Enantioselective photocycloaddition of 3-hydroxyflavones: Total syntheses and absolute configuration assignments of (+)-ponapensin and (+)-elliptifoline

Article abstract of DOI:10.1021/ja305342f

We have previously reported development of biomimetic, asymmetric [3 + 2] photocycloadditions between 3-hydroxyflavones and cinnamate dipolarophiles to access (-)-rocaglamide and related natural products. Herein, we describe enantioselective syntheses of

Full text of DOI:10.1021/ja305342f

Supporting Information
Enantioselective Photocycloaddition of 3-Hydroxyflavones: Total Syntheses
and Absolute Configuration Assignments of (+)-Ponapensin and (+)-
Elliptifoline
Neil J. Lajkiewicz, Stéphane P. Roche, Baudouin Gerard, and John A. Porco, Jr.*
Department of Chemistry and Center for Chemical Methodology and Library
Development (CMLD-BU), Boston University, Boston, MA 02215, United States
E-mail: porco@bu.edu
Table of Contents
I. GENERAL INFORMATION…………………………………………………………………….……...S2
A. Instrumentation and methods..........................................................................................................S2
II. EXPERIMENTAL PROCEDURES AND COMPOUND CHARACTERIZATION…………...…..S3
A. Preparation of Reduced Aglains in Racemic Form………………………………………..……...S3
1
2
3
. [3+2] Photocycloaddition
S3
S3
S7
. Reagent-Controlled Reduction of Aglain
. Transesterification and Ester-Amide Exchange Protocols
B. General Protocols to Access TADDOL Additives……………...……………………………...…S9
C. Compound Characterization toward (+)-Ponapensin and (+)-Elliptifoline…...……….……..….S11
D. X-Ray Crystallographic Data……………………………………………………………………S24
E. Calculations for Cyclic Intermediate (21) and Acyliminium Intermediate (22)………………...S56
F. Select Spectra…..………………………………………………………………………………...S60
III. NATURAL PRODUCT SPECTRA…………………………………………………..……..…….…S76
S1

I. GENERAL INFORMATION
A. Instrumentation and methods
1
3 3
H NMR spectra were recorded at 300, 400, or 500 MHz at ambient temperature with CDCl , CD OD,
1
DMSO-d
6
or benzene-d
6
(Cambridge Isotope Laboratories, Inc.) as solvents. Data for H NMR are reported
as follows: chemical shift, integration, multiplicity (br = broad, ovrlp = overlapping, s = singlet, d = doublet,
1
3
t = triplet, q = quartet, m = multiplet) and coupling constants in Hz. C NMR spectra were recorded at 75.0,
1
00.0, or 125 MHz at ambient temperature with the same solvents unless otherwise stated. Chemical shifts
1
3
are reported in parts per million relative to the deuterated solvents. All C NMR spectra were recorded with
complete proton decoupling. Infrared spectra were recorded on a Nicolet Nexus 670 FT-IR
spectrophotometer. High-resolution mass spectra were obtained in the Boston University Chemical
Instrumentation Center using a Waters Q-TOF API-US mass spectrometer. Melting points were recorded on
a Mel-Temp apparatus (Laboratory Devices). Analytical LC-MS was performed on a Waters Acquity UPLC
(Ultra Performance Liquid Chromatography (Waters MassLynx Version 4.1) with a Binary solvent manager,
SQ mass spectrometer, Water 2996 PDA (PhotoDiode Array) detector, and ELSD (Evaporative Light
Scattering Detector). An Acquity UPLC BEH C18 1.7 μm column was used for analytical UPLC-MS.
Optical rotations were recorded on an AUTOPOL III digital polarimeter at 589 nm, and specific rotations
2
0
are given [α]
D
(concentration in grams/100 mL solvent). SFC analysis of enantioenriched compounds was
®
performed on a Berger SFC (Waters) System with a diode array detector using a SFC Chiralcel OD-H
(Chiral Technologies Inc., 100 × 4.6 mm I.D., 5µm) column. CD spectra were measured on an AVIV
Circular Dichroism Spectrometer, Model 62DS. Preparative HPLC was performed on a Gilson PLC2020
using a Waters SunFire™ Prep C18 OBD™ 5µm 19X50 mm column.
Analytical thin layer chromatography was performed using 0.25 mm silica gel 60-F plates. Flash
chromatography was performed using 200-400 mesh silica gel (Scientific Absorbents, Inc.). Yields refer to
chromatographically and spectroscopically pure materials, unless otherwise stated. HPLC grade
tetrahydrofuran, methylene chloride, diethyl ether, toluene, acetonitrile, and benzene were purchased from
®
Fisher and VWR and were purified and dried by passing through a PURE SOLV solvent purification
system (Innovative Technology, Inc.). Other ACS grade solvents for chromatography were purchased from
Clean Harbors.
Fluorescence emission spectra were recorded using a quartz cuvette at room temperature using a
fluorimeter (Jobin Yvon Horiba FluoroMax 3). Select photochemistry experiments were performed using a
Rayonet RPR-100 photochemical reactor equipped with RPR-3500 irradiation lamps (UVA 315-400 nm).
Photochemical reactions were performed in a photobox using a Hanovia 450 W medium pressure mercury
lamp housed in a quartz immersion well, cooled with a Thermo Neslab-ULT 80 system circulator. Pyrex test
S2

tubes (16 x 100 mm) were mounted on a support approximately 5.0 cm from the immersion well lamp. A
uranium filter (hν > 350 nm) was obtained from James Glass (Hanover, MA). All other reactions were
carried out in oven-dried glassware under an argon atmosphere unless otherwise noted.
II. EXPERIMENTAL PROCEDURES AND COMPOUND CHARACTERIZATION
A. Preparation of Reduced Aglains in Racemic Form
1
. [3+2] Photocycloaddition.
RO C
2
Procedure for [3+2] Photo-cycloaddition of
3-HF 5 and Cinnamic Esters 6a-b (8a-b): A
32 x 240 mm Pyrex test tube was charged
with 3-hydroxyflavone 5 (1.0 g, 3.04 mmol,
5
equiv.
1
Ph
O
HO
6
a, b
MeO
OR
MeO
O
equiv. Ph CO,
2
HO OH
O
OH
hν (300 < λ < 400 nm), MeO
MeO
O
CH Cl /CF CH OH (7:3),
2
2
3
2
5
0 °C, 10 h
OMe
OMe
1
.0 equiv.), benzophenone (555 mg, 3.04
8
a, R = Me, 61% yield, 3:1 dr
b, R = Bn, 60% yield, 3:1 dr
8
mmol, 1.0 equiv.) and dipolarophile 6a-b
(15.2 mmol, 5.0 equiv.) in CH
2
Cl
2
-TFE (7:3, 75 mL) as solvent. After degassing with argon for 10 min, the
o
mixture was stirred and irradiated (Rayonet, λ > 315 nm) at 0 C for 12 h. The crude material was
concentrated under vacuum and the resulting oil was directly chromatographed on SiO
decomposition was observed during chromatographic purification on silica gel. Accordingly, the SiO
first washed successively with (80:20:03 hexanes/EtOAc/Et N, one length) and (80:20 hexanes/EtOAc, one
2
. Note:
2
was
3
length) to neutralize surface silanols. Purification via flash chromatography using a gradient of
hexanes/EtOAc afforded cyclopenta[bc]benzopyrans 8a-b as mixture of isomers (61% yield 8a, 60% 8b).
f
This mixture was recrystallized in acetonitrile to afford pure 8a-b (27% 8a, 24% 8b). 8b: White solid; R =
0
1
.44 (1:1 EtOAc/hexanes); m.p. 110-114 ºC; IR νmax (film): 3484, 3014, 2939, 2840, 1731, 1618, 1590,
-
1 1
3
517, 1490, 1456, 1252, 1217, 1148, 1094, 1003, 980, 831, 754 cm ; H NMR (500 MHz, CDCl ) δ 7.56
(d, J = 9.0 Hz, 2H), 7.33-7.30 (br dd, J = 6.5, 6.5 Hz, 3H), 7.27-7.22 (overlapping m, 3H), 7.18 (d, J = 6.5
Hz, 2H), 7.05 (dd, J = 6.8, 6.8 Hz, 2H), 7.01 (brt, J = 6.8 Hz, 1H), 6.65 (d, J = 9.0 Hz, 2H), 6.21 (d, J = 2.2
Hz, 1H), 6.03 (d, J = 2.2 Hz, 1H), 5.89 (s, 1H), 5.05 (d, J = 12.8 Hz, 1H), 4.94 (d, J = 12.8 Hz, 1H), 4.24 (d,
1
3
J = 9.2 Hz, 1H), 3.79 (d, J = 9.2 Hz, 1H), 3.77 (s, 3H), 3.70 (s, 3H), 3.57 (s, 3H), 3.18 (s, 1H); C NMR
(125 MHz, CD
3
Cl) δ 171.3, 161.5, 158.9, 158.6, 153.8, 140.0, 135.9, 130.2 (2C), 130.0 (2C), 128.7 (2C),
1
5
28.2 (2C), 128.1 (2C), 127.7 (2C), 126.7, 112.9 (2C), 103.7, 98.1, 94.7, 93.0, 88.0, 81.4, 66.7, 63.0, 55.8,
+
32 9
5.5, 55.2, 54.7; HR-MS: m/z Calcd for [C34H O +Na] 607.1844, found 607.1825 (-3.1 ppm).
2
. Reagent-Controlled Reduction
Screening for diastereoselective reduction at C10: Entry 2 (Table SI-1) shows that solubilization in THF
was necessary to generate a reaction with sodium borohydride. Counterion size does not affect the
−
+
+
diastereoselectivity of BH
4
reductions as shown in entries 2 and 3 (Na vs. Bu
4
N , respectively). Entry 4
shows that addition of cerium chloride reduces the diasteroselectivity of the NaBH
4
reduction. Entries 5
S3

