Stemodinone and Stemodin

The syntheses of stemodin and stemodinone, structural relatives of aphidicolin, were accomplished using the A/B double annulation and B/C spiro annulation processes developed for the assembly of aphidicolin. 

Otsuka K-76, a fungal product with strong anticomplement activity, was synthesized from the A/B bicyclic precursor of stemodin. The aromatic subunit was retrosynthetically disconnected to a symmetrical precursor. A surprising non-selectivity of olefinic hydroxylation by osmium tetroxide was noted. 

1 1 mixture ofip, 3(3and2a, 3adiols which were used to carry out the following reactions. 

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Two different syntheses of aphidicolin (106) were reported in 1979. Corey and his co-workers have now completed a third.A key feature of their route is the base-induced conversion of (104) to (105). It was found that the desired alkylation occurred only under carefully controlled reaction conditions (lithium di-t-butylamide at —102 C), the alternative a-alkylation product predominating under most other conditions. A closely related approach has resulted in the synthesis of ( )-stemodin (107) and ( )-stemodinone (108). The Kametani route to the aphidocolanes has been described earlier in this chapter. 

Figure 6 Hydroxylation of stemodin 47 and stemodinone 48 by Cephalosporium aphidicola.

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