Total Synthesis of Natural Hyacinthacine C5, and six Related Hyacinthacine C5 Epimers

Authors

Anthony Carroll, University of WollongongFollow
Kongdech Savaspun, University of WollongongFollow
Anthony C. Willis, Australian National University
Masako Hoshino, University of Toyama
Atsushi Kato, University of Toyama
Stephen G. Pyne, University of WollongongFollow

RIS ID

127373

Publication Details

Carroll, A. W., Savaspun, K., Willis, A. C., Hoshino, M., Kato, A. & Pyne, S. G. (2018). Total Synthesis of Natural Hyacinthacine C5, and six Related Hyacinthacine C5 Epimers. Journal of Organic Chemistry, 83 (10), 5558-5576.

Abstract

The total synthesis of natural (+)-hyacinthacine C₅ was achieved, which allowed correction of its initially proposed structure, as well as six additional hyacinthacine C-type compounds. These compounds were readily accessible from two epimeric anti-1,2-amino alcohols. Keeping a common A-ring configuration, chemical manipulation occurred selectively on the B-ring of the hyacinthacine C-type products through methods of syn-dihydroxylation, S_N2 ring-opening of a cyclic sulfate and also employing either (R)- or (R,S)-α-methylallyl amine for the Petasis borono Mannich reaction. Our small analogue library was then assessed for its glycosidase inhibitory potency against a panel of glycosidases. (-)-6-Epi-hyacinthacine C₅ and (+)-7-epi-hyacinthacine C₅ (compound names are based on the corrected structure of hyacinthacine C₅) proved most active, with inhibitory activities ranging between weak (IC₅₀ = 130 μM) to moderate (IC₅₀ = 9.9 μM) against the α-glucosidases of rat intestinal maltase, isomaltase and sucrase, thus identifying potential new leads for future antidiabetic drug development.

Grant Number

ARC/DP130101968