through 8 examine the effect of solvent on the Me
4
NBH(OAc)
3
reduction. Entry 9 shows that a smaller
NBH(OAc) reduction.
+
counterion (Na ) yields better diastereoselectivity of 9a than the corresponding Me
4
3
Although not shown, temperature marginally affects the diastereoselectivity of these reductions.
Table
SI-1.
Conditions
Evaluated
for
Reduction
of
Hydrated
Aglain
8
a
O
O
O
HO
HO
HO
MeO
MeO
MeO
OMe Conditions
OMe
OMe
H
H
HO OH
OH
HO 1
O
0R
1
0
10S
MeO
MeO
MeO
O
O
(±)-8a
OMe
(±)-9a
OMe
(±)-10a
OMe
T
(
Time
Conversion
(%)
a
Entry Reagent
Additive
Equiv Solvent
o
9a:10a
b
C)
(h)
24
12
24
24
24
24
24
24
24
1
2
3
4
5
6
7
8
9
NaBH
NaBH
4
4
-
75
5
MeOH
THF
0-rt
0-rt
0-rt
0-rt
rt
-
0
-
1:5
1:5
1:2
3.1:1
4:1
5:1
4:1
10:1
100 (93)
100 (98)
100 (88)
100 (95)
100 (95)
100 (95)
100 (95)
100 (95)
Bu
4
NBH
4
-
5
THF
NaBH
4
CeCl
3
5, 1.2 THF
Me
Me
Me
Me
4
4
4
4
NBH(OAc)
NBH(OAc)
NBH(OAc)
NBH(OAc)
3
3
3
3
AcOH
AcOH
AcOH
AcOH
AcOH
6, 6
6, 6
6, 6
6, 6
6, 6
PhH
PhMe
rt
PhCF
CH Cl
PhCF
3
rt
2
2
rt
NaBH(OAc)
3
3
rt
1
1
[
a] Determined by H NMR; [b] Based on crude H NMR analysis; isolated yields are in parentheses.
General Procedure A (Entries 1 through 4): A dry flask was charged with a stir bar and hydrated aglain
a (20 mg, 0.039 mmol, 1 equiv.) under argon, which was then dissolved in the corresponding solvent (2
mL). The resulting solution was then chilled to 0 °C, and the corresponding additive (CeCl ·7H O, 17 mg,
.0468 mmol, 1.2 equiv.) and reducing agent (0.195 mmol, 5 equiv.) were sequentially added in one portion.
8
3
2
0
The reaction was warmed gradually to rt and stirred for the designated time. The reaction was quenched with
saturated ammonium chloride, and ethyl acetate (1 mL) and water (0.5 mL) were added. The organic phase
was then extracted with EtOAc (2 X 10 mL), washed with brine, and dried over sodium sulfate. The filtrate
was concentrated in vacuo and purified by column chromatography to give the corresponding products (9a
2 2 2 2
eluted at 5:95 EtOAc/CH Cl , 10a at 10:90 EtOAc/CH Cl ).
General Procedure B (Entries 5 through 9): A dry flask was charged with a stir bar, reducing agent (0.24
mmol, 6 equiv.), acetic acid (13 µL, 0.24 mmol, 6 equiv.), and solvent (1.5 mL) at rt under argon. The
S4

mixture was then sonicated briefly and stirred at rt for 10 min. The hydrated aglain 8a (20 mg, 0.039 mmol,
.0 equiv) was then added at rt in one portion under argon. The resulting mixture was then stirred for 24 h
1
and was quenched with saturated ammonium chloride. Entries 5 and 6 were extracted with EtOAc, washed
with saturated sodium bicarbonate and brine, and dried over sodium sulfate. Entries 7 through 9 were
extracted with CH
2
Cl
2
, washed with saturated sodium bicarbonate, and dried over sodium sulfate. The
1
filtrate was concentrated in vacuo and H NMR analysis of the crude extract was taken. Column
chromatography was used to purify the compounds (9a eluted at 5:95 EtOAc/CH
2 2
Cl , 10a at 10:90
EtOAc/CH Cl ).
2
2
Procedure
for
Converting Hydrated-
Aglain 8a to ketone
form 11: A dry flask was
charged with a stir bar,
hydrated-aglain 8a (60
mg, 0.12 mmol, 1.0 equiv.), and 4Å molecular sieves (750 mg) in CH
2
Cl
2
(5 mL) under argon. The mixture
1
was stirred for 24 h at room temperature, and formation of the ketone was monitored by H NMR. The
sieves were filtered using a plug of Celite, and the filtrate was concentrated in vacuo to afford the ketone 11
without any purification (58 mg, 0.12 mmol, 100%). White solid; R
f
= 0.42 (3:2 EtOAc/hexanes); m.p. 88
ºC; IR νmax (film): 3496, 3018, 2952, 2840, 1784, 1734, 1616, 1589, 1517, 1495, 1456, 1437, 1337, 1298,
-
1 1
1
7
6
3
253, 1216, 1201, 1161, 1146, 1092, 820, 748 cm ; H NMR (500 MHz, CDCl ) δ 7.26 (d, J = 9.2 Hz, 2H),
.03 (br dd, J = 7.5, 6.5 Hz, 2H), 7.00 (t, J = 7.5 Hz, 1H), 6.85 (d, J = 6.5 Hz, 2H), 6.64 (d, J = 9.2 Hz, 2H),
.19 (d, J = 2.5 Hz, 1H), 6.13 (d, J = 2.5 Hz, 1H), 5.80 (s, 1H), 4.50 (d, J = 9.0 Hz, 1H), 3.85 (s, 3H), 3.77
1
3
(
s, 3H), 3.67 (s, 3H), 3.64 (s, 3H), 3.59 (d, J = 9.0 Hz, 1H); C NMR (125 MHz, CDCl
3
) δ 205.5, 170.8,
1
9
5
62.1, 158.9, 158.2, 153.1, 138.3, 129.0 (2C), 128.9 (2C), 128.3 (2C), 127.1, 125.7, 112.9 (2C), 105.0, 94.6,
+
26 8
3.7, 83.9, 81.0, 57.7, 56.3, 55.6, 55.2, 53.5, 52.4; HR-MS: m/z Calcd for [C28H O +Na] 513.1525, found
13.1529 (+0.8 ppm).
Compound 9a was prepared and purified according to general procedure B
from Table SI-1, Entry 9 listed above. White solid; R = 0.88 (1:9
EtOAc/CH Cl ); m.p. 206-209 ºC; IR νmax (film): 3427, 2952, 1729, 1617,
516, 1456, 1250, 1214, 1186, 1148, 1120, 1079, 831, 752 cm ; H NMR
400 MHz, CDCl ) δ 7.41 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 6.8, 2H), 7.05 (dd,
f
2
2
-
1
1
1
(
3
J = 6.8, 6.8 Hz, 2H), 7.01 (br t, J = 6.8 Hz, 1H), 6.67 (d, J = 9.0 Hz, 2H), 6.09
S5

(d, J = 2.4 Hz, 1H), 6.07 (d, J = 2.4 Hz, 1H), 5.63 (s, 1H), 4.78 (s, 1H), 4.37 (d, J = 9.2 Hz, 1H), 3.85 (s, 3H),
1
3
3
1
9
5
3
.79 (d, J = 9.2 Hz, 1H), 3.73 (s, 3H), 3.70 (s, 3H), 3.60 (s, 3H), 3.35 (s, 1H); C NMR (125 MHz, CDCl ) δ
72.3, 161.3, 158.8, 157.9, 153.8, 141.6, 130.3 (2C), 130.2 (2C), 129.9, 128.1 (2C), 126.3, 113.0 (2C), 104.7,
+
28 8
4.4, 92.5, 89.1, 80.5, 79.2, 65.2, 56.8, 56.0, 55.4, 55.2, 51.8; HR-MS: m/z Calcd for [C28H O +Na]
15.1682, found 515.1699 (+3.3 ppm).
Compound 10a was prepared and purified according to general procedure
A from Table SI-1, Entry 3 listed above. White solid; R = 0.41 (1:9
EtOAc/CH Cl ); m.p. 200+ ºC, decomposition observed; IR νmax (film):
476, 2952, 1792, 1732, 1617, 1589, 1516, 1438, 1235, 1095, 737 cm ; H
NMR (500 MHz, CDCl ) δ 7.28 (d, J = 8.8 Hz, 2H), 7.02 (dd, J = 7.5, 7.2
f
2
2
-
1 1
3
3
Hz, 2H), 6.96 (br t, J = 7.2 Hz, 1H), 6.66 (d, J = 8.8 Hz, 2H), 6.23 (d, J =
2
3
.2 Hz, 1H), 6.12 (d, J = 2.2 Hz, 1H), 5.88 (s, 1H), 4.82 (d, J = 6.2 Hz, 1H), 4.10 (d, J = 9.0 Hz, 1H), 3.86 (s,
1
3
H), 3.77 (s, 3H), 3.68 (s, 3H), 3.59 (s, 3H), 3.33 (d, J = 9.0 Hz, 1H), 2.39 (d, J = 6.2 Hz, 1H); C NMR (100
) δ 171.3, 161.2, 159.4, 158.9, 154.0, 139.9, 129.31 (2C), 129.27, 128.7 (2C), 128.2 (2C), 126.6,
13.3 (2C), 102.4, 94.4, 93.0, 87.4, 80.2, 73.7, 62.0, 56.0, 55.5, 55.2, 54.7, 51.9; HR-MS: m/z Calcd for
MHz, CDCl
3
1
+
28 28 8
[C H O +H] 493.1862, found 493.1861 (-0.2 ppm).
Compound 9b was prepared and purified according to general procedure B
listed above (NaBH(OAc) , dr 10:1, 92% 9b). White solid; R = 0.70 (1:1
EtOAc/hexanes); m.p. 90-96 ºC; IR νmax (film): 3517, 3478, 3015, 1736,
3
f
1
9
2
616, 1588, 1519, 1464, 1341, 1257, 1217, 1202, 1179, 1129, 1094, 1036,
-
1
1
80, 948, 824, 750 cm ; H NMR (500 MHz, CDCl
3
) δ 7.42 (d, J = 8.5 Hz,
H), 7.35-7.29 (overlapping m, 1H), 7.33 (d, J = 7.0 Hz, 2H), 7.26-7.23 (ovrlp
m, 4H), 7.06 (dd, J = 7.0, 7.0 Hz, 2H), 7.02 (t, J = 7.0 Hz, 1H), 6.67 (d, J = 8.5 Hz, 2H), 6.10 (d, J = 2.0 Hz,
1
4
H), 6.01 (d, J =2.0 Hz, 1H), 5.72 (s, 1H), 5.07 (d, J = 12.8 Hz, 1H), 4.96 (d, J = 12.8 Hz, 1H), 4.79 (s, 1H),
1
3
.42 (d, J = 9.0 Hz, 1H), 3.89 (d, J = 9.0 Hz, 1H), 3.74 (s, 3H), 3.70 (s, 3H), 3.58 (s, 3H), 3.42 (s, 1H); C
NMR (125 MHz, CDCl
3
) δ 171.8, 161.4, 158.9, 158.0, 153.9, 141.6, 136.0, 130.3 (4C), 129.9, 128.7 (2C),
1
5
28.12, 128.10, 127.7 (2C), 126.3, 113.0 (2C), 104.7, 94.5, 92.6, 89.2, 80.6, 79.3, 66.5, 65.4, 56.9, 55.8, 55.5,
+
32 8
5.2; HR-MS: m/z Calcd for [C34H O +Na] 591.1995, found 591.1981 (– 2.4 ppm).
O
HO
Compound 15 was prepared and purified according to general procedure B listed
above (NaBH(OAc) , dr 8:1, 90%). White solid; R = 0.49 (1:1 EtOAc/hexanes);
OMe
H
O
OH
3
f
m.p. 220+ °C decomposition observed; IR νmax (film): 3458, 3034, 1701, 1608,
1
5
C H O
5
S6
2
5
22
MW = 402.44
g/mol

