Mixture synthesis and spectroscopic analysis of a stereoisomer library of the phytophthora mating hormone alpha1 and the corresponding bis-MTPA esters

Phytophthora are parasitic fungi like species that attack the roots and stems of plants. The heterothallic species of phytophthora consist of two mating types A1 and A2. A hormone alpha1 secreted by the A1 mating type induces the formation of sexual oospores in the A2 mating type. In 2005 by Ojika and coworkers reported the isolation and constitutional characterization of the hormone alpha1. The absolute configuration of the hormone alpha1 was later assigned by comparison of the hormonal activity of a synthetic sample with the natural sample. Assignment of absolute configuration on the basis of hormonal activity can however be error prone because the activity of any particular sample will depend on its isomeric purity.;In order to provide a spectroscopic method to assign the absolute configuration of hormone alpha1, we have synthesized eight stereoisomers of hormone alpha1 by Fluorous Mixture Synthesis. During the FMS, stereoisomeric starting materials were tagged with different fluorous PMB groups and mixed together. The resulting mixture was taken through a series of steps to make the fluorous-tagged products, which were separated by fluorous HPLC followed by hydrogenolysis to provide pure products. The NMR spectra of the eight isomers of hormone alpha1 provided only limited information about their absolute configuration.;The synthetic isomers of hormone alpha1 were subsequently converted to the corresponding bis-R and S Mosher ester derivatives. By comparison of the 1H NMR spectra of the sixteen bis-Mosher ester derivatives with the bis-Mosher ester derivatives of the natural product, we confirmed the partial configuration of hormone alpha1 as (3R,7R,15 R).