Agnès Pommier

Synthesis of salinomycin

Salinomycin, a commercially significant coccidiostat isolated from Streptomyces albus, has been synthesised from three principal fragments. Key steps include (a) the use of η3-allylmolybdenum cationic complexes 21a,b for the stereoselective construction of two contiguous stereogenic centres in fragment 5a; (b) the electrophilic cyclisation of 2-(prop-2-ynyl)-2-hydroxyoxanes to give molybdenum and chromium carbene complexes which are precursors to the furan fragment 7; (c) the diastereoselective oxidation of a 1,5-diene with potassium permanganate to generate four stereogenic centres in a single step leading to fragment 8; (d) the oxidative rearrangement of acylfuran 89 en route to the 1,6,8-trioxadispiro[4.1.5.3]pentadec-13-ene dispiroacetal core; and finally (e) the use of an allenol ether as an acyl anion equivalent together with the stereoselective hydrolysis of allenol ether intermediate 112 in an alternative synthesis of the dispiroacetal core.

Exploratory theoretical study of the [2 + 2] cycloaddition between ketene and formaldehyde

Abstract Two reaction paths, leading from formaldehyde 1 and ketene 2 to 2-oxetanone 3, are examined. Mechanism A, involving the initial formation of the C2O3 bond, a stepwise mechanism with biradical character, is found to be more favoured than mechanism B, a concerted, but highly-asynchronous mechanism with zwitterionic character involving the initial formation of the C4C5 bond.

An approach to the synthesis of (–)-lipstatin by Wittig reaction and Lewis acid-promoted [2 + 2] cycloaddition

The β-lactone moiety of (–)-lipstatin 1, a potent inhibitor of pancreatic lipase, is prepared via a Lewis acid-promoted [2 + 2] cycloaddition between hexyltrimethylsilyl ketene 3 and the (Z,Z)-dienic aldehyde 4, obtained from hexanal by two stereoselective Wittig reactions.

Synthesis of manoalide using a 1,2-metallate rearrangement

Manoalide, a marine antiinflammatory sesterterpenoid, has been synthesised using a 1,2-metallate rearrangement of a higher order cuprate and a Pd 0 -catalysed carbonylation of an iodo alkene to generate the central dihydropyranone ring.

Formation of 2-cyclohexenones by friedel-crafts acylation of alkenes with β,γ-ethylenic acyl halides

Abstract Friedel-Crafts acylation of alkenes with β,γ-alkenoyl halides leads to conjugated Altrienolates able to cyclize into Al-enolates of 2-cyclohexenones through an allowed thermal disrotatory electrocyclization mechanism. Discussion of the product structure is based on two-dimensional NMR experiments (400 MHz) and molecular mechanics studies (GENMOL and MM2).