Y. Cheng et al.
1
8
682, 1457, 1339, 1282, 1218, 1181, 1093, 1046, 1004,958, 900, Fast-moving diastereomer 1C
À1
35, 746, 612, 553, 535 cm
.
1
H NMR (300 MHz, CDCl
3
) δ 7.41 (d, J = 2.4 Hz, 1H), 6.93 (s, 1H),
6.15 (s, 1H), 5.51 (d, J = 7.5 Hz), 3.61–3.55 (m, 1H), 2.70 (dd,
J = 8.7, 16.2 Hz, 1H), 2.32 (br-d, J = 16.5 Hz, 1H), 2.24 (s, 1.5H),
.00–1.92 (m, 2H), 1.80 (s, 1.5H), 1.67–1.63 (m, 2H), 1.50–1.35
2
+
(
(
(
m, 2H), 1.11 (s, 3H), 1.09 (s, 3H); MS (ESI) m/z 332 [M + H] ; HRMS
ESI) Calcd. for C18CH23O requires 332.1575, Found: 332.1570. IR
5
KBr) ν 2930, 2865, 1782, 1743, 1682, 1445, 1339, 1204, 1180,
1
3
À1
1
152, 1091, 1023, 954, 932, 900, 865, 740, 557 cm
.
CD
3
-(+)-2′-epi-5-DS
Slow-moving diastereomer 2′-epi-1C
1
1
H NMR (300 MHz, CDCl ) δ 7.41 (d, J = 2.1 Hz, 1H), 6.93 (s, 1H),
3
H NMR (300 MHz, CDCl ) δ 7.42 (d, J = 2.7 Hz, 1H), 6.93 (t,
3
6
.16 (s, 1H), 5.51 (d, J = 7.5 Hz, 1H), 3.62–3.54 (m, 1H), 2.70 (dd, J = 1.2 Hz, 1H), 6.13 (s, 1H), 5.52 (d, J = 7.8 Hz), 3.60–3.54 (m, 1H),
J = 9, 16.5 Hz, 1H), 2.32 (br-d, J = 16.5 Hz, 1H), 1.96–1.90 (m, 2H), 2.68 (dd, J = 9, 16.8 Hz, 1H), 2.31 (br-d, J = 17.4 Hz, 1H), 2.23 (t,
.69–1.62 (m, 2H), 1.49–1.24 (m, 2H), 1.10 (s, 3H), 1.09 (s, 3H); J = 1.5 Hz, 1.5H), 2.01–1.88 (m, 2H), 1.80 (t, J = 1.5 Hz, 1.5H),
1
+
MS (ESI) m/z 334 [M + H] . HRMS (ESI) Calcd. for C19
requires 334.1728, Found: 334.1724; [α]
CH
3
1
8
H
20
D
3
O
5
1.69–1.64 (m, 2H), 1.50–1.30 (m, 2H), 1.10 (s, 3H), 1.08 (s, 3H);
+215° (c 0.0500, MS (ESI) m/z 354 [M + Na] . HRMS (ESI) Calcd. for C18CH22O Na
5
2
5
+
13
D
CN); CD (acetonitrile) λmax(△ε) 218(-13), 250(8) nm. IR (KBr) ν requires 354.1398, Found: 354.1399. IR (KBr) ν 2929, 2866, 1782,
091, 2925, 2865, 1781, 1740, 1683, 1457, 1428, 1386, 1339, 1743, 1683, 1472, 1457, 1446, 1385, 1374, 1338, 1244, 1204,
3
À1
306, 1283, 1261, 1244, 1217, 1180, 1091, 1044, 1004, 956, 834, 1181, 1090, 1022, 953, 900, 864, 772, 739, 612, 559 cm
.
À1
01, 732, 647, 553, 532 cm
.
Results and discussion
1
3
7
′- C-7′,7′,7′-trideuterio-5-deoxystrigol and
The preparation of the isotope labelled D-rings is outlined in
scheme 1. Commercially available 2[5H]-furanone was chosen as
the starting material because it contains a suitable carbon
framework appropriate for producing a D-ring intermediate. Based
on this background, treatment of 2[5H]-furanone with bromine,
and then with triethylamine at 0 °C gave 3-bromofuranone (2) in
its 2′-epimer (1B and 2′-epi-1B)
The compound was prepared as described for 1A and 2′-epi-1A.
Compound 7B (137 mg, 0.76 mmol) was used in the process. The
fast-moving diastereomer 1B (59.9 mg, yield 33%) was obtained
as a yellow liquid, and the slow-moving diastereomer 2′-epi-1B
14
(
54 mg, yield 30%) was obtained as a yellow solid.
