Total synthesis of 6-chlorodemethyllavendamycin esters and amides

The synthesis of several 6-Chlorodemethyllavendamycin analogs and their chemistry are described. In this investigation the following compounds were prepared:6-Chlorodemethyllavendamycin methyl ester, 6-Chlorodemethyllavendamycin ethylester, 6-Chlorodemethyllavendamycin butyl ester, 6-Chlorodemethyllavendamycin isoamyl ester, 6-Chlorodemethyllavendamycin octyl ester, and 6-Chlorodemethyllavendamycin amide. Pictet Spengler condensation of 7-amino-6-chloro-2-formylquinoline-5,8-dione with tryptophan methyl ester, tryptophan ethyl ester, tryptophan butyl ester, tryptophan isoamyl ester, tryptophan octyl ester, and tryptophan amide in anisole afforded the compounds. 7-amino-6-chloro-2-formylquinoline-5,8-dione was prepared according to the following general procedures.The first step is the nitration of 8-Hydroxy-2-methylquinoline. 8-Hydroxy-2methylquinoline is reacted with 70% mixture of HNO3/H2SO4 to produce 5,7-dinitro-8hydroxy-2-methylquinoline. The next step requires hydrogenation and acylation. 5,7Dinitro-8-hydroxy-2-methylquinoline was reduced by H2/Pd-C in the presence of HCl and H20 filtered and then treated with sodium sulfite, sodium acetate and acetic anhydride to yield 5,7-diacetamido-8-acetoxy-2-methylquinoline. 5,7-Diacetamido-8-acetoxy-2methylquinoline was oxidized by potassium dichromate to produce 7-acetamido-2methylquinoline-5,8-dione. 7-Acetamido-2-methylquinoline-5,8-dione was chlorinated using hydrogen chloride gas in dry methanol producing 7-amino-6-chloro-2methylquinoline-5,8-dione. Treatment of 7-amino-6-chloro-2-methylquinoline-5,8-dione with selenium dioxide, under reflux in 1,4-dioxane produced 7-amino-6-chloro-2formylquinoline-5, 8-dione.All structures were confirmed by 'H NMR, IR, EIMS, and HRMS.