A Pd-mediated intramolecular ketalization of alkynediols: construction of the central [3.2.1]-bicyclic ketal core of cyclodidemniserinol trisulfate

Article abstract of DOI:10.1016/j.tetlet.2009.06.023

A preliminary study dealing with the Pd-mediated alkynediol cycloisomerization to construct the central bicyclic ketal core of cyclodidemniserinol trisulfate is documented.

Full text of DOI:10.1016/j.tetlet.2009.06.023

Tetrahedron Letters 50 (2009) 4844–4847
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Tetrahedron Letters
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A Pd-mediated intramolecular ketalization of alkynediols: construction
of the central [3.2.1]-bicyclic ketal core of cyclodidemniserinol trisulfate
*
C. V. Ramana , Rosy Mallik, Gokarneswar Sahoo
National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A preliminary study dealing with the Pd-mediated alkynediol cycloisomerization to construct the central
bicyclic ketal core of cyclodidemniserinol trisulfate is documented.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 23 April 2009
Revised 1 June 2009
Accepted 4 June 2009
Available online 9 June 2009
Keywords:
Cyclodidemniserinol trisulfate
Bridged bicyclic ketal
Alkynol cycloisomerization
Yamaguchi oxirane-alkyne coupling
Cyclodidemniserinol trisulfate was isolated in 2000 by Faulkner
and co-workers through a bioassay-guided fractionation of the
methanol extract of Palauan ascidian Didemnum guttatum
(Fig. 1).1 Cyclodidemniserinol trisulfate inhibited the purified HIV
alcohol under the Swern conditions followed by the Ohira–Best-
mann alkynylation10 gave the alkynol fragment 5 in good yields.
D-Gluconolactone was advanced to the known methyl ester 9 fol-
lowing the reported procedure.11,12 The controlled reduction of
methyl ester 9 using DIBAL-H in toluene at ꢀ78 °C gave the alde-
hyde 6. Initial attempts to directly add the lithiated alkyne 5 or
the corresponding Grignard reagent to aldehyde 6 resulted mainly
in the elimination product 10 along with the requisite alkynols 11.
The formation of 10 could be explained by the presence of a poten-
tial leaving group such as acetonide b to the carbonyl.12 Following
Carriera’s protocol,8 that is, employing Et2Zn, Ti(OiPr)4 and (S)-BI-
NOL, the elimination could be circumvented with good yields of
the alkynols 11. However, the diastereomeric ratio was poor
(4:3). As the reaction without chiral ligand also gave a similar dia-
stereomeric ratio, the alkynylation reaction has been optimized
without the chiral ligand to afford a diastereomeric mixture (3:2)
of 11 in 69% yields over two steps. Oxidation of the resulting prop-
argylic alcohol with MnO2 and the selective 1,3-syn reduction13 of
the intermediate alkynone with LiI–LAH at ꢀ100 °C gave the alky-
nol 11b with excellent diastereoselectivity (>20:1). The terminal
isopropylidene group of 11b was selectively deprotected by expos-
ing it to 0.8% H2SO4 in MeOH. Perbenzylation of the resulting triol
12 using NaH and BnBr and subsequent acetonide hydrolysis com-
pleted the synthesis of alkynol 3 (Scheme 1).
integrase with an IC50 of 60
with an IC50 of 72 g/mL. The complete constitution of cyclodi-
demniserinol trisulfate (1) was elucidated with the help of exten-
sive NMR and mass spectral analyses, albeit with partial
lg/mL and also MCV topoisomerase
l
a
assignment of relative/absolute stereochemistry. In continuation
of our interest in the synthesis of bridged/spiro-bicyclic ketal skel-
etons,2–4 we were interested in exploring a Pd-mediated intramo-
lecular ketalization of an alkynediol for the synthesis of 1 (Fig. 1).
The alkynol 3 was identified as a model substrate for construc-
tion of the central [3.2.1]-bicyclic ketal unit through cycloisomer-
ization.5,6 The positioning of the alkyne group was made in
anticipation of a 6-endo-dig mode of cyclization. Indeed, such an
exclusive 6-endo-dig cyclization (Fig. 1) was employed as the key
reaction in our recent synthesis of didemniserinolipid B (2)4b (a re-
lated natural product from an Indonesian Didemnum sp.7). The syn-
thesis of the key
x-alkyne-1,2,4-triol 12 was intended through the
coupling of aldehyde 6 and C9-alkynol 5.8 The synthesis of the alky-
nol 5 was a direct proposition from octane-1,8-diol. Considering the
stereochemical similarity, the easily available D-gluconolactone was
identified as the starting point for the synthesis of aldehyde 6.
The synthesis of the 9-carbon alkyne fragment started from 1,8-
octanediol (7). The 1,8-octanediol was converted to its mono ben-
zyl ether 8 following the reported procedure.9 The oxidation of
Our next concern was the Pd-mediated alkynol cycloisomeriza-
tion reaction of triol 3. With 10 mol % of Pd(CH3CN)2Cl2 complex,
the reaction advanced smoothly with the disappearance of 3 with-
in 1 h and afforded 13. The constitution of the bicyclic ketal unit
present in 13 was investigated with the help of NMR spectral anal-
ysis. This turned out to be an undesired [2.2.1]-bicyclic ketal
* Corresponding author. Tel.: +91 20 25902577; fax: +91 20 25902629.
E-mail address: vr.chepuri@ncl.res.in (C.V. Ramana).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.023