-
1 1
1
586, 1499, 1482, 1456, 1435, 1277, 1236, 1181, 1153, 1080, 1061, 1034, 1014, 993, 961 cm ; H NMR
400 MHz, (CD SO) δ 7.45 (dd, J = 7.4, 1.4 Hz, 2H), 7.31 (br d, J = 7.4 Hz, 1H), 7.24 (d, J = 7.4 Hz, 2H),
.17-6.95 (ovrlp m, 8H), 6.88 (dd, J = 7.4 Hz, 1H), 6.72 (d, J = 7.4 Hz, 1H), 6.46 (d, J = 4.2 Hz, 1H), 5.99 (s,
(
3 2
)
7
1
1
3
H), 4.51 (d, J =4.2 Hz, 1H), 4.27 (d, J = 8.6 Hz, 1H), 3.71 (d, J = 8.6 Hz, 1H), 3.44 (s, 3H); C NMR (100
MHz, (CD
3
)
2
SO) δ 171.7, 151.4, 142.0, 138.4, 129.9 (2C), 128.94 (2C), 128.87, 127.7 (2C), 127.3, 127.0
+
22 5 2
(3C), 126.0, 124.7, 120.0, 114.9, 89.0, 79.3, 77.0, 64.0, 56.6, 51.4; HR-MS: m/z Calcd for [C25H O −H O]
3
85.1440, found 385.1456 (+ 4.2 ppm).
O
Compound 16 was prepared and purified according to general procedure A listed
above (Bu NBH , dr 7:1, 73%). White solid; R = 0.27 (1:1 EtOAc/hexanes); m.p.
7 °C; IR νmax (film): 3452, 3060, 3033, 2940, 1736, 1608, 1584, 1483, 1452,
HO
OMe
4
4
f
H
HO
7
1
O
-
1 1
3
210, 905 cm ; H NMR (400 MHz, CDCl ) δ 7.38 (ovrlp d, J = 7.2 Hz, 3H), 7.28
1
6
(
ddd, J = 8.0, 8.0, 1.2 Hz, 1H), 7.17-6.95 (ovrlp m, 10H), 4.93 (d, J = 8.2 Hz, 1H),
.19 (d, J = 9.0 Hz, 1H), 3.65 (s, 1H), 3.57 (s, 3H), 3.47 (d, J = 9.0 Hz, 1H), 2.38
d, J = 8.2 Hz, 1H); C NMR (125 MHz, CDCl ) δ 170.7, 151.7, 139.6, 136.7, 130.1, 129.2 (2C), 128.2 (2C),
27.91 (2C), 127.85, 127.3 (2C), 126.8, 126.0, 123.7, 121.5, 116.3, 88.2, 78.2, 73.9, 60.0, 54.5, 52.5; HR-
C H O
2
5
22
5
MW = 402.44 g/mol
4
1
3
(
3
1
+
22 5
MS: m/z Calcd for [C25H O +Na] 425.1365, found 425.1355 (− 2.3522 ppm).
3
. Transesterification and Ester-Amide Exchange Protocols
Protocol for transesterification of (±)-9a to (±)-
b: To a solution of aglain methyl ester (±)-9a (25
9
mg, 0.05 mmol, 1 equiv.) in toluene (1.0 mL),
benzyl alcohol (520 µL, 5.0 mmol, 100 equiv.) and
72 4 2 4 4
Otera’s catalyst (C36H N O S Sn , 12 mg, 0.01
mmol, 0.2 equiv.) were added under argon at room temperature. The resulting slurry was then heated at 110
o
C under house vacuum for 24 h. The resulting yellow solution was distilled under high vacuum to remove
excess benzyl alcohol and afford the crude product as an oil. The crude material was purified by flash
chromatography using a gradient EtOAc/hexanes 20:80 to 60:40 affording the corresponding pure aglain 9b
as a white solid (18 mg, 0.032 mmol, 64%) along with recovered starting aglain 9a (7 mg, 0.014 mmol, 28%).
f
R = 0.70 (1:1 EtOAc/hexanes); Other spectroscopic data of compound 9b are listed above.
O
O
Ester-amide exchange protocol to
access amido acetal (±)-19. To a
solution of amine 18 (637 mg, 4.78
mmol, 20 equiv.) in toluene (1.0 mL)
HO
HO
MeO
MeO
OMe
N
H
OMe
OMe
ester-amide
exchange
H
OH
H
OH
MeO
MeO
O
OMe
O
H N
2
19
(
)3 OMe
9
a
C33H39O9
1
8
MW = 593.66
OMe
OMe
S7

under argon and at rt was added dropwise a solution of trimethylaluminum [2M] (2.4 mL, 4.79 mmol, 20
o
equiv.). The resulting solution was heated at 40 C for 1 h to preform the corresponding dimethylaluminum
amide. Then a solution of aglain methyl ester (±)-9a (110 mg, 0.223 mmol, 1 equiv.) in toluene (6.5 mL) was
o
added via cannula, and the reaction mixture was heated at 70 C for 12 h. The reaction mixture was quenched
at 0 °C with saturated ammonium chloride (4 mL), stirred for 1 h, then extracted with EtOAc (3 X 10 mL).
2 4
The combined organic layers were washed with brine, dried over Na SO , and filtered. The solvent was
removed in vacuo to afford a crude white yellow solid. Purification via flash chromatography using a gradient
of EtOAc/hexanes 1:4 to 4:1 afforded accordingly the corresponding pure amide (±)-19 (97 mg, 0.163 mmol,
7
3%). White solid; R
617, 1589, 1517, 1467, 1439, 1252, 1214, 1201, 1183, 1148, 1129, 1075, 830, 752 cm ; H NMR (500
) δ 7.40 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 7.2 Hz, 2H), 7.03 (br dd, J = 7.2, 7.2 Hz, 2H), 6.97 (br t,
J = 7.2 Hz, 1H), 6.67 (d, J = 9.0 Hz, 2H), 6.08 (d, J = 2.2 Hz, 1H), 6.06 (d, J = 2.2 Hz, 1H), 5.90 (s, 1H), 5.74
br dd, J = 5.5, 5.5 Hz), 4.75 (s, 1H), 4.48 (br d, J = 9.0 Hz, 1H), 4.30 (dd, J = 5.5, 5.5 Hz, 1H), 3.84 (s, 3H),
f
= 0.22 (EtOAc/hexanes 4:1); m.p. 98 ºC; IR νmax (film): 3405, 2941, 2837, 1661,
-
1
1
1
MHz, CDCl
3
(
3
6
1
9
.72 (s, 3H), 3.70 (s, 3H), 3.53 (d, J = 9.0 Hz, 1H), 3.18 (ddd, J = 13.5, 7.5, 5.5 Hz, 1H) 3.12 (ddd, J = 13.5,
1
3
3
.5, 5.5 Hz, 1H), 1.56-1.51 (ovrlp m, 2H), 1.51-1.45 (ovrlp m, 2H); C NMR (125 MHz, CDCl ) δ 169.8,
61.2, 158.8, 157.8, 154.0, 142.0, 130.3 (2C), 130.2 (2C), 130.1, 128.0 (2C), 126.1, 113.0 (2C), 104.4, 104.3,
4.7, 92.5, 89.2, 81.0, 79.6, 66.2, 56.1, 55.9, 55.4, 55.2, 53.15, 53.07, 39.5, 30.1, 24.8; HR-MS: m/z Calcd for
+
[C
33
H
39
O
9
+H] 594.2703, found 594.2704 (+0.17 ppm).
S8

B. General Protocols to Access TADDOL Additives
Preparation of dimethyl 2,3-O-cyclohexylidene-L-
tartrate SI-1: To a solution of L-dimethyl tartrate
L-dimethyl tartrate
MeO OMe
BF •Et O
3
2
O
O
(
9.82 g, 55.1 mmol, 1.5 equiv.) in 1,2-
DME, -30 °C → rt
H
H
MeO C
CO Me
o
2
2
dimethoxyethane (DME) (150 mL) at -30 C under
SI-1
inert atmosphere was added successively 1,1-
dimethoxycyclohexane (5.3 g, 36.75 mmol, 1.0 equiv.) and BF
3
·Et
2
O (5.45 mL, 44.1 mmol, 1.2 equiv.)
o
dropwise. The resulting mixture was then stirred for 3 h having the temperature raised from -30 C to RT. The
o
reaction was then cooled to 0 C and carefully quenched with sat. aqueous NaHCO
3
solution. The organic
layer was then separated and the aqueous phase was extracted with EtOAc (3 X 400 mL). The combined
organic phases were washed with water (2 X 400 mL) and brine (1 X 400 mL). The combined organic
2 4
extracts were dried over Na SO , filtered, and concentrated in vacuo to afford a crude oil, which was further
purified by flash chromatography (gradient of EtOAc/hexanes 2:98 to 15:85) affording pure SI-1 as a
colorless oil (8.07 g, 31.23 mmol, 85%) which was spectroscopically identical to a previously reported
S1
1
compound. R
f
= 0.12 (EtOAc/hexanes 10:90); H NMR (500 MHz, CDCl
3
) δ 4.73 (s, 2H), 3.74 (s, 6H),
1
3
1
3
.60 (m, 8H), 1.33 (m, 2H); C NMR (125 MHz, CDCl ) δ (ppm): 170.2 (2C), 114.5, 76.6 (2C), 52.6 (2C),
3
2
0
o
S2
20
o
5.7 (2C), 24.7, 23.6 (2C); [α]
D
= –26.9 (c = 2.00, CHCl
3
); literature report [α]
D
= –19.8 (c = 2.00,
CHCl
3
).
Grignard addition to produce (R, R)-2,2-
RMgCl (5 equiv.),
THF, 12 h,
cyclohexyl-α, α, α', α'-tetrakis(phenanthren-
O
O
O
O
S2
9-yl)-1,3-dioxolane-4,5-dimethanol 17.
A
H
H
H
H
-20 °C to RT
R
R
R
R
MeO C
CO Me
2
2
solution of SI-1 (1.00 g, 3.87 mmol, 1.0
equiv.) in THF (10 mL) was added dropwise to
a solution of (phenanthren-9-yl)magnesium
bromide (19.4 mmol, 5 equiv., (prepared from
OH O
H
17: R = 9-phenanthrenyl
SI-1
C H O
4
6
6
50
MW = 907.10
4
.98 g of 9-bromophenanthrene and 0.46 g of Mg powder and catalytic amount of iodine in THF (70 mL) at
o
rt) at -20 C under inert atmosphere. The reaction mixture was then stirred at rt for 12 h. The reaction was
o
quenched at 0 C by careful addition of ice and a saturated aqueous NH
4
Cl solution. The organic layer was
separated and the aqueous layer was extracted with ether (3 X 50 mL). The combined organic extracts were
dried over Na SO and the solvent was removed in vacuo to afford a yellow oil. The TADDOL was purified
2
4
via flash chromatography using EtOAc/hexanes (20:80). The white solid was then recrystallized from
S1
Cuenca, A.; Medio-Simon, M.; Aguilar, G. A.; Weibel, D.; Beck, A. K.; Seebach, D. Helv. Chim.Acta. 2000, 83, 3153-3162
Gerard, B.; Jones II, G.; Porco Jr., J. A. J. Am. Chem. Soc. 2004, 126, 13620–13621
S2
S9

