Biologically active Phytophthora mating hormone prepared by catalytic asymmetric total synthesis

Abstract

A Phytophthora mating hormone with an array of 1,5-stereogenic centers has been synthesized by using our recently developed methodology of catalytic enantioselective conjugate addition of Grignard reagents. We applied this methodology in a diastereoand enantioselective iterative route and obtained two of the 16 possible stereoisomers of Phytophthora hormone ␣1. These synthetic stereoisomers induced the formation of sexual spores (oospores) in A2 mating type strains of three heterothallic Phytophthora species, P. infestans, P. capsici, and P. nicotianae but not in A1 mating type strains. The response was concentrationdependent, and the oospores were viable. These results demonstrate that the biological activity of the synthetic hormone resembles that of the natural hormone ␣1. Mating hormones are essential components in the sexual life cycle of a variety of organisms. For plant pathogens like Phytophthora, sexual reproduction is important as a source of genetic variation. Moreover, the thick-walled oospores are the most durable propagules that can survive harsh environmental conditions. Sexual reproduction can thus greatly affect disease epidemics. The availability of synthetic compounds mimicking the activity of Phytophthora mating hormone will be instrumental for further unravelling sexual reproduction in this important group of plant pathogens.conjugate addition ͉ oomycyte ͉ oospore ͉ plant pathogen ͉ Grignard reagents

Asymmetric synthesis and structure elucidation of a glycerophospholipid from Mycobacterium tuberculosis

“…Thioester 4 was subjected to a copper catalyzed asymmetric conjugate addition with methylmagnesium bromide and ( S , R Fe )-Josiphos 8 as the ligand ( 28 ). The use of a copper catalyzed asymmetric conjugate addition of Grignard reagents on unsaturated thioesters has recently been applied in a number of natural product syntheses (28)(29)(30)(31)(32)(33). Methyl-branched thioester 9 was isolated in 85% yield with an enantiomeric excess of 90% (see supplemental data).…”

Parallels in Intercellular Communication in Oomycete and Fungal Pathogens of Plants and Humans

“…The chemical nature of both Phytophthora α1 and α2 hormones was recently elucidated [23]–[25]. Only trace amounts of hormone are needed to initiate sexual development, and thus it proved difficult to obtain enough α2 hormone for structural study.…”

Evaluation of PCR markers for Phytophthora infestans mating type determination

“…These hormonal substances, termed α1 for the A1 strains and α2 for A2 strains, were isolated and characterized (Ojika et al 2011;Qi et al 2005;Yajima et al 2008). Synthetic mating type hormones show the same biological activity as the natural hormones of P. infestans and induce the oospores production (Harutyunyan et al 2008;Molli et al 2012).…”