Carbamoylmethyl group as an activated group in protease- and base-catalyzed transesterification of 1,4-dihydropyridines: A novel asymmetric synthesis of valnidipine

Candida antarctica Lipase-Catalyzed Doubly Enantioselective Aminolysis Reactions. Chemoenzymatic Synthesis of 3-Hydroxypyrrolidines and 4-(Silyloxy)-2-oxopyrrolidines with Two Stereogenic Centers

“…Due to the presence of the leaving group at C-4 position, the resulting amine function could experiment a cyclization reaction to yield 3-pyrrolidinols. Optically active 3-pyrrolidinols are constituents of several bioactive compounds and can be used as intermediates for the synthesis of other interesting molecules …”

Effect of Acyl Chain Length and Branching on the Enantioselectivity ofCandidarugosaLipase in the Kinetic Resolution of 4-(2-Difluoromethoxyphenyl)-Substituted 1,4-Dihydropyridine 3,5-Diesters

“…The spacer should contain a group that is easily hydrolyzed by enzymes (e.g., an ester group) in order to allow kinetic resolution or enzymatic asymmetrization. The ethoxycarbonylmethyl spacer has been used to asymmetrize a number of 4-aryl-1,4-DHPs by us and others. , Moderate to excellent ee values were obtained, but this spacer group is not easy to remove. The acyloxymethyl moieties were introduced by the groups of Sih and Achiwa and have the advantage that, after enzymatic hydrolysis, a free carboxyl group is liberated due to the spontaneous loss of formaldehyde.…”

Streptomyces Serine Protease (DHP-A) as a New Biocatalyst Capable of Forming Chiral Intermediates of 1,4-Dihydropyridine Calcium Antagonists

“…The clinical importance of and demand for chiral 1,4-dihydropyridine drugs have been increasing steadily over the past few years because of the growing awareness that the individual isomers of drugs having a chiral center should be evaluated in detail in the process of drug development. Chiral 1,4-dihydropyridines can be obtained by the following methods: (i) chemical resolution of racemate forms (14), (ii) enantioselective chemical synthesis (13), and (iii) enzymatic hydrolysis or transesterification of prochiral diesters (1,4,(7)(8)(9)11). The enzymatic method is very likely to be more advantageous than the other methods because it involves simple processes with both high selectivity and high yield.…”

“…Two research groups have independently reported enantioselective hydrolysis and enantioselective transesterification of prochiral 1,4-dihydropyridines by proteases (1,7,8). It has also been reported that enantioselective hydrolysis occurs with lipases when prochiral 1,4-dihydropyridines containing acyloxymethyl groups at the C-3 and C-5 positions are used as substrates (9,11).…”

“…It has also been reported that enantioselective hydrolysis occurs with lipases when prochiral 1,4-dihydropyridines containing acyloxymethyl groups at the C-3 and C-5 positions are used as substrates (9,11). The resulting chiral half esters of the 1,4-dihydropyridines produced by the proteases or the lipases, regardless of which chirality they have, can be key intermediates for production of (4R)-1,4-dihydropyridine drugs such as Barnidipine (8,30,32) and Dexniguldipine (18). All enzymes used in the previous studies were commercially available.…”