Microconine [N-methyl-2-methyl-3-methoxy-6-(deca-l',3′,5′-trienyl) piperidine, an alkaloid from Microcos paniculata]: Synthesis, stereochemistry and spectroscopic data

Unambiguously corrected H-1 NMR data for the originally isolated sample of microconine [N-methyl-2-methyl-3-methoxy-6-(deca-l',3',5'-trienyl)piperidine], an alkaloid found in Microcos paniculata, are reported. The asymmetric synthesis of the (2S,3R,6S)- and (2S,3S,6S)-stereoisomeric forms [epimeric at C(3)] of this compound allows the unambiguous assignment of the relative 2,3-cis-3,6-cis-configuration of the natural product. The synthesis uses the conjugate addition of enantiopure lithium (S)-N-benzyl-N-(alpha-methylbenzyl)amide to tert-butyl crotonate and ensuing enolate oxidation with (+)-camphorsulfo-nyloxaziridine to generate the requisite C(2) and C(3) stereogenic centres found within the target. After elaboration, an intramolecular reductive amination was used to form the piperidine ring, with concomitant formation of the C(6) stereogenic centre. Comparison of specific rotation data is consistent with the alkaloid having the absolute (2R,3R,6R)-configuration. (C) 2020 Published by Elsevier Ltd.