78773-31-6Relevant articles and documents
Preparation of Macrocyclic Lactones by Ring Closure of Cesium Carboxylates
Kruizinga, Wim H.,Kellogg, Richard M.
, p. 5183 - 5189 (2007/10/02)
A series of ω-halo fatty acids, the longest being 16-iodohexadecanoic acid, was prepared by oxidation of the corresponding ketones with m-chloroperbenzoic acid in boiling chloroform, followed by ring opening usually with hydrogen iodide in acetic acid at 100 deg C.Solutions of these acids in dimethylformamide (DMF) at concentrations of 5E-3 - 5E-2 M were treated with an equivalent amount of dry Cs2CO3.The solutions were stirred at 40 deg C overnight.Workup of the reaction mixture produced a mixture of (macro)cyclic lactone (macrolide) and its dimer (dilide).For the case of 16-iodohexanoic acid the lactone was isolated in 85percent yield.Yields for other large ring macrolides were also excellent.It was demonstrated that substitution by carboxylate on a secondary halide also goes well to afford the corresponding macrolide with no detectable amount of elimination.The effects of ring size, concentration, and solvent on the ring closure of the cesium carboxylates formed in situ were investigated.DMF is the best solvent of those investigated for the ring closure.Cesium carboxylates also undergo more readily ring closure and in far better yield than the carboxylates of lithium, sodium, potassium, rubidium, silver, thallium, magnesium, strontium, or barium.The S-lactone of ricinelaidic acid was prepared optically pure in 80percent yield from optically pure mesylate of R-ricinelaidic acid, which was treated with cesium carbonate in dry DMF.This demonstrates that the ring closure proceeds with the anticipated SN2 inversion at the hydroxyl-bearing carbon atom.With the same approach optically pure S-zearalenone was protected and subjected to ring opening, and the hydroxyl group was activated as mesylate.Some racemization was found to occur in the ring-opening step.On treatment of this material with dry cesium carbonate in DMF, the desired ring closure took place in 80percent yield to provide an excess of the protected R enantiomer of zearalenone.On the basis of these results, some speculations are made concerning the action of cesium in promoting ring closure to macrocyclic lactones.
