Page 21 of 25
The Journal of Organic Chemistry
1H), 6.12 (br, 1H), 5.22 (s, 1H), 5.18 (d, J = 7.1 Hz, 1H), 3.74
Hz, 1H), 2.90 (dd, J = 21.5, 11.4 Hz, 0.2H), 2.74 (dd, J = 21.6,
1
2
3
4
5
6
7
8
(dd, J = 15.6, 8.3 Hz, 2H), 3.65 (d, J = 7.3 Hz, 2H), 3.48 (br, 1H),
3.30−3.09 (m, 2H), 2.64 (s, 2H), 2.10 (br, 1H), 1.93 (s, 3H), 1.76
(s, 3H), 1.61 (s, 9H), 1.49 (s, 9H), 1.05 ppm (t, J = 7.0 Hz, 3H);
13C NMR (101 MHz, CDCl3, mixture of rotamers): δ 171.9,
155.6, 154.3, 143.7, 142.2, 141.6, 139.3, 133.9, 128.8, 128.0,
127.6, 125.7, 125.1, 123.1, 121.6, 117.4, 113.2, 111.7, 82.0, 79.4,
63.8, 59.9, 51.2, 40.5, 37.4, 34.7, 32.8, 29.7, 28.6, 28.4, 25.7,
11.9 Hz, 0.8H), 2.41 (s, 1.8H), 2.36−2.20 (m, 2H), 2.12 (s, 1.2H),
1.97 (s, 1.2H), 1.95–1.91 (m, 1H), 1.86 (s, 1.8H), 1.79 (s, 1.8H),
1.76 ppm (s, 1.2H); 1H NMR (499 MHz, 5% CF3COOH in
CDCl3): δ 7.11 (t, J = 7.6 Hz, 1H), 6.90 (t, J = 7.7 Hz, 1H),
6.83−6.77 (m, 2H), 6.54 (d, J = 7.6 Hz, 1H), 6.28 (d, J = 7.8 Hz,
1H), 6.23 (d, J = 7.5 Hz, 1H), 5.92 (d, J = 8.5 Hz, 1H), 5.76 (s,
1H), 5.14−5.07 (m, 2H), 4.16 (br, 1H), 4.07 (br, 1H), 3.72 (br,
1H), 3.65 (br, 1H), 3.28 (m, 1H), 2.98 (m, 1H), 2.59 (br, 1H), 2.42
(br, 1H), 2.24−2.21 (m, 1H), 2.20 (s, 3H), 2.08 (s, 3H), 2.05−1.98
(m, 1H), 1.86 ppm (s, 3H); 13C NMR (100 MHz, CDCl3, mixture
of rotamers) δ 172.7, 171.5, 149.1, 142.4, 141.3, 136.1, 135.8,
132.0, 131.8, 128.2, 127.2, 124.6, 123.1, 120.5, 117.0, 116.9,
105.2, 100.2, 79.7, 64.4, 52.2, 44.2, 37.9, 36.1, 33.9, 31.9, 30.7,
29.7, 26.0, 22.6, 18.4 ppm; HRMS calcd. For C27H30N4ONa+ [M
+ Na]+ 449.2312, found 449.2314.
+
18.9, 18.6, 13.9 ppm; HRMS calcd. For C37H49N4O5 [M + H]+
629.3697, found 629.3699. (ii) To a flask containing imidate 66a
(semiꢀpurified, obtained above) at room temperature was added a
solution of trifluoroacetic acid (freshely prepared, 5 wt% in
CH2Cl2, 38.0 mL). The resulting mixture was stirred for 2 h beꢀ
fore it was quenched with NaHCO3 (40 mL) and extracted with
CH2Cl2 (3 × 50 mL). The combined organic layer was dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The
resulting crude residue was dissolved in CH2Cl2/MeOH (1:1, 10.0
mL) and treated with silica gel (1.0 g) at room temperature. The
resulting mixture was warmed to 50 °C and stirred for 20 h before
it was filtered and filterate was concentrated under reduced presꢀ
sure. The resulting residue was purified by flash column chromaꢀ
tography (silica gel, hexanes:EtOAc = 1:1) to afford heptacyclic
imine 67 (26.4 mg, 36% over 2 steps) as a pale yellow foam. 67:
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
“Putative” Communesin Common Biosynthetic Precursor 68a:
(i) To a stirred solution of Bocꢀcarbamate 67 (5.7 mg, 11.8 µmol)
in AcOH (0.6 mL) at 0 °C was added sodium borohydride (38.0
mg, 1.00 mmol). The resulting mixture was stirred for 25 min
before it was quenched with NaHCO3 (5 mL, sat. aq.) and extractꢀ
ed with CH2Cl2 (3 × 10 mL). The combined organic layer was
