19954-66-6

(Chemical Equation Presented) The four olefin stereoisomers of farnesol have been synthesized from readily available nerylacetone or commercial geranylacetone. A new variation on the use of β-oxido ylides favored the (2Z)-stereoisomers, whereas the (2E)-isomers were obtained through a classical Horner-Wadsworth-Emmons condensation with triethyl phosphonoacetate and reduction of the resulting ester.

Permanganate oxidation of farnesoate esters 12a - d afforded perhydro-2,2′-bifuranyl compounds 16a - d, with control of relative stereochemistry at four new stereocenters. Subsequent oxidative cleavage of 16a - d then provided tetrahydrofuran-containing fragments 17a - d, one of them 17b possessing the same relative stereochemistry present in the C13-C21 portion of the polyether antibiotic semduramycin (1). Control of the absolute stereochemistry was achieved through the use of the Oppolzer sultam chiral auxiliary. The requisite starting trienes were prepared stereoselectively in just three steps from geranyl chloride or neryl chloride, providing a short and versatile route to polyether fragments.

Hydroprene was obtained with an overall yield of 16percent in the form of a 77:23 mixture of 2E,4E and 2Z,4E isomers by ozonolysis of 1,5-dimethyl-1-cyclooctene and selective transformations of the 4-methyl-1,1-dimethoxy-8-oxononane, including ethoxycarbonylmethylenation of the keto group, alkylation of the formyl group by isopropylmagnesium bromide followed by deoxygenation, and allylic bromination-dehydrobromination.The individual 2E,4E isomer was isolated by HPLC.

Treatment of geranoyl chloride (20) with triethylamine in toluene at reflux gave the vinylketene 21 which underwent a cycloaddition to give 7,7-dimethyl-2-methylenebicycloheptan-6-one (24) in 43percent yield.Isomerization over Pd gave chrysanthenone (6) in quantitative yield.Wolf-Kischner reduction gave β-pinene (5) in 70percent yield.A similar sequence of reactions starting from (Z,E)- and (E,E)-farnesoyl chloride gave ketones 51 and 57, which were converted to β-cis-bergamotene (8) and β-trans-bergamotene (9), respectively. β-Copaene (10) and β-ylangene (11) were prepared from 57 by a three-step sequence.Treatment of the imidazole 59 with tri-n-butyltin hydride in toluene at reflux gave a 46percent yield of a 1:1 mixture of 10 and 11.Selenium dioxide oxidation of 11 gave the antitumor agent lemnalol.The mechanisms of the regiospecific ketene generation and the cycloaddition reaction have been explored, and the reactivity of the novel bicycloheptanones has been examined.