Elimination, direction lactam rings

The lactam derivative dibenz[h/]l 4-oxazepin-ll-(lOH)-one is a primary metabolic product of metabolism and a direct precursor of the urinary hydroxylated metabolites. In rats, the lactam, a dihydro-CR metabolite, an amino alcohol of CR, and an arene oxide are metabolites in CR degradation. In the rat, the major mechanism for elimination is sulfate conjugation and biliary excretion to a limited extent. Phase I metabolism by microsomal mixed fimction oxidases involves reduction of CR to the amino alcohol, oxidation to form the lactam ring, and hydroxylation to form the hydroxylactams. Phase II conjugation reactions sulfate the hydroxylactam intermediates for renal elimination. Amino alcohol intermediates are conjugated with glucuro-nide for biliary secretion. 

Intramolecular reaction of the vinyl triflate with benzo[ ]furan in 7 is a key step in the preparation of the synthetic intermediate 8 of (—)-frondosin A [5], Intramolecular reaction of the iodide with furan in 9 gave the tetracyclic jS-lactam 10 containing furan ring in the presence of TI2CO3 as a base. The rather unusual C-3 substitution occurs in the reactions of 7 and 9, because the C-2 positions are blocked [6], If the cyclizations of 7 and 9 proceed similar to Heck-type carbopalladation and f-H elimination, direct syn y3-H elimination is not possible, and isomerization from anti to syn, followed by syn y3-H elimination should occur. Therefore, direct electrophilic substitution may be a better explanation. 

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