The Journal of Organic Chemistry
Article
1
H NMR (400 MHz, CDCl ): δ 7.24−7.22 (m, 1H, H-5), 7.11 (d, J =
13b), 1.55 (m, 10H, H-9b, H-23), 1.30 (s, 3H, H-19), 1.231 (s, 3H, H-
3
20), 1.228 (s, 3H, H-17), 1.10 (s, 3H, H-18). 13C NMR (125 MHz,
1
1
1
.6 Hz, 1H, H-3), 5.32−5.26 (m, 1H, H-7), 5.25−5.15 (m, 2H, H-11/
5), 3.16 (d, J = 7.2 Hz, 2H, H-6), 2.14−1.96 (m, 8H, H-9/10/13/
4), 1.67 (br s, 6H, H-17/20), 1.59 (br s, 6H, H-18/19), 1.56 (s, 9H,
CDCl ): δ 174.6 (C-24), 148.4 (C-21), 128.0 (C-5), 125.5 (C-3),
3
124.6 (C-2/4), 123.5 (C-2/4), 95.7 (C-25), 88.2 (C-15), 86.8 (C-8),
85.5 (22), 85.4 (C-12), 84.4 (C-11), 77.8 (C-7), 70.4 (C-16), 34.7 (C-
13), 31.4 (C-9), 29.4 (C-6), 28.0 (C-14), 27.9 (C-17/20), 27.7 (C-
23), 25.9 (2C, C-10, C-19), 24.8 (C-17/20), 24.4 (C-18). IR (ATR):
1
3
H-23). C NMR (100 MHz, CDCl ): δ 174.8 (C-24), 148.5 (C-21),
1
1
(
(
1
2
1
3
37.4 (C-8), 135.4 (C-12), 131.4 (C-16), 126.7 (C-5), 125.8 (C-2),
24.9 (C-4), 124.5 (C-3), 124.2 (C-11/15), 124.1 (C-11/15), 121.5
C-7), 95.7 (C-24), 85.7 (C-22), 39.9 (C-9/13), 39.8 (C-9/13), 27.7
C-23), 26.9 (C-10/14), 26.7 (C-10/14), 25.8 (C-17), 25.2 (C-6),
̃
υ = 3370, 2970, 2933, 2876, 1754, 1696, 1451, 1371, 1257, 1152, 1070,
−1
+
8
40, 816, 804, 768, 729 cm . HRMS (ESI-TOF) m/z: [M + Na]
calcd for C H Cl NNaO 604.1601; found 604.1609.
7.9 (C-18), 16.3 (C-19), 16.2 (C-20). IR (ATR): υ
̃
= 2977, 2923,
26 38
3
7
Heronapyrrole C Acid (23). A stirred solution of bis-THF 28
120 mg, 0.21 mmol, 1.0 equiv) in THF (5 mL) and NaOH (5 mL, 2
868, 1752, 1718, 1698, 1449, 1396, 1369, 1323, 1288, 1256, 1151,
−1
+
(
115, 988, 838, 729, 681 cm . HRMS (ESI-TOF) m/z: [M + Na]
M) was heated to 75 °C for 1 h. After complete conversion (TLC),
calcd for C H Cl NNaO 538.1653; found 538.1654.
26
36
3
3
the mixture was cooled to rt, acidified (pH 1.5) with NaHSO (1 M)
tert-Butyl 4-((10R,2E,6E)-10,11-Dihydroxy-3,7,11-trimethyl-
dodeca-2,6-diene-1-yl)-2-trichloroacetyl-1H-pyrrole-1-carbox-
ylate (26). A solution of 24 (1.00 g, 1.93 mmol, 1.00 equiv) in t-
BuOH/H O (50 mL, 1:1) was cooled to 0 °C, and Corey ligand
(
mmol, 1.00 equiv), K CO (0.80 g, 5.79 mmol, 3.00 equiv), K OsO ·
2
5
stirred for 24 h at 0 °C. After addition of saturated Na SO (50 mL),
the solution was stirred for 10 min, diluted with H O (100 mL), and
extracted with ethyl acetate (3 × 50 mL). The combined organic layers
were dried over Na SO , and the solvent was removed under reduced
pressure. Flash chromatography (50% ethyl acetate in hexanes, silica)
of the crude product gave the title compound (0.56 g, 52%, 61% brsm)
and reisolated starting material 24 (0.15 g, 15%) as yellow oils. [α]
4
and the aqueous layer was extracted with ethyl acetate (3 × 10 mL).