dried over anhydrous Na2SO4 and concentrated under reduced
pressure. The resulting crude residue was used directly in the next
step without further purification. (ii) To a stirred solution of crude
residue (obtained above) in CH2Cl2 (3.0 mL) at room temperature
was added trifluoroacetic acid (1.20 mL). The resulting mixture
was stirred for 2 h before it was quenched with NaHCO3 (5 mL,
sat. aq.) and extracted with CH2Cl2 (3 × 10 mL). The combined
organic layer was dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The resulting residue was purified by
flash column chromatography (silica gel, EtOAc) to afford “putaꢀ
tive” communesin common biosynthetic precursor 68a (2.2 mg,
49% over 2 steps) as a pale yellow oil. 68a: Rf = 0.39 (silica gel,
25
Rf = 0.48 (silica gel, hexanes:EtOAc 1:2); [α]D +55.4 (c = 1.47,
CHCl3); IR (film) νmax 2976, 1693, 1640, 1435, 1379, 1251, 750
cm−1; 1H NMR (400 MHz, CDCl3 mixture of rotamers): δ 7.55 (br,
0.4H), 7.18 (br, 0.6H), 7.00 (d, J = 7.2 Hz, 1H), 6.96 (t, J = 7.9 Hz,
1H), 6.91 (t, J = 7.7 Hz, 1H), 6.61 (t, J = 7.3 Hz, 1H), 6.48 (d, J =
7.7 Hz, 1H), 6.45 (d, J = 7.8 Hz, 1H), 5.46 (br, 0.4H), 5.34 (d, J =
8.8 Hz, 1H), 5.11 (br, 0.2H), 4.92 (d, J = 8.9 Hz, 1H), 4.71 (br,
0.2H), 4.36 (br, 0.2H), 3.84 (dd, J = 14.6, 7.7 Hz, 1H), 3.78−3.69
(m, 1H), 3.31−3.17 (m, 2H), 2.90 (td, J = 11.4, 7.8 Hz, 1H), 2.23
(dt, J = 12.6, 8.6 Hz, 1H), 2.18−2.10 (m, 1H), 1.89−1.84 (m, 1H),
1.81 (s, 3H), 1.71 (s, 3H), 1.64 ppm (s, 9H); 13C NMR (101 MHz,
CDCl3) δ 179.9, 142.8, 134.2, 128.3, 128.2, 127.5, 123.8, 122.2,
122.0, 118.8, 115.0, 113.3, 75.1, 59.8, 57.6, 54.8, 45.5, 39.1, 31.9,
29.7, 29.3, 28.5, 27.5, 27.2, 25.7, 25.5, 22.7, 18.5, 14.1 ppm;
25
EtOAc); [α]D −132.6 (c = 0.28, CHCl3); IR (film) νmax 2922,
1
1734, 1604, 1457, 1247, 747 cm−1; H NMR (400 MHz, CDCl3,
mixture of isomeric forms): δ 7.38 (d, J = 7.9 Hz, 0.2H), 7.08 (d,
J = 7.7 Hz, 0.2H), 7.03 (d, J = 7.4 Hz, 0.6H), 6.99−6.92 (m, 1H),
6.78 (t, J = 7.9 Hz, 0.2H), 6.76 (t, J = 7.7 Hz, 1H), 6.71 (t, J = 7.5
Hz, 1H), 6.61 (d, J = 7.6 Hz, 0.8H), 6.47 (d, J = 7.4 Hz, 0.2H),
6.39 (d, J = 7.3 Hz, 0.2H), 6.18 (dd, J = 7.6, 2.2 Hz, 1.6H), 5.37
(d, J = 9.2 Hz, 0.2H), 5.30 (d, J = 8.9 Hz, 0.8H), 5.01 (s, 1H),
4.96 (d, J = 9.0 Hz, 1H), 4.90 (d, J = 9.1 Hz, 0.2H), 4.89 (s, 1H),
4.55 (s, 0.2H), 4.53 (s, 0.2H), 4.19 (s, 0.2H), 3.91 (br, 0.2H), 3.60
(td, J = 11.9, 3.9 Hz, 0.2H), 3.49−3.39 (m, 0.8H), 3.25−3.13 (m,
2H), 2.99−2.81 (m, 0.2H), 2.76−2.59 (m, 2.2H), 2.39−2.29 (m,
0.8H), 2.14−2.06 (m, 0.8H), 2.05−2.01 (m, 0.8H), 1.89 (s, 0.6H),
1.81 (s, 2.4H), 1.77 (s, 2.4H), 1.71 (s, 0.6H), 1.62 ppm (dd, J =
12.2, 11.8 Hz, 0.2H); 13C NMR (100 MHz, CDCl3, mixture of
isomeric forms) δ 148.7, 143.2, 140.7, 135.8, 133.0, 132.3, 127.8,
127.1, 126.6, 125.0, 123.7, 119.6, 117.3, 116.0, 112.9, 105.6,
80.4, 67.0, 64.2, 53.5, 52.2, 50.9, 43.8, 43.3, 38.1, 35.2, 35.0,
34.0, 29.7, 25.9, 18.6 ppm; HRMS calcd. For C25H29N4+ [M + H]+
385.2387, found 385.2389.
