Synthesis of OSW saponin analogs with modified sugar residues and their antiproliferative activities

Article abstract of DOI:10.1016/j.bmcl.2006.11.032

Eight monosaccharide analogs of the potent antitumor OSW saponins (2-9) were synthesized. One analog, 2-O-acetyl-α-l-arabinopyranoside 3, showed antiproliferative activity against the Jurkat cells (IC₅₀ = 0.078 μM) comparable to that of the dis

Full text of DOI:10.1016/j.bmcl.2006.11.032

Bioorganic & Medicinal Chemistry Letters 17 (2007) 1003–1007
Synthesis of OSW saponin analogs with modified sugar residues
and their antiproliferative activities
Pingping Tang,a Fatemah Mamdani,b,c Xiaoyi Hu,b,c Jun O. Liub,c and Biao Yua,*
aState Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
bDepartment of Pharmacology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
cDepartment of Neuroscience, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Received 27 September 2006; revised 25 October 2006; accepted 13 November 2006
Available online 15 November 2006
Abstract—Eight monosaccharide analogs of the potent antitumor OSW saponins (2–9) were synthesized. One analog, 2-O-acetyl-a-
L-arabinopyranoside 3, showed antiproliferative activity against the Jurkat cells (IC50 = 0.078 lM) comparable to that of the disac-
charide derivative (1).
Ó 2006 Elsevier Ltd. All rights reserved.
About twenty OSW saponins, featuring a 16b,17a-
dihydroxycholest-22-one aglycone and an acylated su-
gar residue attached to the 16b-hydroxyl group
(Fig. 1), have been isolated from the bulbs of Ornithog-
alum saudersiae and its taxonomically related plants
since 1992.1 This class of cholestane glycosides have
attracted considerable attention due to their extremely
potent antitumor activities.2 OSW-1, for example,
showed a mean IC50 value of 0.78 nM when tested
against the growth of the NCI (the US National Cancer
Institute) 60 cell lines, which is 10–100 times lower than
those of the clinically used anticancer agents, such as cis-
platin, camptothecin, and taxol.1b Recent studies have
revealed that OSW-1 was able to induce the apoptosis
of tumor cells. However, the detailed molecular mecha-
nism of action still remains unknown.3 Several
approaches toward the total synthesis of OSW-1 have
been developed,4,5 which have allowed access to a vari-
ety of OSW-1 analogs.5,6 In particular, we recently
found that the steroidal C17-side chain could tolerate
certain modifications without significant loss of their
antiproliferative potency.5,6b In fact, the easily accessible
22-ester analog 1 (Fig. 1) showed slightly stronger inhib-
itory activity against the growth of some tumor cell lines
than OSW-1.5 The importance of the sugar residue to
the antiproliferative activity of OSW saponins has been
implicated by changes in activity among the natural con-
geners and their degradative products. The presence of
the 400-O-b-D-glucopyranosyl residue (Fig. 1), the ab-
sence of the 200-O-p-methoxybenzoyl (MBz) or -cinna-
moyl substitution, or the removal of both the 20-O-
acetyl and 200-O-p-methoxybenzoyl groups on the disac-
charide residue of OSW-1 reduced its activity by 10- to
1000-fold.1b–e
In an attempt to identify structurally simpler analogs of
OSW-1 with full antitumor activity, we turned our
attention to the disaccharide moiety. Based on the afore-
mentioned SAR data, we reasoned that truncation of
the disaccharide residue in compound 1 into a monosac-
charide derivative with the acetyl and p-methoxybenzoyl
groups retained at their positions like compound 2
would not significantly affect its antiproliferative activi-
ty. Should that proven true, it would further simplify the
synthesis of this structural class of antitumor agents.
Herein we report the synthesis of the monosaccharide
derivative 2 and its congeners 3–9 and the identification
of one potent analog, 3, that showed activity compara-
ble to OSW-1.
Keywords: OSW saponins; Glycosides; Synthesis; Antiproliferative
activities.
