Aminoacids enantioselective synthesis

An important application of these precursors is the asymmetric synthesis of aminoacids, the key step being an enantioselective benzylation using a chiral auxiliary (route A, Scheme 25) [155] or a chiral phase transfer catalyst (PTC) [156] (route B, Scheme 25). This latter approach avoiding the use of dry reagents is particularly adapted to automated synthesis and enables the production of more than 7.4 GBq (200 mCi) of [6- F]fluoro-L-DOPA from 55.5 GBq (1.5 Ci) of starting [ F] fluoride [157]. 

While the reactions ofketenes with enantiopure alcohols usually give modest selectivities [769], the use of (ethyl lactate (isopropyl lactate (/ )-2.1 (R = Me, R = i-Pr) or (R)-pantolactone 1.16 as proton donors has allowed the highly enantioselective formation of 2-arylpropionic esters. A mild hydrolysis (AcOH/HCl or LiOH) leads to the corresponding adds, which are anti-inflammatory drugs [554,923] (Figure 4.8). This method has been extended by Durst and Koh [861, 999] to the synthesis of enantioenriched a-halogenated esters, which are precursors of aminoacids (Figure 4.8). 

Discovered in the middle of the 19th century, the Strecker reaction is one of the earliest atom-economic multicomponent reactions. Amino nitriles were simply obtained from ammonia, hydrogen cyanide and an aldehyde. These products are important intermediates for the synthesis of natural and unnatural a-aminoacids. Due to the ever-increased demand for enantioenri-chied a-aminoacids, the asymmetric Strecker reaction has emerged as a viable synthetic method. Since the first report published in 1996, the catalytic enantioselective cyanation of preformed imines was intensively studied and several excellent reviews were devoted to this topic. ... 

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