An Efficient Synthesis of (R)-2-Butyl-3-hydroxypropionic Acid

Abstract

An efficient synthesis of (R)-2-butyl-3-hydroxypropionic acid (1) via a classical resolution of (±)-2-butyl-3-hydroxypropionic acid (7) with (R)-α-methylbenzylamine is described. (±)-2-Butyl-3-hydroxypropionic acid (7) was readily available from diethyl butylmalonate (2) in two steps. Results on the enantioselective enzymatic hydrolysis of 2 with pig liver esterase and α-chymotrypsin towards 1 are also described.

Lipase-catalyzed hydrolytic resolution of (R,S)-3-hydroxy-3-phenylpropionates in biphasic media

“…Optically pure 3-hydroxy carboxylic acids and their derivatives are important chiral synthons used for the synthesis of a number of pharmaceuticals such as fluoxetine, b-lactams, pheromones, bblockers, lipid A and L-carnitine (Guaragna et al, 2006;Hu et al, 2007;Padhi et al, 2006;Spengler and Albericio, 2008). They have been prepared via lipase-catalyzed transesterification resolution of (R,S)-3-hydroxy carboxylic esters in organic solvents or hydrolysis at the 3-O-acyl group in the aqueous solution (Bornscheuer et al, 1993;Hoff and Anthonsen, 1999;Huerta and Backvall, 2001;Kaga et al, 1998;Nascimento et al, 2003;Xu and Yuan, 2005).…”

Synthesis of Long‐Chain β‐Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

“…The appropriate alkyl or alkenyl bromide was used in order to prepare the substituted diethyl malonates 5 a , b , which were then hydrolyzed under controlled conditions into the corresponding acids 6 a , b bearing one ester group. The ester groups were reduced using LiBH 4 , and finally the β‐hydroxy acids 7 a , b were cyclized using DEAD/PPh 3 to yield the desired β‐lactones VM004 and VM005 in around 17 % overall yield. To determine whether stereochemical hindrance and/or absence of the α‐proton will make a significant difference in activity, we also prepared the α,α′‐disubstituted β‐lactone VM006 bearing a second small C 4 chain at the α‐position.…”

A General Organocatalytic Enantioselective Malonate Addition to α,β‐Unsaturated Enones

“…Therefore, a mono-hydrolysis decarboxylation strategy was investigated as an alternative way to obtain the monoester 33 directly (Scheme 2). Indeed, the six-membered mono-acids 35 a, b could be produced from the corresponding starting material 7 a, b by sodium hydroxide-mediated hydrolysis [23] or alternatively by the use of the enzyme porcine liver esterase [24] (PLE) ( Table 8). The use of an alternative enzyme mixture, for example, liver acetone powder [25] gave the product without a loss in enantiomeric excess, but the yield decreased dramatically (Table 8, entry 3).…”