Glycosidic coupling of the 16-OH of a cholestane agly-
cone with a sugar trichloroacetimidate donor under mild
conditions has so far been the only solution to the
*
Corresponding author.
byu@mail.sioc.ac.cn
Fax:
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64166128; e-mail:
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doi:10.1016/j.bmcl.2006.11.032

1004
P. Tang et al. / Bioorg. Med. Chem. Lett. 17 (2007) 1003–1007
O
O
22
O
OH
OH
H
O
16
O
O
O
O
RO
2'
O
O
OH
H
H
3
O
4''
O
H
OH
HO
R1O
R1
2'' OR
HO
Natural OSW saponins:
R = p-methoxybenzoyl, cinnamoyl, or H
2: R = Ac, R1 = -(CH2)2OMBz
3: R = Ac, R1 = H
R1 = H or -D-glcp
4: R = Ac, R1 = All
OSW-1: R = p-methoxybenzoyl, R1 = H
O
5: R = MBz, R1 = H
6: R = MBz, R1 = All
7: R = MBz, R1 = -(CH2)2OMBz
8: R = MBz, R1 = -CH2CH=CH(CH2)8OMBz
9: R = MBz, R1 = -CH2CH=CHC(=O)OCH2CH3
22
O
OH
O
16
O
O
3' O
H
OH
O
O
O
O 1''
HO
HO
2''
O
23-Oxa-OSW analog (1)
Figure 1. The natural OSW saponins and their synthetic analogs (MBz = p-methoxybenzoyl).
assembly of OSW saponins.4b–d,5,6 Thus, the prepara-
tion of a relevant monosaccharide trichloroacetimidate
(e.g., 17a) would ensure the attainment of the monosac-
charide analog 2 (Scheme 1). Starting from L-arabinose,
p-methoxybenzyl 3,4-O-isopropylidene- a-L-arabinopyr-
anoside (10) was prepared by five chemical steps and in
46% yield.7 Acetylation of the remaining 2-OH followed
by removal of the isopropylidene protection provided
3,4-diol 11a. Selective allyl substitution of the equatorial
3-OH on 11a was achieved in good yield via a tin-med-
iated allylation, affording 12a. The remaining 4-OH was
then protected with a TES group. Conversion of the 3-
O-allyl group into a C2 alcohol met with no difficulty:
ozonolysis of the double bond followed by NaBH4
reduction provided 20-OH derivative 14a in 83% yield.
The nascent 20-OH was then masked with the MBz
group. Finally, the anomeric p-methoxybenzyl (PMB)
group was selectively cleaved with DDQ, and the result-
ing lactol was subjected to trichloroacetimidation, pro-
viding the desired arabinosyl donor 17a. Coupling of
the aglycone 185 with trichloroacetimidate 17a under
the promotion of a catalytic amount of TMSOTf at
low temperature (ꢀ40 °C) afforded the expected a-glyco-
side 19a in a satisfactory 56% yield. Final removal of the
protecting 3-O-TBS and 40-O-TES groups was achieved
with HFÆpyridine, furnishing the designed analog 2.
meric PMB group followed by trichloroacetimidation.
Alternatively, the diols 11a/b were protected with TES
group and then converted into the trichloroacetimidate
donors 23a/b (Scheme 2). Glycosylation of the aglycone
18 with the newly prepared trichloroacetimidate donors
17b, 20a/b, and 23a/b under similar conditions employed
with donor 17a afforded the corresponding a-glycosides
(19b, 21a/b, and 24a/b) in comparable yields (ꢁ60%). It
should be noted that the a-selectivity was ensured by the
neighboring participation of the 2-O-acetyl and -p-meth-
oxylbenzoyl groups in the imidate donors. Final remov-
al of the TBS and TES groups on the coupling products
(19b, 21a/b, and 24a/b) with HFÆpyridine afforded the
analogs 3–7 with varying monosaccharide residues.
Compounds 4/6 bearing an allyl group could be subject-
ed to further derivatization via the powerful olefin cross
metathesis reaction.5b,8 Thus, treatment of the allyl ether
6 with 9-decen-1-yl benzoate (20 equiv) and ethyl acry-
late (1.5 equiv) in the presence of the Grubbs (II) cata-
lyst (22 mol%) at refluxing CH2Cl2 provided the
corresponding coupling products 8 and 9 in 72% and
30% yield, respectively.
