The synthesis of a range of loline alkaloids is reported.
The C(7)
and C(7a) stereogenic centers for the targets were formed by the established
conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide totert-butyl 5-benzyloxypent-2-enoate, ensuing enolate oxidation
to give an α-hydroxy-β-amino ester, and then formal exchange
of the resultant amino and hydroxyl functionalities (via the intermediacy
of the corresponding aziridinium ion) to give an α-amino-β-hydroxy
ester. Subsequent transformation gave a 3-hydroxyprolinal derivative
which was converted to the correspondingN-tert-butylsulfinylimine. Mannich-type reaction with the
enolate derived fromO-Boc protected methyl glycolate
then formed the remaining C(1) and C(2) stereogenic centers for the
targets. The 2,7-ether bridge was formed by a displacement reaction,
completing construction of the loline alkaloid core. Facile manipulations
then gave a range of loline alkaloids, including loline itself.