Trichodermamides A and B are modified heterocyclic dipeptides isolated from cultures of the marine-derived fungus Trichoderma virens. Both compounds possess a unique 4H-5,6-dihydro-1,2-oxazine ring merged with a highly functionalized cyclohexene ring, a heterocyclic core found for the first time in a natural product. Trichodermamide B displayed significant in vitro cytotoxicity against HCT-116 human colon carcinoma. Starting from affordable, easily available (-) quinic acid, the enantioselective synthesis of this oxazine moiety was achieved in 20 steps. The key steps included the stereoselective introduction of the epoxide moiety using trifluoroacetic anhydride/90% hydrogen peroxide as the oxidant and the intramolecular epoxide-ring opening reaction by oxime.