The in vitro activities of the synthetic monosaccharide
analogs 2–9 of OSW saponins,9 against the proliferation
of several human cancer cell lines including RKO (colon
carcinoma), Jurkat (human T cell leukemia), and HeLa
(human cervical cancer) cell lines, with the 22-ester ana-
log of OSW-1 (1) as a positive control,5 were determined
by following the incorporation of [3H]-thymidine.5b The
results are summarized in Table 1. Contrary to our
expectations, the designed analog 2, with the 20-O-acetyl
and 200-O-p-methoxybenzoyl groups being retained at
their positions as in the disaccharide residue in the par-
ent compound 1, exhibited negligible antiproliferative
activity at concentrations up to 10 lM. Neither did com-
pounds 5–9, all of which bear a 20-O-p-methoxybenzoyl
group, show much activity at 10 lM concentration.
Exploiting the chemistry developed for the synthesis of
the monosaccharide analog 2 of OSW saponins, we also
managed to obtain quickly a group of structurally relat-
ed analogs 3–9 (Schemes 1and 2). Thus, masking of the
2-OH on 10 with MBz group followed by removal of the
3,4-O-isopropylidene group gave 11b, which was trans-
formed into the 2-O-p-methoxybenzoyl-L-arabinopyr-
anosyl trichloroacetimidate 17b successfully employing
a similar procedure as that for 11a ! 17a (Scheme 1).
Retaining the 3-O-allyl group, compounds 13a/b were
readily converted into the corresponding trichloroace-
timidate donors 20a/b via oxidative cleavage of the ano-

P. Tang et al. / Bioorg. Med. Chem. Lett. 17 (2007) 1003–1007
OH OH
HO
1005
O
OTES
c
a,b
d
O
O
O
O
OPMB
OTES
OPMB
OPMB
OPMB
O
O
O
OH
OR
OR
OR
11a R = Ac
12a R = Ac
10
13a R = Ac
13b R = MBz
11b R =MBz
12b R = MBz
OTES
OTES
g
i
e,f
h
O
O
O
OPMB
OPMB
OH
OR
O
O
O
OR
OR
HO
MBzO
MBzO
14a R = Ac
14b R = MBz
15a R = Ac
15b R = MBz
16a R = Ac
16b R = MBz
O
OTES
O
O
O(CH2)11CH3
CCl3
NH
j
OH
O
+
H
16
OH
OR
MBzO
17a R = Ac
17b R = MBz
H
H
k
18
TBSO
O
O(CH2)11CH3
OH
O
O
2 and 7
RO
O
OTES
O
TBSO
19a R = Ac
19b R = MBz
O
O
Scheme 1. Reagents and conditions: (a) Ac2O, pyridine, rt, 88%; (b) 70% HOAc, 40 °C, 85%; (c) Bu2SnO, toluene, reflux, then AllBr, CsF, DMF, rt,
82%; (d) TESOTf, 2,6-lutidine, CH2Cl2, 0 °C, 91%; (e) O3, CH3OH/CH2Cl2, ꢀ78 °C; (f) NaBH4, CH3OH/CH2Cl2, 0 °C, 83% (2 steps); (g) MBzCl,
˚
pyridine/CH2Cl2, rt, 72%; (h) DDQ, H2O (buffer, pH 7)/CH2Cl2, rt, 92%; (i) CCl3CN, DBU, CH2Cl2, rt, 84%; (j) TMSOTf (0.2 equiv), CH2Cl2, 4 A
MS, ꢀ40 °C, 56%; (k) HFÆpyridine, CH2Cl2, rt, 80%.
