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Asymmetric Total Synthesis of (−)‐Pironetin Employing the SAMP/RAMP Hydrazone Methodology
Author(s) -
Enders Dieter,
Dhulut Sylvie,
Steinbusch Daniel,
Herrbach Audrey
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601672
Subject(s) - stereocenter , aldol reaction , stereochemistry , hydrazone , total synthesis , polyketide , chemistry , enantioselective synthesis , metathesis , ketone , ring closing metathesis , alkylation , catalysis , organic chemistry , biosynthesis , polymer , polymerization , enzyme
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 α‐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 α,β‐unsaturated δ ‐lactone was achieved by ring‐closing metathesis in the presence of catalytic amounts of titanium tetraisopropoxide.