title: 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.
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, Warsaw 02-093, Poland. czarnoz@chem.uw.edu.pl.
authors.forename: Kamil
authors.initials: K
authors.lastname: Lisiecki
authors.forename: Krzysztof K
authors.initials: KK
authors.lastname: Krawczyk
authors.forename: Piotr
authors.initials: P
authors.lastname: Roszkowski
authors.forename: Jan K
authors.initials: JK
authors.lastname: Maurin
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Czarnocki
mesh_terms: D001598:Bephenium Compounds / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D055668:Photochemical Processes; D011034:Podophyllotoxin / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013386:Succinates / Q000737:chemistry*
chemical_list: C000609227:3,4-bisbenzylidene succinate amide ester; D001598:Bephenium Compounds; D013386:Succinates; D011034:Podophyllotoxin