Reynald Hocquemiller

Iron-catalysed arylation of heteroaryl halides by Grignard reagents

Abstract Cross-coupling reaction of phenylmagnesium bromide with heteroaryl halides, in the presence of a catalytic amount of iron salts, is reported. Yields are moderate to good, and it is worth noting that this reaction has been applied to non-activate heteroaryl halides.

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.

Iron catalyzed hydrodebromination of 2-aryl-1,1-dibromo-1-alkenes

Abstract 2-Aryl- or 2-heteroaryl-1,1-dibromo-1-alkenes are reduced by Grignard reagents in a THF+NMP mixture in the presence of a catalytic amount of iron salts, to afford the corresponding E vinyl bromides. Further application to the one pot reduction-cross coupling reaction with Grignard reagents is highlighted.

Expeditious preparation of 2-substituted quinolines

Abstract A library of 2-substituted quinolines was synthesized in solution from mixtures of Grignard reagents and a quinolinium salt. Grignard reagents were prepared in one pot, taking advantage of the entrainment method for their preparation from unreactive alkyl halides. Then mixtures of 2-alkylquinolines were readily accessible for biological tests or separated by centrifugal-partition chromatography (CPC) prior to the biological screening.

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

Epimerization of annonaceous acetogenins under basic conditions

Abstract in basic conditions, non-4-hydroxylated annonaeous acetogenins may be epimerized by light basic treatment. The two epimers are inseparable by HPLC, have identical spectroscopic data (MS, IR, UV, 1 H and 13 C NMR). However, specific rotation of the epimeric mixture and enzymatic oxidation after chemical degradation, allow us to characterize this epimerization. In the same reaction conditions, 4-hydroxylated annonaceous acetogenins led to isoacetogenins.

Molvizarin and motrilin : two novel cytotoxic bis-tetrahydro-furanic γ-lactone acetogenins from Annona cherimolia

Abstract Two new cytotoxic adjacent bis-tetrahydrofuranic acetogenins, molvizarin and motrilin, have been isolated from the cytotoxic methanolic extract of Annona cherimolia seeds. Their structures were established on the basis of 2D-NMR spectroscopic techniques. While molvizarin ( 1 ) belongs to the very rare type of C 35 bis-tetrahydrofuranic acetogenins, motrilin ( 2 ) is the first example of a C-29 hydroxylated acetogenin.

Synthesis and structure determination of iso-cladospolide B ☆

iso-Cladospolide B 1 was previously characterized from the fungal isolate I96S215 obtained from a marine sponge collected in Indonesia. However, neither the relative nor the absolute configurations were reported. We describe in this letter a synthetic pathway which allowed us to prepare 1 and attribute the absolute configurations of the three stereogenic centers.

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.

NMR determination of absolute configuration of butenolides of annonaceous type

We report herein the first determination of the absolute configuration of the annonaceous butenolides by a NMR method. This technique uses a chiral solvating agent (CSA), the so-called Pirkles reagent, at low temperature and low concentration, allowing one to apply this method to other natural products as well. Indeed, the presence of basic sites (e.g. tetrahydrofuran, hydroxyl) did not interfere with the major solvation of the reagent with the lactone moiety. A new model is proposed which allowed us to confirm the (S) absolute configuration of the butenolide of annonaceous acetogenins. Furthermore this method can be successfully applied to the measure of the diastereomeric (or enantiomeric) excess of the same butenolide containing compounds.