O
OTES
O(CH2)11CH3
OH
c
a,b
d
O
CCl3
NH
13a/13b
11a/11b
O
4/6
O
O
O
18
RO
OR
O
OTES
20a R = Ac
20b R = MBz
TBSO
21a R = Ac
21b R = MBz
O
OTES
OTES
O(CH2)11CH3
OH
e
c
a,b
d
O
O
CCl3
NH
3/5
O
O
O
OMP
TESO
TESO
RO
18
OR
OR
TESO
OTES
22a R = Ac
22b R = MBz
23a R = Ac
23b R = MBz
24a R = Ac
24b R = MBz
O
O(CH2)11CH3
OH
f
8/9
O
O
O
MBzO
or
(CH2)7
OBz
O
OH
O
6
Scheme 2. Reagents and conditions: (a) DDQ, H2O (buffer, pH 7)/CH2Cl2, rt, 95%; (b) DBU, CCl3CN, CH2Cl2, rt, 91%; (c) TMSOTf (0.2 equiv),
˚
CH2Cl2, 4 A MS, ꢀ40 °C, ꢁ60%; (d) HFÆpyridine, CH2Cl2, rt, ꢁ94%; (e) TESOTf, 2,6-lutidine, CH2Cl2, 0 °C, ꢁ91%; (f) Grubbs II (22 mol%),
CH2Cl2, reflux, 72% (for 8), 30% (for 9).
Interestingly, however, the 2-O-acetyl-a-L-arabinopyr-
anoside 3 possessed highly potent activity against the
growth of Jurkat cells with an IC50 of 78 nM which is
comparable to that of the disaccharide derivative 1
(IC50 = 15 nM). Surprisingly, compound 3 showed no
activity against the RKO cells and a moderate activity
against the HeLa cells (IC50 = 1.2 lM). Compound 4
bearing an additional 3-O-allyl group showed moderate
activities against the RKO and HeLa cells (IC50 = 1.7
and 1.1 lM, respectively), but was inactive against Jur-

1006
P. Tang et al. / Bioorg. Med. Chem. Lett. 17 (2007) 1003–1007
Table 1. The antiproliferative activity of the synthetic OSW-1 analogs
(1–9) against tumor cells
3. (a) Zhu, J.; Xiong, L.; Yu, B.; Wu, J. Mol. Pharm. 2005, 68,
1831; (b) Zhou, Y.; Garcia-Prieto, C.; Carney, D. A.; Xu,
R. H.; Pelicano, H.; Kang, Y.; Yu, W.; Lou, C.; Kondo, S.;
Liu, J.; Harris, D. M.; Estrov, Z.; Keating, M. J.; Jin, Z.;
Huang, P. J. Natl. Cancer Inst. 2005, 97, 1781.
IC50 (lM)
1
2
3
4
5–9
4. (a) Guo, C.; Fuchs, P. L. Tetrahedron Lett. 1998, 39, 1099;
(b) Deng, S.; Yu, B.; Lou, Y.; Hui, Y. J. Org. Chem. 1999,
64, 202; (c) Morzycki, J. W.; Gryszkiewicz, A.; Jastrzebska,
I. Tetrahedron Lett. 2000, 41, 3751; (d) Yu, W.; Jin, Z.
J. Am. Chem. Soc. 2001, 123, 3369; (e) Morzycki, J. W.;
Wojtkielewicz, A. Carbohydr. Res. 2002, 337, 1269; (f) Xu,
Q.; Peng, X.; Tian, W. Tetrahedron Lett. 2003, 44, 9375.
5. (a) Shi, B.; Wu, H.; Yu, B.; Wu, J. Angew. Chem. Int. Ed.
2004, 43, 4324; (b) Shi, B.; Tang, P.; Hu, X.; Liu, J. O.; Yu,
B. J. Org. Chem. 2005, 70, 10354.
6. (a) Ma, X.; Yu, B.; Hui, Y.; Miao, Z.; Ding, J. Bioorg. Med.
Chem. Lett. 2001, 11, 2153; (b) Deng, L.; Wu, H.; Yu, B.;
Jiang, M.; Wu, J. Bioorg. Med. Chem. Lett. 2004, 14, 2781;
(c) Morzycki, J. W.; Wojtkielewicz, A.; Gryszkiewicz, A.;
Wolczynski, S. Bioorg. Med. Chem. Lett. 2004, 14, 3323.
