Efficient syntheses of chiral myo-inositol derivatives-key intermediates in glycosylphosphatidylinositol (GPI) syntheses

Article abstract of DOI:10.1016/j.bmcl.2009.03.151

A facile and effective method was developed for large-scale syntheses of myo-inositol derivatives with the 1,2,6-O-positions differentiated from each other and from other positions as well. The syntheses started from methyl α-d-glucopyranoside, and the ke

Full text of DOI:10.1016/j.bmcl.2009.03.151

Bioorganic & Medicinal Chemistry Letters 19 (2009) 3852–3855
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Efficient syntheses of chiral myo-inositol derivatives—key intermediates
in glycosylphosphatidylinositol (GPI) syntheses
*
Fei Yu, Zhongwu Guo
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI 48202, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and effective method was developed for large-scale syntheses of myo-inositol derivatives with
Received 17 February 2009
Revised 30 March 2009
Accepted 31 March 2009
Available online 5 April 2009
the 1,2,6-O-positions differentiated from each other and from other positions as well. The syntheses
started from methyl
a-D-glucopyranoside, and the key steps are Ferrier rearrangement and a series of
other regioselective and stereoselective reactions. The target compounds are key intermediates in the
synthesis of GPIs.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
myo-Inositol
GPI
Ferrier rearrangement
Methyl a-D-glucopyranoside
R'O OR2
GPI-anchoring of surface proteins to cell membranes is ubiqui-
tous in the eukaryotic world, so GPIs and GPI-anchored proteins
play an important role in various biological processes.1,2 GPIs are
complex glycolipids sharing a highly conserved core structure 1,
and the GPI-linked proteins are invariably attached to the phos-
phoethanolamine moiety at the non-reducing end of the GPI core
glycan.1,2 Due to the microheterogenic property of GPIs in nature,
the access to homogeneous GPIs has to rely on chemical synthesis,
which is currently a challenging topic. One of the challenges is ac-
cess to appropriately protected optically pure myo-inositol deriva-
tives—the key intermediates for GPI synthesis,3–16 such as 2 and 3
that have the 1,6-O- and 1,2,6-O-positions differentiated from each
other and from the remaining hydroxyl groups of inositol. This Let-
ter describes a facile method to prepare these important synthetic
intermediates.
In the past two decades, several methods have been estab-
lished for the synthesis of optically pure inositol derivatives.17,18
Some of the methods exploited naturally occurring optically ac-
tive inositol and sugar derivatives,19,20 while others were based
on de novo syntheses, for example, via microbial oxidation of a
derivatized arene21,22 or via ring-closing metathesis of a chiral
diene followed by stereoselective dihydroxylation.23,24 The
majority of the reported syntheses started with the readily avail-
able free achiral myo-inositol, and these methods needed to re-
solve the enantiomers of a chiral inositol derivative at certain
synthetic stage.17,18
OH
P
O
HO
HO
R6O
R6O
OR'
OR'
O
O
O
R1O
HO
3
HO
O
O
R'O OR'
NH2
HO
OR'
OR'
HO
R1O
HO
O
O
2
HO
HO
OH
O
O
HO
H2N
OR
4
2
HO
OH
OH
O
6
5
O
1
3
R = H or palmitoyl
O P
OH
O
O lipid
O lipid
1
In our research to establish a truly practical method for the syn-
thesis of 1,6-O-differentiated and 1,2,6-O-differentiated chiral
myo-inositol derivatives, we became interested in a strategy21,25–27
based on the stereospecific Ferrier rearrangement of sugar deriva-
tives,28 because the stereochemistries of reactions and intermedi-
ates involved in this synthesis were defined and the strategy
could offer an easy and efficient access to a partially protected
optically active inositol analog 6 starting from the readily available
methyl a-D-glucopyranoside 4 (Scheme 1). However, a major chal-
lenge here is the design and implementation of a series of reactions
for effective differentiation of the latent inositol 1,2,6-O-positions
in 6. Initially, we attempted to first protect the single free hydroxyl
group of 6 to differentiate it from the other hydroxyl groups, but
this strategy failed. Although a THP group could be introduced to
* Corresponding author. Tel.: +1 313 577 2557; fax: +1 313 577 8822.
E-mail address: zwguo@chem.wayne.edu (Z. Guo).
