1
Regioselective Synthesis of the Bridged Tricyclic Core of Garcinia Natural Products via Intramolecular Aryl Acrylate Cycloadditions Eric Tisdale, Chinmay Chowdhury, Binh G. Vong, Hongmei Li and Emmanuel A. Theodorakis*
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358 Supporting Information General techniques. Organic solutions were concentrated by rotary evaporation below 45 °C at about 20 mmHg. All nonaqueous reactions were carried out using flame-dried glassware, under an argon atmosphere in dry, freshly distilled solvents under anhydrous conditions, unless otherwise noted. THF and Et2O were distilled from sodium/benzophenone; CH2Cl2 and toluene from calcium hydride; and benzene from potassium. Pyridine, triethylamine and boron trifluoride etherate were distilled from calcium hydride prior to use. Yields refer to chromatographically and spectroscopically (1H NMR) homogeneous materials, unless otherwise stated. Reactions were monitored by thin-layer chromatography carried out on 0.25 mm E. Merck silica gel plates (60F254) using UV light as visualizing agent and p-anisaldehyde solution and heat as developing agents.
E. Merck silica gel (60, particle size 0.040-0.063 mm) was used for flash
chromatography. Preparative thin-layer chromatography separations were carried out on 0.25 or 0.50 mm E. Merck silica gel plates (60F-254). NMR spectra were recorded on a Varian 400 MHz instrument and calibrated using residual undeuterated solvent as an internal reference. IR spectra were recorded on a Nicolet Avatar 320 FT-IR spectrometer and values are reported in cm-1. High resolution mass spectra (HRMS) were recorded on a VG 7070 HS mass spectrometer under chemical ionization (CI) conditions or on a VG ZAB-ZSE mass spectrometer under fast atom bombardment (FAB) conditions. X-ray data were recorded on a Bruker SMART APEX 3kW Sealed Tube X-ray diffraction system.
2 Lactone 24. To a flask containing with Pb(OAc)4 (266.0 mg, 0.6 mmol) in anhydrous CH2 Cl2 (~10 mL) was added via a syringe freshly distilled O acrylic acid (2.2 mL, 32.0 mmol) and the solution was stirred for O approximately 10 minutes under argon at 25 °C. To the resulting colorless solution was added under argon at 25 °C via a cannula a solution of phenol O 24 23 (112.2 mg, 0.5 mmol) in CH 2 Cl2 (~10 mL) and the mixture was stirred for 10 min. to produce a bright yellow solution. The disappearance of the starting material was followed by TLC and was complete in about 10 min. At that moment, the reaction mixture was quenched with a few drops of ethylene glycol, concentrated and then dissolved in ether. The ethereal solution was washed with water (1 x 10 ml), NaHCO3 (aq) (3 x 10 ml) and brine (1 x 10 ml). The ethereal layer was then dried over MgSO 4 , filtered and concentrated under reduced pressure. The crude material was then dissolved in benzene, the reaction vessel placed