Borrelidin

SCHEME 72. Iterative one-pot homologation of reduced polypropionates viaZACA-Pd-catalyzed vinylation and its application to highly efficient catalytic and asymmetric synthesis of key intermediates of ionomycin and borrelidin... 

There are two criteria forjudging any total synthesis the importance of the molecule that has been prepared, and the creativity evidenced in the synthetic route. When the natural product has only two rings, as with borrelidin 1, the standards are even higher. The enantioselective total synthesis of borrelidin by Jim Morken of the University of North Carolina (J. Am. Chem. Soc. 125 1458,2003) more than exceeds those standards. 

Borrelidin 1 has attracted attention because it inhibits angiogenesis, and so potentially blocks tumor growth, with an IC of 0.8 nM. Retrosynthetic analysis of 1 led the investigators to the prospective intermediates 2 and 3. To assemble these two fragments, they interatively deployed the elegant enantio- and diastereoselective intermolecular reductive ester aldol condensation that they had recently developed. This transformation is exemplified by the homologation of 4 to 6 catalyzed by the enantiomerically-pure Ir complex 5. 

Berger, J., Jampolsky, L. M., and Goldberg, M. W. (1949). Borrelidin, a new antibiotic with antiborrelia activity and penicillin-enhancement properties. Arch. Biochem. 22,476-478. 

Tsuchiya, E. et al., Borrelidin inhibits a cyclin-dependent kinase (CDK), Cdc28/Cln2, of Saccharo-myces cerevisiae, J. Antibiot. (Tokyo), 54, 84, 2001. 

Lumb, M. et al.. Isolation of vivomycin and borrelidin, two antibiotics with anti-viral activity, from a species of Streptomyces (C2989), Nature, 206, 263, 1965. 

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