Synthesis of Sporidesmin Based Antigens

Abstract

In a program aimed at developing a chemically derived vaccine against sporidesmin-A, the toxin which causes the pasture disease facial eczema, two haptens have been prepared, coupled to protein carriers, and tested for immunogenicity. The hapten, 2-amino-5-chloro-3,4-dimethoxybenzyl alcohol has been synthesised from vanillin and the general synthetic methods developed in the course of this work have been used to prepare a large number of related vanillin derivatives for use in cross-hapten studies. The carbon-13 nuclear magnetic resonance spectra of 16 vanillin derivatives have been obtained, and two independent methods of deducing vanillin substitution patterns have been developed. 5-chloro-6, 7-dimethoxy-N-methyl-lH-indole has been prepared by a new route and its 3-oxoacetic acid derivative has been synthesized for use as a hapten. The Vilsmeier-Haack intermediate, l-methyl-3-(N,N-dimethylimonio) methyl-lH-indole chloride was isolated and a number of possible synthetic routes from it to pyrroloindoles were explored. The vanillin and indole haptens have been coupled to protein carriers to form antigens which generated a low antibody response. However, the use of mycobacterium phlei as a carrier greatly increased the antibody response but the antibodies produced did not interact strongly with sporidesmin-A.