Total Synthesis of Neodysiherbaine A via 1,3-Dipolar Cycloaddition of a Chiral Nitrone Template

Abstract

The total synthesis of neodysiherbaine A was achieved via 1,3-dipolar cycloaddition of a chiral nitrone template with a sugar-derived allyl alcohol in the presence of MgBr·OEt. This cycloaddition constructed the C2 and C4 asymmetric centers in a single step. Then reductive cleavage, intramolecular S2 reaction of the tertiary alcohol, and oxidation of the primary alcohol afforded neodysiherbaine A.

Marine Excitatory Amino Acids: Structure, Properties, Biosynthesis and Recent Approaches to Their Syntheses

“…Asymmetric hydrogenation with rhodium DuPhos (DuPhos is a class of organophosphorus compounds that are used as ligands for asymmetric syntheses), followed by deprotection of amino group and alkaline hydrolysis gave the target compound 74 (Scheme 10). A total synthesis of neodysiherbaine A (75) based on 1,3-dipolar cycloaddition of a chiral nitrone to sugar-derived product, containing tetrahydropyran moiety, has also been reported recently [76]. The pyran allylic alcohol was obtained from methyl-α-D-mannopyranoside (87) through conversion into derivative 88 by the previously known multistep procedure, and, after the Swern oxidation and Wittig reaction, gave 89.…”

“…A total synthesis of neodysiherbaine A (75) based on 1,3-dipolar cycloaddition of a chiral nitrone to sugar-derived product, containing tetrahydropyran moiety, has also been reported recently [76]. The pyran allylic alcohol was obtained from methyl-α-D-mannopyranoside (87) through conversion into derivative 88 by the previously known multistep procedure, and, after the Swern oxidation and Wittig reaction, gave 89.…”