on a pre-heated oil-bath (~100 °C) and the reaction mixture refluxed. The bright yellow color of the reaction mixture became less intense as the reaction progressed. When the reaction was judged to be complete by TLC (75% ether/hexane), it was concentrated and triturated with hexane to remove the yellow colored impurities. The white crystals that resulted were then recrystallized from hot cyclohexane to form short, white crystals of pure compound 24 (118.3 mg, 82%). 24: white solid; Rf = 0.19 (silica, 30 % ether/hexanes); IR (film) νmax 1791, 1747, 1631, 1451, 1228; 1 H NMR (400 MHz, CDCl3 ) δ 5.14 (m, 1H), 4.87 (d, 1H, J=7.2 Hz), 3.67 (s, 3H), 3.64 (s, 1H), 3.61 (s, 3H), 2.86 (dd, 1H, J=10.4 Hz, J=5.2 Hz), 2.58-2.43 (m, 2H), 2.06 (d, 1H, J=14.0 Hz), 1.95 (dd, 1H, J=14.4 Hz, J=10.4 Hz), 1.70(s, 3H), 1.62 (s, 3H); 13 C NMR (100 MHz, CDCl3 ) δ 196.8, 174.7, 160.2, 135.0, 118.5, 100.9, 89.6, 55.9, 55.4, 53.3, 41.3, 41.2, 34.1, 26.1, 24.9, 18.0; HRMS, calcd for C 16 H20 O5 (M +Na+) 315.1203, found 315.1205. MeO
OMe
Lactone 14. A round-bottomed flask was equipped with a reflux condenser and charged with the compound 17 (52.2 mg, 0.2 mmol) and m-xylene (2 mL). The reaction vessel was evacuated to remove oxygen, filled with argon, and then placed on a pre-heated oil bath (160 °C). O MeO OMe After refluxing for 45 minutes, TLC (75% ether/hexane) revealed the O reaction to be complete. The reaction mixture was concentrated and the product was purified by column chromatography using 40% ether/hexane O 14 as the solvent system. After evaporation of the eluant, short white needles corresponding to lactone 14 were observed and collected (48.1 mg, 92%). 14: white solid; Rf = 0.35 (silica, 75 % ether/hexanes); IR (film) νmax 1795, 1750, 1451, 1196, 993; 1 H NMR (400 MHz, CDCl3 ) δ 6.23 (d, 1H, J=9.2 Hz), 6.19 (d, 1H, J=9.6 Hz), 4.66 (m, 1H), 3.52 (s, 3H), 3.44 (s, 3H), 3.07 (d, 1H, J=10.8 Hz), 2.86 (dd, 1H, J=13.6 Hz, J=7.2 Hz), 2.64 (dd, 1H, J=13.6 Hz, J=8.8 Hz), 2.34 (d, 1H, J=13.2 Hz), 2.05 (dd, 1H, J=13.2 Hz, J=11.2 Hz), 1.61 (s, 6H); 13 C NMR (100 MHz, CDCl3 ) δ 195.8, 175.3, 136.0, 129.9, 128.8, 116.0, 85.8, 83.7, 82.5, 53.4, 52.2, 41.3, 33.1, 26.1, 26.0, 17.9; HRMS, calcd for C16 H20 O5 (M+Na +) 315.1203, found 315.1208.
3 X-Ray data of compound 24
Table 1. Crystal data and structure refinement for 24. Identification code ericm Empirical formula C16 H20 O5 Formula weight 292.32 Temperature 296(2) K Wavelength 0.71073 ≈ Crystal system Monoclinic Space group C2/c Unit cell dimensions a = 10.548(3) ≈ α= 90∞. b = 12.296(3) ≈ β= 99.532(4)∞. c = 23.831(6) ≈ γ = 90∞. Volume 3048.1(13) ≈3 Z 8 Density (calculated) 1.274 Mg/m3 Absorption coefficient 0.094 mm-1 F(000) 1248 Crystal size 0.40 x 0.20 x 0.20 mm3 Theta range for data collection 1.73 to 27.52∞. Index ranges -13<=h<=13, -15<=k<=15, -30<=l<=30 Reflections collected 12447 Independent reflections 3429 [R(int) = 0.0362] Completeness to theta = 27.52∞ 97.5 % Absorption correction None Max. and min. transmission 0.9814 and 0.9633 Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 3429 / 0 / 190 Goodness-of-fit on F2 1.715 Final R indices [I>2sigma(I)] R1 = 0.1379, wR2 = 0.4533 R indices (all data) R1 = 0.1945, wR2 = 0.4941 Largest diff. peak and hole 1.002 and -0.832 e.≈-3