The combined organic layers were dried over Na SO and all volatiles
2
4
4
9,50
were removed under reduced pressure. Flash chromatography (20%
ethyl acetate + 5% AcOH in hexanes, silica) of the residue gave the
2
22.0 mg, 19.0 μmol, 0.01 equiv), methanesulfonamide (184 mg, 1.93
2
0
title compound (45 mg, 56%) as an oil. [α]
+5.5 (c 1.14, MeOH).
H NMR (300 MHz, MeOH-d ): δ 6.83 (d, J = 1.3 Hz, 1H, H-5), 6.78
4
2
3
2
4
D
1
H O (3.60 mg, 9.70 μmol, 0.005 equiv), and K Fe(CN) (1.91 g,
2
3
6
.79 mmol, 3.00 equiv) were successively added. The suspension was
(d, J = 1.4 Hz, 1H, H-3), 4.02 (dd, J = 8.6 Hz, J = 6.5 Hz, 1H, H-11),
3.82 (dd, J = 8.5 Hz, J = 6.6 Hz, 1H, H-15), 3.59 (dd, J = 10.1 Hz, J =
2.0 Hz, 1H, H-7), 2.81 (dd, J = 14.8 Hz, J = 1.8 Hz, 1H, H-6a), 2.42
(dd, J = 14.8 Hz, J = 10.1 Hz, 1H, H-6b), 2.18−2.10 (m, 1H, H-9a),
2.03−1.72 (m, 5H, H-10, H-13a, H-14), 1.69−1.57 (m, 2H, H-9b, H-
13b), 1.211 (s, 3H, H-19), 1.208 (s, 3H, H-20), 1.16 (s, 3H, H-17/18),
2
3
2
2
4
1.13 (s, 3H, H-17/18). 13C NMR (75 MHz, MeOH-d ): δ 164.9 (C-
4
2
0
21), 124.6 (C-4), 123.5 (C-5), 117.1 (C-3), 88.9 (C-15), 87.1 (C-8),
86.3 (C-12), 86.1 (C-11), 79.4 (C-7), 72.2 (C-16), 35.1 (C-9), 34.7
(C-13), 30.2 (C-6), 28.5 (C-10), 27.6 (C-14), 26.2 (C-17/18), 25.8
D
1
+
9.8 (c 1.08, MeOH). H NMR (400 MHz, CDCl ): δ 7.23 (br s, 1H,
3
H-5), 7.10 (d, J = 1.4 Hz, 1H, H-3), 5.29 (t, J = 6.8 Hz, 1H, H-7), 5.19
(
3
3
t, J = 6.2 Hz, 1H, H-11), 3.35 (dd, J = 10.4 Hz, J = 1.6 Hz, 1H, H-15),
(C-17/18), 25.1 (C-19), 22.3 (C-20). IR (ATR): υ
̃
= 3378, 2971,
.16 (d, J = 7.3 Hz, 2H, H-6), 2.28−2.05 (m, 6H, H-9/10/13), 1.67 (s,
H, H-20), 1.62 (s, 3H, H-19), 1.55 (s, 9H, H-23), 1.46−1.40 (m, 2H,
2874, 1678, 1575, 1474, 1413, 1374, 1307, 1215, 1179, 1071, 980, 888,
636 cm . HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
−1
1
3
H-14), 1.19 (s, 3H, H-17/18), 1.15 (s, 3H, H-17/18). C NMR (100
MHz, CDCl ): δ 174.9 (C-24), 148.5 (C-21), 137.2 (C-8), 135.4 (C-
1
1
C
20
H
31NNaO 404.2044; found 404.2052. Because of its low intensity
6
13
13
in the 1D C spectrum, the C resonance at δ 164.9 was assigned
3
2), 126.7 (C-5), 125.8 (C-2/4), 124.92 (C-2/4), 124.86 (C-11),
24.2 (C-3), 121.6 (C-7), 95.7 (C-24), 85.8 (C-22), 78.5 (C-15), 73.1
using HMBC and HSQC spectra. The quaternary carbon atom
1
3
adjacent to the acid (C-2) could not be detected by either 1D C or
6
0
(C-16), 39.7 (C-9), 37.0 (C-13), 29.9 (C-14), 27.7 (C-23), 26.5 (2C,
2D NMR methods.
