| 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 ). |
