Issue 2, 2016

Formal synthesis of (−)-podophyllotoxin through the photocyclization of an axially chiral 3,4-bisbenzylidene succinate amide ester – a flow photochemistry approach

Abstract

We have developed a strategy for the stereoselective synthesis of cyclolignans related to podophyllotoxin and its derivatives. The crucial step of the synthesis is the photocyclization of a chiral atropoisomeric 1,2-bisbenzylidenesuccinate amide ester, which can be prepared from suitable aromatic aldehydes, diethyl succinate and L-prolinol. The photocyclization was found to be more efficient when irradiation was performed in a home-built continuous flow photochemical reactor. The in-flow irradiation also allowed us to perform the reaction on a multigram scale. The chiral auxiliary was removed by reductive cleavage with the Schwartz's reagent to give the cytotoxic 1R,2R-cis-podophyllic aldehyde, which in turn could be easily reduced to the corresponding alcohol, completing the formal synthesis of (−)-podophyllotoxin.

Graphical abstract: Formal synthesis of (−)-podophyllotoxin through the photocyclization of an axially chiral 3,4-bisbenzylidene succinate amide ester – a flow photochemistry approach

Supplementary files

Article information

Article type
Paper
Submitted
03 Sep 2015
Accepted
23 Oct 2015
First published
05 Nov 2015

Org. Biomol. Chem., 2016,14, 460-469

Author version available

Formal synthesis of (−)-podophyllotoxin through the photocyclization of an axially chiral 3,4-bisbenzylidene succinate amide ester – a flow photochemistry approach

K. Lisiecki, K. K. Krawczyk, P. Roszkowski, J. K. Maurin and Z. Czarnocki, Org. Biomol. Chem., 2016, 14, 460 DOI: 10.1039/C5OB01844G

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