Homochirality of β‐Peptides: A Significant Biomimetic Property of Unnatural Systems

Abstract Homochirality, an interesting phenomenon of life, is mainly an unresolved problem and was thought to be a property of living matter. Herein, we show that artificial β‐peptides have the tendency toward homochiral diastereoselective chain elongation. Chain‐length‐dependent stereochemical discrimination was investigated in the synthesis of foldamers with various side chains and secondary structures. It was found that there is a strong tendency toward the synthesis of homochiral oligomers. The size of the side chain drastically influenced the selectivity of the stereodiscriminative chain‐elongation reaction. It is noteworthy that water as the co‐solvent increases the selectivity. Such behavior is a novel fundamental biomimetic property of foldamers with a potential of future industrial application.


TABLE OF CONTENTS
Experimental section S5-S6 Table S1. HPLC-MS chromatogram and mass spectrum data for the diastereoselective chain elongation of 1-4 in the absence and the presence of water. S7 Table S2. HPLC-MS chromatogram and mass spectrum data for the diastereoselective chain elongation of 5-8 in the absence and the presence of water. S7 Table S3. HPLC-MS chromatogram and mass spectrum data for the diastereoselective chain elongation of 9-12 in the absence and the presence of water. S8 Table S4. HPLC-MS chromatogram and mass spectrum data for the diastereoselective chain elongation of 13-16 in the absence and the presence of water. S8 Figure S1. HPLC-MS chromatogram and mass spectrum of 1. S9 Figure S2. HPLC-MS chromatogram and mass spectrum of 2. S10 Figure S3. HPLC-MS chromatogram and mass spectrum of 3. S11 Figure S4. HPLC-MS chromatogram and mass spectrum of 4. S12 Figure S5. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 1 in the absence of water. S13 Figure S6. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 1 in the presence of water. S14 Figure S7. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 2 in the absence of water. S15 Figure S8. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 2 in the presence of water. S16 Figure S9. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 3 in the absence of water. S17 Figure S10. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 3 in the presence of water. S18 Figure S11. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 4 in the absence of water. S19   were added. The mixtures were stirred for 48 h, CH 2 Cl 2 was removed by evaporation, water was added to the residue followed by liophilization. The product was treated with 95% trifluoroacetic acid (TFA) and 5% water to remove Boc protecting groups. The solutions were then stirred for 30 min, TFA was removed in vacuo, the residue was diluted with water and then lyophilized.
Samples were analyzed by HPLC-MS. set is of triple-ζ quality for all atoms and has been augmented with two sets of polarization functions. The 1s core shells of carbon, nitrogen and oxygen were treated by the frozen-core approximation. [2] An auxiliary set of s, p, d, f and g STOs was used to fit the molecular density and to represent the Coulomb and exchange potentials accurately in each self-consistent field cycle. [1b, 1f] The OLYP functional is based on the exchange functional (OPTX) developed by Handy and Cohen [3] and the well-known Lee-Young-Parr correlation expression. [4] It was found that the overall performance of the OLYP functional is fairly good in combination with large basis set comparing to other popular (e.g.

HPLC-MS
B3LYP) functionals. [5] Solvent effects have been estimated using the conductor-like screening model [6] (COSMO) for both solvents (water and chloroform) as implemented in the ADF program. [7] Transition states were determined by a stepwise process: First, the independent constituents (boc-protected  Table S1. HPLC-MS chromatogram and mass spectrum data for the diastereoselective chain elongation of 1-4 in the absence and the presence of water.  Table S3. HPLC-MS chromatogram and mass spectrum data for the diastereoselective chain elongation of 9-12 in the absence and the presence of water.  Figure S41. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 13 in the absence of water.
S50 Figure S42. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 13 in the presence of water. Figure S43. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 14 in the absence of water.

S51
S52 Figure S44. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 14 in the presence of water.
S53 Figure S45. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 15 in the absence of water.
S54 Figure S46. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 15 in the presence of water.
S55 Figure S47. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 16 in the absence of water.
S56 Figure S48. HPLC-MS chromatogram and mass spectrum for the diastereoselective chain elongation of 16 in the presence of water.