ON THE REMARKABLE PROPENSITY FOR CARBON CARBON BOND-CLEAVAGE REACTIONS IN THE C8-C10 REGION OF FK-506

It has been deduced from a series of transformations that formation of a tetrahedral intermediate at C-9 in FD-506 occasions fragmentation of the C-9-C-10 bond by a retro-Claisen-like pathway or the C-9-C-8 bond by a benzilic acid type rearrangement. Reduction of FK-506 with L-Selectride leads to the formation of a boronate ester 18 rather than to the corresponding diol 17, which had previously been formulated. Direct reduction of FK-506 with sodium triacetoxyborohydride (or hydrolysis of 18) does provide access to (22S)-dihydro FK-506 17. The former reduction also leads to some 22R epimer, which is an intermediate in the total synthesis of FK-506.