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.03.151

F. Yu, Z. Guo / Bioorg. Med. Chem. Lett. 19 (2009) 3852–3855
3853
group followed by 6-O-alkylation and then regioselective reactions
to distinguish 1,2-O-positions. The reaction of 9 and Me2C(OMe)2
was regiospecific, and the location of the ketal functionality in 10
was confirmed via acetylating the remaining free hydroxyl group,
which resulted in a significant downfield shift of the H-6 NMR sig-
nal. Allylation of 10 was straightforward to give 11, which was sub-
jected to acidic hydrolysis to form 12. For the large scale
preparation, reaction intermediates 10 and 11 were not purified,
and the desired product 12 was obtained in an excellent overall
yield (84%) after three steps of transformation. As previously re-
ported,15 regioselective p-methoxybenzylation of the C-1-hydroxyl
group of 12 was achieved via a tin-complex to afford 13, which has
differentiated 1,2,6-O-positions. Compound 13 was the key inter-
mediate in our synthesis of CD52 GPI containing a 2-O-acylated
inositol residue.16 Meanwhile, the free hydroxyl group of 13 was
readily benzylated to form 14, which has differently protected
1,6-O-positions and should be useful for the synthesis of other
GPIs. For example, the allyl (All) and p-methoxybenzyl (PMB)
groups of 14 can be easily and selectively removed to produce 15
and 16, respectively, which are ready for 1-O-phospholipidation
and 6-O-glycosylation which are necessary steps in GPI synthesis.
The other synthetic method developed for differentiating the
free hydroxyl groups of 9 combined regioselective protection of
the 1,2-cis-diol with a benzylidene group and subsequent regiose-
lective ring opening of the resulting acetal (Scheme 3). The reaction
between 9 and PhCH(OMe)2 was highly regioselective for the 1,2-
cis-diol to afford a 1:1 mixture of the endo and exo acetals, 17 and
18, in an excellent yield (95%). The regiochemistry of 17 and 18
was confirmed via acetylating the remaining free hydroxyl groups,
which resulted in major downfield shifts of the H-6 NMR signals.
The stereochemistry of 17 and 18 was determined by NMR NOE
experiments, where strong NOEs were observed between the ace-
tal H and H-2,3 for 17 and strong NOEs were observed between the
acetal H and H-6 for 18. Allylation of 17 and 18 was simple, which
gave 19 and 20, respectively. The reductive ring opening reactions
of 19 and 20 proved to be regiospecific, and each reaction gave only
one product (Table 1, entries 1–6). However, it is interesting to no-
tice that the endo epimer 19 only gave 15 while the exo epimer 20
only gave 21, no matter which reducing reagent and acid catalyst,
including both HCl and sterically hindered Lewis acids, were uti-
lized. Again, the regiochemistry of 15 and 21 was confirmed by
acetylation experiments. These results were in contrast to litera-
O
various reductive
conditions
BnO
BnO
OAc
complex results
BnO
OTHP
7
g (17%)
OAc
HO
HO
HO
O
O
O
f (60%)
a,b,c,d,e BnO
BnO
BnO
OAc
BnO
(78%)
HO
MeO
BnO
6
Ferrier
BnO
OH
MeO reaction
4
5
h (54%)
HO
HO
1
6
i
BnO
BnO
BnO
OAc
OH
5
3
2
(quant.)
BnO
4
BnO
8
BnO
OH
OH
9
alkylation or silylation
complex results
Scheme 1. Reagents and conditions: (a) TrCl, pyr., reflux; (b) BnBr, NaH, DMF, rt; (c)
H2SO4, MeOH, rt; (d) (COCl)2, DMSO, CH2Cl2, ꢀ78 °C; (e) Ac2O, K2CO3, CH3CN, 80 °C;
(f) Hg(OAc)2, CH3COCH3/H2O, rt, then NaCl, rt; (g) DHP, PPTS, CH2Cl2, rt; (h)
NaBH(OAc)3, CH3CN/AcOH, rt; (i) NaOH, MeOH, reflux.
protect the free hydroxyl group of 6, the attempts to reduce the
carbonyl group of 7 under various conditions were unsuccessful.
