Scaling Amatoxin Synthesis with an Improved Route to (2S,3R,4R)-Dihydroxyisoleucine Exemplified by a Toxic, Clickable α-Amanitin Analogue.

Chido M Hambira, Kaveh Matinkhoo, Alla Pryyma, Brian O Patrick, David M Perrin

The Journal of organic chemistry 2021 Apr 02

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Here we report a scalable synthesis of the key amino acid residue, (2S,3R,4R)-4,5-dihydroxyisoleucine (DHIle) in α-amanitin, that in turn enables the scalable synthesis of an equipotent analogue, Asn(N-ethylazide)-S,6'-dideoxy-α-amanitin, suitable for CuAAC conjugation to empower studies on therapeutic antibody-drug conjugates.

Citation

Chido M Hambira, Kaveh Matinkhoo, Alla Pryyma, Brian O Patrick, David M Perrin. Scaling Amatoxin Synthesis with an Improved Route to (2S,3R,4R)-Dihydroxyisoleucine Exemplified by a Toxic, Clickable α-Amanitin Analogue. The Journal of organic chemistry. 2021 Apr 02;86(7):5362-5370