Total synthesis of the fumiquinazoline alkaloids: Solid-phase studies

Abstract

We have previously described an efficient four-step synthesis of the fumiquinazoline alkaloids (Wang, H.; Ganesan, A. J. Org. Chem. 1998, 63, 2432-2433). Here, we demonstrate that this route is readily adaptable to combinatorial synthesis on solid phase. Linear tripeptides containing a central anthranilate unit were assembled on the Wang resin and subjected to dehydration and cyclative release to yield the pyrazino[2,1-b]quinazoline-3,6-diones in high purity. To demonstrate the scope of this protocol, a small library [ca. 20 compounds] of unnatural analogues was prepared by parallel synthesis.