ABSTRACT
The C21-C34 fragment of the potent FKBP12-binding macrolide antascomicin B was prepared using Ireland-Claisen and allylic diazene rearrangements to establish the C26/C27 and the C23 stereocenters, respectively. Directed hydrogenation installed the C29 ß-configuration. The fragment possesses 7 of the 11 fixed stereocenters contained in the natural product.
ABSTRACT
[reaction: see text] The synthesis of an advanced intermediate in the synthesis of the title compound has been achieved. Key steps include an Ireland-Claisen rearrangement to install the C7 tertiary alcohol stereocenter, an SN2' reaction of an alkoxymethyl Cu reagent, and a diastereoselective Re-catalyzed allylic alcohol transposition.
Subject(s)
Bridged-Ring Compounds/chemical synthesis , Diterpenes/chemical synthesis , Furans/chemical synthesis , Bridged-Ring Compounds/chemistry , Catalysis , Copper/chemistry , Cyclization , Diterpenes/chemistry , Furans/chemistry , Molecular StructureABSTRACT
A novel Ireland-Claisen approach to the putative structure of eupomatilone-6 is described. The rearrangement established the C3 and C4 stereocenters and concomitantly generated a vinyl epoxide. The C5 oxygen was installed by cyclization of the pentenoic acid carboxyl group onto the vinyl epoxide in an S(N)2' fashion to afford the C5-epi stereochemistry. The natural C5 stereochemistry was accessed via a substrate directed dihydroxylation.
