An efficient and tunable route to AG7088, a rhinovirus protease inhibitor

Aldol reaction of N,N-dibenzyl valinal with propiolic acid ethyl ester derived lithium reagent provides anti-aminoalcohol 8 and syn-aminoalcohol 9, which are converted into the lactone 6 via two different routes. Alkylation of 6 followed by lactone ring opening afford the acid 2a, which is coupled with the amine 3 and 5-methylisoxazole-3-carboxylate acid 1, respectively, to deliver AG7088.