416 J . Org. Chem., Vol. 62, No. 2, 1997
Muller et al.
8c. NMR (D2O): 3.68, s, 2H; 3.18-3.08, m, 4H; 1.85-1.56,
m, 4H; 1.47, s, 9H.
8d . NMR (D2O): 3.67, s, 2H; 3.16-3.04, m, 4H; 1.82-1.67,
m, 2H; 1.60-1.32, m, 15H.
8e,f (Ca Salt). NMR (D2O): 3.76, q, J ) 7.1 Hz, 1H; 3.18,
t, J ) 6.6 Hz, 2H; 3.07, t, J ) 7.8 Hz, 2H; 1.92-1.85, m, 2H;
1.51, d, J ) 7.2 Hz, 3H; 1.43, s, 9H.
8g (Ca Salt). NMR (D2O): 3.26, q, J ) 7.0 Hz, 1H; 3.00, t,
J ) 6.7 Hz, 2H; 2.68-2.59, m, 2H; 1.54-1.42, m, 4H; 1.42, s,
9H; 1.36-1.29, m, 4H; 1.27, d, J ) 7.0 Hz, 3H.
8h ,i (Ca Salt). NMR (D2O): 7.34-7.22, m, 5H; 3.29, t, J )
9g. NMR (CDCl3): 7.77-7.72, m, 2H; 7.56, d, J ) 7.4 Hz,
2H; 7.40-7.36, m, 2H; 7.31-7.28, m, 2H; 5.92, broad s, 0.8H;
5.41, broad s, 0.2H; 4.63, m, 0.38H; 4.57-4.48m, 1.6H; 4.42-
4.39, m, 0.65H; 4.32-4.28, m, 0.20H; 4.23-4.20, m, 1.17H;
4.04, d, J ) 6.1 Hz, 0.1H; 3.48-3.43, m, 0.12H; 3.37-3.30, m,
0.3H; 3.11-2.88, m, 2.9; 2.94-2.88, m, 0.5H; 1.55-1.53, m,
0.5H; 1.51, d, J ) 6.6 Hz, 0.2H; 1.44-1.41, m, 11H; 1.40, d, J
) 7.2 Hz, 1.8H; 1.32, d, b of abx, J ) 7.0 Hz, 1H; 1.29, m, 2H;
1.18, m, 0.8H; 1.05, m, 1.2H.
9h ,i. NMR (MeOD): 7.71-7.65, m, 2H; 7.57-7.46, m, 2H;
7.31-7.19, m, 4H, 7.16-6.96, m, 4H; 6.66-6.64, m, 1H; 4.49,
dd, J 1 ) 10.3 Hz, J 2 ) 5.6 Hz, 0.54H; 4.39-4.32, m, 1.1H;
4.14-4.10, m, 1.96H; 3.99-3.97, m, 0.40H; 3.14, dd, J Râ ) 14.1
Hz, J ââ ) 4.7 Hz, 0.7H; 3.08-3.01m, 0.7H; 2.98-2.90, m, 0.5H;
2.83, dd, J Râ ) 14.8 Hz, J ââ ) 4.6 Hz, 0.6H; 2.82-2.75, m, 0.5H;
2.68, t, J ) 6.2 Hz, 0.9H; 2.58-2.49, m, 1.4H; 2.46-2.37, m,
0.9H; 1.30-0.97, 11H.
12a . NMR (CDCl3): 7.76, t, J ) 7.1 Hz, 2H; 7.57-7.55, m,
2H; 7.42-7.37, q, J ) 7.0 Hz, 2H; 7.33-7.28, m, 2H; 4.45, d,
J ) 5.1 Hz, 0.4H; 4.43, d, J ) 5.0 Hz, 0.6H; 4.26-4.22, t, J )
6.9 Hz, 2H; 4.16, s, 1.2H; 4.07, s, 0.8H; 4.06, s, 1.2H; 4.01, s,
0.8H; 1.50, s, 4.5H; 1.48, s, 4.5H.
7.3 Hz, 1H; 3.08-2.97, m, 2H; 2.90, dd, J Râ ) 13.3 Hz, J ââ
)
6.7 Hz, 2H; 2.59-2.48, m, 0.9H; 2.46-2.39, m, 1, 1H; 1.70-
1.49, m, 2H; 1.39, s, 9H.
