Tryptophan, protected, free-radical

A number of reports have stressed the importance of antioxidants in protecting cells from free radical damage, the kind that can lead to an array of degenerative diseases, including cancer.319320 Therefore, it is appropriate to mention that a number of tryptophan metabolites have been reported to have antioxidant activities.321 Under certain conditions, such effects may play a role in relation to tryptophan and its preventative effect in carcinogenesis. 

The Liu synthesis of Aa-methyl-A18-isokoumidine (137) (214) starts from L-tryptophan (138), which was transformed to intermediate 139 in six steps. The Dieckmann condensation of 139 afforded the /3-ketoester 140. Oxidative free radical cyclization of /3-ketoester 140, initiated with Mn(0Ac)3, H20/Cu/(0Ac)2 H2O, followed by the removal of the Na-protecting group, led almost quantitatively to 141. Hydrolysis and decarboxylation using the Barton method afforded, via compound 142, intermediate 143. Treatment of 143 with (CH3)2S = CH2/dimethyl sulfoxide (DMSO) THF yielded the epoxy derivative 144, which was reduced with A1H2C1 in THF to the, not yet naturally found, jVa-methyl-A18-isokoumidine (137) (Scheme 12). 

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