Therefore, the carbonyl group of 6 was reduced with NaBH(OAc)3
to give 8 stereospecifically.25 The stereochemistry of 8 was con-
firmed by the observed large coupling constants between H-6
and H-1/H-5 for its 1H NMR spectrum. In this transformation, the
free hydroxyl group of 6 might have assisted the stereoselectivity
by, for example, coordinating with the reducing reagent. Next,
we tried to selectively protect one of the two hydroxyl groups of
8 with an alkyl or silyl group, but under various conditions, includ-
ing the use of mild bases and acids as catalysts, the reaction gave
complex results, probably due to acetyl migration and/or due to
the lack of regioselectivity. Consequently, 8 was deacetylated.
We developed three synthetic methods for differentiating the
free hydroxyl groups of 9. The first method (Scheme 2) was based
on the protection of the 1,2-cis-diol of 9 with an isopropylidene
ture results observed with cyclic acetals of carbohydrates.29,30
A
AllO
HO
a
BnO
BnO
b
O
O
9
BnO
BnO
BnO
11
BnO
O
O
HO
HO
10
a
BnO
BnO
BnO
BnO
O
O
9
+
(95%)
c (84%, overall)
BnO
17
b (80%)
BnO
O
18
b (80%)
O
H
H
Ph
Ph
AllO
AllO
BnO
BnO
Ph
H
d
BnO
OPMB
OH
OH
BnO
(89%)
BnO
13
BnO
12
OH
AllO
AllO
BnO
BnO
BnO
O
O
BnO
AllO
e (94%)
BnO
BnO
O
20
O
BnO
OH
BnO
19
Ph
H
BnO
15
OBn
AllO
see Table 1
see Table 1
BnO
BnO
OPMB
HO
BnO
14
AllO
15
OBn
BnO
OPMB
BnO
BnO
BnO
OBn
BnO
16
OBn
BnO
OH
21
Scheme 2. Reagents and conditions: (a) 2,2-dimethoxypropane, p-TsOH, DMF, rt;
(b) AllBr, NaH, DMF, rt; (c) HCl, MeOH, rt; (d) Bu2SnO, TBAI, toluene, reflux, then
PMBCl, CsF, reflux; (e) BnBr, NaH, DMF, rt.
Scheme 3. Reagents and conditions: (a) PhCH(OMe)2, p-TsOH, CH3CN, rt; (b) AllBr,
NaH, DMF, rt.

3854
F. Yu, Z. Guo / Bioorg. Med. Chem. Lett. 19 (2009) 3852–3855
Table 1
Acknowledgments
Results of the reductive ring opening of acetals 19, 20, 22 and 23 under various
conditions
This research was supported in part by NSF (CHE-0407144 and
0715275) and Mizutani Foundation for Glycoscience. We thank Dr.
B. Shay and Dr. L. Hryhorczuk for the HR MS measurements and Dr.
B. Ksebati for some help with NMR NOE measurements.
Entry
Reaction conditions
Reactant
Product yield (%)
1
2
3
4
5
6
7
8
9
NaBH3CN, AlCl3, THF, 0 °C
NaBH3CN, HCl, Et2O, THF, 0 °C
NaBH3CN, AlCl3, THF, 0 °C
NaBH3CN, HCl, Et2O, THF, 0 °C
Et3SiH, BF3ꢃEt2O, CH2Cl2, 0 °C
LiAlH4, AlCl3, CH2Cl2, Et2O, refl.
NaBH3CN, AlCl3, THF, 0 °C
NaBH3CN, HCl, Et2O, THF, 0 °C
LiAlH4, AlCl3, CH2Cl2, Et2O, refl.
NaBH3CN, AlCl3, THF, 0 °C
19
19
20
20
20
20
22
22
22
23
23
23
15 (81)
15 (67)
21 (82)
21 (83)
21 (58)
21 (71)
24 (62)
24 (72)
24 (56)
13 (67)
13 (72)
13 (54)
References and notes
1. Ferguson, M. A. J.; Williams, A. F. Ann. Rev. Biochem. 1988, 57, 285.
2. Thomas, J. R.; Dwek, R. A.; Rademacher, T. W. Biochemistry 1990, 29, 5413.
3. Udodong, U. E.; Madsen, R.; Roberts, C.; Fraser-Reid, B. J. Am. Chem. Soc. 1993,
115, 7886.
