PART I. MODEL STUDIES DIRECTED TOWARD AND THE TOTAL SYNTHESIS OF (+)-COMPACTIN. PART II. THE FORMAL TOTAL SYNTHESIS OF (+,-)-THIENAMYCIN

Part I. The enantiospecific synthesis of (+)-compactin is discussed in detail. The synthesis centers around the Diels-Alder reaction between 3(E)-(2S,4R,6R)-tetrahydro-2,4-methoxy-6-{6-(phenylthio)-3,5-hexadienyl}-2H-pyran and methyl-(1R,4S)-7-oxabicyclo{2.2.1}hept-2-ene-2-carboxylate. The adduct provides the desired configuration at C(8), C(8a') and C(1') in a single operation and allows for the stereoselective incorporation of the C(2') methyl group. A unique Grob fragmentation liberates the C(8') hydroxy group from the oxabicyclo system to provide the hexahydronaphthol system which is readily converted into compactin.;Part II. The stereoselective synthesis of the potent (beta)-lactam antibiotic thienamycin is discussed in detail. The construction of the biologically important C(8) hydroxyl group centers around the treatment of {1R-(exo-anti)}-5-bromospiro{bicyclo{2.2.1}heptane-2,2'-{1,3}-dioxolane}-7-carboxaldehyde with dilithium dimethyl cyano cuprate to provide the desired R isomer in greater than 90% selectivity. Incorporation of the nitrogen atom is accomplished via a Beckmann rearrangement. Oxidative cleavage of the corresponding unsaturated (delta)-lactam provided a (beta)-amino acid which was readily converted into 4-nitrophenyl{2(alpha),3(beta)(R*)}-3-(1-hydroxyethyl)-(beta),4-dioxo-2-azetidinebutanoate, a known thienamycin precursor.