Cycloaddition of a chiral nitrone to allylic motifs: an access to enantiopure sugar-based amino acids displaying a stable glycosidic bond and to 4(S)-4-hydroxy-l-ornithine

A (−)-menthone-derived nitrone and various allyl O-, and S-glycosides reacted at 110 °C to afford the corresponding cycloadducts in good yields. For an N-acetylated allyl N-glycoside, an N-glycoside-based product was formed in poor yield with loss of the N-acetyl residue, while the major product 4 (60%), in which the sugar moiety was absent, arose from cleavage of the N-glycosidic bond, under the cycloaddition conditions. The cycloadducts of the O-, and S-glycoside type were ring-opened and subjected to acidic and basic hydrolysis, for removing the chiral auxiliary. This resulted in glycosidic bond cleavage for O-glycosides and loss of material, while an S-glycoside amino acid was isolated in 78% yield, indicating a higher resistance of the S-glycosidic bond. N-O Bond cleavage and hydrolytic treatments applied to 4 afforded 4(S)-4-hydroxy-l-ornithine in high yield. Use of the nitrone derived from (+)-menthone should afford the enantiomer of 4, both precursors of 4-hydroxy arginine derivatives by guanidination.

Graphical abstractDownload full-size image