4. Campbell, A. S.; Fraser-Reid, B. J. Am. Chem. Soc. 1995, 117, 10387.
5. Baeschlin, D. K.; Chaperon, A. R.; Charbonneau, V.; Green, L. G.; Ley, S. V.;
Lucking, U.; Walther, E. Angew. Chem., Int. Ed. 1998, 37, 3423.
6. Baeschlin, D. K.; Chaperon, A. R.; Green, L. G.; Hahn, M. G.; Ince, S. J.; Ley, S. V.
Chem. Eur. J. 2000, 6, 172.
10
11
12
NaBH3CN, HCl, Et2O, THF, 0 °C
LiAlH4, AlCl3, CH2Cl2, Et2O, refl.
7. Martin-Lomas, M.; Khiar, N.; Garcia, S.; Koessler, J.-L.; Nieto, P. M.; Rademache,
T. W. Chem. Eur. J. 2000, 6, 3608.
8. Dietrich, H.; Espinosa, J. F.; Chiara, J. L.; Jimenez-Barbero, J.; Leon, Y.; Varela-
Nieto, I.; Mato, J.-M.; Cano, F. H.; Foces-Foces, C.; Martin-Lomas, M. Chem. Eur.
J. 1999, 5, 320.
9. Murakata, C.; Ogawa, T. Tetrahedron Lett. 1990, 31, 2439.
10. Murakata, C.; Ogawa, T. Carbohydr. Res. 1992, 235, 95.
11. Murakata, C.; Ogawa, T. Tetrahedron Lett. 1991, 32, 671.
12. Mayer, T. G.; Kratzer, B.; Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1994, 33,
2177.
13. Mayer, T. G.; Weingart, R.; Münstermann, F.; Kawada, T.; Kurzchalia, T.;
Schmidt, R. R. Eur. J. Org. Chem. 1999, 2563.
14. Kratzer, B.; Mayer, T. G.; Schmidt, R. R. Eur. J. Org. Chem. 1998, 291.
15. Xue, J.; Guo, Z. Bioorg. Med. Chem. Lett. 2002, 12, 2015.
16. Xue, J.; Guo, Z. J. Am. Chem. Soc. 2003, 125, 16334.
potential explanation for these observations is that the O-1 posi-
tion of 19 is less sterically hindered than the O-2 position, thus,
the acid catalyst would preferably attack O-1 to afford 15 as the
ring opening product, but for 20 the O-2 position may be more
accessible for the acid catalyst. We have also examined the ring
opening reaction using other reagents and catalysts, such as
BH3ꢁTHF/TMSOTf, BH3ꢁTHF/CoCl2, BH3ꢁTHF/Cu(OTf)2, and DIBAL-
H, but we observed that under these conditions the reaction was
either very complex or did not proceed at all.
Finally, the 1,2-cis-diol of
9 was also protected with a
p-methoxybenzylidene group, which was followed by allylation
to give isomers 22 and 23 in a combined over yield of 80% (Scheme
4). The configurations of 22 and 23 were determined by NOE
experiments and by comparing their 1H NMR spectra with that
of 19 and 20.22 Similar to 19 and 20, the reductive ring opening
of the acetal group of 22 and 23 was regiospecific to afford only
24 and 13, respectively, under several reductive conditions (Table
1, entries 7–12). Since compound 24 has 1,2,6-O-positions differ-
entiated as well, it should be also useful for GPI syntheses.
In summary, three efficient and practical synthetic methods
have been developed for large-scale preparations of chiral myo-
inositol derivatives that have distinctive protections at 1,2,6-O-
positions. Compound 1332 was prepared in 11–12 steps starting
17. Sureshan, K. M.; Shashidhar, M. S.; Praveen, T.; Das, T. Chem. Rev. 2003, 103,
4477.
18. Guo, Z.; Bishop, L. Eur. J. Org. Chem. 2004, 3585.
19. Luchetti, G.; Ding, K.; Kornienko, A.; d’Alarcao, M. Synthesis 2008, 3148.
20. Kornienko, A.; Turner, D. I.; Jaworek, C. H.; d’Alarcao, M. Tetrahedron:
Asymmetry 1998, 9, 2783.
