Bicyclic β-amino acids

Synthesis of 3‐Azabicyclo[3.2.0]heptane‐Derived Building Blocks via [3+2] Cycloaddition

“…Taking into account importance of bicyclic β‐amino acids, first of all we aimed at the preparation of conformationally restricted β‐proline analogue 5 , as well as its two monoprotected derivatives 6 and 7 . All these compounds were obtained from the debenzylated intermediate 8 by acidic hydrolysis (for the amino acid 5 , 83 % yield as hydrochloride), transesterification (for the ester 6 , 86 % yield), and N ‐Boc‐protection with subsequent hydrolysis of intermediate 9 (for 7 , 84 % yield from 8 ), respectively (Scheme ).…”

“…Due to the increased ring strain of the cyclobutene fragment, the obtained intermediate 1 is a valuable starting material not only for the construction of bicyclo-[n. 2.0]alkane ring systems, but also for other strain-releasing reactions leading to 1,2-disubstituted cyclobutanes. [24][25][26] The subsequent 1,3-dipolar cycloaddition of 1 and ylide generated from MTB allowed us to obtain 120 g of the key interme- Taking into account importance of bicyclic -amino acids, [27][28][29] first of all we aimed at the preparation of conformationally restricted -proline analogue 5, as well as its two monoprotected derivatives 6 and 7. All these compounds were obtained from the debenzylated intermediate 8 by acidic hydrolysis (for the amino acid 5, 83 % yield as hydrochloride), transesterification (for the ester 6, 86 % yield), and N-Boc-protection with subsequent hydrolysis of intermediate 9 (for 7, 84 % yield from 8), respectively (Scheme 4).…”

1-Aminobicyclo[2.2.2]octane-2-carboxylic Acid and Derivatives As Chiral Constrained Bridged Scaffolds for Foldamers and Chiral Catalysts

“…It is noteworthy that bicyclic carbo-bridged scaffolds have been less studied than bicyclic-fused and heterobridged systems. Among them, the synthesis of bicyclo[2.2.1]­heptane derivatives was the most reported along with a few examples of the synthesis of 3-aminobicyclo[2.2.2]­octane-2-carboxylic acids and derivatives. − In the following parts, we discuss our efforts toward the synthesis of the enantiopure ( R )- and ( S )-1-aminobicyclo­[2.2.2]­octane-2-carboxylic acids (ABOC), a highly constrained bicyclic β-amino acid bearing a bridgehead amino group as well as its diamine derivative, the 1,2-diaminobicyclo[2.2.2]­octane (DABO) . Our first motivation was to investigate the propensity of such building blocks to accommodate secondary structures in hybrid/mixed oligoamides ,,, and in oligoureas. ,, Then, we assessed ABOC and DABO derivatives as effective enantioselective catalysts. , …”

Polyhydroxylated cyclopentane β-amino acids derived from D-mannose and D-galactose: synthesis and protocol for incorporation into peptides

“…The enantioselective synthesis of β-amino acids has received great attention in recent times, [1][2][3][4][5] mainly because peptidomimetics 6 based on these amino acids may overcome the pharmacological limitations of natural peptides. [7][8][9][10] They are more resistant than α-peptides to protease and peptidase degradation [11][12][13] and their conformational properties and stability facilitate their interaction with receptors and enzymes, which usually results in improved activity and no side effects.…”

“…13 C{ 1 H} NMR (62.5 MHz, CDCl3, ppm): δ -5.8, -5.6, 18.1, 25.6, 68.9, 70 4,. 72.2, 74.7, 80.5, 81.4, 82.6, 119.2, 127.2, 127.3, 127.5, 127.6, 127.8, 127.9, 128.0, 128.1, 134.9, 136.9, 137.8, 138.0, 208.0.…”