Commercialization and late-stage development of a semisynthetic antifungal aft anidulafungin/D-fructose (Eraxis)

Many years ago anidulafungin 1 was identified as a potentially useful medicine for the treatment of fungal infections. Its chemical and physical properties as a relatively high molecular weight semisynthetic derived from echinocandin B proved to be a significant hurdle to its final presentation as a useful medicine. It has recently been approved as an intravenous treatment for invasive candidaisis, an increasingly common health hazard that is potentially life-threatening. The development and commercialization of this API, which is presented as a molecular mixture of anidulafungin and D-fructose is described. This includes, single crystal X-ray structures of the starting materials, the echinocandin B cyclic-peptide nucleus (ECBN center dot HCl) and the active ester 1-({[4 ''(pentyloxy)-1,1':4',1 ''-terphenyl-4-yl]carbonyl}oxy)-1,H-1,2,3-ben- zotriazole (TOBt). Details of the structure and properties of starting materials, scale-up chemistry and unusual crystallization phenomena associated with the API formation are discussed.