21. Jia, Z. J.; Olsson, L.; Fraser-Reid, B. J. Chem. Soc., Perkin Trans. 1 1998, 631.
22. Hudlicky, T.; Mandel, M.; Rouden, J.; Lee, R. S.; Bachmann, B.; Dudding, T.; Yost,
K. J.; Merola, J. S. J. Chem. Soc., Perkin Trans. 1 1994, 1553.
23. Conrad, R. M.; Grogan, M. J.; Bertozzi, C. R. Org. Lett. 2002, 4, 1359.
24. Luchetti, G.; Ding, K.; d’Alarcao, M.; Kornienko, A. Synthesis 2008, 3142.
25. Bender, S. L.; Budhu, R. J. J. Am. Chem. Soc. 1991, 113, 9883.
26. Estevez, V. A.; Prestwich, G. D. J. Am. Chem. Soc. 1991, 113, 9885.
27. Lu, J.; Jayaprakash, K. N.; Fraser-Reid, B. Tetrahedron Lett. 2004, 45, 879.
28. Ferrier, R. J.; Middleton, S. Chem. Rev. 1993, 93, 2779.
29. Johansson, R.; Samuelsson, B. J. Chem. Soc., Chem. Commun. 1984, 201.
30. Johnsson, R.; Olsson, D. U. E. J. Org. Chem. 2008, 73, 5226.
31. Crossman, A., Jr.; Paterson, M. J.; Ferguson, M. A. J.; Smith, T. K.; Brimacombea,
J. S. Carbohydr. Res. 2002, 337, 2049.
from methyl
a-D-glucopyranoside (Schemes 1, 2 and 4) to obtain
15–19% overall yields. Compounds 15, 21 and 2432 were prepared
in 10–11 steps (Schemes 1, 3 and 4) with 13–17% overall yields. All
these compounds are useful intermediates in GPI synthesis,
depending on the specific design for a GPI synthesis and the inter-
mediates involved; therefore, all three synthetic methods are use-
ful. However, the method described in Scheme 2 is recommended
for most applications, because of its higher overall yield and flexi-
bility to introduce different protecting groups at 1,2,6-O-positions
in the synthesis.
32. Spectroscopic data of some synthetic targets 13:15
½
a 2D2
ꢂ
¼ ꢀ7:9 (c 1.0, CHCl3); 1
H
NMR (400 MHz, CDCl3): d 7.37–7.23 (m, 17 H, Ph), 6.90 (d, J = 8.8 Hz, 2H, Ph),
6.04–5.94 (m, 1H, ACH@), 5.30 (dd, J = 1.6, 18.0 Hz, 1H,@CH2), 5.18 (dd, J = 1.6,
8.8 Hz, 1H,@CH2), 4.94–4.81 (m, 4H, Bn), 4.72–4.61 (m, 4H, Bn), 4.40 (dd,
J = 5.6, 12.0, Hz, 1H, CH2AC@), 4.34 (dd, J = 5.6, 12.0 Hz, 1H, CH2AC@), 4.17 (t,
J = 2.4 Hz, 2-H), 3.99–3.91 (m, 1H, 4-H), 3.88–3.74 (m, 1H, 6-H), 3.82 (s, 3 H,
OMe), 3.40 (t, J = 9.6 Hz, 1H, 5-H), 3.37 (dd, J = 2.4 Hz, 1H, 1-H), 3.31 (dd, J = 2.4,
8.8 Hz, 1H, 3-H), 2.46 (s, 3 H, OH). 13C NMR (CDCl3, 100.0 MHz): d 159.3,
138.73, 138.65, 137.9, 135.3, 130.1, 129.8, 129.4, 128.4, 128.3, 128.0, 127.82,
127.79, 127.6, 127.5, 116.6, 83.1, 81.1, 80.8, 79.7, 79.2, 75.95, 75.89, 74.5, 72.6,
72.4, 67.6. MS (ESI) m/z: calcd for C38H42O7 [M+], 610.3. Found: 649.1 (M+K+),
633.1 (M+Na+).
