Synthesis of Rosavin and its analogues based on a Mizoroki-Heck type reaction

The Rosavin framework could be constructed with either phenylboronic acids, the protected arabinopyranosyl bromide 4 or the protected xylopyranosyl bromide 5, along with allyl O-β-d-glucopyranoside 7 that could be easily prepared based on direct β-glucosidation between allyl alcohol and d-glucose using the immobilized β-glucosidase (EC 3.2.1.21). The key reaction was the Pd(II)-catalyzed Mizoroki-Heck type reaction between allyl β-d-glucopyranoside congeners 9 or 10 and arylboronic acids. Deprotection of the coupling products afforded synthetic Rosavin 1, 4-methoxycinnamyl 6-O-(α-l-arabinopyranosyl)-β-d-glucopyranoside 2, and cinnamyl 6-O-(β-d-xylopyranosyl)-β-d-glucopyranoside 3, which were identical with the natural products in respect to the specific rotation and spectral data.

The synthesis of Rosavin 1 was achieved by the coupling reaction of allyl β-d-glucopyranoside congener 2 and bromide 3 followed by the Pd(II)-catalyzed MH-type reaction with phenylboronic acid. Moreover, Rosavin analogues were obtained using same synthetic strategy.Figure optionsDownload as PowerPoint slide

Allyl 6-O-tert-butyldimethylsilyl-β-d-glucopyranosideC15H30O6Si[α]D27=-45.9 (c 0.75, CHCl3)Ee = >99%Source of chirality: d-glucose

Allyl 2,3,4-tri-O-benzoyl-β-d-glucopyranosideC30H28O9[α]D27=-0.7 (c 0.54, CHCl3)Ee = >99%Source of chirality: d-glucose

Allyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-α-l-arabinopyranosyl)-β-d-glucopyranosideC56H48O16[α]D27=-72.9 (c 0.62, CHCl3)Ee = >99%Source of chirality: d-glucose

Allyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-β-d-xylopyranosyl)-β-d-glucopyranosideC56H48O16[α]D27=-24.9 (c 0.51, CHCl3)Ee = >99%Source of chirality: d-glucose

Cinnamyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-α-l-arabinopyranosyl)-β-d-glucopyranosideC62H52O16[α]D27=+51.8 (c 0.50, CHCl3)Ee = >99%Source of chirality: d-glucose

4-Methoxycinnamyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-α-l-arabinopyranosyl)-β-d-glucopyranosideC63H54O17[α]D27=+54.6 (c 0.28, CHCl3)Ee = >99%Source of chirality: d-glucose

Cinnamyl2,3,4-tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-β-d-xylopyranosyl)-β-d-glucopyranosideC62H52O16[α]D27=-35.3 (c 0.53, CHCl3)Ee = >99%Source of chirality: d-glucose

Rosavin (Cinnamyl 6-O-(α-l-arabinopyranosyl)-β-d-glucopyranoside)C20H28O10[α]D27=-54.7 (c 0.70, CHCl3/MeOH 1:1)Ee = >99%Source of chirality: d-glucose

4-Methoxycinnamyl 6-O-(α-l-arabinopyranosyl)-β-d-glucopyranosideC21H30O11[α]D25=-46.6 (c 0.31, MeOH)Ee = >99%Source of chirality: d-glucose

Cinnamyl 6-O-(β-d-xylopyranosyl)-β-d-glucopyranosideC20H28O10[α]D24=-71.9 (c 0.40, MeOH)Ee = >99%Source of chirality: d-glucose