5606
M. A. Pullar et al. / Tetrahedron Letters 56 (2015) 5604–5606
OH
OH
HO
HO
O
N
O
H
N
N
H
H2N
N
H
O
O
OH
OH
19. A 1:5 mixture of cis-prolyl tunichrome Sp-1⁄ and trans-prolyl tunichrome Sp-1
Figure 2. Structure of cis-prolyl tunichrome Sp-1.
⁄
was characterized; are used to denote shifts for the cis conformer that differ
from the corresponding signal in the trans-conformer: IR mmax (ATR) 3284,
20
2973, 1666, 1638, 1513, 1187, 1130, 954, 721 cmꢁ1; [
a
]
D ꢁ71 (c 1.0, CH3OH);
present, but not reported, cis-prolyl conformer. The route used is
amenable to the synthesis of un-natural analogues of 1 that will
prove useful for investigation of the metal chelating and oxida-
tion/reduction properties of the tunichromes.
1H NMR (500 MHz, DMSO-d6) d 10.27⁄ (1H, d, J = 9.9 Hz, dc
(1H, br d, J = 10.0 Hz, dc
DOPA(5)-NH), 8.94–8.62 (6H, m, 2 ꢂ DOPA(1)-OH,
2 ꢂ DOPA(2)-OH, 2 ꢂ dc DOPA(5)-OH), 8.74–8.68 (1H, m, DOPA(2)-NH) 8.18
(1H, t, J = 4.9 Hz, Gly(3)-NH), 7.91 (2H, br s, DOPA(1)-NH2), 7.10⁄ (1H, dd,
J = 14.6, 10.0 Hz, dc DOPA(5)- CH), 7.05 (1H, dd, J = 14.6, 10.0 Hz, dc DOPA
(5)- CH), 6.78–6.47 (9H, m, DOPA(1)-ArH, DOPA(2)-ArH, dc DOPA(5)-ArH),
6.13⁄ (1H, d, J = 14.6 Hz, dc
DOPA(5)-bCH), 6.05 (1H, d, J = 14.6 Hz, dc DOPA-
bCH), 4.62–4.51 (1H, m, DOPA(2)- CH), 4.32 (1H, dd, J = 8.3, 3.8 Hz, Pro(4)-
CH), 4.04 (1H, dd, J = 17.1, 5.5 Hz, Gly(3)- CH2a), 3.90 (1H, dd, J = 17.1, 4.9 Hz,
CH2b), 3.85–3.81 (1H, br m, DOPA(1)- CH), 3.61–3.35 (1H, br m, Pro
DDOPA(5)-NH), 9.96
D
D
D
a
D
a
D
D
D
Acknowledgment
a
a
a
Gly(3)-
a
a
We acknowledge the University of Auckland for funding.
(4)-dCH2), 3.04–2.99 (1H, m, DOPA(1)-bCH2a), 2.96–2.85 (1H, m, DOPA(2)-
bCH2a), 2.68–2.59 (2H, m, DOPA(1)-bCH2b, DOPA(2)-bCH2b), 2.15–2.05 (1H, m,
Pro(4)-bCH2a), 1.99–1.84 (2H, m, Pro(4)-cCH2), 1.91–1.79 (1H, m, Pro(4)-
Supplementary data
bCH2b); 13C NMR (125 MHz, DMSO-d6) d 171.0 (DOPA(2)-C@O), 169.5 (Pro(4)-
C@O), 168.2 (DOPA(1)-C@O), 166.9 (Gly(3)-C@O), 145.5 (DOPA(1)-Ar-Ob),
145.2 (DOPA(1)-Ar-Ob), 144.9 (DOPA(2)-Ar-Ob), 144.6 (DOPA(2)-Ar-Ob), 144.4
Supplementary data (experimental details and compound char-
acterization) associated with this article can be found, in the online
data include MOL files and InChiKeys of the most important com-
pounds described in this article.