Compound 15:31
½
a 2D2
ꢂ
¼ ꢀ8:3 (c 0.6, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.40–
7.24 (m, 20H), 6.02–5.88 (m, 1H, ACH@), 5.26 (dd, J = 2.4, 17.1 Hz, 1H, @CH2),
5.15 (d, J = 10.0 Hz, = CH2), 5.04–4.66 (m, 8 H, Bn), 4.36 (dd, J = 7.6, 16.0 Hz, 1 H,
CH2AC@), 4.28 (dd, J = 7.6, 16.0 Hz, 1H, CH2AC@), 4.06–4.00 (m, 2H, 2,4-H),
3.67 (t, J = 12.0, Hz, 1H, 5-H), 3.50–3.40 (m, 3H, 1,3,6-H). 13C NMR (CDCl3,
100.0 MHz): d 138.7, 135.1, 128.4, 128.3, 128.0, 127.9, 127.75, 127.68, 127.6,
127.5, 117.1, 83.5, 81.9, 81.8, 81.1, 77.1, 75.9, 75.8, 74.7, 74.3, 73.0, 72.3. MS
(ESI) m/z: calcd for C37H40O6 [M+], 580.0. Found: 619.1 (M+K+), 603.1 (M+Na+).
AllO
AllO
a,b
(80%)
BnO
BnO
O
O
H
9
+
BnO
BnO
BnO
BnO
O
23
O
H
PMP
22
PMP
Compound 21: ½a 2D2
ꢂ
¼ ꢀ6:0 (c 0.85, CHCl3); 1H NMR (400 MHz, CDCl3): d 7.40–
seeTable1
seeTable1
7.22 (m, 20H, Ph), 6.02–5.90 (m, 1H, ꢀCH@), 5.27 (d, J = 16.8 Hz, 1H,@CH2),
5.16 (d, J = 10.8 Hz, 1H,@CH2), 4.90–4.64 (m, 8H, Bn), 4.38 (dd, J = 5.6, 12.0 Hz,
1H, CH2AC@), 4.33 (dd, J = 5.6, 12.0 Hz, CH2AC@), 4.19 (t, J = 2.1 Hz, 1H, 2-H),
3.98–3.91 (m, 1H, 4-H), 3.84 (t, J = 9.6 Hz, 1H, 5-H), 3.42–3.28 (m, 3H, 1,3,6-H).
13C NMR (CDCl3, 100.0 MHz): d 138.7, 138.6, 137.9, 135.2, 128.4, 128.3, 128.0,
127.84, 127.81, 127.59, 127.56, 116.7, 83.1, 81.1, 80.8, 79.7, 79.6, 76.0, 75.9,
74.6, 72.8, 72.7, 67.6. HRMS (ESI): calcd for C37H40O6Na [M+Na+]: 603.2723.
Found: 603.2701.
AllO
13
BnO
BnO
OH
BnO
24
OPMB
Compound 24: ½a 2D2
ꢂ
¼ ꢀ5:8 (c 1.1, CHCl3); 1H NMR (400 MHz, CDCl3) d 7.38–
Scheme 4. Reagents and conditions: (a) p-MeOPhCH(OMe)2, p-TsOH, CH3CN, rt; (b)
AllBr, NaH, DMF, rt.
7.26 (m, 17H, Ph), 6.86 (d, J = 8.0 Hz, 2H, Ph), 6.00–5.88 (m, 1H, ACH@), 5.25 (d,

F. Yu, Z. Guo / Bioorg. Med. Chem. Lett. 19 (2009) 3852–3855
3855
J = 16.8 Hz, 1H,@CH2), 5.15 (d, J = 9.2 Hz,@CH2), 4.96–4.78 (m, 5H, Bn), 4.71–
4.62 (m, 3H, Bn), 4.34 (dd, J = 5.2, 12.0 Hz, 1H, CH2AC@), 4.25 (dd, J = 5.2,
12.0 Hz, 1H, CH2AC@), 4.04–3.96 (m, 2H, 2,4-H), 3.80 (s, 3H, OMe), 3.64 (t,
J = 9.6, Hz, 1H, 5-H), 3.46–3.36 (m, 3H, 1,3,6-H), 2.75 (d, J = 6.8 Hz, 1H, OH); 13C
NMR (CDCl3, 100.0 MHz): d 135.1, 129.5, 128.4, 128.3, 128.0, 127.9, 127.7,
127.5, 117.0, 113.7, 83.5, 82.0, 81.7, 81.1, 76.4, 75.9, 75.7, 74.3, 72.0, 72.3, 55.3;
HRMS (ESI): calcd for C38H42O7Na [M+Na+]: 633.2828. Found: 633.2830.