7. Ple, K.; Chwalek, M.; Voutquenne-Nazabadioko, L. Eur.
J. Org. Chem. 2004, 7, 1588.
RKO
Jurkat
HeLa
0.0007
0.015
0.071
ND
ND
ND
ND
0.078
1.2
1.7
ND
1.1
ND
ND
ND
ND, IC50 not determined. These compounds did not show consider-
able inhibitory activities at a concentration of 10 lM.
kat cells. The differential sensitivity of different cell lines
to the same compound is also seen with the OSW-1
disaccharide analog 1 and is therefore not unique for
the monosaccharide analogs. It is intriguing that analog
1 is about 100-fold more potent against RKO than
HeLa cells, while analog 4 has a similar potency against
both cell lines. Similarly, analogs 3 and 4 are equally po-
tent against HeLa cells, but for Jurkat T cells, they differ
dramatically in their activity. The precise molecular
mechanism underlying these disparities in potency
among this class of OSW-1 analogs remains to be
elucidated.
8. (a) Blackwell, H. E.; O’Leary, D. J.; Chatterjee, A. K.;
Washenfelder, R. A.; Bussmann, D. A.; Grubbs, R. H.
J. Am. Chem. Soc. 2000, 122, 58; (b) Chatterjee, A. K.;
Choi, T. L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem.
Soc. 2003, 125, 11360.
In summary, based on the previous SAR data on the
highly potent antitumor OSW saponins, we rationally
designed and synthesized an analog bearing a truncated
sugar residue (2). The synthesis was achieved in 16 steps
and 6% overall yield starting from L-arabinose; and the
synthetic approach was adaptable to the quick elabora-
tion of the related compounds. Thus, the monosaccha-
ride analogs 3–9 were also prepared. Although the
designed analog 2, along with compounds 5–9, did not
show antiproliferative activity against cancer cell lines
tested, one monosaccharide analog, 2-O-acetyl-a-L-ara-
binopyranoside 3, showed activity comparable to that
of the disaccharide derivative (1) against the Jurkat cells
(IC50 = 0.078 lM). These results suggest that the sugar
moiety in the OSW saponins is essential for their potent
antitumor activity.
9. Analytical data for the monosaccharide analogs 2–9.
24
Compound 2: ½aꢂD ¼ 13:7 (c 0.47, CHCl3); 1H NMR
(500 MHz, CDCl3): d 7.98 (d, J = 8.8 Hz, 2H), 6.91 (d,
J = 8.8 Hz, 2H), 5.33 (br s, 1H), 4.91 (d, J = 1.9 Hz, 1H),
4.54 (m, 1H), 4.38 (m, 2H), 4.26 (m, 1H), 4.14 (m, 1H),
3.90–3.71 (m, 9H), 3.64 (m, 1H), 3.50 (m, 2H), 2.89 (q,
J = 7.5 Hz, 1H), 2.61 (m, 1H), 2.30–2.20 (m, 3H), 2.06 (s,
3H), 0.98 (s, 3H), 0.80 (s, 3H); 13C NMR (125 MHz,
CDCl3): d 178.9, 169.5, 166.2, 163.6, 140.6, 131.7, 122.2,
121.4, 113.7, 99.9, 90.4, 84.7, 71.7, 68.3, 64.9, 63.9, 63.5,
55.4, 49.5, 48.2, 45.7, 40.8, 36.4, 31.9, 31.8, 31.6, 29.6, 29.5,
29.5, 29.3, 29.2, 28.5, 25.8, 22.7, 20.8, 19.3, 14.1, 13.3, 12.9.
