Alain Laurens

Acetogenins from Annonaceae

In 1982, Jolad et al. isolated uvaricin, a new antitumor agent, from the roots of Uvaria acuminata (Annonaceae), a bis-tetrahydrofuranoid fatty acid lactone (1) related to polyketides or acetogenins. However, it contained a number of original structural characteristics, particularly a linear acetogenin, a bis-tetrahydrofuran pattern flanked by hydroxyls and a terminal unsaturated lactone. Two years later, Dabrah and Sneden (2, 3 and Cortes et al. (4) described four new products presenting the same structural characteristics. Because these products formed a new class of natural compounds, and are only found in species belonging to the family of Annonaceae, they are commonly called acetogenins from Annonaceae.

Solamin, a cytotoxic mono-tetrahydrofuranic γ-lactone acetogenin from Annona muricata seeds

Abstract Using activity-directed fractionation, the chromatography of the bioactive petroleum ether extract of Annona muricata seeds led to the isolation of a new monotetrahydrofuranic γ-lactone acetogenin, solimin. Comparative structure-activity relationships were performed, using the acetogenins from A. muricata in KB and VERO cell lines in in vitro tests.

Stereospecific synthesis of (+)-muricatacin: a biologically active acetogenin derivative☆

(+)-muricatacin and analogs have been synthesized without ambiguity about the absolute configuration at the C-4 and C-5 centres. The observed [α]D are reported as well as the results obtained for the cytotoxicity assay with KB and VERO cell lines.

Murisolin: A New Cytotoxic Mono-tetrahydrofuran-g-lactone from Annona muricata

Using cytotoxicity as a bioassay guide led to the isolation of a new active acetogenin from the seed of Annona muricata. Murisolin, 1 is the first example of a mono-tetrahydrofuran-γ-lactone acetogenin with only three hydroxyl groups. Its structure was characterised by mass spectrometry and 2D homonuclear and heteronuclear correlations nmr spectroscopy. The relative stereochemistry of four of its six chiral centers was established bh 1 H-nmr comparative spectral studies between the murisolin triacetate and some bistetrahydrofuran acetogenin acetates

Muricadienin, muridienins and chatenaytrienins, the early precursors of annonaceous acetogenins

Abstract Chatenaytrienins-1,-2 and -3, muridienins-3 and -4 and muricadienin were characterized by tandem mass spectrometry (MS/MS) in a mixture of natural precursors of annonaceous acetogenins from Annona muricata . Chatenaytrienin-1, -2, -3 and -4 were then isolated from A. nutans and fully characterized by spectroscopic methods (NMR, MS) and by chemical and enzymatic oxidative processes. Isolation of these trienes confirmed the postulated biosynthetic pathway leading to the acetogenins.

A novel 1-indanone isolated from Uvaria afzelii roots

Bioactivity-guided fractionations of chloromethylenic extract of the roots of U. afzelii (Annonaceae), using Leishmania donovani and Trypanosoma brucei brucei bioassay, resulted in the isolation of the two known compounds, emorydone (1) and demethoxymatteucinol (2), previously isolated from the stems, which were characterised from this source. In addition, the novel 1-indanone, afzeliindanone (3), was also isolated. The structure determination of afzeliindanone (3) was elucidated on the basis of spectral data as 4-[4-hydroxy-3-methoxyphenyl]-indan-1-one. This compound is the first 1-indanone derivative isolated from plants.

ß-Lactamase Inhibitors from Anacardium occidentale

The antimicrobial activity of cashew nut shell liquid (CNSL) and anacardic acids isolated from nuts of Anacardium occidentale were tested against several strains responsible of cutaneous infection or olfactory disagreement. CNSL exhibited minimal inhibitory concentrations (MIC) against Propionibacterium acnes (1.56 µg/mL), Corynebacterium xerosis (6.25 µg/mL), and various strains of Staphylococcus aureus (25 µg/mL), but was not active against the fungus Pityrosporum ovale. The ß-lactamase inhibition was tested by the agar diffusion method with penicillin G, against two strains of S. aureus, both resistant to penicillin by synthesis of ß-lactamase, but one strain being insensitive to all ß-lactamines antibiotics due to a modification of protein linking penicillin (PLP 2a). The results showed clearly the ß-lactamase inhibitory activity of CNSL and anacardic acids on S. aureus enzyme, without activity on PLP 2a.

Semisynthesis of cis- and trans-Solamin by Acidic Opening of Natural Diepomuricanin A − a Mechanistic Investigation

MS/MS spectroscopy allowed us to determine the mechanism of the acidic opening of diepomuricanin A, by analysis of the product distribution after treatment with H218O in the presence of HClO4 in anhydrous acetone.

Muridienin-1 and -2: The missing links in the biogenetic precursors of acetogenins of annonaceae

Isolation of Δn,n+4 diunsaturated γ-lactone derivatives of lacceroic and ghedoic acids, allows us to confirm the biogenetic pathway of the bioactive acetogenins of Annonaceae.