C. V. Ramana et al. / Tetrahedron Letters 50 (2009) 4844–4847
4845
bon peak appeared at 110.7 ppm and a CH2 triplet resonating at
37.2 ppm was noticed. The appearance of the other CH2 triplets be-
low 30 ppm clearly indicated the presence of a single methylene
carbon inside the bicyclic ring. The undesired cycloisomerization
of 3 led us to do some experimentation with this model system
to understand the mode of cyclization.
The pentitol 4 was prepared either by the acetonide deprotec-
tion of 12 or by the global deprotection of 11b. Cycloisomerization
of 4 with Pd(CH3CN)2Cl2 proceeded smoothly in CH3CN–THF and
gave exclusively 14 which was characterized as its triacetate 15.
Structural analysis of compound 15 using COSY, NOESY and HMBC
spectra indicated the presence of an undesired 2,8-dioxabicyclo
[3.2.1]-octane skeleton (Supplementary data).15 Although there
was a scope for 6-endo-cyclizaton with both the substrates 3 and
4, the exclusive formation of 5-exo-cyclization product indicates
a dominant acyclic stereocontrol over the regiochemistry of this
cycloisomerization reaction.16
As the above strategy led to the products resulting from the
undesired 5-exo-cyclization, we revised the strategy by choosing
the diol 17 that has an extra carbon in between the alkyne and
the next chiral centre. The competition is now between 6-exo-
dig and 7-endo-dig, the latter being energetically more demand-
ing. The key retrosynthetic disconnections for the preparation of
17 are given in Figure 2. The synthesis began with the known
O
NaO3SHN
NaO3SO
OSO3Na
O
15
O
13
17
23
30
O
H
O
1
11
1
Cyclodidemniserinol trisulphate( )
O
H
N
3
O
O
OR
OP
BnO
5
?
O
HO
HO
R'
H
6-endo-dig
O
OR
3 (R = Bn)
4 (R = H)
R
OR
OH
O
O
O
O
O
O
+
OBn
5
HO
OH
5
6
OH
D-glucono-1,5-lactone
O
OH
10
28
29
30
O
H
O
13
8
O
NaO3SO
NH2
CO2Et
4
1
Didemniserinolipid B (2)
OH
H
OH
OPMB
Sharpless ADH
HO
6-endo-dig
13
BnO
PMBO
OH
O
O
O
H
HO
HO
HO
13
6
BnO
6
OBn
O
OBn
OBn
4
4
Yamaguchi
protocol
OH
16
17
BnO
BnO
Figure 1. Structure of cyclodidemniserinol trisulfate (1) and the projected 6-endo-
O
+
dig cyclization.
6
OBn
18
5
resulting from the unpredicted 5-exo-dig mode of cyclization.14 For
example, in the 13C NMR spectrum of 13, characteristic ketal car-
Figure 2. Revised strategy for the central [3.2.1]-bicyclic ketal core.
b), c)
a)
OH
BnO
OH
BnO
HO
OH
OH
6
6
O
6
O
7
8
5
10
O
+
O
O
O
O
O
O
O
O
O
O
O
O
f), g)
3 steps
e)
d)
HO
HO
O
MeO
O
ref. 11,12
HO
OH
O
O
O
O
O
O
11
OH
9
6
11
β
6
6
BnO
HO
BnO
h)
OBn
OH
6
O
i), j)
BnO
OBn
H
l)
O
O
OBn
OBn
O
H
BnO
HO
nOe
BnO
OBn
H
O
5
2
3
H
O
HO OH
H
7'
6
1
AcO
BnO
13
HMBC
4
H
OBn
12
6
OH
HO
OAc
BnO
H
7
k)
AcO
H
HO
6
H
3
6
H
O
O
m)
H
3'
nOe
HO OH
RO
nOe
OR
RO
4
6
BnO
14
R = H
n)
15 R = Ac
Scheme 1. Reagents and conditions: (a) Ref. 9, 80%; (b) oxalyl chloride, DMSO, Et3N; (c) Ohira–Bestmann reagent, K2CO3, MeOH, rt, 14 h, 79% in two steps; (d) DIBAL-H,
toluene, ꢀ78 °C, 20 min; (e) 5, Et2Zn, toluene, reflux, 1 h, 6, rt, 14 h, 69% in two steps; (f) MnO2, CH2Cl2, rt, 24 h, 70%; (g) LiI, THF, ꢀ40 °C, 30 min, LAH, ꢀ100 °C, 1 h, 82%; (h)
MeOH, 0.8% aq H2SO4, rt, 8 h, 75%; (i) NaH, BnBr, DMF, 0 °C?rt, 10 h, 83%; (j) MeOH, p-TSA, rt, 2 h, 87%, (k) MeOH, p-TSA, rt, 18 h, 88%; (l) 10 mol % Pd(CH3CN)2Cl2, CH3CN, rt,
1 h, 59%; (m) 10 mol % Pd(CH3CN)2Cl2, CH3CN/THF (6:2), rt, 30 min, 67%; (n) Ac2O, Et3N, DMAP, rt, 4 h, 87%.

