Synthesis of the C1−C21 Fragment of the Serine/Threonine Phosphatase Inhibitor Tautomycin

Compound 40 containing the C-1-C-21 region of tautomycin has been synthesized. The two halves (4 and 5) of this spirocyclic section were each constructed using Matteson's chloromethylene insertion reaction. Cr/Ni-mediated coupling of compounds 4 and 5 resulted in a structure containing the C-1-C-21 section of tautomycin. Oxidation of the resultant allylic alcohol to the ketone and removal of the alpha,beta unsaturation yielded compound 39. Treatment with DDQ removed both PMB protecting groups and allowed the spirocyclic ketal to form producing compound 40, ready for further extension to the natural product tautomycin.