Case Studies in Natural Products Total Synthesis

5 Case Studies in Natural Products Total Synthesis 

The true power of macrocyclic stereocontrol is best appreciated in its applications to the construction of complex natural products. Indeed, strategic incorporation of this strategy in the planning and execution of a total synthesis has proven rewarding, allowing installation of remote stereogenic cen- 

Paterson s synthesis of oleandolide, the aglycon of the macrolide antibiotic oleandomycin, relied on an analogous use of macrocyclic stereocontrol for the introduction of an epoxide late in the route (Equation 5) [20]. The reaction between ketone 48 and trimethylsulfonium ylide thus furnished epoxide 49 in 83 % yield and dr 97 3. 

Evans has disclosed the diastereoselective double epoxidation of 12-mem-bered ring 1,5-diene lactone 50 for the preparation of a key fragment en route to the polyether antibiotic lonomycin A (Equation 6) [21], The inherent facial biases imposed by the macrocycle led to the preferential formation of 51 in 9 1 dr. 

In investigations of the trichothecanoids, Still conducted an impressive triple epoxidation of 53, leading to the functionalization of the trisubstituted olefin embedded in the cyclohexene ring, of the 1,1-disubstituted alkene, and of the olefin found within the macrocycle (Equation 7) [22]. This intermediate triepoxide 54 was obtained as a single isomer and was subsequently elaborated into the antileukemic agent baccharin B5. 

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