SYNTHESES AND PRELIMINARY IN-VIVO PHOTODYNAMIC EFFICACY OF BENZOPORPHYRIN DERIVATIVES FROM PHYLLOERYTHRIN AND RHODOPORPHYRIN-XV METHYL-ESTERS AND ASPARTYL AMIDES
Rk. Pandey et al., SYNTHESES AND PRELIMINARY IN-VIVO PHOTODYNAMIC EFFICACY OF BENZOPORPHYRIN DERIVATIVES FROM PHYLLOERYTHRIN AND RHODOPORPHYRIN-XV METHYL-ESTERS AND ASPARTYL AMIDES, Tetrahedron, 52(15), 1996, pp. 5349-5362
Efficient approaches to the synthesis of methyl esters and aspartyl am
ides of so-called ring 'A'-benzoporphyrin derivatives from rhodoporphy
rin XV dimethyl ester 10 and 3-vinylphylloerythrin methyl ester 22 are
reported. The benzo-rings in the products are obtained by way of Diel
s-Alder [4+2] cyclizations which employ : a dieneophile and the vinyl
and 2,3-double bonds in the starting materials as the diene. In the 3-
vinylphylloerythrin series, the presence of the 13(1)-keto-group in ri
ng E inhibits the Diels-Alder reaction with dimethyl acetylenedicarbox
ylate, but with more reactive dienophiles, such as tetracyanoethylene,
the Diels-Alder adduct was isolated in modest yield. Protection of th
e 13(1)-keto- group as a ketal or thioketal afforded the intermediate
benzoporphyrin adducts, which were rearranged to trans- and cis- isome
rs on reacting with triethylamine and 1,8-diazabiclo[5,4,0]undec-7-ene
, respectively, Among the sensitizers tested so far, the benzoporphyri
n derivative (cis- isomer) obtained from rhodoporphyrin XV di-tert- bu
tyl aspartate showed the best in vivo photosensitizing activity in DBA
/2 mice transplanted with SMT/F tumors. Copyright (C) 1996 Elsevier Sc
ience Ltd