Chiral azetidone

One of the first compounds to be introduced to the clinic, aztreonam (40-9), has been produced by total synthesis. Constmction of the chiral azetidone starts with amide formation of L-threonine (40-1) via its acid chloride treatment with ammonia leads to the corresponding amide (40-2). The primary amino group in that product is then protected as its carbobenzyloxy derivative (40-3). Reaction of that product with methanesulfonyl chloride affords the mesylate (40-4). Treatment of that intermediate with the pyridine sulfur trioxide complex leads to the formation of the A -sulfonated amide (40-5). Potassium bicarbonate is sufficiently basic to ionize the very acidic proton on the amide the resulting anion then displaces the adjacent mesylate to form the desired azetidone the product is isolated as its tetrabutyl ammonium salt (40-6). Catalytic hydrogenation over palladium removes the carbobenzyloxy protecting group to afford the free primary amine (40-7). The... 

Another example of how ene reductases can work in tandem with the ADHs to give valuable products is represented by the microbial reduction of the doubly activated substrate 76 (Scheme 3.20). Indeed, the (2S,3S)-hydroxyester 77, one of the products of this biotransformation, was converted after a few chemical manipulations to the chiral azetidone 78, precursor of several P-lactam antibiotics [93]. 

---