Amphotericin chemistry

The body of chemistry described above for amphotericin B (1) allowed, for the first time, the preparation of a series of novel derivatives of this polyene macrolide antibiotic and set the stage for a total synthesis of this target molecule. Below we unfold the adventure that led to the accomplishment of this goal.910... 

The described chemistry leading to the synthesis of key building blocks 16-19 sets the stage for the completion of the total synthesis of both amphotericin B (1) and its aglycon, amphoteronolide B (2). 

Nystatin [nye STAT in] is a polyene antibiotic its structure, chemistry, mode of action, and resistance resemble those of amphotericin B. Its use is restricted to topical treatment of Candida infections because of its systemic toxicity. The drug is negligibly absorbed from the gastrointestinal tract, and it is never used par-enterally. It is administered as an oral agent ( swish and swallow ) for the treatment of oral candidiasis. Excretion in the feces is nearly quantitative. Adverse effects are rare because of its lack of absorption, but occasionally nausea and vomiting occur. 

Perhaps the best known clinical agent is the heptaene polyene, amphotericin B 50, isolated from Streptomyces nodosus and first reported in 1956. The full structure was not elucidated until 1970 when it was determined by X-ray crystallography,56 closely followed by a description of the absolute configuration determined by utilising the iodo-derivative for X-ray and by mass spectroscopy.57 Quite recently, 50 years after its initial discovery, a full review giving the highlights of the chemistry around the compound was published by Cereghetti and Carreira.58... 

---