Easy access to constrained peptidomimetics and 2,2-disubstituted azetidines by the unexpected reactivity profile of α-lithiated N-Boc-azetidines
The reactivity profile of lithiated N-Boc-2-arylazetidines has been investigated filling a gap in the chemistry of this class of four-membered heterocycles. Two unexpected and unprecedented results have been observed: an "ortho-effect" accounting for the regioselective functionalization of the azetidine ring, and self-condensation leading to new and interesting azetidine-based peptidomimetics.
Parisi, Giovanna,Capitanelli, Emanuela,Pierro, Antonella,Romanazzi, Giuseppe,Clarkson, Guy J.,Degennaro, Leonardo,Luisi, Renzo
supporting information
p. 15588 - 15591
(2015/10/28)
Enzymatic preparation of (S)-3-amino-3-(o-tolyl)propanoic acid, a key intermediate for the construction of Cathepsin inhibitors
Enantiomerically pure (S)-3-amino-3-(o-tolyl)propanoic acid [(S)-6], identified as the preferred enantiomeric form for the construction of novel β-amino acid derivatives as inhibitors of Cathepsin, was prepared through both indirect and direct enzymatic strategies. Resolution of hydroxymethylated β-lactam (±)-1 through Burkholderia cepacia lipase PSIM-catalysed R-selective butyrylation (E > 200) was first carried out in t-BuOMe. Treatment of the unreacted (S)-1 with 18% HCl then furnished the desired (S)-6·HCl. Next, Candida antarctica lipase B catalysed the ring cleavage of racemic 4-(o-tolyl)azetidin-2-one [(±)-2] with excellent R enantioselectivity (E > 200), either in t-BuOMe with added H2O as nucleophile or in H2O at 60 C. Hydrolysis of the less reactive β-lactam enantiomer [(S)-2] with 18% HCl afforded (S)-6·HCl. A direct enzymatic route to enantiomeric (S)-6 was finally optimized through the lipase PSIM-catalysed S-enantioselective (E > 200) hydrolysis of racemic ethyl 3-amino-3-(o-tolyl)propanoate [(±)-3] in t-BuOMe with added H 2O at 45 C or in H2O at 3 C.
Forro, Enik,Tasnadi, Gabor,Fueloep, Ferenc
p. 8 - 14
(2013/07/19)
Chlorosulphonyl Isocyanate Addition to o-Dialkylaminostyrenes: Preparation of 6-(o-Dialkylaminophenyl)-uracils
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Hollywood, Frank,Suschitzky, Hans
p. 662 - 665
(2007/10/02)
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