CH
CH
HR-MS: m/z Calcd for [C66
2
Cl
2
/MeOH (10:90), affording pure TADDOL 17 as a white powder (2.036 g, 58%). R
f
= 0.35
2
0
o
S2
20
o
(
2
Cl
2
/hexanes 1:1); [α]
D
= + 268 (c = 2.0, CHCl
3
); literature report [α]
D
= + 79 (c = 2.0, CHCl );
3
+
H
50
O
4
+Na] 929.3609, Found 929.3607 (+0.0 ppm). Other spectroscopic data
for compound 17 are identical to literature reports.
S10

C. Compound Characterization Toward (+)-Ponapensin (3) and (+)-Elliptifoline (4)
1
)
5 equiv.
MeO C
Procedure
for
enantioselective
O
HO
MeO
OMe
2
H
photocycloaddition: A 16 x 100 mm Pyrex
OH
Ph
MeO
O
MeO
6
a
O
OH
test tube was flame dried under vacuum and
1
equiv. 17,
hν (300 < λ < 400 nm),
MeO
O
then
charged
with
anhydrous
3-
OMe
+)-9a, 47% yield,
5
OMe
CH2Cl2, -78 °C, 10 h
(
hydroxyflavone 5 (dried overnight in
2
)
NaBH(OAc)3
85.5:14.5 er, > 98.5:1.5 er
after 2 recrystallizations
vacuum oven) (100 mg, 1.0 equiv., 0.305
mmol, 1.0 equiv.), methyl cinnamate 6a (247 mg, 5.0 equiv., 1.52 mmol), and TADDOL 17 (276 mg, 0.305
2 2
mmol, 1.0 equiv.) in anhydrous CH Cl (0.05 M; 6 mL). After degassing with argon for 10 min, the mixture
o
was stirred and irradiated at -78 C in the Rayonet RPR-3100 (300 < λ < 400 nm) for 10 h. The solution was
concentrated in vacuo to afford a brown-yellow oil. Silica gel was washed successively with 80:20:03
3
hexanes/EtOAc/NEt (one column length) and 80:20 hexanes/EtOAc (one column length) to neutralize
acidity. Purification via flash chromatography using a gradient of hexanes/EtOAc (80:20 to 30:70) afforded
cyclopenta[bc]benzopyran 8a, a light yellow foam, as a mixture of isomers (107 mg, 0.210 mmol, 69%). This
mixture of isomers was used without further purification and transformed into the desired reduced 10S-aglain
9
a using sodium triacethoxyborohydride (see general procedure B for diastereoselective reduction of
hydrated aglains). The four diastereomers were separated via flash chromatography using a gradient of
hexanes/EtOAc (90:10 to 50:50) to afford the desired reduced 10S aglain 9a (49 mg, 0.099 mmol, 47%)
which was spectroscopically identical to the racemic compound (±)-9a (see above). Enantiopure crystals of 9a
were obtained by slow evaporation from isopropanol (>96:04 er), then another recrystallization by slow
2
0
o
evaporation from acetonitrile (>98.6:1.4 er). [α]
D
= + 136.5 (c = 1.0, CHCl
3
).
S11

®
o
Analysis of Aglain 9a: SFC Chiralcel OD-H column (temperature 35 C) was used
with isocratic elution of MeOH (NEt 0.1% / Vol) : CO (08:92) with a flow rate of 1.5
2
2
mL/min at 100 bar (CO
2
pressure) for 45 minutes.
(
72% ee)
Single Recrystallization
Racemic sample
o
In CH
2 2
Cl -78 C
(
12% ee)
>
97% ee after two
recrystallizations
S12

O
O
Procedure for the amidation of 9b to
produce (±)-19 (2 steps): A dry flask
was charged with 9b (70 mg, 0.124
mmol, 1.0 equiv.) and a stir bar. 9b was
HO
HO
MeO
MeO
OBn
N
H
OMe
OMe
1
) H , Pd/C
H
OH
2
H
OH
MeO
MeO
O
O
2) EDCI, HOBt, 18
(
±)-9b
(±)-19
OMe
OMe
then dissolved in a CHCl
added, and the mixture was stirred. The reaction vessel was then purged with H
with H and a vacuum manifold. The reaction was stirred under H for 1 h, and then purged/charged with
3
/EtOH (1:3, 12 mL). 10% Pd on carbon (14 mg, 0.013 mmol, 0.1 equiv.) was then
2
gas using a balloon filled
2
2
argon. The Pd/C was filtered using a Celite plug, and the filtrate was concentrated in vacuo to produce the
crude carboxylic acid (58 mg, 100%) which was used in the next reaction without further purification. A flask
was charged with the carboxylic acid (58 mg, 1.0 equiv., 0.124 mmol), EDCI (35 mg, 0.182 mmol, 1.5 equiv.),
HOBt•H
mL). A solution of amine 18 (49 mg, 0.365 mmol, 3.0 equiv.) in CH
vessel at 0 ºC under argon. The reaction was then brought to rt and stirred for 16 h. Water (10 mL) and
CH Cl (10 mL) were added and the organic layer was extracted with CH Cl (3 X 10 mL). Brine was used to
aid separation of the layers. The combined organic extracts were dried over sodium sulfate and purified via
flash chromatography (product eluted with 8:2 EtOAc/hexanes, 51 mg, 71% yield). White solid; R = 0.22 (4:1
EtOAc/hexanes); m.p. 98 ºC; IR νmax (film): 3405, 2941, 2837, 1661, 1617, 1589, 1517, 1467, 1439, 1252,
2
O (22 mg, 0.146 mmol, 1.2 equiv.), and a stir bar. The contents were then dissolved in CH
2 2
Cl (3.5
2
Cl (1 mL) was added to the reaction
2
2
2
2
2
f
-
1 1
1
7
6
3
214, 1201, 1183, 1148, 1129, 1075, 830, 752 cm ; H NMR (500 MHz, CDCl ) δ 7.40 (d, J = 9.0 Hz, 2H),
.22 (d, J = 7.2 Hz, 2H), 7.03 (br dd, J = 7.2, 7.2 Hz, 2H), 6.97 (br t, J = 7.2 Hz, 1H), 6.67 (d, J = 9.0 Hz, 2H),
.08 (d, J = 2.2 Hz, 1H), 6.06 (d, J = 2.2 Hz, 1H), 5.90 (s, 1H), 5.74 (br dd, J = 5.5, 5.5 Hz), 4.75 (s, 1H), 4.48
(br d, J = 9.0 Hz, 1H), 4.30 (dd, J = 5.5, 5.5 Hz, 1H), 3.84 (s, 3H), 3.72 (s, 3H), 3.70 (s, 3H), 3.53 (d, J = 9.0
Hz, 1H), 3.18 (ddd, J = 13.5, 7.5, 5.5 Hz, 1H) 3.12 (ddd, J = 13.5, 6.5, 5.5 Hz, 1H), 1.56-1.51 (ovrlp m, 2H),
1
3
1
1
5
3
.51-1.45 (ovrlp m, 2H); C NMR (125 MHz, CDCl ) δ 169.8, 161.2, 158.8, 157.8, 154.0, 142.0, 130.3 (2C),
30.2 (2C), 130.1, 128.0 (2C), 126.1, 113.0 (2C), 104.4, 104.3, 94.7, 92.5, 89.2, 81.0, 79.6, 66.2, 56.1, 55.9,
+
5.4, 55.2, 53.15, 53.07, 39.5, 30.1, 24.8; HR-MS: m/z Calcd for [C33
H
39
O
9
+H] 594.2703, found 594.2704
(+0.17 ppm).
®
o
Analysis of (±)-19: SFC Chiralcel OD-H column (temperature 35 C) was used with an elution of MeOH
NEt 0.1% / Vol) : CO with a flow of 2.5 mL/min at 100 bar (CO pressure): isocratic 05:95 (3 min) then
ramped from 05:95 to 20:80 over 43 min (rate: 0.35). T = 25.7 min, T = 32.4 min.
(
2
2
2
1
2
S13

O
O
Ester-amide exchange protocol
to access aglain-amide (+)-19. To
a solution of amine 18 (637 mg,
4.78 mmol, 20 equiv.) in toluene
HO
HO
MeO
MeO
OMe
N
H
OMe
OMe
ester-amide
exchange
H
OH
H
OH
MeO
MeO
O
OMe
O
H N
2
(+)-19
(
)3 OMe
(
+)-9a
C33H39O9
1
8
MW = 593.66
OMe
OMe
(1.0 mL) under argon and at room
temperature was added dropwise a solution of trimethylaluminum [2M] (2.4 mL, 4.79 mmol, 20 equiv.). The
o
resulting solution was heated at 40 C for 1 h to preform the corresponding aluminate. Then a solution of
aglain methyl ester (+)-9a (110 mg, 0.223 mmol, 1 equiv.) in toluene (6.5 mL) was added via cannula, and
o
the reaction mixture was heated at 70 C for 12 h. The reaction mixture was quenched at room temperature
with a solution of NH
4
Cl sat. (4 mL), stirred for 30 min, extracted with EtOAc (3 X 10 mL), and the
SO , the solvent was
combined organic layers washed with brine. The organic layer was dried over Na
2
4
removed in vacuo to afford a crude white yellow solid. Purification via flash chromatography using a
gradient of EtOAc/hexanes 1:4 to 4:1 afforded pure amide (+)-19 (85 mg, 0.143 mmol, 64%) along with
f
recovered starting material (+)-9a (5 mg, 0.010 mmol, 5%). White solid; R = 0.22 (EtOAc/hexanes 4:1);
S14

2
0
[
α]
D
3
= + 94.8° (c = 1.0, CHCl ); Other spectroscopic data of compound (+)-19 are identical to its racemate
(see above).
®
o
Analysis of enantioenriched (+)-19: SFC Chiralcel OD-H column (temperature 35 C) was used with an
elution of MeOH (NEt
2
0.1% / Vol) : CO
2
with a flow rate of 2.5 mL/min at 100 bar (CO pressure): isocratic
2
0
5:95 (3 min) then ramped from 05:95 to 20:80 over 43 min (rate: 0.35). T
1
= 25.7 min, T = 31.1 min.
2
Procedure to prepare (+)-ponapensin (3): A dry
flask was charged with aglain amide (+)-19 (53 mg,
0.090 mmol, 1.0 equiv.) and a stir bar under argon.
OMe
O
N
HO
HO
MeO
MeO
N
H
OMe
OMe
O
1
5 equiv. MeOH
H
OH
50 mol% CSA
H
OH
MeO
MeO
O
EtOAc, 40 °C
O
1
9
(+)-19 was dissolved in EtOAc (9.0 mL) and
OMe
ponapensin (3) OMe
chilled to 0 °C. Under argon, CSA (10.4 mg, 0.045
mmol, 0.5 equiv.) and MeOH (54 µL, 1.34 mmol, 15 equiv) were added, and the reaction was warmed up to rt,
then heated at 40 °C for 2 h. Triethylamine (7 µL, 0.045 mmol, 0.5 equiv.) was added and stirred for 30 min.
S15

