The total synthesis of biologically active natural products drives the development of new chemistry and generates lead compounds for medical research. The object of this proposal is the asymmetric total synthesis of tubelactomicin A and kijanolide, both biologically active natural products. The kijanolide synthesis will couple a known upper half fragment with a novel dioxinone containing diene via a Suzuki cross-coupling reaction. A tandem IMDA/ketene sequence should furnish both the decalin core and the requisite keto ester moiety in a single step. Installation of the last structural element of the molecule, the spirotetronate moiety, will employ a Dieckmann cyclization of the keto ester. Deprotection and a functional group transformation will afford kijanolide. Tubelactomicin A has biological activity suggesting potential as a lead for antitubercular drugs. A cross-coupling reaction of two chiral halves of the molecule will precede the cycloaddition reaction. The salient part of this synthesis is based upon the use of a steric directing group to achieve a highly stereoselective IMDA reaction to give the trans-fused decalin portion of the molecule. Macrolactonization will afford the natural product.
| Trullinger, Tony K; Qi, Jun; Roush, William R (2006) Studies on the synthesis of quartromicins a(3) and d(3): synthesis of the vertical and horizontal bis-spirotetronate fragments. J Org Chem 71:6915-22 |
