Lentiginosine, a dihydroxyindolizidine alkaloid that inhibits amyloglucosidase

Abstract

Lentiginosine, a dihydroxyindolizidine alkaloid, was extracted from the leaves of Astragalus lentiginosus with hot methanol and was purified to homogeneity by ion-exchange, thin-layer, and radial chromatography. A second dihydroxyindolizidine, the 2-epimer of lentiginosine, was also purified to apparent homogeneity from these extracts. Gas chromatography of the two isomers (as the TMS derivatives) showed that they were better than 95% pure; lentiginosine eluted at 8.65 min and the 2-epimer at 9.00 min. Both compounds had a molecular ion in their mass spectra of 157, and the NMR spectra demonstrated that both were dihydroxyindolizidines differing in the configuration of the hydroxyl group at carbon 2. Lentiginosine was found to be a reasonably good inhibitor of the fungal alpha-glucosidase, amyloglucosidase (Ki = 1 x 10(-5) M), but it did not inhibit other alpha-glucosidases (i.e., sucrase, maltase, yeast alpha-glucosidase, glucosidase I) nor any other glycosidases. The 2-epimer had no activity against any of the glycosidases tested.

A Straightforward Route to Enantiopure Pyrrolizidines and Indolizidines by Cycloaddition to Pyrroline N-Oxides Derived from the Chiral Pool

“…Nitrones 1 have been successfully applied to straightforward syntheses of polyhydroxyindolizidines, compounds that have been recently recognized as glycosidase inhibitors and important pharmacological tools [7]. The synthesis of the naturally occurring alkaloid (+)-lentiginosine (4) [8], a potent inhibitor of amyloglucosidases [8][9][10] serves to illustrate the potentialities of enantiopure nitrones 1. The first synthesis of the pure natural compound [11,9] has been attained by a sequential methylenecyclopropane (2) cycloaddition to the nitrone 1a followed by thermal rearrangement to the indolizidinone 3 (Scheme 2), according to a general methodology developed in our group [12].…”

Enantiospecific total synthesis of (+)-lentiginosine

“…1 Owing to the growing interest in hydroxylated indolidizines as different glycosidase inhibitors, there has been a plethora of publications concerning the synthesis of hydroxylated indolidizines including lentiginosine. 2 Reently, we demonstrated the versatility of γ-oxo-amides derived from tartaric acid in the synthesis of a variety of natural products.…”

Acute toxicity and histopathological assessment of methanol extract of Cleome viscosa (Linn.) whole plant.

“…Consuming some secondary metabolites can have severe consequences. Alkaloids can block ion channels (Hamill and McBride, 1996), inhibit enzymes (Pastuszak et al, 1990), or interfere with neurotransmission producing hallucinations (Gaudreau and Gagnon, 2005), convulsion, vomiting and even death (Audi, 2005), diterpene gossypol blocks phosphorylation and is very toxic, spinasterol from spinach interferes animal hormone actions, gallotannins also binds to protein and block digestion (Hartmann, 2007). Plants containing cyanogenic glycosides can liberate cyanide which blocks cytochrome C-oxidase thus, becoming potentially poisonous (Venturi, 2011).…”