Water (2 mL) was added to the reaction, and the organic layer was separated and dried over sodium sulfate.
The organic extract was concentrated and purified using preparative TLC (49:1 CHCl /MeOH) using a TLC
plate that was neutralized with MeOH/triethylamine (99:1). Compound 3 was isolated (34 mg, 0.062 mmol,
8%) as a white solid. The reaction of (±)-19 to (±)-3 was reacted and purified in the exact same fashion and
was crystallized via slow evaporation in benzene (600 µL) and hexanes (100 µL). White solid; R = 0.46 (1:4
); m.p. 235-240 ºC, decomposition observed; IR νmax
3
6
f
2
0
hexanes/EtOAc); [α]
D
= + 170° (c = 0.2, CHCl
film): 3476, 3011, 2935, 2840, 1619, 1591, 1517, 1436, 1251, 1215, 1148, 1128, 1081, 750 cm ; H NMR
500 MHz, CD OD) δ 7.40 (d, J = 9.0 Hz, 2H), 7.18 (br d, J = 7.0 Hz), 7.00-6.91 (m, 3H), 6.61 (d, J = 9.0 Hz,
H), 6.12 (d, J = 2.2 Hz, 1H), 6.03 (d, J = 2.2 Hz, 1H), 5.80 (br d, J = 3.5 Hz, 1H), 4.62 (br s, 1H), 4.40 (br d,
J = 9.5 Hz, 1H), 4.36 (d, J = 9.5 Hz, 1H), 3.78 (s, 3H), 3.73 (s, 3H), 3.67 (s, 3H), 3.34 (m, 2H), 2.80 (s, 3H),
3
-
1 1
(
(
3
2
1
3
2
1
6
5
3
.04-2.00 (m, 1H), 1.94-1.88 (ovrlp m, 3H); C NMR (100 MHz, CDCl ) δ 172.4, 162.7, 160.0, 159.8, 155.0,
43.1, 132.0, 131.7 (2C), 131.4 (2C), 128.6 (2C), 127.0, 113.4 (2C), 107.2, 95.2, 92.8, 90.0, 89.6, 83.1, 80.9,
+
3.6, 58.5, 56.5, 55.8, 55.4, 54.3, 46.3, 32.7, 21.7; HR-MS: m/z Calcd for [C32
H
35NO
8
+Na] 584.2260, found
84.2252 (-1.4 ppm).
S16

1
13
Table SI-2. Comparison of H and C spectra for natural and synthetic ponapensin (3)
1
3
13
C
C
1
S3
1
S3
H Literature
H Observed
Literature
Observed
Chemical
Chemical
Chemical
Chemical
Appearance
Appearance
Shift (ppm)
Shift (ppm)
Shift (ppm)
Shift (ppm)
d, J = 8.9
Hz, 2H
d, J = 9.0
Hz, 2H
7
.40
7.40
172.4
172.4
d, J = 6.8
Hz, 2H
m, 3H
d, J = 8.9
Hz, 2H
br d, J =
7.0 Hz, 2H
m, 3H
d, J = 9.0
Hz, 2H
7
6
6
.18
.96
.61
7.18
6.96
6.61
162.7
160.0
159.8
162.7
160.0
159.8
d, J =2.2
Hz, 1H
d, J =2.2
Hz, 1H
d, J =2.2
Hz, 1H
d, J =2.2
Hz, 1H
6
6
.12
.03
6.12
6.03
155.0
143.1
155.0
143.1
br d, J =
br d, J =
3.5 Hz, 1H
br s, 1H
br d, J =
9.5 Hz, 1H
d, J = 9.5
Hz, 1H
5
4
4
.80
.62
.40
5.80
4.62
4.40
132.0
132.0
3
.3 Hz, 1H
s, 1H
131.7 (2C)
131.4 (2C)
131.7 (2C)
131.4 (2C)
d, J = 9.4
Hz, 1H
d, J = 9.4
Hz, 1H
s, 3H
4
.36
4.36
128.6 (2C)
128.6 (2C)
3
3
3
3
2
2
1
1
.79
.73
.67
.34
.80
.02
.90
.88
3.78
3.73
3.67
3.34
2.80
2.02
1.91
1.89
s, 3H
s, 3H
s, 3H
m, 2H
s, 3H
m, 1H
m, 2H
m, 1H
127.0
113.4 (2C)
107.3
95.2
127.0
113.4 (2C)
107.2
95.2
s, 3H
s, 3H
m, 2H
s, 3H
m, 1H
m, 2H
m, 1H
92.8
90.0
89.6
83.1
92.8
90.0
89.6
83.1
8
6
5
5
5
5
5
4
3
2
0.9
3.6
8.5
6.5
5.8
5.5
4.3
6.3
2.7
1.7
80.9
63.6
58.5
56.5
55.8
55.4
54.3
46.3
32.7
21.7
S3
Salim, A. A.; Pawlus, A. D.; Chai, H.-B. ; Farnsworth, N. R.; Kinghorn, A. D.; Carcache-Blanco, E. J. Bioorg. Med. Chem. Lett.
007, 17, 109-112.
2
S17

((3S,4R,5R,10S)-5,10-dihydroxy-6,8-dimethoxy-2-(4-methoxyphenyl)-3-phenyl-
OEt
N
HO
MeO
2,3,4,5-tetrahydro-2,5-methanobenzo[b]oxepin-4-yl)((S)-2-ethoxypyrrolidin-1-
O
H
OH
MeO
yl)methanone ((±)-20): Aglain 20 was prepared using the procedure above, except
O
MeOH was not added, and the reaction vessel was sealed. After quenching, the
2
0
OMe
mixture was concentrated and purified using preparative TLC (49:1 CHCl
3
/MeOH)
C33H37NO8
MW = 575.65 g/mol
using a TLC plate that was neutralized with a MeOH/triethylamine solution (99:1
MeOH/triethylamine). Fractions from the prep. TLC were further purified using reverse phase preparative
HPLC (Gilson PLC2020 system, Waters SunFire™ Prep C18 OBD™ 5µm 19X50 mm column, 20.0 mL/min
flow rate, 30:70 MeCN/H
mg, 12% yield) was isolated as a white solid. R
film): 3468, 2975, 1618, 1590, 1518, 1496, 1457, 1437, 1252, 1214, 1202, 1181, 1148, 1130, 1096, 1080
2
O to 80:20 MeCN/H
2
O gradient, 10 min). Ethyl hemiaminal derivative (±)-20 (6
f
= 0.46 (4:1 EtOAc/hexanes); m.p. 195-200 °C; IR νmax
(
-
1 1
cm ; H NMR (400 MHz, CDCl
3
) δ (rotamers observed) 7.42 (d, J = 9.0 Hz, 2H), 7.17 (d, J = 7.2 Hz, 2H),
.00 (dd, J = 7.2, 7.0 Hz, 2H), 6.95 (t, J = 7.0 Hz, 1H), 6.68 (d, J = 9.0 Hz, 2H), 6.10 (d, J = 2.2 Hz, 1H),
.04 (d, J = 2.2 Hz, 1H), 5.69 (d, J = 4.0 Hz, 1H), 5.66 (s, 1H), 4.82 (s, 1H), 4.61 (d, J = 9.2 Hz, 1H), 4.22 (d,
7
6
J = 9.2 Hz, 1H), 3.78 (s, 3H), 3.72 (s, 3H), 3.70 (s, 3H), 3.46-3.41 (m, 1H), 3.37-3.30 (m, 1H), 3.24 (s, 1H),
2
2
.88 (dt, J = 14.0, 7.2 Hz, 1H), 2.73 (dt, J = 14.0, 7.2 Hz, 1H), 2.05-1.93 (ovrlp m, 2H), 1.88-1.74 (ovrlp m,
1
3
3
H), 0.76 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl ) δ 169.1, 161.1, 158.8, 157.8, 153.8, 141.9, 130.5
(2C), 130.3, 130.1 (2C), 127.9 (2C), 126.0, 113.1 (2C), 105.1, 94.5, 92.2, 89.2, 86.4, 81.7, 80.1, 63.3, 61.7,
+
5
5
7.1, 56.0, 55.4, 55.2, 45.2, 32.9, 21.0, 15.0; HR-MS: m/z Calcd for [C33
H37NO
8
+Na] 598.2417, found
98.2416 (-0.17 ppm).
(
4bR,5aR,10aR,11S,14R)-14-hydroxy-2,4-dimethoxy-12-(4-methoxyphenyl)-11-
H
N
O
MeO
phenyl-5a,6,7,8,11,12-hexahydro-4b,12-methanobenzo[6,7]oxepino[4,5-
O
H
OH
MeO
e]pyrrolo[2,1-b][1,3]oxazin-10(10aH)-one ((±)-21): Aglain 21 was prepared using the
procedure above, except MeOH was not added, and the reaction vessel was sealed.
After quenching, the mixture was concentrated and purified using preparative TLC
O
2
1
OMe
C31H31NO7
MW = 529.58
3
(49:1 CHCl /MeOH) using a TLC plate that was neutralized with a
MeOH/triethylamine solution (99:1 MeOH/triethylamine). Fractions from the prep. TLC were further
purified using reverse phase preparative HPLC (Gilson PLC2020 system, Waters SunFire™ Prep C18
OBD™ 5µm 19X50 mm column, 20.0 mL/min flow rate, 30:70 MeCN/H
2
O to 80:20 MeCN/H
2
O gradient,
= 0.46 (4:1
) δ 7.37
1
0 min). Cyclic intermediate (±)-21 (1.5 mg, 2% yield) was isolated as a white solid. R
f
-
1 1
EtOAc/hexanes); IR νmax (film): 3530, 2962, 1614, 1261, 1091 cm ; H NMR (400 MHz, CDCl
3
S18

