Synthetic studies on indolic enamide natural products: 1. Total syntheses of coscinamide A, concinamide B and igzamide: 2. Synthetic studies towards the synthesis of halocyamine B

Abstract

The 3-substituded indolic enamide moiety has been found in many marine compounds over the past 20 years. These indolic enamides exhibit various biological properties such as cytotoxic, anthelmintic, antimicrobial and HW-inhibitory activities. Among these indolic enamides, some are (E)-enamides, like coscinamide A and coscinamide B, others are (Z)-configuration in their natural form, like igzamide and halocyamine B. A general method to selectively construct (E)- and (Z)-indolic enamides was devised through an bydroxyl amide formed from amino alcohol followed by a thermally assisted dehydration as the key step. Solvent effects were tested for the dehydration reaction. (Z)-Indolic enamides could be obtained in a moderate yield with xylene as the solvent for the dehydration reaction. (E)-Indolic enamides were the main products with N, N-dimethylformamide as the solvent. Total syntheses of three indolic enamides: coscinamide A, coscinamide B and igzamide have been described. The (E)- or (Z)-isomers of these natural compounds were obtained during the syntheses as well. A synthetic study of halocyamine B is also reported in this thesis.