PAPER
Selective Conversion of N-Trichloroethoxycarbonyl Groups into N-Acetyl Groups
1265
N-Acetyl-S-(3,4,6-tri-O-acetyl-2-acetamido-2-deoxy- -D-glu-
copyranosyl)-L-homocysteinyl-L-alanine Benzyl Ester (3)
Glycoside 1 (1.2 g, 1.4 mmol) was dissolved in Ac2O (17 mL),
freshly activated Zinc dust (0.4 g) was added, and the suspension
was stirred for 8 h. The mixture was filtered through Celite and the
filtrate was concentrated under vacuo to give the crude product. Pu-
rification by flash column chromatography (EtOAc–MeOH, 15:1)
afforded 3 (793 mg, 85%) as a white amorphous solid; [ ]D –39.5
(c = 1.0 CHCl3–MeOH, 1:1).
Ac-Lys(Boc)-OMe (11)10
[ ]D +12.0 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 6.28 (d, J = 7.2 Hz, 1 H), 4.60 (m,
2 H), 3.75 (s, 3 H), 3.10 (q like, 2 H), 2.04 (s, 3 H), 1.91–1.65 (m, 2
H), 1.44 (s, 9 H), 1.40 (m, 4 H).
13C NMR (CDCl3, 62.8 MHz): = 172.9, 170.2, 156.0, 78.7, 52.0,
51.8, 39.7, 31.4, 29.3, 28.1, 22.6, 22.2.
MALDI-MS: m/z = 324.8 [MNa+], 340.8 [MK+].
1H NMR (CDCl3/CD3OD, 250 MHz): = 8.10 (d, J = 6.8 Hz, 1 H),
7.76 (d, J = 8.9 Hz, 1 H), 7.61 (d, J = 8.0 Hz, 1 H), 7.35 (m, 5 H),
5.25 (t, J = 9.7 Hz, 1 H), 5.19 (m, 2 H), 5.08 (t, J = 9.6 Hz, 1 H),
4.82 (d, J = 10.5 Hz, 1 H), 4.53 (m, 2 H), 4.25 (dd, J = 12.4, 4.4 Hz,
1 H), 4.13 (m, 1 H), 3.93 (t, J = 10.3 Hz, 1 H), 3.77 (m, 1 H), 2.72
(m, 2 H), 2.08, 2.04, 2.01, 1.95 (4 s, 15 H), 1.95 (m, 2 H), 1.46 (d,
J = 7.3 Hz, 3 H).
Ac-Lys(Boc)-Val-OMe (12)
[ ]D –22.1 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 6.66 (d, J = 8.3 Hz, 1 H), 6.35 (d,
J = 7.5 Hz, 1 H), 4.74 (br s, 1 H), 4.49 (m, 2 H), 3.75 (s, 3 H), 3.12
(m, 2 H), 2.20 (m, 1 H), 2.03 (s, 3 H), 1.80 (m, 2 H), 1.45 (m, 4 H),
1.44 (s, 9 H), 0.92 (t, J = 6.8 Hz, 6 H).
13C NMR (CDCl3, 62.8 MHz): = 172.4, 171.6, 171.5, 171.3,
171.0, 170.7, 169.6, 135.1, 128.3, 128.1, 127.8, 83.6, 75.3, 73.6,
68.4, 66.9, 62.0, 53.0, 51.3, 48.0, 31.9, 26.0, 22.3, 22.2, 20.3, 20.2,
16.7.
13C NMR (CDCl3, 62.8 MHz): = 172.4, 171.9, 170.3, 156.0, 78.7,
57.4, 52.7, 51.9, 39.8, 31.9, 30.4, 29.3, 28.2, 22.7, 22.2, 18.8, 17.6.
MALDI-MS: m/z = 424.0 [MNa+], 440.1 [MK+].
Anal. Calcd for C19H35N3O6 (401.5): C, 56.84; H, 8.79; N, 10.47.
Found: C, 56.61; H, 8.79; N, 10.41.
MALDI-MS: m/z = 689.8 [MNa+], 705.9 [MK+].
Anal. Calcd for C30H41N3O12S·3H2O (721.8): C, 49.92; H, 5.73; N,
5.82. Found: C, 49.77; H, 5.86; N, 6.05.
N -[N-tert-Butoxycarbonyl-S-(3,4,6-tri-O-acetyl-2-acetamido-
2-deoxy- -D-glucopyranosyl)-L-cysteinyl]-N -tert-butoxycarbo-
nyl-L-lysine Methyl Ester (13)
Selective Conversion of N-Troc Groups into N-Ac Groups;
General Procedure
[ ]D –31.1 (c = 1.0 CHCl3).
Freshly activated Zn dust (0.65 g) was added to a solution of the ap-
propriate N-Troc derivative (0.5 mmol) in Ac2O (6 mL) containing
Et3N (0.14 mL). The reaction vessel was then sonicated in a classic
ultrasonic cleaning bath below r.t. until the disappearance of start-
ing material, as determined by TLC (typically 2–3 h). At this time
the mixture was filtered through Celite, the filtrate was evaporated
and the residue was chromatographed (petroleum ether–EtOAc) to
give the corresponding N-Ac compound.