(d, J = 8.8 Hz, 2H), 7.15 (d, J = 7.6 Hz, 2H), 7.06 (dd, J = 7.6, 7.2 Hz, 2H), 7.00 (t, J = 7.2 Hz, 1H), 6.66 (d,
J = 8.8 Hz, 2H), 6.04 (d, J = 2.4 Hz, 1H), 6.01 (d, J = 2.4 Hz, 1H), 5.68 (dd, J = 6.4 Hz, 1H), 4.82 (s, 1H),
4
1
2
7
.23 (d, J = 10.6 Hz, 1H), 4.12 (d, J = 10.6 Hz, 1H), 3.75 (s, 3H), 3.714 (s, 3H), 3.708 (s, 3H), 3.57 (brdd, J =
0.8, 9.2 Hz, 1H), 3.42 (ddd, J = 10.8, 6.8, 4.4 Hz, 1H), 2.85 (s, 1H), 2.44 (ddd, J = 14.0, 7.6, 6.4 Hz, 1H),
.37 (ddd, J = 14.0, 7.6, 6.4 Hz, 1H), 2.13 (dddd, J = 13.4, 7.6, 7.2, 4.4 Hz, 1H), 1.92 (brddd, J = 13.4, 9.2,
1
3
3
.2 Hz, 1H); C NMR (100 MHz, CDCl ) δ 167.7, 161.3, 158.9, 158.5, 154.5, 141.2, 130.4 (2C), 130.0
(3C), 128.1 (2C), 126.2, 112.9 (2C), 105.5, 94.1, 93.3, 91.1, 90.7 (2C), 85.8, 60.0, 55.8, 55.4, 55.2, 51.2,
+
4
3.6, 31.5, 22.5; HR-MS: m/z Calcd for [C31
H
31NO
7
+H] 530.2179, found 530.2164 (+2.8 ppm).
O
Me
O
NH Me
O
H N
Me
2
O
N
HO
Me
HO
MeO
MeO
N
H
OMe
OMe
H
OH
50 mol% CSA
H
OH
Procedure to Prepare elliptifoline (4): A
dry flask was charged with aglain amide 19
38 mg, 0.064 mmol, 1.0 equiv.) and a stir
MeO
MeO
O
EtOAc, 40 °C
O
1
9
(
OMe
elliptifoline (4) OMe
bar under argon. (+)-19 was dissolved in EtOAc (6.0 mL) and chilled to 0 °C. Under argon, CSA (7.5 mg,
.032 mmol, 0.5 equiv.) and tigloyl amide (32 mg, 0.32 mmol, 5 equiv.) were added, and the reaction was
0
warmed up to rt then heated at 40 °C for 6 h. Triethylamine (5 µL, 0.032 mmol, 0.5 equiv.) was added and
stirred for 30 min. Water (2 mL) was added to the reaction, and the organic layer was separated and dried over
3
sodium sulfate. The organic layer was concentrated and purified using preparative TLC (49:1 CHCl /MeOH)
using a TLC plate that was neutralized with a MeOH/triethylamine solution (99:1 MeOH/triethylamine).
Elliptifoline 4 was isolated (32 mg, 0.051 mmol, 81%) as a white solid. The reaction of (±)-19 to (±)-4 was
reacted and purified in the exact same fashion and was crystallized via slow evaporation in CH
2
2
Cl (200 µL)
2
0
and 2,2,4-trimethylpentane (100 µL). White solid; R
f
= 0.24 (1:4 hexanes/EtOAc); [α]
D
= + 172° (c = 0.2,
-
1
1
CHCl
CDCl
3
3
); m.p. 185 ºC; IR νmax (film): 3441, 3018, 1621, 1517, 1215, 1149, 751 cm ; H NMR (500 MHz,
) δ 7.40 (d, J = 9.0 Hz, 2H), 7.11 (br dd, J = 6.5, 2.5 Hz, 1H), 6.91-6.88 (overlapping m, 3H), 6.67-6.58
(
m, 1H), 6.63 (d, J = 9.0 Hz, 2H), 6.14-6.01 (m, 1H), 6.10 (d, J = 2.0 Hz, 1H), 6.05 (d, J = 2.0 Hz, 1H), 5.38
d, J = 8.0 Hz, 1H), 4.78 (s, 1H), 4.46 (d, J = 9.0 Hz, 1H), 4.14 (d, J = 9.0 Hz, 1H), 3.81 (s, 3H), 3.72 (s, 3H),
.68 (s, 3H), 3.66 (s, 1H), 3.60 (m, 1H), 3.21 (ddd, J = 12.0, 9.8, 7.0 Hz, 1H), 2.07 (ddd, J = 12.5, 12.5, 6.5
(
3
1
3
Hz, 1H), 2.00-1.89 (ovrlp m, 2H), 1.78-1.71 (m, 1H), 1.64 (dd, J = 7.0, 1.5 Hz, 3H), 1.48 (br s, 3H); C NMR
(100 MHz, CDCl
3
) δ 169.8, 167.7, 161.2, 158.7, 157.9, 153.8, 141.9, 132.0, 130.8, 130.41 (2C), 130.37 (C1’),
1
5
30.2 (2C), 127.9 (2C), 125.7, 112.9 (2C), 105.2, 94.5, 92.2, 89.2, 81.9, 80.00, 63.6, 62.6, 57.2, 56.1, 55.4,
+
40 2 8
5.2, 46.1, 34.6, 21.6, 14.0, 12.2; HR-MS: m/z Calcd for [C36H N O +Na] 651.2682, found 651.2663 (-2.9
S19

ppm).
S20

1
13
Table SI-3. Comparison of H and C spectra for natural and synthetic elliptifoline (4)
1
3
C
1
3
LS4iterature
C
1
S4
1
H Literature
H Observed
Observed
Chemical
Shift
Chemical
Shift
Chemical
Appearance
Chemical
Appearance
Shift (ppm)
Shift (ppm)
(ppm)
(ppm)
d, J = 9.0 Hz,
7
.41
m, 2H
7.40
169.9
169.8
2
H
7
6
6
6
.11
.91
.89
.63
m, 2H
m, 1H
m, 2H
m, 1H
7.11
6.90
6.89
6.63
m, 2H
m, 1H
167.9
161.0
158.4
158.1
167.7
161.2
158.7
157.9
m, 2H
m, 1H
d, J = 9.0 Hz,
6
6
6
.60
.09
.06
m, 2H
m, 1H
m, 1H
6.63
6.10
6.05
153.7
141.8
131.8
153.8
141.9
132.0
2
H
d, J = 2.0 Hz,
1
H
d, J = 2.0 Hz,
1
H
6
5
.02
.88
m, 1H
s, 1H
6.08
5.75
m, 1H
s, 1H
130.7
130.4
130.4
130.4
d, J = 7.9
Hz, 1H
s, 1H
d, J = 8.0 Hz,
1H
5
.57
5.38
130.2
130.2
4
4
.80
.62
4.78
3.66
s, 1H
127.7
125.6
127.9
125.7
s, 1H
s, 1H
d, J = 9.2
Hz
d, J = 9.2
Hz
d, J = 9.0 Hz,
1H
d, J = 9.0 Hz,
1H
4
4
.45
.15
4.46
4.15
112.6
105.4
112.9
105.2
3
3
3
3
3
2
1
.80
.71
.66
.58
.21
.02
.84
m, 3H
m, 3H
s, 3H
3.81
3.72
3.68
3.60
3.22
2.08
1.94
s, 3H
94.2
91.9
88.9
81.9
79.7
63.7
62.3
57.1
94.5
92.2
89.2
81.9
80.0
63.6
62.6
57.2
s, 3H
s, 3H
m, 1H
m, 1H
m, 2H
m, 2H
m, 1H
m, 1H
m, 1H
m, 2H
1
.75
m, 1H
d, J = 7.0,
dd, J = 7.0,
1.5 Hz, 3H
br s, 3H
1
1
.63
.47
1.64
1.48
56.0
56.1
3
H
s, 3H
55.2
55.4
55.2
46.1
34.6
21.6
14.0
12.2
5
4
3
2
1
1
5.0
6.1
4.5
1.4
3.9
2.0
S4
Wang, S. K.; Cheng, Y.J.; Duh, C.-Y. J. Nat. Prod. 2001, 64, 92-94.
S21

MeO
HO
Procedure to prepare (−)-methyl rocaglate 1
from enantioenriched (+)-8a: Enantioenriched
MeO
HO
HO
O
MeO
2
CO Me
HO OH
O
Me4NBH(OAc)3
NaOMe/MeOH,
0 °C
MeO
(+)-8a was prepared using the following
6
O
MeO
procedure: a 16 x 100 mm Pyrex test tube was
flame dried under vacuum and then charged with
anhydrous 3-hydroxyflavone 5 (dried overnight
in vacuum oven) (100 mg, 1.0 equiv, 0.305
mmol), methyl cinnamate 6a (247 mg, 5.0 equiv,
(
+)-aglain 8a
OMe
SI-2
OMe
HO
HO
HO
HO
MeO
CO Me
MeO
CO Me
2
2
O
O
MeO
MeO
1
.52 mmol), and TADDOL 17 (276 mg, 0.305
mmol, 1.0 equiv) in anhydrous CH Cl (0.05M;
.0mL). After degassing with argon for 10 min,
2
2
OMe
OMe
6
(
−)-methyl rocaglate (1)
SI-3
o
the mixture was stirred and irradiated at -78 C in
the Rayonet RPR-3100 (315 < λ < 400 nm) for 10 h. The solution was concentrated in vacuo to afford a
brown-yellow oil. Silica gel was washed successively with 80:20:03 hexanes/EtOAc/NEt (one column
3
length) and 80:20 hexanes/EtOAc (one column length) to neutralize acidity. Purification via flash
chromatography using a gradient of hexanes/EtOAc (80:20 to 30:70) afforded cyclopenta[bc]benzopyran 8a,
a light yellow foam, as a mixture of isomers (107 mg, 0.210 mmol, 69%). This mixture of isomers was used
without further purification in a base mediated ketol rearrangement to form a cyclopenta[bc]benzofuran SI-2
S5
using the following procedure: To a solution of 8a (107 mg, 0.210 mmol, 1 equiv) in MeOH (4 mL) under
an inert atmosphere was added a solution of freshly prepared NaOMe in methanol (0.3 M, 1.8 mL, 0.540
mmol, 2.6 equiv) at rt. The resulting solution was stirred for 30 min at 60 °C. After removal of the MeOH
under vacuum, the crude reaction mixture was quenched with a sat. NH Cl solution (10 mL) and HCl (1M, 5
4
mL) giving a yellowish, cloudy solution which was extracted with EtOAc (3 x 10 mL). The combined
organic layers were then washed with brine (10 mL), dried over sodium sulfate, filtered, and concentrated in
vacuo to afford quantitatively a crude yellow oil SI-2 (107 mg, 0.24 mmol) which was used without further
S5
purification in the next step: To a solution of trimethoxy-cyclopenta[b]benzofurans SI-2 (107 mg, 0.21
mmol, 1.0 equiv.) in CH
115 µL, 2.10 mmol, 10 equiv.) and Me
solution was stirred for 12 h at 0 °C to rt before being quenched with a sat. NH
mixture was then extracted with EtOAc (3 x 5 mL) and the combined organic layers were washed with sat.
NaHCO (20 mL), dried over Na SO , filtered, and concentrated in vacuo. Note: removal of the generated
AcOH by a basic wash (NaHCO ) prior to concentration avoided degradation of the crude material. The
3
CN (6.0 mL) at 0 °C under inert atmosphere were added successively acetic acid
NBH(OAc) (340 mg, 1.26 mmol, 6 equiv). The resulting yellow
Cl solution (4 mL). The
(
4
3
4
3
2
4
3
crude material was purified by flash chromatography (gradient of EtOAc/hexane, 10:90 → 40:60) to afford
methyl rocaglate (1) (61 mg, 0.124 mmol, 52% over two steps) and its diastereomer SI-3 (19 mg, 0.039
mmol, (16% over two steps).
Chiral HPLC Analysis of racemic methyl rocaglate (1): Regis Pirkle covalent (R,R) WHELK-O 1 column
was used, with an isocratic mobile phase of isopropanol/hexanes (20:80) with a flow rate of 1.0 mL/min for
4
0 min.
S5
Roche, S. P.; Cencic, R.; Pelletier J. ; Porco Jr., J. A. Angew. Chem. Int. Ed. 2010, 49, 6533-6538.
S22