4 Table 2. Atomic coordinates ( x 104 ) and equivalent isotropic displacement parameters (≈2 x 10 3 ) for 24. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. ________________________________________________________________________________ x
y
z
U(eq)
________________________________________________________________________________ O(1)
-790(3)
-5966(3)
-3760(2)
75(1)
O(2)
-1171(5)
-7644(3)
-4111(2)
114(2)
O(3)
-3271(4)
-5793(3)
-3423(2)
96(2)
O(4)
-237(8)
-3732(5)
-4216(3)
141(3)
O(5)
-1579(15)
-3882(5)
-5230(3)
286(8)
C(1)
-1520(5)
-6733(5)
-4078(3)
80(2)
C(2)
-2731(7)
-6206(5)
-4364(3)
103(2)
C(3)
-2490(11)
-5641(6)
-4915(3)
151(4)
C(4)
-2161(12)
-4418(6)
-4788(3)
145(4)
C(5)
-3265(15)
-3901(7)
-4623(5)
187(7)
C(6)
-3710(8)
-4362(6)
-4179(4)
130(4)
C(7)
-2920(5)
-5321(5)
-3918(3)
82(2)
C(8)
-1521(5)
-4970(4)
-3760(2)
66(1)
C(9)
-1188(9)
-4302(5)
-4260(3)
108(3)
C(10)
-1130(4)
-4435(4)
-3188(2)
63(1)
C(11)
-1852(5)
-3405(4)
-3116(2)
64(1)
C(12)
-2585(5)
-3212(4)
-2739(2)
72(2)
C(13)
-3328(8)
-2139(6)
-2757(3)
122(3)
C(14)
-2874(7)
-3989(6)
-2306(3)
102(2)
C(15)
-1810(12)
-3966(10)
-5695(5)
170(5)
C(16)
-4521(8)
-6257(8)
-3472(6)
192(6)
________________________________________________________________________________
5 Table 3. Bond lengths [≈] and angles [∞] for 24 _____________________________________________________ O(1)-C(1)
1.365(7)
O(1)-C(8)
1.447(5)
O(2)-C(1)
1.186(7)
O(3)-C(7)
1.419(8)
O(3)-C(16)
1.423(9)
O(4)-C(9)
1.213(10)
O(5)-C(15)
1.098(12)
O(5)-C(4)
1.460(13)
C(1)-C(2)
1.492(8)
C(2)-C(3)
1.544(11)
C(2)-C(7)
1.557(8)
C(3)-C(4)
1.561(11)
C(4)-C(5)
1.438(16)
C(4)-C(9)
1.494(11)
C(5)-C(6)
1.351(17)
C(6)-C(7)
1.516(10)
C(7)-C(8)
1.524(8)
C(8)-C(10)
1.509(7)
C(8)-C(9)
1.536(9)
C(10)-C(11)
1.502(7)
C(11)-C(12)
1.300(7)
C(12)-C(14)
1.475(9)
C(12)-C(13)
1.532(8)
C(1)-O(1)-C(8)
109.4(4)
C(7)-O(3)-C(16)
117.5(7)
C(15)-O(5)-C(4)
129.4(12)
O(2)-C(1)-O(1)
122.4(5)
O(2)-C(1)-C(2)
129.1(6)
O(1)-C(1)-C(2)
108.4(4)
C(1)-C(2)-C(3)
109.6(7)
C(1)-C(2)-C(7)
100.8(5)
C(3)-C(2)-C(7)
108.9(6)
C(2)-C(3)-C(4)
109.4(5)
C(5)-C(4)-C(9)
101.6(6)
6 C(5)-C(4)-O(5)
117.0(9)
C(9)-C(4)-O(5)
104.6(9)
C(5)-C(4)-C(3)
108.3(10)
C(9)-C(4)-C(3)
110.8(6)
O(5)-C(4)-C(3)
113.7(6)
C(6)-C(5)-C(4)
115.6(7)
C(5)-C(6)-C(7)
114.1(9)
O(3)-C(7)-C(6)
117.2(6)
O(3)-C(7)-C(8)
106.6(4)
C(6)-C(7)-C(8)
109.0(6)
O(3)-C(7)-C(2)
111.2(5)
C(6)-C(7)-C(2)
112.8(6)
C(8)-C(7)-C(2)
98.0(5)
O(1)-C(8)-C(10)
107.7(4)
O(1)-C(8)-C(7)
104.7(4)
C(10)-C(8)-C(7)
117.1(4)
O(1)-C(8)-C(9)
105.2(4)
C(10)-C(8)-C(9)
