Aglycone macrolactam

Scheme 6.1. Demonstration of the utility of (ebthi)Zr-catalyzed ethylmagnesation in the enantioselective synthesis of the macrolactam aglycon of fluvirucin.

Cyclization via intramolecular olefination of complex phosphonates remains the most important method of synthesis for complex natural macrocycles. Examples include syntheses of 20-membered macrolide antibiotic, aglycones of venturicidins A and B,108 oleandomycin (a 14-membered macrolide antibiotic), 109 the 19-membered macrocyclic antibiotic, anti-tumour agent (-t-)-hitachimycin,ll0 and the macrocyclic lactones (183).1H Cyclization of the phosphonate (184) under Masamune-Roush conditions has been used to synthesize the 28-membered macrolactam myxovirescin B.112... 

Usually no reaction of alkenyloxiranes bearing a methyl group at the terminus as in 149 takes place instead isomerization to enone occurs. The reaction of the epoxide 149 with the Meldrum s acid derivative 148 proceeded at room temperature in THF using a precatalyst generated by mixing Pd2(dba)3 (1.5 mol%) and cyclic phosphite TMPP (III-2) (20 mol%) to afford 150 in 75 % yield, and macrolactam aglycon of fluviricin B1 was synthesized [53]. 

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