HO
HO
MeO
2
CO Me
O
MeO
OMe
(
±)-methyl rocaglate (1)
Chiral HPLC Analysis of enantioenriched (−)-methyl rocaglate (1): Regis Pirkle covalent (R,R) WHELK-O 1
column was used, with an isocratic mobile phase of isopropanol/hexanes (20:80) with a flow rate of 1.0
mL/min for 45 min.
HO
MeO
2
CO Me
HO
O
MeO
OMe
(
−)-methyl rocaglate (1)
After HPLC analysis of enantioenriched methyl
2
0
rocaglate (1), the optical rotation was measured. [α]
D
= -32 °
(
71.5% ee), consistent with previous literature reports for (−)-
S2
methyl rocaglate. All other spectroscopic properties were
identical to previous reports.
S2
Gerard, B.; Jones II, G.; Porco Jr., J. A. J. Am. Chem. Soc. 2004, 126, 13620–13621.
S23

D. X-ray Crystallographic Data
X-ray crystallographic data for enantiopure (+)-9a
(
Absolute and relative stereochemistry)
Crystals of compound (+)-9a suitable for X-ray analysis were obtained by slow evaporation from
isopropanol, then another recrystallization by slow evaporation from acetonitrile. Crystallographic data have
been deposited with the Cambridge Crystallographic Data Centre (CCDC #833990). Copies of the data can
be obtained free of charge on application to the CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax:
(+44)- 1223-336-033; e-mail: deposit@ccdc.cam.ac.uk.
Table SI-4. Crystal data and structure refinement for the absolute stereochemistry of the reduced aglain (+)-9a.
Identification code 9a
Crystal data
C
28
H
28
O
8
F(000) = 1040
x
D = 1.374 Mg m
-
3
M
r
= 492.50
Orthorhombic, P2
1
2
1
2
1
Cu Kα radiation, λ = 1.54178 Å
Cell parameters from 9257 reflections
θ = 13.7–131.9°
Hall symbol: P 2ac 2ab
a = 6.3478 (2) Å
-
1
b = 12.4544 (4) Å
c = 30.1079 (10) Å
µ = 0.84 mm
T = 100 K
3
V = 2380.27 (13) Å
Block, colorless
S24

Z = 4
0.20 × 0.08 × 0.06 mm
Data collection
Bruker Proteum-R
diffractometer
4168 independent reflections
Radiation source: rotating anode
graphite
4141 reflections with I > 2σ(I)
R
int = 0.033
φ & ω scans
θmax = 66.2°, θmin = 3.8°
Absorption correction: multi-scan
h = -7→7
SADABS (Sheldrick, 1996)
T
min = 0.686, Tmax = 0.753
k = -14→14
l = -35→35
1
20163 measured reflections
Refinement
2
Refinement on F
Secondary atom site location: difference Fourier
map
Least-squares matrix: full
Hydrogen site location: inferred from
neighbouring sites
2
2
R[F > 2σ(F )] = 0.024
H-atom parameters constrained
2
2
2
2
wR(F ) = 0.061
o
w = 1/[σ (F ) + (0.0333P) + 0.5417P]
2
2
where P = (F
o c
+ 2F )/3
S = 1.04
(Δ/σ)max = 0.002
-
3
4
3
1
168 reflections
67 parameters
3 restraints
Δ〉max = 0.22 e Å
-
3
Δ〉min = -0.17 e Å
Absolute structure: Flack H D (1983), Acta
Cryst. A39, 876-881
Primary atom site location: structure-invariant
direct methods
Flack parameter: -0.03 (11)
Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance
matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles;
correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate
(
isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
2
2
Refinement. Refinement of F against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F ,
2
2
2
conventional R-factors R are based on F, with F set to zero for negative F . The threshold expression of F > 2sigma(F ) is used
2
only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F are
S25

statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
The crystallized compound was known to be a single enantiomer with >98% ee separated by chiral chromatography. The
absolute structure was determined unambiguously from the crystal data alone, with all relevant indicators of correctness in
agreement. Upon completion of refinement with XL, OLEX2 calculates and outputs values for these parameters. This output is
given here:
Bijvoet pair analysis using Gaussian distribution Bijvoet pairs (all): 1742 Bijvoet pairs (used): 1737 Bijvoet pairs coverage:
0
.99 G: 1.01 (3) P2(true): 1.000 P3(true): 1.000 P3(false): 0.000 P3(racemic twin): 0.000 Hooft y: -0.005 (15) Flack x: -0.03 (11)
CheckCIF alerts and response:
Alert level B PLAT220_ALERT_2_B Large Non-Solvent C Ueq(max)/Ueq(min) ···4.52 Ratio PLAT230_ALERT_2_B
Hirshfeld Test Diff for O7 –C28A .. 8.28 su PLAT413_ALERT_2_B Short Inter XH3 .. XHn H17 .. H28F .. 1.92 Ang. Alert
level C PLAT213_ALERT_2_C Atom C26B has ADP max/min Ratio ···.. 3.20 prola PLAT222_ALERT_3_C Large Non-Solvent
H Uiso(max)/Uso(min) ···5.60 Ratio
The structure includes three disordered OMe groups, each refined with its own occupancy free variable, and the diffuse
electron densities associated with these disorders give rise to the level B and level C alerts. Anisotropic refinement of the major
and minor components C26A and C26B leads to somewhat prolate ellipsoids, and the riding H atoms have correspondingly large
isotropic thermal parameters. The short inter-molecular H17 .. H28F contact is most likely due to imprecise positions for the three
hydrogen atoms on C28B, which is part of a minor (23%) component of the C28 disorder. The relatively low electron density for
the minor component atom C28B also likely gives rise to a slightly mis-oriented thermal ellipsoid for this atom, generating the
Hirshfield test alert.
Despite the slight anomalies for these disordered groups, the chemical characteristics of inter-est for this research, the regio-
and stereochemistry, are unambiguous.
2
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å )
x
y
z
U
iso*/Ueq
Occ. (<1)
O2
O3
H3
O1
O6
O4
H4
O7
O8A
O5
C16
0.63728 (13)
0.13731 (13)
0.0785
0.45064 (6)
0.52418 (7)
0.5843
0.32457 (2)
0.37597 (3)
0.3784
0.01780 (17)
0.02269 (18)
0.034*
1.13444 (13)
0.60473 (17)
0.28545 (14)
0.3497
0.63226 (7)
0.83364 (7)
0.72388 (7)
0.7816
0.23874 (3)
0.31928 (3)
0.35232 (3)
0.3473
0.02269 (18)
0.0327 (2)
0.02514 (19)
0.038*
0.28132 (17)
0.6000 (12)
0.86467 (16)
0.4986 (2)
0.00827 (7)
0.7690 (9)
0.69235 (8)
0.35964 (12)
0.37268 (3)
0.4474 (3)
0.41110 (3)
0.53217 (4)
0.0366 (2)
0.0379 (15)
0.0346 (2)
0.0340 (3)
0.60 (3)
S26

H16
C17
H17
C11
H11
C18
H18
C24
H24
C1
0.4800
0.3289
0.5608
0.041*
0.6947 (3)
0.8119
0.39232 (15)
0.3850
0.51847 (5)
0.5378
0.0464 (4)
0.056*
0.59038 (18)
0.7457
0.50155 (9)
0.5023
0.40315 (4)
0.3977
0.0169 (2)
0.020*
0.7226 (2)
0.8594
0.43616 (12)
0.4576
0.47635 (4)
0.4671
0.0324 (3)
0.039*
0.56519 (19)
0.6999
0.26001 (10)
0.2841
0.38010 (4)
0.3896
0.0201 (2)
0.024*
1.2536 (2)
1.2801
0.72764 (10)
0.7649
0.23044 (4)
0.2586
0.0245 (3)
0.037*
H1C
H1A
H1B
C7
1.1741
0.7749
0.2105
0.037*
1.3881
0.7085
0.2166
0.037*
0.87442 (19)
0.9316
0.54562 (9)
0.4789
0.28002 (4)
0.2706
0.0182 (2)
0.022*
H7
C9
0.31375 (18)
0.2726
0.53313 (9)
0.5249
0.34756 (4)
0.3157
0.0188 (2)
0.023*
H9
C10
C12
H12
C13
C15
H15
C22
C21
H21
C6
0.48211 (18)
0.51390 (19)
0.3914
0.45127 (9)
0.62024 (9)
0.6256
0.36091 (4)
0.40371 (4)
0.4245
0.0166 (2)
0.0188 (2)
0.023*
0.55406 (19)
0.3287 (2)
0.1928
0.44888 (9)
0.37175 (11)
0.3491
0.44792 (4)
0.50404 (4)
0.5133
0.0179 (2)
0.0279 (3)
0.033*
0.3203 (2)
0.1751 (2)
0.0417
0.11561 (10)
0.18818 (10)
0.1637
0.36849 (4)
0.35177 (4)
0.3417
0.0239 (3)
0.0248 (3)
0.030*
0.70610 (18)
0.5177 (2)
0.6192
0.54864 (9)
0.15195 (10)
0.1025
0.30923 (4)
0.38233 (4)
0.3932
0.0168 (2)
0.0225 (3)
0.027*
C23
H23
C3
0.8684 (2)
0.9226
0.73938 (10)
0.8048
0.27651 (4)
0.2650
0.0211 (2)
0.025*
H3A
C5
0.61287 (19)
0.95809 (19)
0.41916 (19)
0.43202 (18)
0.6803 (2)
0.2249 (2)
0.1242
0.64468 (9)
0.64148 (10)
0.33482 (9)
0.63886 (9)
0.69747 (10)
0.29713 (10)
0.3464
0.32260 (4)
0.26473 (4)
0.36415 (3)
0.35552 (4)
0.41900 (4)
0.34979 (4)
0.3384
0.0185 (2)
0.0188 (2)
0.0176 (2)
0.0194 (2)
0.0224 (3)
0.0218 (3)
0.026*
C2
C19
C8
C25
C20
H20
C4
0.6981 (2)
0.73928 (10)
0.30537 (4)
0.0215 (2)
S27

