Efficient Degradation of FK-506 to a Versatile Synthetic Intermediate

Article abstract of DOI:10.1021/jo00307a014

An 11-step degradation of natural FK-506 (1) to selectively protected C10-C34 synthetic intermediate 2 has been accomplished in 14percent overall yield.The key steps include; (a) lead tetracetate mediated C9-C10 bond cleavage of 24,32-bis(triisopropylsilyl)-FK-506 (3), (b) simultaneous C10 ester, C22 ketone reduction/C26 oxygen deacylation, and (c) selective bis(triethylsilylation) of the resulting triols 7a,b.The degradate 2 is ready for reacylation at the C26 hydroxyl terminus; hydrolysis of the dimethyl acetal moiety then provides an aldehyde ready for homologation at the C10 terminus.