11b. NMR (D2O): 3.77, s, 2H; 3.36, t, J ) 6.6 Hz, 2H; 2.80,
t, J ) 6.6 Hz, 2H; 1.48, s, 9H.
11c. NMR (D2O): 4.09, s, 0.4 H; 3.75, s, 1.6H; 3.56, t, J )
7.2 Hz, 0.4H; 3.12, t, J ) 7.8 Hz, 1.6H; 2.54, t, J ) 7.1 Hz,
0.4H; 2.45, t, J ) 7.1 Hz, 1.6H; 2.12-2.09, m, 0.4H; 2.03-
1.94, m, 1.6H; 1.47, s, 9H.
11d (Ca Salt). NMR (D2O): 3.57, s, 0.7H; 3.46, s, 1.3H; 3.02,
t, J ) 7.6 Hz, 0.7H; 2.95, t, J ) 6 Hz, 1.3H; 2.36, t, J ) 7.0 Hz,
0.7H; 2.31, t, J ) 7.2 Hz, 1.3H; 1.72-1.64, m, 2.7H (2CH2 and
3CH2 [E]); 1.64-1.58, m, 1.3H; 1.47, s, 3.2H; 1.46, s, 5.8H.
11e (Ca Salt). NMR (D2O): 3.45s, 0.4H; 3.39, s, 1.6H; 2.88,
t, J ) 7.5 Hz, 0.4H, 2.81, t, J ) 7.6 Hz, 1.6H; 2.39, t, J ) 7.3
Hz, 0.4H; 2.31, t, J ) 7.3 Hz, 1.6H; 1.66-1.57, m, 2H; 1.46, s,
9H; 1.38-1.25, m, 4H.
12b. NMR (CDCl3): 7.75, d, J ) 15.0 Hz, 1.05H; 7.74, d, J
) 15.0 Hz, 0.95H; 7.58, d, J ) 7.3 Hz, 1.05H; 7.52, d, J ) 7.2
Hz, 0.95H; 7.39, q, J ) 7.0 Hz, 2H; 7.33-7.28, m, 2H; 4.53, d,
J ) 6.1 Hz, 1.05H; 4.44, d, J ) 6.2 Hz, 0.95H; 4.27, t, J ) 5.9
Hz, 0.53 H; 4.19, t, J ) 5.9 Hz, 0.47H; 4.11, s, 1.05H; 4.02, s,
0.95H; 3.55, t, J ) 6.1 Hz, 0.95H; 3.43, t, J ) 6.6 Hz, 1.05H;
2.55, t, J ) 6.2 Hz, 0.95H; 2.30, t, J ) 6.54 Hz, 1.05H; 1.44, s,
5.6H; 1.42, s, 3.4H.
Meth od L: P r ep a r a tion of Nr-F m oc-Nr-[ω-(Boc-a m in o)-
a lk yl]a m in o Acid s 9 a n d Nr-F m oc-Nr-[ω-(ter t-Bu tylca r -
boxy)a lk yl]a m in o Acid s 12. Twenty mmol of triethylamine
was added to a solution of 10 mmol of 8 or 11 in 40 mL of
water. The mixture was stirred until a clear solution was
obtained. Then a solution of 20 mmol of Fmoc-OSu in 80 mL
of acetonitrile was added. The reaction mixture was stirred
at room temperature for 4 h. Water (150 mL) was added, and
the mixture was washed with petroleum ether (3 × 100 mL)
and with a mixture of ether:petroleum ether 3:7 (2 × 100 mL).
The aqueous solution was cooled to 0 °C and acidified with 40
mL of 1 N HCl, and the product was extracted with ethyl
acetate (4 × 100 mL). The organic solution was washed with
water (4 × 100 mL) and dried over Na2SO4, and the solvent
was evaporated in vacuo. The product was recrystallized from
ether:petroleum-ether 1:10.
