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Stereoselective Synthesis of α,α′-Dihydroxy-β,β′-diaryl-β-amino Acids by Mannich-Like Condensation of Hydroarylamides: Stereoselective Synthesis of α,α′-Dihydroxy-β,β′-diaryl-β-amino Acids by Mannich-Like Condensation of Hydroarylamides
| Content Provider | Semantic Scholar |
|---|---|
| Author | Pecnikaj, Ilir Foschi, Francesca Bucci, Raffaella Gelmi, Maria Luisa Castellano, Carlo Meneghetti, Fiorella Penso, Michele |
| Copyright Year | 2019 |
| Abstract | Dual α,α'-Dihydroxy-β-amino acids are very interesting tools for several industrial applications. Nevertheless, few derivatives are reported in the literature concerning the substitution pattern as well as their enantioselective syntheses are lacking. Here, we report on the preparation of enantiopure α,α'-dihydroxy-β,β'-diaryl-β-amino acid (dual) derivatives by an efficient Mannich-like condensation of hydroarylamides with 5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-one (triethylsilyl)ketene acetal. The synthetic protocol has been optimized affording the dual compounds in very good yields and with different aryl substitution patterns. Taking advantage of the “double stereodifferentiation” concept, a highly stereoselective reaction was performed: of the 16 possible isomers, only two diastereoisomers (d.r. up to 93:7) formed. Insights on the high stereocontrol of this condensation were given. Introduction Over the last two decades, there has been increasing interest in the chemistry of β-amino acid derivatives since these non-proteinogenic molecules have been extensively used to build new bioactive poly-functionalized molecules,[1] peptidomimetics and foldamers[2] and materials.[3] Focusing on αhydroxy-β-amino acids, they are particularly profitable as pharmaceutical compounds.[4] As documented by several patents, the parent dual α-hydroxy-β-amino acid derivatives 2 (Scheme 1) have found industrial application as chelating agents in detergents,[5] bleaching processes for photography,[6] electrostratographic toner preparation,[7] biological treatment of waste water,[8] to prevent corrosion processes, and in formulations for skin care products[9] and biocides.[10] On the other hand, dual amino acids could be very appealing for the preparation of peptidomimetic with exotic architectures. Nevertheless, only few racemic duals 2 are described in the literature. In the known structures, both Cβ/Cβ' are unsubstituted (2a) or bear an additional carboxylic function (2b). The simplest duals 2a have been prepared via tertiary N,N-bis(2,3-dihydroxy-propyl)amines 1a, through O2 oxidation of the hydroxy-methylene groups,[11] or by amine nucleophilic ring-opening of glycidic acid derivatives 1b (R2 = H). This protocol applied to the oxirane-2,3-dicarboxylic acid produces the more polar compounds 2b (R2 = CO2H).[12] It is to be point out that the above compounds are produced in racemic form and diastereisomeric mixture. HO2C N CO2H OH OH R2 R2 R1 2a, R1 = H, alkyl, Ar(CO2H)n; R2 = H 2b, R1 = alkyl, Ar(CO2H)n; R2 = CO2H HO N OH OH OH R2 R2 R1 1a [O2] O R2 CO2H R2 = H 2a R2 = CO2H 2b +R1 NH2 |
| Starting Page | 6707 |
| Ending Page | 6713 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| DOI | 10.1002/ejoc.201901325 |
| Volume Number | 2019 |
| Alternate Webpage(s) | https://air.unimi.it/retrieve/handle/2434/677414/1312668/Duals%20Manuscript.pdf |
| Alternate Webpage(s) | https://doi.org/10.1002/ejoc.201901325 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
