A stereoselective method for the synthesis of enantiopure 3-substituted 4-hydroxyproline derivatives via 1,3-dipolar cycloadditions

Abstract

The stereoselective 1,3-dipolar cycloaddition between (Z)-1,4-dichloro-2-butene and a menthone-derived nitrone led to the corresponding isoxazolidine. Regioselective azidation of a single chlorine atom followed by another Cu(I)-catalyzed azideealkyne 1,3-dipolar cycloaddition (CuAAC) induced enantiopure 1,2,3-triazolyl-functionalized isoxazolidines. The subsequent acidic cleavage of the menthone chiral auxiliary and reductive cleavage of the isoxazolidine NeO bond triggered an intramolecular cyclization through the displacement of the second chlorine. This rapid and stereoselective synthetic strategy provided reliable access to a series of enantiopure 3-substituted 4-hydroxyproline derivatives.

Zinc(ii) triazole meso-arylsubstituted porphyrins for UV-visible chloride and bromide detection. Adsorption and catalytic degradation of malachite green dye

“…These compounds were prepared using the so-called "click reaction" (CuAAC) by reacting the 3-methoxy-4-(prop-2-ynlyloxy)benzaldehyde ( 2) with the 1-azidobenzene or the 1azido-4-chlorobenzene or the 1-azido-4-iodinebenzene and the diisopropylethylamine (DIPEA) reagents in the presence of copper(I) (CuI) catalyst. 22 The success of the click reaction is veried in IR by the disappearance of the two absorption bands of the azido group (n as (N 3 ) $ 2130 and $2080 cm À1 ) and the alkyne group of compound 2 and the appearance of a new band at 1726 cm À1 assigned to n(C]N, N]N) of the triazole group (Fig. SI-2 †).…”

“…The second step is the synthesis of the three substituted [1,2,3](triazol-4-ylmethoxy)-benzaldehyde: 3-methoxy-4-(3phenyl-3H-[1,2,3]triazol-4-ylmethoxy)-benzaldehyde (3a), the 4-[3-(4-chloro-phenyl)-3H-[1,2,3]triazol-4-ylmethoxy]-3methoxy-benzaldehyde (3b) and the (4-iodine-phenyl)-3H-[1,2,3]triazol-4-ylmethoxy]-3-methoxy-benzaldehyde(3c). These compounds were prepared using the so-called "click reaction" (CuAAC) by reacting the 3-methoxy-4-(prop-2-ynlyloxy)benzaldehyde (2) with the 1-azidobenzene or the 1azido-4-chlorobenzene or the 1-azido-4-iodinebenzene and the diisopropylethylamine (DIPEA) reagents in the presence of copper(I) (CuI) catalyst 22. The success of the click reaction…”

Synthesis and characterization of novel isoxazolidine-thiosemicarbazone hybrid derivatives as precursor of unnatural amino acids

“…[21] In addition, TSCs have been used to access complexes with marked and diverse biological applications [22][23][24][25][26][27][28]. In addition, our research group has been worked for years on the synthesis of enantiopure isoxazolidine derivatives [29][30][31][32][33][34][35][36][37][38]. Some analogues show antimicrobial [31], antioxidant [32] and anti-diabetic [39,40] activities.…”

Multifunctional isoxazolidine derivatives as α-amylase and α-glucosidase inhibitors

“…In turn, the isoxazolidine functional group, obtained by 1,3-dipolar cycloaddition between a nitrone and an alkene, plays a crucial role in several chemical transformations due to the lability of the N-O bond [12]. In this context, our research team has been interested for some years in the study of the 1,3-dipolar cycloaddition reaction between chiral nitrones and dipolarophiles to access natural organic compounds such as 4-hydroxyisoleucine [13], 4-hydroxy-L-ornithine [14], and other non-naturally occurring compounds such as 4-hydroxyproline derivatives [15], (αS,3R,4S)-3-glycinyl-4-hydroxypyrrolidine [16] and 4-ylidene (3S)-3-hydroxy-1-aryl (alkyl)pyrrolidine-2,5-diones [17]. Additionally, the prediction of possible interactions between chemical compounds and the target proteins remains a very important task in research and development process.…”