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Reactions of furocoumarins. II . Synthetic aminomethyl psoralens via chloromethylation or benzylic bromination
Author(s) -
Kaufman Kurt D.,
Erb Dennis J.,
Blok Thomas M.,
Carlson Robert W.,
Knoechel Donald J.,
Mcbride Lincoln,
Zeitlow Thomas
Publication year - 1982
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570190515
Subject(s) - chemistry , furocoumarins , psoralen , halogenation , formylation , electrophilic substitution , stereochemistry , organic chemistry , photochemistry , catalysis , dna , biochemistry
Abstract Several psoralen derivatives have been synthesized in order to evaluate their efficacy as photochemotherapeutic (PUVA) agents, including a variety of 4′‐substituted‐4,5′,8‐trimethypsoralen compounds ( 1d‐j ). Improved synthesis of the very potent photosensitizers 8‐methylpsoralen ( 6a ) and 4,8‐dimethylpsoralen ( 6b ) are described and 6a has been shown to undergo formylation in the 4′‐position. Free radical bromination of 6a and 6b with NBS affords primarily 8‐bromomethyl derivatives ( 8a and d ), which are readily converted into the 8‐aminomethyl derivatives ( 8c and f ) by the Gabriel method. If the 4′‐position is blocked, electrophilic substitution apparently occurs primarily in the 5′‐position of the psoralen system. At least, chloromethylation of 4′‐methylpsoralen ( 9 ) affords mainly 5′‐chloromethyl derivatives ( 10a and d ), which also lead to aminomethylpsoralens ( 10c and f ).