Publication Source (Journal or Book title)

European Journal of Organic Chemistry

First Page

3661

Last Page

3665

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