anti-HIV Alkaloid Research Articles

A concise synthesis of (+)-batzelladine B from simple pyrrole-based starting materials.

Alkaloids, secondary metabolites that contain basic nitrogen atoms, are some of the most well-known biologically active natural products in chemistry and medicine1. Although the efficient laboratory syntheses of alkaloids would enable researchers to study and optimize their biological properties,2 the basicity and nucleophilicity of nitrogen, its susceptibility to oxidation, and its ability to alter reaction outcomes in unexpected ways – for example, through stereochemical instability and neighboring group participation – complicates their preparation in the laboratory. Efforts to address these issues have led to the invention of a large number of protecting groups that temper the reactivity of nitrogen3; however, the use of protecting groups typically introduce additional steps and obstacles into the synthetic route. Alternatively, the use of aromatic nitrogen heterocycles as synthetic precursors can attenuate the reactivity of nitrogen and streamline synthetic strategies4. In this manuscript, we use such an approach to achieve a synthesis of the complex anti-HIV alkaloid (+)-batzelladine B in nine steps (longest-linear sequence) from simple pyrrole-based starting materials. The route employs several key transformations that would be challenging or impossible to implement using saturated nitrogen heterocycles and highlights some of the advantages conferred by the use of aromatic starting materials.

Revised Structure of the Alkaloid Drymaritin

In 2004, a new anti-HIV alkaloid named drymaritin was isolated from Drymaria diandra. The authors identified the alkaloid as 5-methoxycanthin-4-one on the basis of spectroscopic data. Here we describe a synthetic approach that unambiguously gave 5-methoxycanthin-4-one, but the synthetic product showed spectroscopic data significantly different from those of the Drymaria alkaloid. Extensive re-evaluation of the spectroscopic data published for this and related alkaloids has led to the conclusion that drymaritin does not have a canthin-4-one backbone, but is identical to the known alkaloid cordatanine (4-methoxycanthin-6-one).

A new anti-HIV alkaloid, drymaritin, and a new C-glycoside flavonoid, diandraflavone, from Drymaria diandra.

A novel anti-HIV alkaloid, drymaritin (1), and a new C-glycoside flavonoid, diandraflavone (2), along with eight known compounds, torosaflavone A, isovitexin, spinasterol beta-d-glycoside, p-hydroxybenzoic acid, p-hydroxybenzaldehyde, cis-p-coumarate, methyl 5-hydroxy-4-oxopentanoate, and glycerol-alpha-lignocerate, were isolated from Drymaria diandra. Drymaritin (1) exhibited anti-HIV effects in H9 lymphocytes with an EC(50) value of 0.699 microg/mL and a TI of 20.6. Compound 2 showed significantly selective inhibition on superoxide anion generation from human neutrophils stimulated by fMLP/CB with an IC(50) value of 10.0 microg/mL.

Inhibitory effects of triterpene-azidothymidine conjugates on proliferation of human immunodeficiency virus type 1 and its protease.

The conjugates of some dicarboxylic acid hemiesters of triterpenes which show potent inhibition against human immunodeficiency virus type 1 protease (HIV-1 PR) with a reverse transcriptase inhibitor azidothymidine (AZT) or anti-HIV alkaloid FK 3000 were prepared, and their inhibitory activities were investigated against HIV-induced cytopathic effects (CPE) and HIV-1 PR. Most of the triterpene-AZT conjugates showed potent anti-HIV activity as well as moderate to potent PR inhibitory activity, though AZT itself showed no PR inhibitory activity at all. However, the triterpene-FK 3000 conjugates showed neither PR inhibitory activity nor anti-HIV activity.

Quantitation of the Anti-HIV Alkaloids Michellamines A and B by High Pressure Liquid Chromatography

Quantitation of the Anti-HIV Alkaloids Michellamines A and B by High Pressure Liquid Chromatography

Quantitation of the Anti-HIV Alkaloids Michellamines A and B by High Pressure Liquid Chromatography

Michellamines A and B, naphthylisoquinoline dimeric alkaloids from the leaf of a previously undescribed species of the genus Ancistrocladus, show anti-human immunodeficiency virus (HIV) activity in an in vitro screen. In order to determine the distribution of these alkaloids in the genus, the level of production in the new species, and to gain an understanding of the horticultural aspects of production, a sensitive high pressure liquid chromatography analytical method requiring a small biomass was developed. This method resolved michellamines A and B and congeners and enabled quantitation of each. The production of the michellamines was found to be limited to the new species, A. korupensis. © 1997 John Wiley & Sons, Ltd.

An enantiospecific synthesis of the tricyclic guanidine segment of the anti-HIV marine alkaloid batzelladine A

An enantiospecific synthesis of the tricyclic guanidine segment 19 of the new anti-HIV alkaloid batzelladine A, isolated from a marine sponge of genus batzella, starting from [3R(1′R,4R)]-4-acetoxy-3-[1-(ferf-butyldimethylsilyloxy)ethyl]-2-azetidinone 3 is described.