Total Synthesis of (+)‐Hyacinthacine A1, (+)‐7a‐epi‐Hyacinthacine A1, (6R)‐6‐Hydroxyhyacinthacine A1 and (6S)‐6‐Hydroxy‐7a‐epi‐hyacinthacine A1

• DOI: 10.1002/ejoc.201101096
• Publication Date: 2011-10-24T09:38:08Z
• Authors: Giampiero D'Adamio; Andrea Goti; Camilla Parmeggiani; Elena Moreno‐Clavijo; Inmaculada Robina; Francesca Cardona
• Keywords: Nitrone; Deoxygenation

Abstract The total synthesis of natural (+)‐hyacinthacine A 1 ( 6 ), (+)‐7a‐ epi ‐hyacinthacine 7 ) and their 6‐hydroxy analogues 21 16 was achieved using a nitrone cycloaddition strategy with D ‐ribose‐derived cyclic 8 as the dipole tert ‐butyl acrylate dipolarophile. After separation adducts, reductive cleavage N–O bond followed by lactam reduction deprotection afforded two non‐natural hydroxy in excellent yields. which required deoxygenation at C(6), accomplished DIBAL‐H mesylate derivatives pyrrolizidinols 20 15 , respectively. Evaluation synthesized compounds against panel 12 commercially available glycosidases showed that hyacinthacine its (6 R )‐hydroxy analogue are good inhibitors amyloglucosidase; compound is also strong inhibitor β‐glucosidase, while only moderate inhibition. amyloglucosidase α‐ L ‐fucosidase; presence S group led to diminished activity.