C-10 + C17/18), 25.2 (C-6), 23.5 (C-17/18), 16.2 (C-19), 16.1 (C-
2
1
0). IR (ATR): υ
̃
= 3411, 2978, 2931, 1746, 1697, 1477, 1449, 1397,
ASSOCIATED CONTENT
■
−1
323, 1151, 1118, 909, 839, 768, 728, 682 cm . HRMS (ESI-TOF)
*
S
Supporting Information
+
m/z: [M + Na] calcd for C H Cl NNaO 572.1708; found
5
1
26
38
3
5
72.1720.
tert-Butyl 4-((2S)-Hydroxy-2-((2S,2′R,5R,5′R)-5′-(2-hydroxy-
propan-2-yl)-2′,5-dimethyloctahydro-[2,2′-bifuran]-5-yl)-
ethyl)-2-trichloroacetyl-1H-pyrrole-1-carboxylate (28). To a
stirred solution of (R)-diol 26 (226 mg, 0.41 mmol, 1.00 equiv) in
MeCN/(CH O) CH (15.6 mL, 1:2) were added Na B O ·10H O in
4
0
1
AUTHOR INFORMATION
Notes
■
*
3
2
2
2
4
7
2
−4
× 10 M Na EDTA (0.05 M, 10.4 mL), n-Bu NHSO (16.0 mg,
2 4 4
53
.046 mmol, 0.11 equiv), and (+)-Shi ketone (127 mg, 0.49 mmol,
.20 equiv). The mixture was cooled to 0 °C, and solutions of Oxone
The authors declare no competing financial interest.
−
4
(
855 mg, 1.39 mmol, 3.40 equiv) in Na EDTA (4 × 10 M, 6.5 mL)
2
and K CO (795 mg, 5.75 mmol, 14.0 equiv) in H O (6.5 mL) were
ACKNOWLEDGMENTS
Financial support of this research by the Fonds der
Chemischen Industrie is gratefully acknowledged.
2
3
2
■
added separately via syringe pump over 90 min at 0 °C. The reaction
mixture was diluted with H O (20 mL) and extracted with ethyl
acetate (3 × 10 mL). The combined organic layers were dried over
Na SO , and the solvent was removed under reduced pressure. The
2
2
4
REFERENCES
crude mixture was dissolved in dry toluene (10 mL), and
+)-camphorsulfonic acid (9.5 mg, 0.041 mmol, 0.10 equiv) was
■
(
(1) Breitmaier, E. Terpenes; Wiley-VCH: Weinheim, Germany, 2006.
(2) Young, I. S.; Thornton, P. D.; Thompson, A. Nat. Prod. Rep.
2010, 27, 1801−1839.
added at 0 °C. The solution was stirred for 4 h until complete
consumption of the intermediary bis-epoxide was monitored. Triethyl-
amine (2 mL) was added, and all volatiles were removed under
reduced pressure. Flash chromatography (50% ethyl acetate in
hexanes, silica) of the residue gave the title compound (140 mg,
(3) Liu, Y.; Zhang, S.; Abreu, P. J. M. Nat. Prod. Rep. 2006, 23, 630−
651.
̈
(4) Furstner, A. Synlett 1999, 1523−1533.
2
0
1
5
9%) as a yellowish oil. [α]D +7.0 (c 1.00, MeOH). H NMR (500
(5) Kato, S.; Shindo, K.; Kawai, H.; Odagawa, A.; Matsuoka, M.;
Mochizuki, J. J. Antibiot. 1993, 46, 892−899.
(6) Fumoto, Y.; Eguchi, T.; Uno, H.; Ono, N. J. Org. Chem. 1999, 64,
6518−6521.
MHz, CDCl ): δ 7.39 (d, J = 1.4 Hz, 1H, H-5), 7.29 (d, J = 1.4 Hz,
3
1
2
1
1
H, H-3), 4.05−4.01 (m, 1H, H-11), 3.79−3.75 (m, 2H, H-7, H-15),
.57 (dd, J = 14.8 Hz, J = 2.0 Hz, 1H, H-6a), 2.43 (dd, J = 14.8 Hz, J =
0.3 Hz, 1H, H-6b), 2.23−2.17 (m, 1H, H-9a), 2.01−1.92 (m, 3H, H-
0a, H-14), 1.84−1.77 (m, 2H, H-10b, H-13a), 1.75−1.69 (m, 1H, H-
(7) Barton, D. H. R.; Zard, S. Z. J. Chem. Soc., Chem. Commun. 1985,
1098−1100.
1
927
dx.doi.org/10.1021/jo402240g | J. Org. Chem. 2014, 79, 1920−1928