The total synthesis of natural (+)-hyacinthacine C 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, S2 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 C and (+)-7- epi-hyacinthacine C (compound names are based on the corrected structure of hyacinthacine C) proved most active, with inhibitory activities ranging between weak (IC = 130 μM) and moderate (IC = 9.9 μM) against the α-glucosidases of rat intestinal maltase, isomaltase, and sucrase, thus identifying potential new leads for future antidiabetic drug development.

A highly diastereoselective synthesis (dr = 99 : 1 97 : 3) of enantioenriched anti-α-allyl-β-fluoroamines (ee = 86–92%) has been developed involving a highly diastereoselective Petasis allyl borono-Mannich reaction of (S)- or (R)-α-fluoroaldehydes.

Background: The inherent glycosidase inhibitory activity and potentially therapeutic value of the polyhydroxylated pyrrolizidine alkaloids containing a hydroxymethyl substituent at the C-3 position have been well documented. Belonging to this class, the naturally occurring hyacinthacine C-type alkaloids are of general interest among iminosugar researchers. Their selective micromolar α -glycosidase inhibitory ranges (10 – 100 μM) suggest that these azasugars are potential leads for treating type II diabetes. However, the structures of hyacinthacine C1, C3 and C4 are insecure with hyacinthacine C5 being recently corrected. Objective: This review presents the hyacinthacine C-type alkaloids: their first discovery to the most recent advancements on the structures, biological activities and total synthesis. Conclusion: The hyacinthacine C-type alkaloids are of exponentially increasing interest and will undoubtedly continue to be reported as synthetic targets. They represent a challenging but rewarding synthetic feat for the community of those interested in accessing biologically active iminosugars. Since 2009, ten total syntheses have been employed towards accessing similarly related products but only three have assessed the glycosidase inhibitory activity of the final products. This suggests the need for an accessible and universal glycosidase inhibitory assay so to accurately determine the structure-activity relationship of how the hyacinthacine C-type alkaloids inhibit specific glycosidases. Confirming the correct structures of the hyacinthacine C-type alkaloids as well as accessing various analogues continues to strengthen the foundation towards a marketable treatment for type II diabetes and other glycosidase related illnesses.

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.

cyclohexene (9Z)-octadec-9-enyl ethers isolated from the Structure elucidation of cyclohexene (9Z)-octadec-9-enyl ethers isolated from the leaves of Uvaria cherrevensis (Annonaceae) leaves of Uvaria cherrevensis (Annonaceae)