C14
0.3552 (2)
0.2369
0.41686 (10)
0.4260
0.46227 (4)
0.4433
0.0244 (3)
0.029*
H14
C28A
H28B
H28A
H28C
C27A
H27C
H27B
H27A
C27B
H27E
H27F
H27D
C26A
H26B
H26C
H26A
C28B
H28E
H28F
H28D
O8B
0.0882 (3)
0.0824
-0.03279 (14) 0.35960 (8)
0.0402 (6)
0.060*
0.772 (4)
0.772 (4)
0.772 (4)
0.772 (4)
0.809 (4)
0.809 (4)
0.809 (4)
0.809 (4)
0.191 (4)
0.191 (4)
0.191 (4)
0.191 (4)
0.60 (3)
-0.1097
-0.0223
0.0046
0.3665
0.0702
0.3276
0.060*
-0.0248
0.6151 (3)
0.7575
0.3755
0.060*
0.92590 (12)
0.9562
0.28969 (6)
0.2904
0.0284 (5)
0.043*
0.5137
0.9803
0.2994
0.043*
0.5810
0.9033
0.2594
0.043*
0.7203 (15)
0.8609
0.9325 (6)
0.9315
0.3066 (3)
0.3201
0.0284 (5)
0.043*
0.6429
0.9956
0.3172
0.043*
0.7336
0.9359
0.2742
0.043*
0.7445 (11)
0.8594
0.8444 (10)
0.8057
0.4661 (4)
0.4809
0.059 (2)
0.088*
0.60 (3)
0.6710
0.8894
0.4879
0.088*
0.60 (3)
0.8024
0.8897
0.4425
0.088*
0.60 (3)
0.3506 (12)
0.2468
-0.0556 (5)
-0.1123
-0.0150
-0.0878
0.7847 (10)
0.8716 (9)
0.8416
0.4031 (2)
0.4085
0.0358 (18)
0.054*
0.228 (4)
0.228 (4)
0.228 (4)
0.228 (4)
0.40 (3)
0.3740
0.4306
0.054*
0.4835
0.3933
0.054*
0.588 (2)
0.741 (2)
0.8468
0.4360 (6)
0.4494 (8)
0.4697
0.043 (2)
0.074 (3)
0.112*
C26B
H26E
H26F
H26D
0.40 (3)
0.40 (3)
0.6649
0.9296
0.4644
0.112*
0.40 (3)
0.8116
0.8999
0.4229
0.112*
0.40 (3)
2
Atomic displacement parameters (Å )
1
1
22
33
12
13
23
U
U
U
U
U
U
O2
O3
O1
O6
O4
O7
O8A
0.0202 (4)
0.0162 (4)
0.0223 (4)
0.0459 (6)
0.0232 (4)
0.0516 (6)
0.0168 (4)
0.0276 (4)
0.0221 (4)
0.0176 (4)
0.0229 (4)
0.0207 (4)
0.0164 (4)
0.0244 (4)
0.0237 (4)
0.0344 (5)
0.0294 (4)
0.0376 (5)
0.040 (3)
0.0000 (3)
0.0037 (3)
0.0039 (3)
0.0093 (4)
0.0212 (5)
0.0053 (4)
0.0016 (3)
0.0026 (3)
0.0013 (4)
0.0052 (4)
0.0084 (4)
0.0038 (3)
0.0037 (3)
0.0044 (4)
0.0056 (4)
-0.0083 (4) -0.0002 (5) 0.0013 (4)
-0.0019 (17) -0.0018 (16) -0.025 (2)
0.0295 (17) 0.044 (3)
S28

O5
0.0276 (5)
0.0411 (8)
0.0318 (8)
0.0165 (5)
0.0225 (6)
0.0199 (6)
0.0226 (6)
0.0195 (6)
0.0156 (5)
0.0149 (5)
0.0210 (6)
0.0214 (6)
0.0303 (7)
0.0306 (7)
0.0244 (6)
0.0179 (5)
0.0259 (6)
0.0249 (6)
0.0185 (5)
0.0184 (6)
0.0204 (6)
0.0185 (6)
0.0292 (7)
0.0230 (6)
0.0267 (6)
0.0235 (6)
0.0330 (5)
0.0420 (8)
0.0434 (6)
0.0189 (6)
-0.0090 (4) 0.0080 (4)
-0.0113 (4)
0.0104 (6)
C16
C17
C11
C18
C24
C1
0.0115 (7)
0.0110 (8)
0.0006 (5)
0.0014 (6)
0.0057 (6)
0.0819 (12) 0.0256 (7)
-0.0040 (6) 0.0175 (8)
0.0174 (5)
0.0514 (9)
0.0241 (6)
0.0263 (6)
0.0188 (5)
0.0234 (6)
0.0211 (6)
0.0171 (6)
0.0172 (5)
0.0308 (6)
0.0199 (6)
0.0268 (6)
0.0188 (5)
0.0218 (6)
0.0184 (5)
0.0213 (6)
0.0238 (6)
0.0201 (6)
0.0198 (6)
0.0203 (6)
0.0236 (6)
0.0179 (6)
0.0303 (6)
0.0169 (5)
0.0233 (6)
0.0165 (5)
0.0247 (6)
0.0163 (5)
0.0173 (5)
0.0137 (5)
0.0182 (5)
0.0152 (5)
0.0225 (6)
0.0211 (6)
0.0233 (6)
0.0136 (5)
0.0198 (6)
0.0199 (5)
0.0156 (5)
0.0142 (5)
0.0123 (5)
0.0199 (6)
0.0177 (5)
0.0188 (6)
0.0198 (5)
0.0196 (6)
0.0005 (4)
0.0001 (5)
-0.0001 (4)
0.0066 (6)
-0.0006 (5)
0.0042 (5)
-0.0005 (5) 0.0007 (4)
-0.0020 (5) 0.0051 (5)
C7
0.0022 (5)
0.0010 (5)
-0.0001 (5) 0.0009 (4)
C9
0.0004 (4)
0.0027 (5)
0.0006 (4)
0.0004 (4)
-0.0018 (4)
0.0017 (5)
-0.0009 (5)
C10
C12
C13
C15
C22
C21
C6
-0.0002 (5) 0.0024 (4)
0.0005 (5)
0.0033 (5)
0.0044 (5)
0.0007 (5)
-0.0012 (6) 0.0079 (5)
-0.0031 (5) 0.0029 (5)
-0.0056 (5) -0.0028 (5) -0.0003 (5)
0.0009 (5)
0.0032 (5)
-0.0015 (4) 0.0030 (4)
C23
C3
0.0016 (5)
0.0019 (5)
0.0035 (4)
0.0019 (4)
0.0025 (5)
0.0002 (4)
0.0020 (5)
0.0005 (5)
-0.0011 (5) 0.0030 (5)
C5
0.0020 (5)
0.0006 (5)
0.0008 (5)
0.0015 (4)
C2
C19
C8
-0.0009 (5) 0.0025 (4)
0.0047 (5)
0.0002 (5)
0.0028 (5)
0.0012 (5)
C25
C20
C4
-0.0008 (5) -0.0035 (5) 0.0009 (5)
0.0028 (5)
0.0027 (5)
0.0010 (5)
0.0012 (5)
C14
C28A
C27A
C27B
C26A
C28B
O8B
C26B
-0.0012 (5) 0.0002 (5)
0.0288 (10) 0.0215 (9)
0.0347 (11) 0.0179 (7)
0.0347 (11) 0.0179 (7)
0.0704 (14) -0.0027 (7) 0.0067 (10) -0.0081 (9)
0.0325 (10) 0.0052 (7)
0.0325 (10) 0.0052 (7)
0.0084 (8)
0.0084 (8)
0.008 (3)
0.002 (3)
0.0067 (7)
0.0067 (7)
-0.044 (3)
0.000 (2)
-0.020 (3)
-0.021 (4)
0.052 (3)
0.054 (4)
0.053 (3)
0.099 (6)
0.055 (4)
0.023 (3)
0.019 (2)
0.024 (3)
0.069 (4)
0.030 (3)
0.056 (6)
0.101 (9)
-0.018 (2)
-0.001 (3)
0.0084 (18) -0.012 (3)
-0.011 (3) -0.037 (6)
Geometric parameters (Å, º)
O2—C6
O2—C10
O3—C9
1.3762 (13)
C12—C25
1.5012 (17)
1.4722 (13)
1.4138 (14)
C12—C8
1.5583 (16)
1.0000
C12—H12
S29

O3—H3
0.8400
C13—C14
1.3924 (18)
1.3877 (18)
0.9500
O1—C2
1.3706 (14)
1.4303 (15)
1.3811 (15)
1.4553 (18)
1.484 (7)
1.4128 (14)
0.8400
C15—C14
O1—C1
C15—H15
O6—C4
C22—C21
1.3856 (18)
1.3961 (19)
1.3944 (17)
0.9500
O6—C27A
O6—C27B
O4—C8
C22—C23
C21—C20
C21—H21
O4—H4
C6—C5
1.3939 (16)
0.9500
O7—C28B
O7—C22
O7—C28A
O8A—C25
O8A—C26A
O5—C25
C16—C17
C16—C15
C16—H16
C17—C18
C17—H17
C11—C13
C11—C12
C11—C10
C11—H11
C18—C13
C18—H18
C24—C23
C24—C19
C24—H24
C1—H1C
C1—H1A
C1—H1B
C7—C6
1.290 (6)
1.3654 (15)
1.386 (2)
1.336 (8)
1.429 (11)
1.1958 (17)
1.373 (2)
1.379 (2)
0.9500
C23—H23
C3—C4
1.3871 (17)
1.3917 (17)
0.9500
C3—C2
C3—H3A
C5—C4
1.3963 (17)
1.5186 (16)
1.3887 (17)
1.335 (12)
0.9500
C5—C8
C19—C20
C25—O8B
C20—H20
1.392 (2)
0.9500
C14—H14
0.9500
C28A—H28B
C28A—H28A
C28A—H28C
C27A—H27C
C27A—H27B
C27A—H27A
C27B—H27E
C27B—H27F
C27B—H27D
C26A—H26B
C26A—H26C
C26A—H26A
C28B—H28E
C28B—H28F
C28B—H28D
O8B—C26B
C26B—H26E
C26B—H26F
C26B—H26D
0.9800
1.5165 (15)
1.5560 (15)
1.5755 (15)
1.0000
0.9800
0.9800
0.9800
0.9800
1.3794 (18)
0.9500
0.9800
0.9800
1.3808 (17)
1.3994 (17)
0.9500
0.9800
0.9800
0.9800
0.9800
0.9800
0.9800
0.9800
0.9800
0.9800
1.3843 (17)
1.3854 (17)
0.9500
0.9800
C7—C2
0.9800
C7—H7
1.510 (18)
0.9800
C9—C10
C9—C8
1.5307 (16)
1.5346 (16)
1.0000
0.9800
C9—H9
0.9800
C10—C19
1.5075 (16)
S30