113.9(5)
C(7)-C(8)-C(9)
107.2(6)
O(4)-C(9)-C(4)
124.8(7)
O(4)-C(9)-C(8)
122.3(7)
C(4)-C(9)-C(8)
112.9(7)
C(11)-C(10)-C(8)
113.7(4)
C(12)-C(11)-C(10)
127.1(5)
C(11)-C(12)-C(14)
125.6(5)
C(11)-C(12)-C(13)
119.8(6)
C(14)-C(12)-C(13)
114.4(5)
_____________________________________________________________ Symmetry transformations used to generate equivalent atoms:
7 Table 4. Anisotropic displacement parameters (≈2 x 10 3 ) for 24. The anisotropic displacement factor exponent takes the form: -2π 2 [ h2 a*2 U11 + ... + 2 h k a* b* U12 ] ______________________________________________________________________________ U11
U22
U33
U23
U13
U12
______________________________________________________________________________ O(1)
75(2)
61(2)
89(3)
-16(2)
12(2)
16(2)
O(2)
126(4)
60(3)
149(4)
-28(3)
1(3)
29(2)
O(3)
64(3)
81(3)
145(4)
-32(3)
20(3)
-10(2)
O(4)
245(7)
84(3)
114(4)
-27(3)
90(4)
-41(4)
O(5)
690(30)
98(5)
60(4)
-3(3)
30(7)
-15(7)
C(1)
82(4)
60(3)
92(4)
-17(3)
3(3)
19(3)
C(2)
127(6)
62(4)
104(5)
-39(3)
-24(4)
23(3)
C(3)
279(12)
77(5)
75(5)
-29(4)
-36(6)
27(6)
C(4)
300(12)
61(4)
59(4)
-14(3)
-15(5)
31(6)
C(5)
322(17)
77(6)
113(7)
-33(5)
-106(9)
74(8)
C(6)
119(5)
75(5)
162(8)
-66(5)
-74(6)
40(4)
C(7)
68(3)
63(3)
104(4)
-31(3)
-23(3)
10(3)
C(8)
82(3)
49(3)
64(3)
-11(2)
6(2)
10(2)
C(9)
204(8)
53(3)
68(4)
-17(3)
30(5)
15(4)
C(10)
51(3)
75(3)
61(3)
-10(2)
1(2)
-2(2)
C(11)
72(3)
50(3)
67(3)
-14(2)
3(2)
-9(2)
C(12)
72(3)
64(3)
79(3)
-21(3)
10(3)
7(3)
C(13)
165(7)
84(5)
125(6)
-24(4)
43(5)
34(5)
C(14)
101(5)
106(5)
107(5)
-10(4)
34(4)
1(4)
C(15)
181(10)
205(12)
147(9)
-66(7)
90(8)
-25(7)
C(16)
78(5)
151(8)
349(18)
-110(10)
36(8)
-47(5)
______________________________________________________________________________
8 Table 5. Hydrogen coordinates ( x 104 ) and isotropic displacement parameters (≈2 x 10 3 ) for 24. ________________________________________________________________________________ x
y
z
U(eq)
________________________________________________________________________________
H(2A)
-3452
-6718
-4433
123
H(3A)
-3251
-5698
-5205
181
H(3B)
-1784
-5994
-5057
181
H(5A)
-3647
-3291
-4809
224
H(6A)
-4437
-4113
-4045
156
H(10A)
-1266
-4944
-2893
76
H(10B)
-218
-4272
-3136
76
H(11A)
-1767
-2844
-3369
77
H(13A)
-3091
-1680
-3049
183
H(13B)
-3125
-1780
-2395
183
H(13C)
-4234
-2284
-2838
183
H(14A)
-2381
-4641
-2324
154
H(14B)
-3774
-4163
-2377
154
H(14C)
-2656
-3669
-1935
154
H(15A)
-1199
-3561
-5868
256
H(15B)
-2659
-3691
-5826
256
H(15C)
-1772
-4720
-5796
256
H(16A)
-4639
-6549
-3110
289
H(16B)
-4610
-6828
-3750
289
H(16C)
-5155
-5706
-3588
289
________________________________________________________________________________
9 X-Ray data of compound 14