9a . NMR (MeOD): 7.71-7.67, m, 2H; 7.53, d, J ) 7.4H,
0.95H; 7.49, d, J ) 7.4H, 1.05H; 7.29, q, J ) 7.0, 2H; 7.25-
7.18, m, 2H; 4.33, d, J ) 6.3 Hz, 0.95 H; 4.25, d, J ) 6.3 Hz,
1.05H; 4.19, t, J ) 6.2 Hz, 0.45H; 4.10, t, J ) 6.6 Hz, 0.55H;
3.895, s, 0.45H; 3.887, s, 0.55H; 3.30, t, J ) 6.2 Hz, 1.05H;
3.21, m, 0.95H; 3.09, t, J ) 6.1 Hz, 1.05H; 2.91, t, J ) 6.0 Hz,
0.95H; 1.31, s, 4.3H; 1.30, s, 4.7H.
9b. NMR (CDCl3; 305 K): 7.76-7.72, m, 2H; 7.57-7.53,
m, 2H; 7.38, q, J ) 8.0 Hz, 2H; 7.33-7.28, m, 2H; 6.06, broad
s, 0.8H; 5.18, broad s, 0.2H; 4.59, m, 0.8H; 4.44, m, 1.2H; 4.23,
m, 0.4H; 4.19, m, 0.6H; 3.96, s, 1.2H; 3.88, s, 0.8H; 3.49, t, J
) 7.0 Hz, 1.1H; 3.10, m, 2H; 2.87, m, 0.9H; 1.65, m, 0.95H;
1.43, m, 10.05H.
9c. NMR (CDCl3): 7.77-7.71, m, 2H; 7.55, t, J ) 7.55, t, J
) 7.5 Hz, 2H; 7.35, q, J ) 8.0 Hz, 2H; 7.30-7.27, m, 2H; 5.9,
broad s, 0.5H; 5.7, broad s, 0.5H; 4.56, d, J ) 5.5 Hz, 1.1H;
4.42, d, J ) 6.4 Hz, 0.90H; 4.24-4.17, m, 1H; 3.96, s, 1.1H;
3.90, s, 0.9H; 3.35, t, J ) 7.0 Hz, 0.9H; 3.08, t, J ) 7.0 Hz, 2H;
2.98, m, 1.1H; 1.60-1.44, m, 10H; 1.29-1.26, m, 0.9H; 1.23-
1.18, m, 1.1H.
12c. NMR (CDCl3): 7.77-7.71, m, 2H; 7.57, d, J ) 7.3 Hz,
1.2H; 7.52, d, J ) 7.4 Hz, 0.8H, 7.41-7.36, m, 2H; 7.34-7.28,
m, 2H; 4.53, d, J ) 5.9 Hz, 1.2H; 4.45, d, J ) 6.2 Hz, 0.8H;
4.26, t, J ) 5.7 Hz, 0.6H; 4.19, t, J ) 5.9 Hz, 0.4H; 4.00, s,
1.2H; 3.88, s, 0.8H; 3.48, t, J ) 6.9 Hz, 0.8H; 3.17, t, J ) 6.9
Hz, 1.2H; 2.24, t, J ) 7.2 Hz, 0.8H; 2.04, t, J ) 7.2 Hz, 1.2H;
1.79, t, J ) 7.1 Hz, 0.8H; 1.60, t, J ) 7.1 Hz, 1.2H; 1.43, s,
5.6H.
12d . NMR (CDCl3): 7.77-7.71, m, 2H; 7.57, d, J ) 7.4 Hz,
1.2H; 7.52, d, J ) 7.4 Hz, 0.8H; 7.38, q, J ) 7.0 Hz, 2H; 7.30,
q, J ) 8.0 Hz, 2H; 4.54, d, J ) 5.9 Hz, 1.2H; 4.44, d, J ) 6.3
Hz, 0.8H; 4.25, t, J ) 5.8 Hz, 0.6H; 4.19, t, J ) 6.2 Hz, 0.4H;
3.98, s, 1.2H; 3.88, s, 0.8H; 3.32, t, J ) 6.2 Hz, 0.8H; 3.11, t,
J ) 7.1 Hz, 1.2H; 2.22, t, J ) 6.6 Hz, 0.8H; 2.12, t, J ) 7.1 Hz,
1.2H; 1.67-1.54, m, 1.4H; 1.43, s, 9H; 1.40-1.27, m, 2.1H;
1.21-1.13, m, 0.5H.
