Total Synthesis of Eleuthoside A; Application of Rh-Catalyzed Intramolecular Cyclization of Diazonaphthoquinone

Abstract

The first total synthesis of (±)-eleutherol and eleuthoside A, the natural cytotoxic substances extracted from medicinal Indonesian plant, is described. First, the synthesis of (±)-eleutherol has been ­accomplished in nine steps starting from bromo methoxy aldehyde with the aid of diazo-transfer chemistry approach. Second, a metal-­catalyzed intramolecular cyclization reaction of the corresponding ­diazonaphthoquinone led to the desired eleuotherol, which served as a precursor to eleuthoside A. Then, several glycosidation routes, using different glucosyl donors, were experimented to reach effective O-glycosidation of eleutherol. The only successful strategy involved Koenigs–Knorr glycosidation using peracetyl glycosyl bromide in the presence of Ag2O and quinoline. This strategy furnished our desired acetylated glycoside of β-configuration, regioselectively. Finally, deacetylation and successive separation of diastereomers were conducted to give eleuthoside A.

Asymmetric Ruthenium‐Catalyzed C−H Activation by a Versatile Chiral‐Amide‐Directing Strategy

“…Notably, although racemic Eleutherol has been previously synthesized via 5—10 steps, [39] this work represents the first asymmetric synthesis of Eleutherol. It should be mentioned that Eleutherol is a key intermediate to synthesize Eleuthoside A ( 19 ah , Scheme 9f) [39a] …”