Asymmetric total synthesis of (-)-pironetin employing the SAMP/RAMP hydrazone methodology

摘要

A convergent asymmetric total synthesis of pironetin (1), a polyketide with immunosuppressive, antitumor, and plant-growth regulating activities is described. The synthesis was realized by coupling between the C-8-C-14 2 and C-7-C-2 15 fragments, respectively, by using a Mukaiyama-aldol reaction. The stereogenic centers of each fragment were generated by employing the SAMP/RAMP hydrazone (SAMP (S)-1-amino-2-methoxymethylpyrrolidine, RAMP= (R)-1-amino-2-methoxymethylpyrrolidine) methodology as a key step. An asymmetric a-alkylation of diethyl ketone permitted the introduction of the C-10 stereogenic center of 2, whereas the stereocenters C-4 and C-5 of 15 were installed by an asymmetric aldol reaction. Finally, the formation of the alpha,beta-unsaturated delta-lactone was achieved by ring-closing metathesis in the presence of catalytic amounts of titanium tetraisopropoxide.