Short-step Synthesis of Cordytakaoamide B and Cordycepamide C via Intramolecular Regioselective Oxidation-Lactone Formation

The ortho-tyrosinol derivative, as a key synthetic intermediate for alkaloidal metabolites of Cordyceps, was synthesized from L-phenylalanine methyl ester via condensation with crotonic acid and oxidative intramolecular lactone formation by using phenyliodine(III) bis(trifluoroacetate). Subsequent elongation of the side chain involving a cross-metathesis reaction and deprotection yielded cordytakaoamide B and cordycepamide C in notably few synthetic steps. Furthermore, the S-configurations at the C-2 position of both cordytakaoamide B and cordycepamide C were confirmed by comparison with the sign of the optical rotation of the synthetic sample.

Automated summary

The ortho-tyrosinol derivative, a key synthetic intermediate for alkaloidal metabolites of Cordyceps, was synthesized from L-phenylalanine methyl ester through condensation with crotonic acid and oxidative intramolecular lactone formation. Subsequent elongation of the side chain involving a cross-metathesis reaction and deprotection resulted in the efficient synthesis of cordytakaoamide B and cordycepamide C in a few steps. The S-configurations at the C-2 position of both cordytakaoamide B and cordycepamide C were confirmed by comparing their optical rotation with synthetic samples.