HRMS (ESI) calcd for C51H78O13Na (M+Na+): 921.5382;
25
found: 921.5335. Compound 3: ½aꢂD ¼ 27:5 (c 0.75, CHCl3);
1H NMR (300 MHz, CDCl3): d 5.45 (d, J = 3.6 Hz, 1H),
4.80 (dd, J = 3.0, 2.4 Hz, 1H), 4.44 (d, J = 2.7 Hz, 1H),
4.33–4.24 (m, 1H), 4.01–3.83 (m, 5H), 3.72 (dd, J = 11.7,
8.1 Hz, 1H), 3.65–3.48(m, 2H), 3.05 (d, J = 8.4 Hz, 1H),
2.89 (q, J = 7.5 Hz, 1H), 2.48–2.40 (m, 1H), 2.40–2.20 (m,
3H), 2.11 (s, 3H), 1.36 (d, J = 7.5 Hz, 3H), 1.07 (s, 3H), 0.88
(s, 3H); 13C NMR (75 MHz, CDCl3): d 178.8, 169.8, 140.7,
121.3, 99.9, 90.9, 84.5, 71.7, 70.7, 68.9, 65.1, 64.9, 61.1, 49.5,
48.1, 45.9, 42.2, 40.9, 37.2, 36.4, 34.5, 32.1, 31.9, 31.8, 31.6,
29.6, 29.5, 29.5, 29.3, 29.2, 28.4, 25.8, 22.6, 20.8, 20.5, 19.3,
14.1, 13.6, 13.0; HRMS (ESI) calcd for C41H68O10Na
(M+Na+): 743.4707; found: 743.4705. Compound 4:
Acknowledgments
This work was supported by the National Natural Sci-
ence Foundation of China (20372070 and 20321202),
the Chinese Academy of Sciences (KGCX2-SW-209),
and the Committee of Science and Technology of
Shanghai (04DZ14901).
19
½aꢂD ¼ ꢀ30:5 (c 0.66, CHCl3); 1H NMR (300 MHz,
CDCl3): d 5.99–5.81 (m, 1H), 5.34–5.21 (m, 3H), 4.93 (br
s, 1H), 4.36–4.25 (m, 3H), 4.05–3.71 (m, 6H), 3.58–3.48 (m,
3H), 2.93 (q, J = 7.5 Hz, 1H), 2.43–2.19 (m, 4H), 2.09 (s,
References and notes
3H), 1.36 (d, J = 7.5 Hz, 3H), 1.01 (s, 3H), 0.75 (s, 3H); 13
C
1. (a) Kubo, S.; Mimaki, Y.; Terao, M.; Sashida, Y.; Nikaido,
T.; Ohmoto, T. Phytochemistry 1992, 31, 3969; (b) Mimaki,
Y.; Kuroda, M.; Kameyama, A.; Sashida, Y.; Hirano, T.;
Oka, K.; Maekawa, R.; Wada, T.; Sugita, K.; Beutler, J. A.
Bioorg. Med. Chem. Lett. 1997, 7, 633; (c) Kuroda, M.;
Mimaki, Y.; Yokosuka, A.; Sashida, Y. Chem. Pharm. Bull.
2001, 49, 1042; (d) Kuroda, M.; Mimaki, Y.; Yokosuka, A.;
Sashida, Y.; Beutler, J. A. J. Nat. Prod. 2001, 64, 88; (e)
Kuroda, M.; Mimaki, Y.; Yokosuka, A.; Hasegawa, F.;
Sashida, Y. J. Nat. Prod. 2002, 65, 1417.