12e. NMR (CDCl3): 7.77-7.72, m, 2H; 7.58-7.52, m, 2H;
7.41-7.34, m, 2H; 7.33-7.28, m, 2H; 4.54, d, J ) 5.9 Hz, 1.2H;
4.45, d, J ) 5.9 Hz, 0.8H; 4.25, t, J ) 5.6 Hz, 0.6H; 4.19, t, J
) 5.6 Hz, 0.4H; 3.99, s, 1.2H; 3.86, s, 0.8H; 3.30, t, J ) 7.0 Hz,
0.8H; 3.13, t, J ) 7.3 Hz, 1.2H; 2.19-2.16, m, 2H; 1.48-1.49,
m, 2.9H; 1.44, s, 9H; 1.37-1.29, m, 1.6H; 1.16-1.12, m, 1.2H;
1.21-1.13, m, 0.3H.
12f. NMR (CDCl3): 7.77-7.75, m, 2H; 7.71-7.52, m, 2H;
7.40-7.10, m, 8.5H; 6.76-6.80, m, 0.5H; 4.84, dd, J 1 ) 10.7
Hz, J 2 ) 4.5 Hz, 0.5H; 4.66, dd, J 1 ) 10.6 Hz, J 2 ) 5.7 Hz,
0.6H; 4.57, dd, J 1 ) 11.1 Hz, J 2 ) 4.2 Hz, 0.6H; 4.43, dd, J 1
)
10.8 Hz, J 2 ) 6.2 Hz, 0.9H; 4.27-4.24, m, 0.5H; 4.21-4.19,
m, 0.5H; 4.03, dd, J 1 ) 10.3 Hz, J 2 ) 4.2, 0.5H; 3.35-3.26, m,
1.3H; 3.24-3.10, m, 0.7H; 2.97-2.90, dd, J 1 ) 12.6 Hz, J 2
4.1 Hz, 0.5H; 2.70-2.51, m, 1.3H; 2.48-2.40, m, 0.7H; 2.19-
2.09, m, 0.9H; 2.03-1.95, m, 0.6H; 1.40, s, 5.6H; 1.37, s, 3.4H.
)
9d . NMR (CDCl3): 7.73t, J ) 8.0 Hz, 2H; 7.54, t, J ) 6.9
Hz, 2H; 7.39-7.34, m, 2H; 7.33-7.24, m, 2H; 5.9, broad s,
0.3H; 4.57, broad s, 0.7H; 4.48, d, J ) 6.1 Hz, 1.3H; 4.38, d, J
) 6.5 Hz, 0.7H; 4.22-4.17, m, 1H; 3.93, s, 1.3H; 3.9, s, 0.7H;
3.50-3.48, m, 1.1H; 3.12-3.08, m, 2.9H; 1.44, s, 9H; 1.29, m,
2H; 1.20, m, 2H; 1.10, m, 2H.
9e,f. NMR (CDCl3): 7.75, m, 2H; 7.55, d, J ) 7.2 Hz, 2H;
7.39-7.36, m, 2H; 7.30, m, 2H; 6.51, broad s, 0.2 H; 6.36, broad
s, 0.3H; 5.26, broad s, 0.5H; 4.61, m, 0.95H; 4.48, m, 0.6H;
4.36, m, 0.4H; 4.21, m, 1.05H; 3.64, m, 0.3H; 3.43, m. 0.6H;
3.14-3.02, m, 2H; 2.87-2.84, m, 1.9H; 2.65, m, 0.3H; 1.64, m,
0.5H; 1.45, s, 4H; 1.42, s, 5H; 1.36-1.29, m, 3.4H; 1.54-1.40,
m, 0.1H; 0.88-0.82, m, 0.5H.
Ack n ow led gm en t. This research was financed by
Peptor Co. Ltd. Rehovot, Israel, and by the GIF Foun-
dation.
Su p p or tin g In for m a tion Ava ila ble: A listing of NMR
spectra including detailed assignment of proton chemical shifts
(6 pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O961580E