Table 1. Crystal data and structure refinement for 14 Identification code a Empirical formula C16 H20 O5 Formula weight 292.32 Temperature 100(2) K Wavelength 0.71073 Å Crystal system Orthorhombic Space group Pna2(1) Unit cell dimensions a = 6.7300(7) Å α= 90°. b = 27.296(3) Å β= 90°. c = 7.9110(9) Å γ = 90°. Volume 1453.3(3) Å3 Z 4 Density (calculated) 1.336 Mg/m3 Absorption coefficient 0.099 mm-1 F(000) 624 Crystal size 0.60 x 0.15 x 0.05 mm3 Theta range for data collection 1.49 to 27.53°. Index ranges -8<=h<=8, -35<=k<=35, -9<=l<=10 Reflections collected 11479 Independent reflections 3247 [R(int) = 0.0398] Completeness to theta = 27.53° 98.9 % Absorption correction None Max. and min. transmission 0.9951 and 0.9431 Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 3247 / 1 / 190 Goodness-of-fit on F2 1.035 Final R indices [I>2sigma(I)] R1 = 0.0431, wR2 = 0.1117 R indices (all data) R1 = 0.0504, wR2 = 0.1159 Absolute structure parameter 0.3(10) Largest diff. peak and hole 0.325 and -0.178 e.Å-3
10 Table 2. Atomic coordinates ( x 104 ) and equivalent isotropic displacement parameters (Å2 x 10 3 ) for 14. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. ________________________________________________________________________________ x
y
z
U(eq)
________________________________________________________________________________ O(1)
8118(2)
2648(1)
6082(2)
20(1)
O(2)
9189(2)
2307(1)
8482(2)
24(1)
O(3)
8283(2)
3071(1)
3542(2)
24(1)
O(4)
4966(2)
3403(1)
5166(2)
23(1)
O(5)
8138(2)
4595(1)
6439(2)
25(1)
C(1)
9083(3)
2659(1)
7600(3)
20(1)
C(2)
9853(3)
3172(1)
7895(2)
21(1)
C(3)
8179(3)
3485(1)
8680(3)
20(1)
C(4)
7076(3)
3782(1)
7283(2)
18(1)
C(5)
8610(3)
4114(1)
6469(3)
21(1)
C(6)
10229(3)
3892(1)
5870(3)
22(1)
C(7)
10239(3)
3346(1)
6063(3)
22(1)
C(8)
8359(3)
3129(1)
5252(3)
20(1)
C(9)
6568(3)
3437(1)
5825(2)
18(1)
C(10)
5200(3)
4036(1)
7935(3)
20(1)
C(11)
5484(3)
4303(1)
9563(3)
22(1)
C(12)
4746(3)
4182(1)
11068(3)
24(1)
C(13)
3486(4)
3738(1)
11384(3)
35(1)
C(14)
5156(4)
4486(1)
12606(3)
32(1)
C(15)
9496(3)
4902(1)
5547(3)
32(1)
C(16)
9823(3)
2771(1)
2807(3)
28(1)
________________________________________________________________________________
11 Table 3. Bond lengths [Å] and angles [°] for 14. _____________________________________________________ O(1)-C(1)
1.366(2)
O(1)-C(8)
1.476(2)
O(2)-C(1)
1.189(2)
O(3)-C(8)
1.363(3)
O(3)-C(16)
1.444(2)
O(4)-C(9)
1.201(2)
O(5)-C(5)
1.352(2)
O(5)-C(15)
1.425(2)
C(1)-C(2)
1.512(3)
C(2)-C(3)
1.545(3)
C(2)-C(7)
1.547(3)
C(3)-C(4)
1.558(3)
C(4)-C(5)
1.518(3)
C(4)-C(9)
1.528(3)
C(4)-C(10)
1.530(3)
C(5)-C(6)
1.334(3)
C(6)-C(7)
1.497(3)
C(7)-C(8)
1.538(3)
C(8)-C(9)
1.537(3)
C(10)-C(11)
1.493(3)
C(11)-C(12)
1.332(3)
C(12)-C(14)
1.498(3)
C(12)-C(13)
1.499(3)
C(1)-O(1)-C(8)
108.69(15)
C(8)-O(3)-C(16)
116.03(16)
C(5)-O(5)-C(15)
115.31(16)
O(2)-C(1)-O(1)
121.90(18)
O(2)-C(1)-C(2)
129.53(18)
O(1)-C(1)-C(2)
108.55(16)
C(1)-C(2)-C(3)
108.98(15)
C(1)-C(2)-C(7)
101.42(16)
C(3)-C(2)-C(7)
109.16(16)
C(2)-C(3)-C(4)
110.53(16)
C(5)-C(4)-C(9)
101.56(15)
12 C(5)-C(4)-C(10)
115.69(16)
C(9)-C(4)-C(10)
110.44(15)
C(5)-C(4)-C(3)
