Absolute Configuration
Assignment by Asymmetric Syntheses
of the Homalium Alkaloids (−)‑(<i>R</i>,<i>R</i>,<i>R</i>)‑Hoprominol and (−)-(4′<i>S</i>,4″<i>R</i>,2‴<i>R</i>)‑Hopromalinol
- Publication date
- Publisher
Abstract
The conjugate addition of lithium (<i>R</i>)-<i>N</i>-(3-chloropropyl)-<i>N</i>-(α-methylbenzyl)amide
to α,β-unsaturated esters was used as the key step in
the syntheses of all possible diastereoisomers of the homalium alkaloids
hoprominol and hopromalinol. Comparison of the specific rotation data
for these synthetic samples with those of samples isolated from the
natural source enabled the absolute configurations within these alkaloids
to be confidently assigned for the first time as (−)-(<i>R</i>,<i>R</i>,<i>R</i>)-hoprominol and
(−)-(4′<i>S</i>,4″<i>R</i>,2‴<i>R</i>)-hopromalinol. The asymmetric syntheses
of (−)-(<i>R</i>,<i>R</i>,<i>R</i>)-hoprominol (in 10 steps and 4.0% overall yield) and (−)-(4′<i>S</i>,4″<i>R</i>,2‴<i>R</i>)-hopromalinol (in 10 steps and 9.3% overall yield), from commercially
available starting materials in each case, therefore represent the
first total asymmetric syntheses of these alkaloids to be reported