Dolastatin 10 is a highly potent antineoplastic peptide chain of S-dovaline at the C-terminus, S-valine, (3R, 4S, 5S)-dolaisoleuine, (2S,2'R,3'R)-dolaproine and S-dolastatin at the N-terminus. Dolastatin 10 was originally isolated from the Indian Ocean sea hare Dolabella auricularia. However, sufficient amounts of Dolastatin 10 cannot reasonably be obtained from Dolabella a. Consequently, to support commercial production of Dolastatin 10, various methods have been developed to synthesize the C-terminus unit, S-dolaphenine. However, these methods for synthesizing S-dolaphenine typically require many synthetic steps, often resulting in reduced product yields and/or racemic mixtures of R- and S-dolaphenine.
Therefore, a need exists for a simpler method of stereoselectively forming S-dolaphenine with higher product yields.
USPTO Backgrounds
USPTO Backgrounds