4
7.6% yield . Then treatment of triisopropylsilyl trifluorome-
thanesulfonate with 2 and triethylamine gave compound 3 in
15
Fast-moving diastereomer 1B
68.9% yield . Isotopes labelled methyl iodides (5) were prepared
1
from isotopes labelled methanol by addition of hydriodic acid
H NMR (300 MHz, CDCl ) δ 7.41 (d, J = 3 Hz, 1H), 6.93 (s, 1H), 6.16
3
16
(
2
HI) in up to 80% yield . Under a N atmosphere, compound 3
(s 1H), 5.51 (d, J = 8.1 Hz), 3.60–3.55 (m, 1H), 2.70 (dd, J = 9.3,
was treated with n-butyllithium and 5, followed by an acidification
to give three kinds of isotope labelled D-ring analogues (6) in
1
1
7.1 Hz, 1H), 2.31 (br-d, J = 17.4 Hz, 1H), 1.96–1.90 (m, 2H), 1.70–
.61 (m, 2H), 1.50–1.34 (m, 2H), 1.10 (s, 3H), 1.08 (s, 3H); MS
15
+
13
around 50% yield.
EI-MS analysis of compound 6A (Figure S1) suggested that the
(ESI) m/z 335 [M + H] ; HRMS (ESI) Calcd. for C18CH20
3 5
D O
requires 335.1762, Found: 335.1759. IR (KBr) ν 2929, 2865, 1782,
+
+
compound showed [M] ion at m/z = 101, [M À 2] ion at
1
1
744, 1682, 1457, 1385, 1339, 1244, 1213, 1180, 1094, 1044,
+
À1
m/z = 99 (deuterated) and [M À 3] ion at m/z = 98 (unlabeled).
003, 957, 899, 845, 830, 744 cm
.
Peak value calculations suggested that the deuterate abundance
1
of compound 6A was 99.6%. The H NMR spectra of compound
Slow-moving diastereomer 2′-epi-1B
6
A showed no absorption at C5. Similarly, EI-MS analysis of
+
1
compound 6B (Figure S2) indicated an [M] ion at m/z = 102,
H NMR (300 MHz, CDCl ) δ 7.43 (d, J = 3 Hz, 1H), 6.94 (t, J = 1.2 Hz,
3
+
+
[
M À 1] ion at m/z = 101 (deuterated) without the [M À 3] ion
1
2
H), 6.13 (d, J = 0.3 Hz, 1H), 5.52 (d, J = 8.1 Hz), 3.60–3.54 (m, 1H),
.68 (dd, J = 9, 16.8 Hz, 1H), 2.31 (br-d, J = 17.1 Hz, 1H), 2.04–1.89
being observed. Peak value calculations suggested that the 13-C
and D3 abundance of compound 6B was 94.1%. EI-MS analysis of
(
(
m, 2H), 1.69–1.63 (m, 2H), 1.51–1.30 (m, 2H), 1.10 (s, 3H), 1.09
+
+
compound 6C (Figure S3) suggested that [M] at m/z = 99 was
s, 3H); MS (ESI) m/z 335 [M + H] ; HRMS (ESI) Calcd. for
+
1
3
found, and that no [M À 1] signal was detected. The corresponding
C CH D O requires 335.1762, Found: 335.1758. IR (KBr) ν
1
8
20 3 5
peak value calculations suggested that the 13-C abundance of
compound 6C was 99.9%.
2
1
929, 2865, 1782, 1744, 1682, 1457, 1385, 1339, 1213, 1181,
094, 1043, 1003, 957, 899, 845, 830, 748, 702 cm
À1
.
With the D-ring analogues in hand, they were further linked to
ring ABC (Scheme 2). Compound 7 was obtained by treatment of
1
3
7
′- C-5-deoxystrigol and its 2′-epimer (1C
17
6
with N-bromosuccinimide in moderate to good yield, with
and 2′-epi-1C)
isotopic abundance of 7 unaffected. Following a procedure
18
The compound was prepared as described for 1A and 2′-epi-1A. established by MacAlpine and co-workers, ring ABC (8) was
Compound 7C (152 mg, 0.86 mmol) was used in the process. The prepared in 31% yield. Formylation of the lactone 8 with sodium
fast-moving diastereomer 1C (54 mg, yield 26.7%) was obtained hydride and ethyl formate, followed by an alkylation with
as a yellow solid, and the slow-moving diastereomer 2′-epi-1C compound
7 using excess potassium carbonate in N-
(58 mg, yield 28.4%) was obtained as a yellow solid. methylpyrrolidone, gave the enantiomeric, isotope labelled 1
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Copyright © 2015 John Wiley & Sons, Ltd.
J. Label Compd. Radiopharm 2015, 58 355–360