(dc
D
DOPA(5)-Ar-Ob), 143.8 (dc
DOPA(5)-
Cc), 125.5 (DOPA(1)-
D
DOPA(5)-Ar-Ob), 128.3 (DOPA(2)-
Cc), 120.6 (dc
DOPA(5)-
DOPA(5)-ArH), 116.8
DOPA(5)-ArHd), 115.6
DOPA(5)-bCH), 111.9
CH), 53.6 (DOPA(1)-
CH2), 37.1 (DOPA(2)-bCH2), 36.6
(DOPA(1)-bCH2), 29.4 (Pro(4)-bCH2), 24.4 (Pro(4)-
CH2); 1H NMR (500 MHz,
CD3OD) d 7.23⁄ (1H, d, J = 14.6 Hz, dc
DOPA(5)- CH), 7.16 (1H, d, J = 14.6 Hz,
dc DOPA(5)- CH), 6.80–6.50 (9H, m, DOPA(1)-ArH, DOPA(2)-ArH, dc DOPA
(5)-ArH), 6.23⁄ (1H, d, J = 14.6 Hz, dc
DOPA-bCH), 6.16 (1H, d, J = 14.6 Hz,
dc DOPA-bCH), 4.66 (1H, t, J = 7.1 Hz, DOPA(2)-
CH), 4.60–4.51⁄ (1H, m, Pro
(4)- CH), 4.44 (1H, dd, J = 8.7, 4.2 Hz, Pro(4)- CH), 4.08–4.00 (1H, m, DOPA(1)-
CH), 4.05–3.98 (2H, m, Gly(3)- CH2), 3.65–3.58 (1H, m, Pro(4)-dCH2a), 3.56–
c
Cc), 127.8
(dcD
c
c
D
D
D
D
a
CHd), 120.4
(DOPA(1)-ArHd), 120.0 (DOPA(2)-Ar-Hd), 117.0 (dc
(DOPA(1)-ArHd), 116.7 (DOPA(2)-ArHd), 115.9 (dc
(DOPA(1)-ArHd), 115.3 (DOPA(2)-ArHd), 112.7 (dc
(dcDDOPA(5)-ArH), 59.8 (Pro(4)-aCH), 54.6 (DOPA(2)-a
aCH), 46.0 (Pro(4)-dCH2), 41.5 (Gly(3)-
a
References and notes
c
D
a
D
a
D
8. Note that between the publication of Refs. 6 and 7, the name of tunichrome B-1
was changed to An-1.
D
D
a
a
a
a
a
3.47 (1H, m, Pro(4)-dCH2b), 3.06–2.96 (2H, m, DOPA(1)-bCH2a, DOPA(2)-
bCH2a), 2.90 (1H, dd, J = 14.0, 7.5 Hz, DOPA(1)-bCH2b), 2.79 (1H, dd, J = 14.0,
8.5 Hz, DOPA(2)-bCH2b), 2.39–2.33⁄ (1H, m, Pro(4)-bCH2a), 2.26–2.18 (1H, m,
Pro(4)-bCH2a), 2.18–2.09⁄ (1H, m, Pro(4)-bCH2b), 2.10–1.97 (2H, m, Pro(4)-
c
CH2), 2.06–1.94 (1H, m, Pro(4)-bCH2b) 1.96–1.88⁄ (1H, m, Pro(4)- CH2); 13C
c
NMR (125 MHz, CD3OD) d 173.1 (DOPA(2)-C@O), 171.9 (Pro(4)-C@O), 171.2⁄
(Pro(4)-C@O), 169.5 (DOPA(1)-C@Oa), 169.4 (Gly(3)-C@Oa), 146.6 (DOPA(1)-
Ar-Ob), 146.4 (DOPA(1)-Ar-Ob), 146.1 (DOPA(2)-Ar-Ob), 146.0 (DOPA(2)-Ar-Ob),
145.7 (dc
129.6 (dc
(DOPA(2)-Ar-H), 121.1 (dc
(DOPA(1)-ArHd), 117.4 (DOPA(2)-ArHd), 116.8 (dc
(DOPA(1)-ArHd), 116.3 (DOPA(2)-ArHd), 116.1 (dc
(dc DOPA(5)-ArH), 61.9 (Pro(4)-
CH), 61.2⁄ (Pro(4)-
CH), 55.5 (DOPA(1)-
CH), 47.9 (Pro(4)-dCH2), 47.7⁄ (Pro(4)-dCH2), 43.1 (Gly
(3)-
CH2), 43.0⁄ (Gly(3)- CH2), 38.2 (DOPA(1)-bCH2e), 37.9 (DOPA(2)-bCHe2),
33.4⁄ (Pro(4)-bCH2), 30.8 (Pro(4)-bCH2), 25.7 (Pro(4)- CH2) 23.4⁄ (Pro(4)-
CH2); (+)-HRESIMS m/z 664.2615 [M+H]+ (Calcd for C33H38N5O10, 664.2613).
D
D
DOPA(5)-Ar-Ob), 145.2 (dc
DOPA(5)-
Cc), 126.5 (DOPA(1)-
DOPA(5)- CH), 119.1 (dcDDOPA(5)-ArH), 117.6
D
DOPA(5)-Ar-Ob), 129.7 (DOPA(2)-
c
Cc),
c
c
C), 122.0 (DOPA(1)-ArH), 121.7
D
a
D
DOPA(5)-ArHd), 116.5
D
DOPA(5)-bCHd), 113.2
D
a
aCH), 56.3 (DOPA(2)-
a
a
a
a
c
c
21. All NMR resonances could be assigned to either the cis- or trans-prolyl
conformers, showing that no diastereomers had formed during the Buchwald
coupling step.