Synthesis of unnatural analogues of narciclasine: Chemoenzymatic synthesis of 2-epi-1-hydroxymethylnarciclasine

An approach to the synthesis of novel C-1 analogues of narciclasine has been developed. The synthesis relies on chemoenzymatic dihydroxylation of an arene, Stille coupling, and an intramolecular Heck reaction to affect key transformations. The synthesis of the targeted C-1 analogues addresses a gap in literature where few narciclasine analogues have been prepared, with no C-1 homologues existing to date. The synthetic route to 2-epi-1-hydroxymethylnarciclasine, as well as a possible route to several other derivatives, is described in detail. Experimental and spectral data are provided for all newly synthesized compounds

Repetition of chemistry from a recently retracted paper. A cautionary note.

The base-catalyzed condensation reaction between (E)-4-phenylbut-2-enal and phenylpropargyl aldehyde recently reported in the literature to provide formylcyclobutadiene was repeated under the published conditions. The product obtained was identified as (E)-5-phenyl-2-((E)-styryl)pent-2-en-4-ynal rather than the reported 2-phenyl-3-styrylcyclobutadiene-1-carboxaldehyde. The structure assignment is supported by NMR and IR data and a x-ray structure of the crystalline alcohol obtained by Luche reduction.NSERC Idea to Innovation - I2IPJ-470630-14 NSERC Discovery Grant - RGPIN-2018-0372

Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity

A 15-step chemoenzymatic total synthesis of C-1 methoxycarbonyl narciclasine (10) was accomplished. The synthesis began with the toluene dioxygenase-mediated dihydroxylation of ortho-dibromobenzene to provide the corresponding cis-dihydrodiol (12) as a single enantiomer. Further key steps included a nitroso Diels–Alder reaction and an intramolecular Heck cyclization. The C-1 homolog 10 was tested and evaluated for antiproliferative activity against natural narciclasine (1) as the positive control. Experimental and spectral data are reported for all novel compounds