Asymmetric total synthesis of (-)-pironetin employing the SAMP/RAMP hydrazone methodology.
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 alpha-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.
Enders
Dieter
D
Institut für Organische Chemie, RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany. Enders@RWTH-Aachen.de
Dhulut
Sylvie
S
Steinbusch
Daniel
D
Herrbach
Audrey
A
D006835:Hydrazones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011753:Pyrones / Q000138:chemical synthesis*; D021241:Spectrometry, Mass, Electrospray Ionization
D006835:Hydrazones; D011753:Pyrones; C088446:pironetin