HCl salt (17, 400 mg, 0.610 mmol) was dissolved in DMF (1.2 mL). To the solution were added i-Pr2NEt (0.44 mL,
2.50 mmol) and FDPP (472 mg, 1.22 mmol). The solution was degassed under reduced pressure and filled with argon.
After stirring for 5 h at rt, the solution was concentrated in vacuo. The residue was dissolved in CHCl3-TFE and the
solution was successively washed with 1M HCl (10 mL x 1), sat. NaHCO3 (10 mL x 1), and brine. The solution was
dried over anhydrous Na2SO4 and evaporated in vacuo. The residue was washed with Et2O and recrystallized from
CHCl3-TFE-Et2O to afford cyclic peptide (18, 284 mg, 77%) as colorless crystals. [α]D -102.8° (c 0.13, DMF); mp
309-310 °C (decomp); 1H NMR (400 MHz, DMF-d7, DMF-CHO = 8.01 ppm) δ 0.89 (6H, m), 1.34 (3H, d, J = 7.3 Hz),
1.65 (4H, m), 2.10 (1H, m), 2.55 (2H, m), 3.07 (1H, m), 3.28 (1H, m), 3.76 (3H, s), 3.81 (1H, d, J = 9.3 Hz), 4.33 (2H,
m), 4.62 (1H, m), 6.85 (2H, d, J = 7.8 Hz), 7.12 (2H, d, J = 7.8 Hz), 7.29 (3H, m), 7.54 (2H, m), 7.63 (1H, d, J = 9.3 Hz),
7.86 (1H, d, J = 9.8 Hz), 8.00 (2H, m) ; IR (cm-1, nujol) 3285, 2924, 2855, 1651, 1536, 1512, 1246, 1036; EI-HR-MS
602.2030 [M]+ calcd for C29H38N4 O580Se 602.2007, 600.2006 [M]+ calcd for C29H38N4 O578Se 602.2016.
∆
Cyclo( Ala-L-Ala-L-Val-L-Amp) (4)
To a solution of cyclic peptide (18, 39.8 mg, 0.0662 mmol) in CH2Cl2 (6 mL) and TFE (2 mL) was slowly added a
solution of TBHP in CH2Cl2 (4.03 M, 0.48 mL, 1.93 mmol) at -5 °C. After stirring for 6 h at rt, the mixture was
extracted with CHCl3 (10 mL x 3). The combined extracts were washed with sat. NaHCO3 (10 mL x 3) and brine.
The organic phase was dried over anhydrous Na2SO4 and evaporated in vacuo. The residue was washed with Et2O
and chromatographed on silica gel (5% i-PrOH-CHCl3) to give dehydropeptide (4, 24.7 mg, 84%) as colorless crystals.
[α]D -176.1° (c 0.055, DMF); mp 199-200 °C (decomp, recryst from CHCl3-hexane)[lit.,4a mp 220-223 °C]; 1H NMR
(400 MHz, DMF-d7, DMF-CHO = 8.01 ppm, -20 °C) δ 0.88 (6H, m), 1.13 (3/2H, d, J = 6.0 Hz), 1.38 (3/2H, d, J = 6.9
Hz), 1.35-2.00 (9/2H, m), 2.15 (1/2H, m), 2.49 (2H, m), 3.53 (1/2H, m), 3.73, 3.74 (total 3H, s each), 3.89 (1/2H, m),
4.37 (1/2H, m), 4.69 (1/2H, m), 4.77 (1/2H, m), 4.86 (1/2H, m), 5.03 (1/2H, d, J = 8.3 Hz), 5.71 (1/2H, d, J = 20.0 Hz),
6.24 (1/2H, d, J = 20.0 Hz), 6.83 (2H, m), 7.10 (2H, m), 7.34 (1/2H, d, J = 8.3 Hz), 7.66 (1/2H, d, J = 10.4 Hz), 7.81
(1/2H, m), 8.20 (1/2H, d, J = 8.5 Hz), 8.61 (1/2H, d, J = 9.3 Hz), 8.71 (1/2H, m), 8.75 (1/2H, br s), 8.84 (1/2H, br s),
10.37 (1/2H, br s) ; IR (cm-1, nujol) 3281, 2924, 2855, 1686, 1642, 1512, 1246, 1036; FAB-HR-MS 445.2458 [M+H]+
calcd for C23H33N4 O5 445.2451.