RESUMEN
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 to tert-butyl 5-benzyloxypent-2-enoate, ensuing enolate oxidation to give an α-hydroxy-ß-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-ß-hydroxy ester. Subsequent transformation gave a 3-hydroxyprolinal derivative which was converted to the corresponding N-tert-butylsulfinylimine. Mannich-type reaction with the enolate derived from O-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.
Asunto(s)
Alcaloides , Alcaloides de Pirrolicidina , Oxidación-Reducción , EstereoisomerismoRESUMEN
Two synthetic routes have been developed for the asymmetric syntheses of (2 R,3 S)- and (2 S,3 S)-3-hydroxyproline. The key synthetic step in each of these strategies is the conversion of protected α,δ-dihydroxy-ß-amino esters (either 2,3- anti- or 2,3- syn-configured) into ß,δ-dihydroxy-α-amino esters (protected forms thereof), via the intermediacy of the corresponding aziridinium ions. The products of these stereospecific rearrangements were then cyclized and deprotected to afford (2 R,3 S)-3-hydroxyproline and (2 S,3 S)-3-hydroxyproline as single diastereoisomers (>99:1 dr) in >26% overall yield.
RESUMEN
The first total synthesis of (+)-lophirone H (1) and its pentamethyl ether 29, featuring an oxonium-Prins cyclization/benzylic cation trapping reaction, is described.