106.68(15)
C(9)-C(4)-C(3)
108.74(15)
C(10)-C(4)-C(3)
112.97(16)
C(6)-C(5)-O(5)
128.90(18)
C(6)-C(5)-C(4)
115.75(17)
O(5)-C(5)-C(4)
115.35(17)
C(5)-C(6)-C(7)
114.84(17)
C(6)-C(7)-C(8)
109.70(16)
C(6)-C(7)-C(2)
113.65(18)
C(8)-C(7)-C(2)
97.70(15)
O(3)-C(8)-O(1)
109.51(16)
O(3)-C(8)-C(9)
109.07(16)
O(1)-C(8)-C(9)
105.57(14)
O(3)-C(8)-C(7)
119.32(17)
O(1)-C(8)-C(7)
104.35(15)
C(9)-C(8)-C(7)
108.14(16)
O(4)-C(9)-C(8)
122.26(18)
O(4)-C(9)-C(4)
125.15(18)
C(8)-C(9)-C(4)
112.60(15)
C(11)-C(10)-C(4)
113.97(16)
C(12)-C(11)-C(10)
127.07(18)
C(11)-C(12)-C(14)
121.33(19)
C(11)-C(12)-C(13)
124.1(2)
C(14)-C(12)-C(13)
114.58(19)
_____________________________________________________________ Symmetry transformations used to generate equivalent atoms:
13 Table 4. Anisotropic displacement parameters (Å2 x 10 3 ) for 14. The anisotropic displacement factor exponent takes the form: -2π 2 [ h2 a*2 U11 + ... + 2 h k a* b* U12 ] ______________________________________________________________________________ U11
U22
U33
U23
U13
U12
______________________________________________________________________________ O(1)
20(1)
22(1)
19(1)
1(1)
-1(1)
-1(1)
O(2)
23(1)
26(1)
24(1)
4(1)
0(1)
1(1)
O(3)
24(1)
30(1)
18(1)
0(1)
3(1)
3(1)
O(4)
17(1)
29(1)
21(1)
1(1)
-2(1)
0(1)
O(5)
24(1)
22(1)
28(1)
3(1)
3(1)
-2(1)
C(1)
13(1)
25(1)
21(1)
0(1)
1(1)
2(1)
C(2)
18(1)
25(1)
19(1)
2(1)
-4(1)
1(1)
C(3)
17(1)
24(1)
18(1)
1(1)
-3(1)
-2(1)
C(4)
15(1)
23(1)
17(1)
-1(1)
-1(1)
0(1)
C(5)
19(1)
26(1)
18(1)
2(1)
-4(1)
-3(1)
C(6)
17(1)
26(1)
25(1)
3(1)
-1(1)
-5(1)
C(7)
15(1)
27(1)
23(1)
1(1)
2(1)
-1(1)
C(8)
20(1)
21(1)
21(1)
0(1)
0(1)
-1(1)
C(9)
19(1)
20(1)
16(1)
4(1)
-1(1)
-3(1)
C(10)
17(1)
25(1)
19(1)
2(1)
0(1)
0(1)
C(11)
20(1)
23(1)
24(1)
-1(1)
0(1)
-1(1)
C(12)
26(1)
26(1)
20(1)
0(1)
0(1)
4(1)
C(13)
49(1)
37(1)
19(1)
-1(1)
1(1)
-14(1)
C(14)
42(1)
30(1)
23(1)
-2(1)
-2(1)
-4(1)
C(15)
32(1)
25(1)
39(1)
5(1)
9(1)
-4(1)
C(16)
29(1)
31(1)
25(1)
-2(1)
7(1)
2(1)
______________________________________________________________________________
14 Table 5. Hydrogen coordinates ( x 104 ) and isotropic displacement parameters (Å2 x 10 3 ) for 14. ________________________________________________________________________________ x
y
z
U(eq)
________________________________________________________________________________
H(2A)
11088
3175
8598
25
H(3A)
8753
3714
9520
24
H(3B)
7223
3270
9272
24
H(6A)
11292
4066
5359
27
H(7A)
11475
3198
5585
26
H(10A)
4735
4271
7068
24
H(10B)
4146
3787
8088
24
H(11A)
6278
4590
9522
27
H(13A)
3286
3561
10321
53
H(13B)
2195
3840
11838
53
H(13C)
4152
3524
12201
53
H(14A)
5979
4767
12292
48
H(14B)
5858
4287
13446
48
H(14C)
3898
4601
13085
48
H(15A)
9035
5242
5596
48
H(15B)
9572
4796
4365
48
H(15C)
10814
4877
6067
48
H(16A)
9631
2752
1581
42
H(16B)
9757
2440
3291
42
H(16C) 11124 2915 3051 42 ________________________________________________________________________________
9
O
22
OMe
