We have previously reported enantiomeric α/β‐ and β‐peptides derived from aminopyrancarboxylic acids (APyCs). We now report the synthesis of diastereomeric β‐peptides synthesized from alternating (R,R)/(S,S)‐APyCs and C‐linked carbo β3‐amino acids [(R)/(S)‐β3‐Caas] and their conformational analysis. Extensive studies of these peptides revealed the presence of enantiomeric helical structures, that is, left‐ and right‐handed 12/10‐helices, that are well stabilized by five‐membered electrostatic interactions between the pyran oxygen atom and the succeding amide proton. The study thus reveals, irrespective of the nature of the peptides, that the APyC monomers influence on the outcome of the helical handedness, as established by NMR, CD and molecular dynamics (MD) analyses.

(R,R)‐ and (S,S)‐aminopyrancarboxylic acids (APyCs) were used in the design of mixed β‐ and α/β‐peptides in alternation with β‐hGly and L‐Ala/D‐Ala, respectively. The enantiomeric β‐ and α/β‐tetrapeptides were then coupled in a 1:1 fashion to give octapeptides with 12/10‐ and 9/11‐mixed helices, respectively. The structure of the helices, with their characteristic hydrogen‐bonding patterns and an additional stabilizing interaction between peptide‐bond NH groups and pyran‐ring oxygen atoms, was investigated by NMR spectroscopy, molecular dynamics, and quantum chemical studies. The presence of equal parts of left‐ and right‐handed helices was confirmed by the cancellation of their respective CD patterns. Despite the disruption of the hydrogen bonding in the transition region, the helical conformation was maintained in the octamers. This study demonstrates the possibility of accommodating helices of opposite handedness within the same peptide.

Triazine-aryl-bis-indole derivative inhibits phosphodiesterase activity.

Copies of 1 H NMR, 13 C NMR and HRMS spectra S10-S21 S2 GENERAL PROCEDURESSolvents were dried over standard drying agents and freshly distilled prior to use. All commercially available chemicals were used without further purification. All reactions were performed under Nitrogen. 1 H NMR and 13 C NMR spectra were measured with Varian Gemini FT 200 MHz spectrometer, Bruker Avance 300 MHz, Unity 400 MHz and Inova 500 MHz with tetramethylsilane as internal standard for solutions in CDCl 3 . J values are given in Hz. Chemical shifts were reported in ppm relative to solvent signal. All column chromatographic separations were performed using silica gel (Acme's, 60-120 mesh). Organic solutions were dried over anhydrous Na 2 SO 4 and concentrated below 40 ºC in vacuo. IR spectra were recorded on FT IR (Perkin-Elmer IR-683) spectrophotometer with NaCl optics. JASCO DIP 300 digital polarimeter was used for measurement of optical rotations at 25 °C. Mass spectra were recorded on direct inlet system or LC by MSD trap SL (Agilent Technologies),the HRMS data were obtained using Q-TOF mass spectrometry. (S)-4-(Benzyloxy)-2-hydroxybutyl benzoate (18):To a stirred solution of 17 (19 g, 96.9 mmol) in CH 2 Cl 2 (50 mL), Et 3 N (27.1 mL, 193.8 mmol), BzCl (11.2 g, 96.9 mmol) and Bu 2 SnO (0.37 g, 1.9 mmol) were added at 0 ºC. The reaction mixture was stirred at room temperature for 2 h and extracted into chloroform (2 × 50 mL). Organic layers werewashed with water (2 × 50 mL), brine (50 mL) and dried (Na 2 SO 4 ). Solvent was evaporated and purified the residue by column chromatography (60-120 mesh Silica gel, EtOAc:hexane, 1:4) to furnish 18 (22 g, 75%) as a yellow syrup.[] D 25