Anne Gaucher

First expeditious synthesis of 6,11-diamino-[6]carbohelicenes

The first synthesis of 6,11-diamino-[6]carbohelicenes is described: the short 5 step sequence involves Suzuki-Miyaura coupling, functional group transformations and electrophilic aromatic cyclisation; the original strategy allows the preparation of di- and tetra-substituted helicenes in comfortable yields.

Regio-Defined Amino[5]Oxa- and Thiahelicenes: A Dramatic Impact of the Nature of the Heteroatom on the Helical Shape and Racemization Barriers

The present approach to heterohelicenes provides original [5]oxa- and thiahelicenes, where both oxygen and sulfur atoms are located at the end of the inner helix. Quantum chemical calculations are carried out to determine the pathway for interconversion between two enantiomers and demonstrate that the energy barrier is strongly dependent on the nature of the heteroatom present on the helical shape.

Novel α,α-disubstituted α-aminoacids with axial dissymmetry and their N- or C-protected derivatives

Abstract Racemic as well as enantiomerically pure 1,1′-binaphthyl-substituted α-aminoisobutyric acid (Bin), a new chiral atropoisomeric α,α-disubstituted glycine, and its biphenyl analogue (Bip), have been prepared with good yields by bis-alkylation of a glycine tert-butyl ester Schiff base with 2,2′-bis(bromomethyl)-1,1′-binaphthyl and 2,2′-bis(bromomethyl)-1,1′-biphenyl, respectively, under phase transfer conditions. The free aminoacids Bin and Bip, as well as their N-protected (Z, Boc, Fmoc) and/or C-protected (ethyl or tert-butyl esters) derivatives, useful for the incorporation of these new aminoacids into peptides, have been obtained. A slow interconversion between the two enantiomers of the Bip derivatives is generally observed in 1H NMR at room temperature, with a rotational energy barrier of 59 kJ mol−1.

A new chiral α-aminoacid with only axial dissymmetry: Synthesis and X-ray analysis of a 1,1′-binaphthyl-substituted α-aminoisobutyric acid (Bin) and of its biphenyl analogue (Bip)

Abstract Racemic as well as optically pure 1,1′-binaphthyl-substituted α-aminoisobutyric acid (Bin), a new chiral atropoisomeric α,α-disubstituted glycine, and its biphenyl analogue (Bip), have been prepared by bis-alkylation of a glycine tert-butyl ester Schiff base. The free aminoacids Bin and Bip, as well as their C-and/or N-protected derivatives have been obtained. X-ray analysis of H-Bip-OtBu and H-(S)Bin-OH is presented.

Synthesis of α,α-disubstituted-β-aminoacids with axial chirality

6-aminomethyl-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-6-carboxylic acid ethyl ester H-β2-Bip-OEt1a and its 1,1′-binaphthyl optically pure analog (R) H-β2-Bin-OEt2a, have been readily synthesized by bis-alkylation of ethyl cyanoacetate with 2,2′-bis-(bromomethyl)-1,1′-diphenyl or optically pure (+)-(R)-2,2′-bis-(bromomethyl)-1,1′-binaphthyl, followed by NaBH4CoCl2 selective reduction of the cyano group. The N-Boc protected derivatives and short peptides of these novel aminoacids have also been prepared.

Synthesis and conformational study of homo-peptides based on (S)-Bin, a C2-symmetric binaphthyl-derived Cα,α-disubstituted glycine with only axial chirality

Abstract We synthesised the [( S )-Bin] n ( n =2–5) homo-peptides by solution methods. Only the acid fluoride derivative Fmoc-( S )-Bin-F could be efficiently coupled with H-[( S )-Bin] n -OMe ( n =2–4). Spectroscopic experimental analyses of the [( S )-Bin] n homo-peptides in solution performed by CD, FT-IR absorption, and VCD, supported by VCD calculations, confirmed the ( S ) configuration of the Bin residues and identified the most largely populated secondary structures as right-handed β-turns which eventually evolve to 3 10 -helices in the highest oligomers.

Practical resolution of an atropoisomeric α,α-disubstituted glycine with l-phenylalanine cyclohexylamide as chiral auxiliary

Abstract l -Phenylalanine cyclohexylamide has been used as a chiral auxiliary for the medium-scale resolution of 2′,1′:1,2;1″,2″:3,4-dinaphthcyclohepta-1,3-diene-6-amino-6-carboxylic acid (Bin), an α,α-disubstituted glycine with only axial dissymmetry. Coupling of X–Bin–OH (X=Ac; Bz) with H–( l )-Phe–NH–C 6 H 11 by the EDC/HOBt method gave the dipeptide diastereoisomers X–( R )-Bin–( l )-Phe–NH–C 6 H 11 and X–( S )-Bin–( l )-Phe–NH–C 6 H 11 , which were separated by crystallization (X=Bz) and/or chromatography. Extensive acidic hydrolysis, followed by esterification of the resulting free amino acid enantiomers, led to enantiomerically pure (−)-( R )-H–Bin–OMe and (+)-( S )-H–Bin–OMe with high yields.

N-t-Boc 6-amino-1,11-(20-crown-6)-6,7-dihydro-5H-dibenzo[a,c] cycloheptene-6-carboxylic acid methyl ester, the first prototype of a crown-carrier-axially dissymmetric-α,α-disubstituted glycine

Abstract N-t-Boc 6-amino-1,11-(20-crown-6)-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-6-carboxylic acid methyl ester: Boc-[20-C-6]-Bip-OMe 1 , a new crown-carrier-α,α-disubstituted glycine with axial dissymmetry and a potential building block for the synthesis of polypeptide supramolecular devices, has been synthesized at the racemic state by phase transfer bis-alkylation of a glycine tert -butyl ester Schiff base with 2,2′- bis -(bromomethyl)-6,6′-dimethoxy-1,1′-diphenyl, followed by demethylation, esterification, N-protection and crown formation upon cyclization of the di-cesium salt of the resulting diphenol with pentaethyleneglycol ditosylate.

Towards peptide versions of Cram's host–guest chemistry: the synthesis of Cα,α-disubstituted glycines with binaphthol-based crowned side-chains

Abstract Dietherification of the hydroxy groups of various α,α-disubstituted α-amino acids or their precursors, possessing either an achiral frame derived from α-hydroxymethylserine, or a 2,2′,6,6′-tetrasubstituted biphenyl frame with only an axial chirality, or a frame with α-carbon chirality derived from α-methyl-( L )-DOPA, using ( R )-2,2′-bis-(5-tosyloxy-3-oxa-1-pentyloxy)-1,1′-binaphthyl as alkylating agent, gave a new series of amino acids bearing binaphthol-based crown-ethers, as building blocks for the construction of short-chain peptide helices with topologically well-localized receptors.

Binaphthyl platform as starting materials for the preparation of electron rich benzo[g,h,i]perylenes. Application to molecular architectures based on amino benzo[g,h,i]perylenes and carborane combinations

Valuable amino benzo[g,h,i]perylenes have been obtained through a one pot electrophilic aromatic substitution--Scholl reaction sequence. Novel molecular architectures combining 3D-o-carborane and planar amino benzo[g,h,i]perylene units are described. Photophysical properties of amino benzo[g,h,i]perylene and the carborane-appended derivatives are discussed.