Corrected Structure of Natural Hyacinthacine C₁ via Total Synthesis

Abstract

Hyacinthacines C 1 and C 4 are natural products that were isolated from Hyacinthoides non-scripta and Scilla socialis in 1999 and 2007, respectively. Despite their different 1 H NMR and 13 C NMR spectroscopic data, these compounds have been assigned the same structures, including absolute configurations. This work details the total synthesis of natural (+)-hyacinthacine C 1 , whose structure is confirmed as being the C-6 epimer of that reported. The synthetic strategy focused on inverting the configuration at C-1 of the final hyacinthacines via operating the inversion at the corresponding carbon atom in three previously synthesized intermediates. To do this, the advanced intermediates were subjected to Swern oxidation, followed by a stereoselective reduction with L-Selectride. This approach led to the synthesis of (+)-5-epi-hyacinthacine C 1 (15), the corrected structure for (+)-hyacinthacine C 1 ( 19), (+)-6,7-di-epi-hyacinthacine C 1 (23), and (+)-7-epi-hyacinthacine C 1 (29). Glycosidase inhibition assays revealed that (+)-hyacinthacine C 1 (19) proved the most active, with IC 50 values of 33.7, 55.5, and 78.2 μM, against the α-glucosidase of rice, human lysosome, and rat intestinal maltase, respectively.

My 37 years of working with nitrogen heterocycles and alkaloids

“…In 2019 we were able to correct the structure of hyacinthacine C 1 through its total synthesis as shown in Scheme 30. [69] Our advanced intermediate 112 was subjected to a Swern oxidation, followed by a stereoselective reduction with Lselectride. This approach led to the synthesis of (+)-5-epihyacinthacine C 1 which was identical to the original isolate named hyacinthacine C 1.…”

Synthesis of diastereomeric pheromones: adjacent methyl-branched alcohols and ketones

“…Oxidation of the respective alcohols is one of promisingly ways to fabricate pheromone products in large scale. Many reactions can be in situ from DMSO and oxalyl chloride which allows to prepare aldehydes and ketones under mild conditions[17][18][19][20].…”