M. Omote et al., SYNTHESIS OF L(2,2,2-TRIFLUORO-1-HYDROXYETHYL)DEUTEROPORPHYRINS AND THEIR DERIVATIZATION TO PORPHYRIN DERIVATIVES WITH ELONGATED SIDE-CHAINS, Chemical and Pharmaceutical Bulletin, 43(7), 1995, pp. 1107-1110
We previously synthesized 3- and 8-mono-, and is(2,2,2-trifluoro-1-hyd
roxyethyl)deuteroporphyrin dimethyl esters (2-4) by Friedel-Crafts rea
ction of deuteroporphyrin dimethyl ester (1) with trifluoroacetaldehyd
e, and trifluorohematoporphyrin analogs (5 and 6) by acetylation of 2
and 3 followed by reduction, These fluorine analogs of natural porphyr
ins have interesting biological properties; some of them accumulate se
lectively in certain tumor cells, In order to introduce larger substit
uents at the 8- or 3-position of 2 and 3, 2 and 3 were converted in se
veral steps to 8- and 3-formyl derivatives (13 and 14), respectively,
These were treated with vinylmagnesium bromide to give 8- or 3-(1-hydr
oxy-2-propenyl) derivatives (15 or 16), Further, reaction of 7 or 8 wi
th the enol ether of 2-octanone gave the 8- or 3-(3-oxo-1-nonenyl) com
pounds (17 or 18), The affinities of the porphyrin derivatives, obtain
ed by hydrolysis of the above porphyrin esters, for tumor tissues were
examined, Among them, the porphyrin obtained by hydrolysis of 16 was
found to accumulate in liver cancer transplanted in nude mice to a gre
ater extent than hematoporphyrin.