There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
<p class="first" id="P1">The akuammiline alkaloids are a structurally diverse class
of bioactive natural products
isolated from plants found in various parts of the world. A particularly challenging
subset of akuammiline alkaloids are those that contain a methanoquinolizidine core.
We describe a synthetic approach to these compounds that has enabled the first total
syntheses of (+)-strictamine, (−)-2(
<i>S</i>)-cathafoline, (+)-akuammiline, and (−)-
<b>Ψ</b>-akuammigine. Our strategy relies on the development of the reductive interrupted
Fischer indolization reaction to construct a common pentacyclic intermediate bearing
five contiguous stereocenters, in addition to late-stage formation of the methanoquinolizidine
framework using a deprotection–cyclization cascade. The total syntheses of (−)-
<b>Ψ</b>-akuammigine and (+)-akuammiline mark the first preparations of akuammiline
alkaloids
containing both a methanoquinolizidine core and vicinal quaternary centers. Lastly,
we describe the bioinspired reductive rearrangements of (+)-strictamine and (+)-akuammiline
to ultimately provide (−)-10-demethoxyvincorine and a new analogue thereof.
</p><p id="P2">
<div class="figure-container so-text-align-c">
<img alt="" class="figure" src="/document_file/5c5d20c3-b54f-49b6-90fe-fdb90959c817/PubMedCentral/image/nihms-982936-f0001.jpg"/>
</div>
</p>