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 (OE-OA), the decarboxylated OA (DC-OA), the O-methyl ether of OA (OM-OA), and the methyl ester of ochratoxin α (M-Oα) were synthesized using OA or ochratoxin α (Oα) as the starting material. The reactions involved activation of OA to the N-hydroxysuccinimide ester (OA-NHS) and of Oα to acyl chloride (Oα-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 Oα was also developed. The chemical structures of all analogs were elucidated and/or confirmed using EI-MS and 1 H 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 Oα 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