Enzyme-mediated enantioselective acylation of secondary amines in organic solvents

Synthesis of “Trioxaquantel”® Derivatives as Potential New Antischistosomal Drugs

“…[43,44] Kinetic resolution of 3 by an enzymatic acylation reaction was also tried. The stereospecific acylation of the secondary amines of piperidine derivatives in the presence of porcine pancreatic lipase (PPL) in ethyl acetate was reported by Asensio et al [45] Different lipases (Pseudomonas cepacia lipase, Candida antarctica lipase B, Candida cylindracea lipase, PPL), different acylating agents (ethyl acetate, acetic anhydride, isopropenyl acetate, and vinyl acetate) and many solvents (diisopropyl ether, THF, DMSO/H 2 O, chloroform, ethyl acetate) were tried. In all cases, when ethyl acetate was used as acylating agent, no acylation of 3 was observed, while the other acylating agents gave racemic acylpraziquanamine (Ϯ)-30.…”

Hydrolases in the Stereoselective Synthesis of N-Heterocyclic Amines and Amino Acid Derivatives

“…Taking advantage of the excellent properties displayed by lipases, Kamal and coworkers reported the chemoenzymatic synthesis of optically active 3-methoxy-4-methylaminopyrrolidines 69, where the key step was the PSL catalyzed acetylation of trans-and cis-3-azido-1-benzyloxycarbonyl-4-hydroxypyrrolidine (67) in i Pr 2 O (Scheme 25). 68,69 Herrad on and Valverde extended the preliminary studies performed by Asensio and co-workers 33 to the resolution of racemic 3-piperidinyl methanol (70) using Aspergillus niger acylase I (AA-I) as biocatalyst in the presence of vinyl acetate (VA) as acyl donor (Table 5). 70 The reaction is known to occur in a two-step sequence.…”

“…Although with low stereoselectivity Asensio et al studied the acetylation of 2-piperidinyl methanol (1), testing porcine pancreas lipase (PPL) and lipase Amano P from Pseudomonas fluorescens as biocatalysts (Scheme 1). 33 Although the starting material (þ)-1 was recovered with low enantiomeric excess and high yield when using PPL, the N-acetylated product (À)-2a was recovered in moderate to high optical purities depending on the conversion grade. On the other hand, lipase Amano P led to the formation of a complex mixture of optically active starting material, the N-acetylated product (À)-2a, and the N,O-diacetylated compound (À)-3.…”

Lipase-catalyzed synthesis of the chiral tetrahydroisoquinoline (R)-salsolinol

“…16 However, only a few examples of the enzymatic kinetic resolution of secondary amines have been reported. [16][17][18][19][20][21][22] For this reason, studies on the synthesis of 1-methyl-1,2,3,4-tetrahydroisoquinoline using lipase catalysts are rare because the structure of the secondary amines in tetrahydroisoquinoline causes steric hindrance in the enzyme active site. 23 Candida rugosa lipase and a pentamethylcyclopentadienyl iridium(III) iodide dimer have been used as resolution and racemization catalysts in the dynamic kinetic resolution of 1-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline.…”