1H NMR (CDCl3, 250 MHz): = 7.11 (d, J = 7.2 Hz, 1 H), 6.12 (d,
J = 8.3 Hz, 1 H), 5.69 (d, J = 7.3 Hz, 1 H), 5.13 (m, 2 H), 4.74 (m,
1 H), 4.70 (d, J = 10.5 Hz, 1 H), 4.53 (m, 1 H), 4.42 (m, 1 H), 4.23–
4.12 (m, 3 H), 3.78 (s, 3 H), 3.77 (m, 1 H), 3.05 (m, 4 H), 2.09, 2.04,
2.03, 1.96 (4 s, 12 H), 1.80 (m, 2 H), 1.46, 1.44 (2 s, 18 H), 1.42 (m,
4 H).
13C NMR (CDCl3, 62.8 MHz): = 172.4, 170.9, 170.7, 170.5,
170.3, 169.3, 156.1, 155.2, 85.0, 80.4, 79.2, 76.2, 73.7, 68.3, 62.3,
54.4, 52.9, 52.5, 52.3, 42.8, 40.2, 32.4, 31.7, 29.4, 28.4, 28.3, 23.2,
22.4, 20.6.
N-tert-Butoxycarbonyl-S-(3,4,6-tri-O-acetyl-2-acetamido-2-
deoxy- -D-glucopyranosyl)-L-homocysteinyl-L-alanine Benzyl
Ester (2)
MALDI-MS: m/z = 814.8 [MNa+], 830.7 [MK+].
[ ]D –26.5 (c = 1.0 CHCl3).
Anal. Calcd for C34H56N4O15S (792.9): C, 51.50; H, 7.12; N, 7.07.
Found: C, 51.97; H, 7.19; N, 6.78.
1H NMR (CDCl3, 250 MHz): = 7.37 (m, 5 H), 7.23 (d, J = 7.2 Hz,
1 H), 6.24 (d, J = 8.5 Hz, 1 H), 5.34 (t, J = 9.7 Hz, 1 H), 5.29 (d,
J = 8.1 Hz, 1 H), 5.20 (AB peak, J = 12.3 Hz, 2 H), 5.08 (t, J = 9.6
Hz, 1 H), 4.92 (d, J = 10.3 Hz, 1 H), 4.61 (m, 1 H), 4.39 (m, 1 H),
4.25 (dd, J = 12.3, 4.7 Hz, 1 H), 4.12 (dd, J = 12.3, 2.1 Hz, 1 H),
3.82 (m, 1 H), 3.70 (m, 1 H), 2.79 (m, 2 H), 2.08, 2.04, 2.03, 1.96 (4
s, 12 H), 1.95 (m, 2 H), 1.45 (d, J = 7.4 Hz, 3 H), 1.43 (s, 9 H).
13C NMR (CDCl3, 62.8 MHz): = 172.6, 171.7, 170.8, 170.63,
170.56, 169.3, 155.6, 135.3, 128.5, 128.3, 127.9, 83.4, 79.8, 75.7,
73.4, 68.6, 67.0, 62.1, 53.8, 52.4, 48.1, 32.5, 28.2, 26.2, 23.1, 20.61,
20.56, 20.5, 17.5.
Phenyl 2-Acetamido-4,6-O-benzylidene-3-O-(N-tert-butoxycar-
bonyl-O-tert-butyl-L-threonyl)-2-deoxy-1-thio- -D-glucopyra-
noside (14)
[ ]D –47.2 (c = 1.0 CHCl3).
1H NMR (CDCl3, 250 MHz): = 7.50 (m, 2 H), 7.38 (m, 2 H), 7.29
(m, 6 H), 6.55 (d, J = 6.5 Hz, 1 H), 6.00 (d, J = 10.3 Hz, 1 H), 5.86
(t like, J = 9.2 Hz, 1 H), 5.48 (s, 1 H), 5.36 (d, J = 8.4 Hz, 1 H), 4.36
(d like, J = 8.6 Hz, 1 H), 4.15 (m, 1 H), 4.00 (dd, J = 8.3, 1.9 Hz, 1
H), 3.82–3.68 (m, 3 H), 2.97 (m, 1 H), 1.96 (s, 3 H), 1.46 (s, 9 H),
1.18 (d, J = 6.2 Hz, 3 H), 0.81 (s, 9 H).
MALDI-MS: m/z = 764.8 [MK+].
13C NMR (CDCl3, 62.8 MHz): = 171.4, 171.3, 157.1, 136.9,
132.6, 132.5, 129.2, 129.0, 128.0, 127.8, 126.7, 102.2, 85.4, 80.2,
78.9, 74.2, 72.2, 70.4, 68.7, 66.5, 60.5, 57.6, 28.4, 28.0, 23.4, 21.0.
N-Acetyl-N -(tert-butoxycarbonyl)hexane-1,6-diamine (10)9
1H NMR (CDCl3, 250 MHz): = 5.90 (br s, 1 H), 4.62 (br s, 1 H),
3.23 (q, J = 6.6 Hz, 2 H), 3.11 (m, 2 H), 1.99 (s, 3 H), 1.44 (s, 9 H),
1.42 (m, 8 H).
MALDI-MS: m/z = 680.0 [MNa+], 695.9 [MK+].
13C NMR (CDCl3, 62.8 MHz): = 170.1, 156.1, 78.8, 40.1, 39.2,
29.9, 29.4, 28.4, 26.1, 26.0, 23.3.
Anal. Calcd for C34H46N2O9S (658.8): C, 61.99; H, 7.04; N, 4.25.
Found: C, 62.16; H, 7.33; N, 4.05.
MALDI-MS: m/z = 296.9 [MK+].
Acknowledgment
This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie.
Synthesis 2003, No. 8, 1262–1266 ISSN 1234-567-89 © Thieme Stuttgart · New York