Studies towards the synthesis of polyhydroxylated pyrrolidine alkaloids isolated from Broussonetia kazinoki (moraceae)

• Published in: Tetrahedron 2022-12, Vol.128, p.133104, Article 133104
• Main Authors: Bouillon, Marc E., Nash, Robert J., Pyne, Stephen G.
• Format: Article
• Language: English
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2022.133104

The syntheses of L-AB1, L-DMDP, and the novel compounds, (−)-phenethyl-L-AB1, (−)-10′-deoxobroussonetine C, (−)-10′-deoxobroussonetine E, (−)-1′-epi-10′-deoxobroussonetine E, and (−)-(6S)-12′-hydroxydodecylmoranoline are reported. These syntheses start from d-xylose employing the Petasis borono-Mannich reaction to stereoselectively introduce the amino group, followed by a chemo- and regioselective O-mesylation to deliver the fully functionalized pyrrolidine moiety after intramolecular SN2-cyclisation. The synthesis of the latter targeted compound involved a ring expansion process of a prolinol moiety to a piperidine derivative under Mitsunobu reaction conditions. An attempted synthesis of desired ent-broussonetine C was unsuccesful due to formation of an unexpected tetrahydrofuran derivative in the final stage of the synthesis. The glycosidase inhibitory activities of four of the new target compounds against a panel of ten glycosidaes is also presented. [Display omitted]