3
-Amino-5- and -6-hydroxybicyclo[2.2.1]heptane-2-carboxylic Acid
2053
hydrochloric acid at room temperature gave N-acetyl-hydroxy amino acid 8. When
8
was boiled in acidic solution, endo ! exo isomerization took place and the
forced conditions resulted in 3,5-di-endo-2-exo-3-amino-5-hydroxybicyclo[2.2.1]
heptane-2-carboxylic acid hydrochloride (9) as the main product. The mother
liquor was treated with a large excess of propylene oxide and, after fractional
crystallisation, compound 10 was isolated as a diastereomerically enriched (8:2)
mixture (Scheme 2). The correct configurations of hydroxylated amino acids 9
a
Table 1. Characteristic IR frequencies and H NMR data for compounds 2–5, 7–9, and 11
1
b
c
d
e
f
g
g
h
Compound Amide-I band ꢂC¼O band CH s(9H) CH t(3H) CH qa(2H) NH broad
3
3
2
r
2
3
4
5
7
8
9
1
1688
1693
–
1788
1775
1763
1730
1733
1732
1714
1732
1.44
1.42
–
–
–
–
–
–
–
4.15
4.81
4.67
6.4
r
1654
1676
1680
–
1.86
1.86
2.35
–
1.20
1.24
–
4.04
4.10
–
–
12.9
–
–
ꢁ12.6
ꢁ7.9
1
–
–
1.21
4.10
Compound
Norbornane=ene moiety
i
k
0
l
0
m
n
o
r
p
H–1
H–2
H–3
H–4
H–5
H–6
CH (7)
2
r
2
3
4
5
7
8
9
3.24
3.24
3.40
3.10
2.08
2.80
2.78
2.95
3.13
3.02
3.25
4.15
4.11
3.82
4.72
4.03
4.24
3.76
3.77
2.90
2.56
2.63
3.10
2.35
ꢁ4.9
5.17
4.81
5.01
6.27
1.94, 2.34
1.58, 1.73
1.70, 1.77
1.35, 1.45
1.41, 1.48
1.53, 1.64
1.26, 1.33
1.27, 1.33
ꢁ1.75
1.82, 1.90
r
r
r
r
6.14
4.55
5.21
4.35
4.35
2.02, 2.19
1.75, 2.20
1.22, 2.05
1.23, 2.07
ꢁ2.45
2.36
ꢁ2.45
r
r
2.54
2.59
2.52
2.54
1
1
2.35
a
ꢂ1
In KBr discs (cm ); further bands, ꢂOH band: ꢁ3345 (9), 3460 (11), ꢂNH band: ꢁ3230 (2), 3247
þ
(
(
3), 3318 (5), coalesced ꢂOH (acidic & alcoholic) and=or ꢂN H bands: 3250–2250 (4), 3600–3250
3
8), 3500–2500 (9, 11), ꢂC–O: 1014 (2), 1167 (3), 1108 (4), 1182 and 1047 (5), 1184 and 1060 (7),
b
185 and 1155 (11); in CDCl solution (D O for 4 and DMSO-d for 8, 9, and 11) at 500 MHz;
1
3
2
6
c
chemical shifts in ppm (ꢃTMS ¼ 0 ppm), coupling constants in Hz; assignments were supported by
HMQC (except for 2), for 5, 7, 9, and 11 by HMBC, and for 8 and 11 also by DIFFNOE measurements;
d
e
urethane group (2, 3), ꢂC¼N band (7); COOH (1, 4, 8, and 9), lactone (2 and 3), COOEt (5, 7, and
f
1); 3H (5, 7, and 8); ethyl group, J: 7.1; Intensity 1H (2, 3, 5, and 9), 2H (8), coalesced signal of
g
h
1
þ
the acidic protons and the solvent (4), or the amide-NH and COOH (8), or the OH and NH3 groups
k
(
i
11), d (J: 6.5, 5); ꢁt (2, 4, and 7), ꢁs (9) with coalesced lines, t (J: 4.7 for 3), d (J: 4.5 for 11); dd,
l
J: 10.3 and 4.7 (2–4), ꢁdd (5), ddd (7), td (8) with coalesced lines, d, J: 4.3 (9), 5.1 (11); broad m (2),
m
ꢁ
t(3), ꢁd, J: 9.3 (4), 4.3 (9), dt, J: 8.9 ad 3.5 (5), m (7, 8, and 11); signals with coalesced lines, m (2,
n
5
, and 8), ꢁs (3, 4, and 9), ꢁ t (7 and 11); broad m (1H) for 2 and 7–9, dd, J: 5.6 and 2.9 (5), m (2H)
o
for 3, 2ꢃm (2ꢃ1H) for 4, m for 11; d (1H), J: 5.0 (2), m (2H, 3), t (1H), J: 6.3 (4), dd (1H), J: 5.6
p
and 3.0 (5), 2ꢃm (2ꢃ1H, 7–9, and 11); AB-type multiplet, 2ꢃd (2ꢃ1H), J: 11.8 (2 and 4), 11.2 (3),
9
.0 (5), 10.8 (7 and 8), ꢁ10 (9), 11.5 (11), further split by long-range couplings of downfield=upfield d
, r
to td (2=7), both doublets to dd (9) and downfield d to m (7 and 8), respectively; overlapping signals