FMOC-D-GLU-OTBU

The automated SPPS was done with resin 7 (434 mg, 0.48 mmol) and Fmoc-(R)-Glu-Ot-Bu 14 (0.41 g, 0.96 mmol, 2 equiv) via PS3 synthesizer. Deprotection was performed with piperidine solution 20% in DMF and activation with HBTU (0.36 g, 0.96 mmol, 2 equiv) and with N-methylmorpholine 0.4 M in DMF. The resin was filtered and rinsed with DCM and acetone and then dried under vacuum. Fmoc deprotection was done with the automated SPPS using piperidine solution 20% in DMF. Dried resin was stirred with 8 mL of TFA/H2O (50%) for 1 hour, then resin was filtered and rinsed with 10 mL of solution (TFA/H2O). Conversion of 57% of 7, 31% of 5 and 12% of AG-homodimer was measured by HPLC. The filtrate was evaporated under vacuum and mixture was purified by semi-preparative HPLC giving 16 mg of (Z/E)-dehydropeptide as a white solid (yield = 3%); MS(ESI): m/z = 522 [M+H]+; HPLC/ tR= 13.6 min (Method A); 1H NMR (400 MHz, D2O) delta 7.41 (s, 5H, CHCbz), 6.73 (br m, 1H, CH=C), 5.73 (br m, 1H, CH=C), 5.12 (m, 2H, CH2Cbz), 4.28 (m, 1H, CHalpha(S)-A2PM), 3.95 (m, 1H, CHalphaGlu), 3.75 (s, 3H, CH3), 2.47 (m, 2H, CH2GluCO ), 2.30 (m, 2H, CH2(S)-A2PMCH=C), 2.15 (m, 2H, CH2GluCHalpha), 2.01 (m, 1H, CH2(S)-A2PMCHalpha(S)-A2PM), 1.86 (m, 1H, CH2(S)-A2PMCHalpha(S)-A2PM), 1.48 (s, 9H, CH3t-Bu); 13C NMR (101 MHz, D2O) delta 175.24, 173.87, 168.35, 156.54, 139.23, 136.63, 128.76, 128.48, 127.57, 126.15, 85.87, 67.11, 52.83, 52.55, 52.28, 30.40, 28.77, 27.01, 25.31, 23.77.(S)-Ala-gamma-(R)-Glu-(S)-AG-(R)-Ala-Wang resin 16 was synthetized from Fmoc-(R)-Ala-Wang resin 13 (1 g, 0.9 mmol), Fmoc-(S)-AG-OH 4 (0.61 g, 1.79 mmol, 2 equiv), Fmoc-(R)-Glu-Ot-Bu 14 (0.76 g, 1.79 mmol, 2 equiv) and Boc-(S)-Ala-OH 15 (0.34 g, 1.79 mmol, 2 equiv) via PS3 synthesizer. Cycles of deprotection-coupling were done with piperidine solution 20% in DMF and activation with HBTU (0.68 g, 1.79 mmol, 2 equiv) and with N-methylmorpholine 0.4 M in DMF. The resin was filtered and rinsed with DCM and acetone and then dried under vacuum. A small sample was cleaved with TFA/DCM (50%) giving 16* for analysis. White solid 16*; MS(ESI): m/z = 387 [M+H]+.

Molecular Weight:425.5
XLogP3:3.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:10
Exact Mass:425.18383758
Monoisotopic Mass:425.18383758
Topological Polar Surface Area:102
Heavy Atom Count:31
Complexity:635
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes