Alkoxyallene-Based Stereodivergent Syntheses of (-)-Hyacinthacine B-4 and of Putative Hyacinthacine C-5 Epimers: Proposal of Hyacinthacine C-5 Structure

作者：Pecchioli Tommaso; Cardona Francesca; Reissig Hans Ulrich^*; Zimmer Reinhold; Goti Andrea^*

来源：Journal of Organic Chemistry, 2017, 82(11): 5835-5844.

DOI：10.1021/acs.joc.7b00667

Hyacinthacines are members of the class of polyhydroxylated pyrrolizidines exhibiting outstanding biological activity as glycosidases inhibitors. Their structural complexity is embodied in the densely functionalized core, possessing a series of contiguous stereogenic centers. In this synthetic study we report a route to the more complex congeners of this class of alkaloids exploiting the diastereoselective addition of an axially chiral lithiated alkoxyallene to an enantiopure cyclic nitrone. Our stereodivergerit approach enabled the installation of the targeted configuration at the ring A by minimal synthetic manipulations and at ring B by using stage dependent selective functionalizations. The versatility and robustness of this methodology were demonstrated by the syntheses of (-)-hyacinthacine B-4 and of two epirners of (+)-hyacinthacine C-5, allowing a suggestion of the likely structure of the isolated natural product.

• 出版日期2017-6-2