A New and Expedient Total Synthesis of Ochratoxin A and d ₅-Ochratoxin A

Abstract

A new total synthesis of the mycotoxin ochratoxin A (OTA) is presented, in which it is prepared in 9% overall yield from commercially available substrates. The key step consists of the condensation reaction between protected l-phenylalanine and 5-chloro­-8-hydroxy-3-methyl-1-oxoisochromane-7-carboxylic acid (ochratoxin α, OTα). The same strategy could be successfully applied to l-d ₅-phenylalanine, leading to the first total synthesis of d ₅-OTA, a molecular tracer for the detection and analytical quantification of the natural mycotoxin in food samples by means of stable isotope dilution assay (SIDA).

Key words

heterocycles - natural products - ochratoxin A - stable isotope dilution assay - total synthesis

References

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13

The only method reported in the literature so far for the synthesis of d ₅-OTA (2a) was based on a semi-synthetic sequence involving: (a) acid hydrolysis of OTA to give (R)-OTα; (b) conversion of (R)-OTα into the corresponding acyl chloride by reaction with SOCl₂; (c) reaction between the acyl chloride and l-d ₅-phenylalanine methyl ester to give methyl-protected d ₅-OTA; (d) deprotection of the latter with NaOH in MeOH to give d ₅-OTA (2a). The overall yield based on starting OTA was 5% over 4 steps. See ref. 5a.