NMR (75 MHz, CDCl3): d 179.0, 169.5, 140.6, 133.9, 121.5,
117.6, 99.9, 90.5, 84.7, 74.6, 71.7, 70.5, 68.1, 61.9, 63.9, 60.8,
49.5, 48.3, 45.7, 42.3, 40.7, 37.1, 36.4, 34.5, 32.2, 31.9, 31.8,
31.6, 29.7, 29.6, 29.5, 29.5, 29.3, 29.2, 28.5, 25.8, 22.6, 20.8,
20.6, 19.3, 14.1, 13.4, 12.9; HRMS (ESI) calcd for
C44H72O10Na (M+Na+): 783.5022; found: 783.5018. Com-
19
pound 5: ½aꢂD ¼ ꢀ8:4(c 1.01, CHCl3); 1H NMR (300 MHz,
CDCl3): d 7.97 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H),
5.34 (br s, 1H), 4.98 (br s, 1H), 4.64 (m, 1H), 4.22 (m, 1H),
4.11–4.04 (m, 4H), 3.87 (s, 3H), 3.70 (m, 2H), 3.60–3.50 (m,
2. Rouhi, A. M. Chem. Eng. News 1995, 11, 28.

P. Tang et al. / Bioorg. Med. Chem. Lett. 17 (2007) 1003–1007
1007
1H), 3.18–2.91 (m, 1H), 1.01 (s, 3H), 0.87 (s, 3H), 0.85 (s,
3H); 13C NMR (75 MHz, CDCl3): d 178.4, 164.3, 163.4,
140.2, 131.4, 120.9, 120.7, 113.2, 99.3, 90.8, 84.0, 71.1, 69.7,
67.9, 64.9, 63.8, 59.6, 54.9, 48.9, 47.6, 45.4, 41.7, 40.3, 36.6,
35.9, 33.9, 31.5, 31.4, 31.2, 31.1, 29.2, 29.1, 29.0, 28.8, 28.7,
27.8, 25.2, 22.1, 20.0, 18.8, 13.5, 13.3, 12.4; HRMS
(MALDI) calcd for C47H72O11Na (M+Na+): 835.4997;
found: 875.5279. Compound 7: 1H NMR (300 MHz,
CDCl3): d 7.99–7.95 (m, 4H), 6.92–6.87 (m, 4H), 5.34 (br
s, 1H), 5.10 (br s, 1H), 4.54 (m, 2H), 4.42 (m, 1H), 4.25–4.18
(m, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 3.56 (m, 2H), 2.93 (m,
1H), 2.63 (m, 1H), 1.10 (s, 3H), 0.99 (s, 3H), 0.96 (s, 3H),
0.88 (s, 3H). Compound 8: 1H NMR (500 MHz, CDCl3): d
8.05 (d, J = 8.3 Hz, 2H), 7.97 (d, J = 8.8 Hz, 2H), 7.56–7.43
(m, 2H), 6.91 (d, J = 8.8 Hz, 2H), 5.78 (m, 1H), 5.56 (m,
1H), 5.35 (br s, 2H), 5.11 (d, J = 2.0 Hz, 2H), 4.53 (br, 1H),
4.36–4.29 (m, 3H), 4.21 (m, 1H), 4.07–3.89 (m, 3H), 3.86 (s,
3H), 3.81–3.73 (m, 3H), 3.53 (m, 2H), 3.00 (q, J = 7.5 Hz,
1H), 1.01 (s, 3H); HRMS (MALDI) calcd for C65H96O13Na
21
found: 835.4967. Compound 6: ½aꢂD ¼ ꢀ17:5 (c 1.18,
CHCl3); 1H NMR (300 MHz, CDCl3):
d 7.97 (d,
J = 8.4 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H), 5.94 (m, 1H),
5.37 (m, 2H), 5.24 (m, 1H), 5.13 (br s, 1H), 4.55 (br s, 1H),
4.43 (m, 1H), 4.23 (m, 1H), 4.11–4.04 (m, 2H), 3.87 (s, 3H),
3.60–3.50 (m, 2H), 2.98 (m, 1H), 1.02 (s, 3H), 0.88 (s, 3H),
0.86 (s, 3H); 13C NMR (75 MHz, CDCl3): d 179.1, 164.7,
163.8, 140.6, 134.0, 131.8, 121.6, 121.4, 117.6, 113.7, 107.8,
99.8, 90.6, 84.8, 74.3, 71.7, 70.6, 67.9, 65.1, 63.8, 55.4, 49.5,
48.3, 45.7, 42.3, 40.7, 36.4, 34.5, 31.9, 31.8, 29.7, 29.6, 29.5,
29.3, 29.2, 28.4, 25.8, 22.6, 19.4, 14.1, 13.5, 12.8; HRMS
(MALDI) calcd for C50H76O11Na (M+Na+): 875.5279;
1
(M+Na+): 1107.6764; found: 1107.6743. Compound 9: H
NMR (300 MHz, CDCl3): d 7.98 (d, J = 9.0 Hz, 2H), 7.06–
6.91 (m, 3H), 6.15–6.09 (m, 0.5H), 5.36 (br s, 1.5H), 5.10
(m, 1H), 4.64 (m, 1H), 4.56 (br s, 1H), 4.32–4.22 (m, 4H),
4.02 (m, 2H), 3.88 (s, 3H), 3.83–3.56 (m, 5H), 2.91–2.88
(m, 1H), 1.02 (s, 3H), 0.88 (s, 3H), 0.87 (s, 3H), 0.86
(s, 3H).