Design, synthesis and evaluation of novel hydroxyamides as orally available anticonvulsants

An Enzymatic Toolbox for the Kinetic Resolution of 2‐(Pyridin‐x‐yl)but‐3‐yn‐2‐ols and Tertiary Cyanohydrins

“…Acetate 1e was included for a better understanding of the influence of R 2 and to facilitate a comparison with 1d and 1l. [20] The screening of 1f-j allowed the performance of the enzymes to be determined in the conversion of tertiary alcohol acetates bearing a CN substituent in position R 3 . Table 1 summarizes the enantioselectivity of the esterases towards 1a-1j.…”

“…[2] The precursor for the synthesis of anticonvulsants can also be obtained from 1i. [3] Moreover, optically pure tertiary alcohols have recently received attention as potential inhibitors of HIV protease [4] and reverse transcriptase. [5] The synthesis of these compounds by both chemical and biocatalytic routes is challenging and no standard method has been developed so far.…”

Asymmetric Friedel–Crafts Reaction of Indoles with Ethyl Trifluoropyruvate Using a Copper(I)‐Bisoxazolidine Catalyst

“…This structural motif has become an important component in several drugs. Selected examples include anticonvulsants, [2] peptidomimetic matrix metalloproteinase (MMP) inhibitors, [3] CJ-17,493, a neurokinin 1 receptor antagonist, [4] and the anti-HIV agent Efavirenz [5] (Figure 1). To date, indoles have been used extensively in asymmetric Friedel-Crafts reactions with a wide range of carbonyl electrophiles [6] but few examples of this reaction with methyl or ethyl trifluoropyruvate have been reported, Scheme 1.…”

“…Our reaction protocol also tolerates indole substrates carrying a methyl group in position 6 and, more importantly, in position 7 (entries 7 and 8). The synthesis of 10 from 7-methylindole and ethyl trifluoropyruvate was accomplished with 97% yield and 94% ee at À98 8C [a] ZnA C H T U N G T R E N N U N G (OTf) 2 CH 2 Cl 2 91 10 18 [b] CuA C H T U N G T R E N N U N G (OTf) 2 CH 2 Cl 2 98 60 19 [b] A C H T U N G T R E N N U N G (CuOTf) 2 -toluene CH 2 Cl 2 96 74 20 [b] A…”

Catalytic Nucleophilic Addition of 3, 5-Dialkyl-4-nitroisoxazoles to Trifluoromethyl Ketones on Water

“…[1,2] Particularly, some trifluoromethylsubstituted tertiary alcohols are important pharmaceuticals and agrochemicals, such as the critical anti-HIV drug (Efavirenz, I), [3] anticonvulsant II, [4] glucocorticoid agonist (BI-653048, III), [5] selective glucocorticoid receptor agonist (ZK-216348, IV), [6] anticancer agents V, [7] the platelet-activating factor antagonists VI [8] (Figure 1). Accordingly, the creation of bearing trifluoromethyl-substituted tertiary alcohols from readily available starting substrates under mild reaction conditions is of great synthetic and industrial interest.…”