Short Total Synthesis of (+)-Hyacinthacine A1

Short Total Synthesis of (+)-Hyacinthacine A1

Author: ChemistryViews.org

(+)-Hyacinthacine A1 (pictured) is a pyrrolizidine derivative that acts as a glycosidase inhibitor at a low micromolar range. This makes it interesting for biomedical studies. However, (+)-hyacinthacine A1 is challenging to synthesize.

Michel Gravel, University of Saskatchewan, Saskatoon, Canada, and colleagues have developed the shortest synthesis of (+)-hyacinthacine A1 to date. The team started from commercially available D-serine methyl ester, which was converted to an amino aldehyde derivative with a doubly protected amine. This intermediate was used in an aldehyde–aldehyde cross-benzoin reaction with furfural, i.e., an aldehyde-substituted furan. This reaction gave an α-hydroxy-β-aminoketone. This ketone was reduced to the corresponding alcohol and both protecting groups at the amine were removed to give a free aminodiol.

A complex photooxygenation–amine cyclization cascade, followed by hydrogenation and hydrogenolysis, then gave the desired product as a single diastereomer with an overall one-pot process yield of 27 % from the aminodiol. According to the researchers, the method might also be suitable for other diastereomers or similar synthetic targets.


 

 

 

 

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