OMe
8
7.260 6.800 6.778 6.675 6.668
7
6.514
6.206
6
5.30 5.29 4.99 4.87
6.507 6.492 6.485 6.178 6.162 6.134 5.186 5.183
5
10.51
5.142 5.139 5.123 5.120 5.095 5.094
4 34.32
3.779 3.717
3 2 34.72
1.470
1 ppm
15
200
O
22
OMe
OMe
180 160 153.075 146.993 145.689
140
144.005
120 113.191 112.819 110.218
100
106.525
80.754
80
77.311 77.000 76.681
60
56.569 55.590
40 26.634
20 0 ppm
16
OMe
OMe
9
16
OH
8 7.260
7 1.11
6.652 6.630
1.09
6.347 6.325
6 0.90
5.719
1.02
5.243 5.240
5
5.237
3.00 3.13
4 3.831 3.770
2.14
3.377 3.360
3 2 2.98 2.762.94
1.780 1.671 1.565
1 ppm
17
16
OH
200
OMe
OMe
180 160 152.361 144.056
140
141.084
131.459
120
122.396 116.845
107.790
100
101.108
80
77.325 77.014 76.832 76.695
60
56.461 56.044
40 25.920
20
22.742 17.904
0 ppm
18
O
O
MeO
9
24
OMe O
8 7.260
7 6 5.160 5.123
5
0.05 0.05
5.141 4.878 4.860 3.670 3.636 3.614
4
2.880
0.33
2.867 2.854 2.841 2.578
0.05
3
2.560 2.540 2.522
0.10
2.481 2.463
2
0.10
2.444 2.425 2.076 0.31
2.041 1.979
0.01
1.953 1.943
1
1.918 1.695 1.616 1.247
ppm
19
24
OMe
200
O
O
MeO
196.797
O
180 174.713
160
160.159
140 135.018
120
118.454
100
100.943
89.552
80
77.319 77.000 76.689
60
55.863 55.416 53.308
40
41.302 41.226 34.052 26.134 24.943
20
18.049
0 ppm
20
9
O
O
26
OMe
OMe
OH
8 7.260
7 6.454 11.05
6.432 6.421 6.398
6 5.70
5.198
5 35.87 5.27
4
3.826 3.822
3 2 3.41 38.71
1.455 1.422 1.361
1 ppm
21
200
O
O
26
OMe
OMe
OH
180 160 143.300
140
143.072
132.045 129.959
120 103.089
100
102.224 93.624
80
77.319 77.000 76.689 74.520
60
56.402 56.197
40 30.396 22.797
20
22.061
0 ppm
22
MeO
OMe
9
27
OH
O
8 7 6.567 0.05 0.05 0.05
6.544 6.345 6.322 6.254
6
6.227 6.210
0.05
6.183 5.602
5
0.05 0.05
5.268 5.224 5.089 5.062
4 0.34
3.822 3.748 3.736
3 2 0.35
1.466 1.422 1.248
1 ppm
23
27
OH
O
200
MeO
OMe
180 160 149.033 143.702
140
141.988 141.388 132.492
120 112.933 106.487
100
101.762
90.067 82.498
80
77.319 77.000 76.681
60
56.493 55.969 55.765
40 30.396 29.759 26.559
20 0 ppm
24
MeO
8
9
O
O
17
O
OMe
7.260 6.725 6.704 6.651 6.628
7
6.622 6.619
0.15
6.579 6.576
6
0.04 0.05 0.05
6.390 6.363 6.346 6.320 6.149 6.122 6.106
5
0.05 0.05
6.078 6.009 6.006 5.982 5.980 5.134 5.091
4 0.31
4.973 4.971 4.946 4.944 3.763
3
3.759
2 0.32
1.428 1.413
1 ppm
25
O
O
17
O
200
MeO
OMe
180 160
163.041
149.147 146.219
140
143.421 138.787 135.617 132.204 127.593
120 112.281 109.134 106.434
100 82.847
80
77.319 77.000 76.681
60
56.356 56.326
40 26.718
20 0 ppm
26
MeO
9 14
O
O O OMe
8 7.260
7 6.247 6.244 9.25
6.224 6.221
6
6.199 6.175
4.685 4.683
5
4.668
4.69
4.664 4.650 4.647 4.643 3.519
4
3.444 3.085
28.80
3.058 2.887
3 2
5.34 5.61 5.02 5.45 5.56
2.869 2.853 2.836 2.664 2.642 2.630 2.609 2.360
30.29
2.327 2.078 2.050 2.045 2.017
1
1.610
ppm
27
200
MeO O
O
14
195.781
180
O OMe
175.304
160 140 136.049 129.853 128.837
120 116.035
100 85.760 83.674
80
82.529 77.319 77.000 76.689
60 53.444 52.185
40
41.302
33.104 26.134 26.013
20
17.883
0 ppm
28
