SYNTHESIS AND STRUCTURAL ELUCIDATION OF ANALOGS OF OCHRATOXIN-A

Five analogs of ochratoxin A (OA) including the ethylamide of OA (OE-OA), the D-phenylalanine form of OA (d-OA), the decarboxylated OA (DC-OA), the O-methyl ether of OA (OM-OA), and the methyl ester of ochratoxin alpha (M-O alpha) were synthesized using OA or ochratoxin alpha (O alpha) as the starting material. The reactions involved activation of OA to the N-hydroxysuccinimide ester (OA-NHS) and of O alpha to acyl chloride (O alpha-Cl) followed by nucleophilic substitution with primary amines, amino acids, and alcohols to form corresponding amides and esters. All analogs were obtained in pure forms, and all but OM-OA were crystallized. A simplified procedure for the isolation and crystallization of O alpha was also developed. The chemical structures of all analogs were elucidated using EI-MS and H-1 NMR. Other physicochemical parameters such as melting point, UV-vis absorption, fluorescence, and HPLC elution pattern for each analog are presented. The procedures that have been developed for the synthesis of the analogs of OA from OA or O alpha are simple and efficient. The reactions generally result in high yields of the desired compounds. The overall yields of final products range approximately from 85 to 90% of the starting materials. The analogs synthesized together with the natural analogs of OA can be used to establish the structure-activity relationship of OA and for metabolic and immunological studies.