Premium
Chlorin e 6 13 1 :15 2 ‐Anhydride: A Key Intermediate in Conjugation Reactions of Chlorin e 6
Author(s) -
Chen Hui,
Jinadasa R. G. Waruna,
Jiao Lijuan,
Fronczek Frank R.,
Nguyen Alex L.,
Smith Kevin M.
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201500478
Subject(s) - chlorin , chemistry , conjugate , diazo , photochemistry , nucleophile , photodynamic therapy , stereochemistry , medicinal chemistry , organic chemistry , catalysis , mathematical analysis , mathematics
Since the patent for the photodynamic therapy agent Talaporfin (mono‐ L ‐aspartylchlorin e 6 ) was issued in 1987, confusion has existed regarding which of the three carboxylic acid groups in the chlorophyll degradation product, chlorin e 6 ( 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 15 2 ‐carboxylic acid, such reactions proceeding in numerous examples via a 13 1 :15 2 ‐anhydride for which a high resolution X‐ray structure is reported. Conjugation with eight oxygen and nitrogen nucleophiles, in every case, afforded the 15 2 ‐conjugate, reinforcing the earlier conclusion that Talaporfin is the 15 2 ‐aspartyl conjugate of chlorin e 6 and suggesting that reports of 17 3 ‐conjugation of chlorin e 6 using stoichiometric peptide coupling procedures should be subjected to further scrutiny.