The structural elucidation of a closely related group of steroidal antibiotics, fusidic acid2 (I), cephalosporin P.,3 and helvolic acid4 has established that these antibiotics possess unique structures and stereochemistry. Recent attention has focused on the synthesis of the novel tetracyclic m, syn_, trans ring system of fusidic acids36 (I_). The two reported syntheses have as an intermediate target a tetracyclic steroid skeleton bearing a C-17 ketone function for ultimate elaboration to fusidic acid. We wish to report a successful synthetic method for introduction of the characteristic 17(2O)Z isooctenoic acid side chain of these antibiotics on to a tetracyclic intermediate, such as the C-17 ketone (2). The tetracyclic C-17 ketone (J), 7 which can also serve as a convenient relay intermediate, was obtained from the methyl ester of diacetoxyfusidic acid (2) by oxidative cleavage of the A17(20) bond with ruthenium tetraoxide .a The product was isolated by silica gel column chromatography eluting with 10% ether-benzene. The CD spectrum [CD-curve: xdloxane 298 nm (As = -4.15)), of ketone 2 indicated that the C-13a stereochemistry of fusidic acid was retained. This result is in agreement with previously reported work.g We have previously reported that the addition of lithium a-lithiopropionate to C-17 ketones in the androstane series offers a convenient route to 17B-hydroxybisnorcholanic acid derivatives.lO Extension of this reaction to the addition of the lithium dianion of 6-methyl-5-heptenoic acid to the C-17 ketone (A) was investigated for application to fusidic acid synthesis. The desired 6-methyl-5-heptenoic acid" was conveniently prepared in 50% yield by the reaction of l-bromo-4-methyl-3-pentene12 with the dilithium salt of acetic acid in tetrahydrofuran. I3 Lithium 2-lithio-6-methyl-5-heptenoate was then generated in the usual manner with lithium diisopropylamide in THF and condensed with the C-17 ketone (3) to give after esterification with methyl iodide and sodium bicarbonate in dimethylacetamide a stereoisomeric mixture 14. w. 0. Godtfredsen, W. von Oaehne, L. Tybring, and S. Vangedal. J. Med. Chem. 2. 15 1966). 15. We have converted methyl diacetoxy fusidate to fusidic acid by selective saponification procedures. Thus this synthesis offers a relay route for any formal total synthesis of fusidic acid.