Experiments in Scheme 3
O
O
O
O
N
H
N
H
N
HN
O
i-Pr
N
HN
O
i-Pr
H2, Pd/C
O
O
BnO2C
HO2C
THF, rt, 3 h
88% yield
NH
NH
NHBoc
NHBoc
D
24
Ph
Ph
Me
Me
Peptide D was prepared by using solution phase peptide assembly techniques described elsewhere.9 Peptide (D)
Characterization data: 1H NMR: (400 MHz, CDCl3, ppm) δ 7.38-7.19 (10H, m) 6.79 (1H, d, J = 8.6 Hz) 6.59 (1H, d, J
= 8.8 Hz) 5.18-5.01 (5H, m) 4.84-4.78 (1H, m) 4.58-4.56 (1H, m) 4.18 (1H, dd, J = 8.6, 6.8 Hz) 4.00 (1H, t, J = 7.1
Hz) 3.73-3.68 (2H, m) 2.96 (1H, dd, J = 16.2, 8.8 Hz) 2.71 (1H, dd, J = 16.4, 4.8 Hz) 2.34-2.29 (2H, m) 2.16-1.91
(4H, m) 1.46-1.38 (12H, m) 0.94 (3H, d, J = 6.8 Hz) 0.91 (3H, d, J = 6.8 Hz) 0.84 (3H, d, J = 6.8 Hz) 0.77 (3H, d, J =
6.8 Hz).
The deprotection of the benzyl ester in B was performed by dissolving B (489 mg, 0.677 mmol, 1.0 equiv) in THF
(2.2 mL, 0.3 M), flushing the reaction flask with N2 for ~10 minutes, charging the reaction flask with Pd/C (Strem,
10% Pd on graphite, 150 mg) and exposing this suspension to a balloon charged with H2. The resulting suspension
was stirred at rt for 3 h until no D could be detected by TLC (Rf D = 0.43, 6:4 hexanes:acetone; Rf 24 = 0.26
(streak), 1:1 hexanes:acetone). The resulting suspension was then diluted with 100 mL EtOAc and filtered through
celite to remove the Pd catalyst. The celite pad was generously washed with EtOAC (~200 mL) and the filtrate
concentrated under reduced pressure to yield 378 mg of pure 24 as a white powder (88% yield). Peptide (24)
+
Characterization data: Rf: 0.26 (streak), 1:1 hexanes:acetone. MS: (ES) Molecular ion calculated for C32H50N5O8 :
1
632.3654; found m/z = 632.3649, error = 0.7 ppm. IR: (neat, cm-1) 3306, 2969, 1712, 1685, 1632. H NMR: (500
MHz, CDCl3, ppm) δ 7.50 (2H, d, J = 7.9 Hz) 7.65 (1H, d, J = 8.1 Hz) 7.56-7.51 (2H, m) 7.24-7.15 (5H, m) 5.10-5.01
(2H, m) 4.84-4.77 (1H, m) 4.73 (1H, d, J = 7.1 Hz) 4.22 (1H, dd, J = 7.3, 3.8 Hz) 4.09 (1H, dd, J = 10.6, 8.8 Hz)
3.98 (1H, t, J = 8.8 Hz) 3.88 (1H, dd, J = 17.4, 9.6 Hz) 2.97 (1H, dd, J = 17.4, 11.1 Hz) 2.81 (1H, dd, J = 17.7, 4.5
Hz) 2.62 (1H, dd, J = 11.6, 6.1 Hz) 2.31-2.21 (1H, m) 2.15-1.98 (2H, m) 1.97-1.75 (2H, m) 1.48 (3H, d, J = 7.1 Hz)
1.42 (9H, s) 0.94 (3H, d, J = 6.8 Hz) 0.88 (3H, d, J = 6.8 Hz) 0.85 (3H, d, J = 6.8 Hz) 0.43 (3H, d, J = 6.8 Hz) . 13
C
NMR: (125 MHz, CDCl3) δ 175.03, 172.47, 171.996, 171.33, 142.47, 128.35, 126.95, 125.82, 80.23, 77.20, 60.06,
59.94, 59.87, 49.16, 47.60, 37.42, 30.94, 28.98, 28.24, 26.77, 24.096, 21.96, 19.54, 19.36, 18.65, 16.18. [α]D = -55
(c = 1.26, CHCl3).
O
i-Pr
DIC (10 equiv)
H2O2 (12.5 equiv)
DMAP (0.25 equiv)
O
O
O
N
H
N
HN
O
i-Pr
O
O
+
HO2C
DCM/H2O, rt
32h, then SiO2, 20 min
74% yield
Ph
NH
Ph
26
OH
25
NHBoc
OH
24
Ph
Me
30% ee
(0.25 equiv)
Known ketone10 25 (39.4 mg, 0.21 mmol, 1.0 equiv), catalyst 24 (32.7 mg, 0.052 mmol, 0.25 equiv) and DMAP
(Aldrich, 6.3 mg, 0.052 mmol, 0.25 equiv) were dissolved in 0.52 mL DCM (0.4 M). Aq. H2O2 (Aldrich, 0.29 mL of a
30% solution in H2O (~8.8 M), 2.6 mmol, 12.5 equiv) was added and DIC (Acros, 0.32 mL, 2.1 mmol, 10.0 equiv)
S8