+
HRMS calcd. For C30H35N4O2 [M + H]+ 483.2755, found
483.2759.
“Putative” Communesin 68: (i) To a stirred solution of Bocꢀ
carbamate 67 (5.7 mg, 11.8 µmol) in AcOH/Ac2O (1:1, 1.2 mL) at
0 °C was added sodium borohydride (38.0 mg, 1.00 mmol). The
resulting mixture was stirred for 10 min before it was quenched
with sodium carbonate (5 mL, sat. aq.) and extracted with CH2Cl2
(3 × 10 mL). The combined organic layer was dried over anhyꢀ
drous Na2SO4 and concentrated under reduced pressure. The reꢀ
sulting crude residue was used directly in the next step without
further purification. (ii) To a stirred solution of crude residue (obꢀ
tained above) in CH2Cl2 (2.5 mL) at room temperature was added
trifluoroacetic acid (1.0 mL). The resulting mixture was stirred for
1 h before it was quenched with sodium carbonate (5 mL, sat. aq.)
and extracted with CH2Cl2 (3 × 10 mL). The combined organic
layer was dried over anhydrous Na2SO4 and concentrated under
reduced pressure. The resulting residue was purified by flash colꢀ
umn chromatography (silica gel, hexanes:acetone 4:1) to afford
“putative” communesin 68 (1.8 mg, 36% over 2 steps) as a pale
Bis-Acetate Ac-68: To a stirred solution of amine 68a (2.2 mg,
6.0 µmol) in AcOH (0.30 mL) at 0 °C was added acetic anhydride
(0.30 mL). The resulting mixture was stirred for 15 min before it
was quenched with NaHCO3 (5 mL, sat. aq.) and extracted with
CH2Cl2 (3 × 10 mL). The combined organic layer was dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The
resulting residue was purified by flash column chromatography
(silica gel, hexanes:Acetone 3:1) to afford bisꢀacetate Ac-68 (2.2
mg, 82%) as a pale yellow oil. Ac-68: Rf = 0.23 (silica gel,
25
yellow foam. 68: Rf = 0.43 (silica gel, hexanes:EtOAc 1:2); [α]D
−205.7 (c = 0.23, CHCl3); IR (film) νmax 3738, 1746, 1651, 1507,
1318, 749 cm−1; 1H NMR (400 MHz, CDCl3 mixture of rotamers):
δ 7.02 (t, J = 7.2 Hz, 1H), 6.78 (t, J = 7.7 Hz, 1H), 6.70 (t, J = 8.0
Hz, 3H), 6.25 (d, J = 7.6 Hz, 0.3H), 6.19 (d, J = 7.7 Hz, 0.7H),
6.12 (d, J = 7.5 Hz, 1H), 5.48 (s, 0.4H), 5.38 (d, J = 8.4 Hz,
0.4H), 5.22 (d, J = 8.4 Hz, 0.6H), 5.11 (s, 0.6H), 5.07 (d, J = 8.8
Hz, 1H), 4.99 (s, 2H), 4.15 (br, 1H), 3.85 (dd, J = 11.4, 9.2 Hz,
0.8H), 3.69 (t, J = 9.4 Hz, 0.2H), 3.41−3.37 (m, 0.2H), 3.34 (dd, J
= 15.4, 9.4 Hz, 0.8H), 3.18−3.09 (m, 2H), 3.05 (td, J = 11.5, 7.7
25
hexanes:EtOAc 1:3); [α]D −6.80 (c = 0.28, CHCl3); IR (film)
νmax 2928, 1643, 1386, 1460, 1250, 752 cm−1; 1H NMR (400 MHz,
CDCl3, mixture of rotamers) δ 6.96 (dt, J = 11.0, 5.4 Hz, 2H),
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