4846
C. V. Ramana et al. / Tetrahedron Letters 50 (2009) 4844–4847
O
O
O
i)
O
OH
c), d)
a)
b)
O
O
O
HO
OH
OEt
OH
OBn
22
e), f)
19
20
21
O
BnO
PMBO
OH
BnO
OR
g)
69%
6
6
OBn
OBn
OBn
18
OH
17
23 R = H
+
h)
j)
OBn
24
R = PMB
6
OPMB
40.9 ppm
5
35.2 ppm
(34.0 ppm)
(41.0 ppm)
BnO
O
H
O
16
37.6 ppm
(chemical shifts in 1)
(36.2 ppm) BnO
Scheme 2. Reagents and conditions: (a) (i) IBX, DMSO, rt, 2 h, (ii) Ph3P@CHCO2Et, 5 h, 85% in two steps; (b) DIBAL-H, CH2Cl2, ꢀ78 °C, 2 h, 86%; (c) NaH, BnBr, DMF, 0 °C?rt,
4 h, 95%; (d) MeOH, p-TSA, rt, 8 h, 98%; (e) n-Bu2SnO, TsCl, Et3N, CH2Cl2, rt, 2 h, 89%; (f) NaH, DMF, 0 °C?rt, 4 h, 82%; (g) 5, n-BuLi, BF3ꢂEt2O, THF, ꢀ78 °C, 1 h, 77%; (h) NaH,
PMBCl, DMF, 0 °C?rt, 8 h, 75%; (i) AD-mix-b, MeSO2NH2, t-BuOH/H2O (1:1), 0?10 °C, 48 h, 73%, (dr 7:3); (j) 10 mol % Pd(CH3CN)2Cl2, CH3CN, rt, 1 h, 51%.
acetonide 19.17 One-pot sequential oxidation of alcohol 19 with
Supplementary data
IBX in DMSO, followed by a 2-carbon Wittig homologation fur-
nished the trans-olefin 20. Reduction of 20 with DIBAL-H gave
the ally alcohol 21. Protection of the free –OH group in 21 as
its benzyl ether followed by acetonide hydrolysis gave the diol
22. The diol 22 was transformed to the oxirane fragment 18 fol-
lowing selective 1°-OH tosylation and base treatment. The read-
ily available C9-alkynol fragment 5 was coupled with the oxirane
18 following the Yamaguchi protocol.18 The resulting alkynol 23
was treated with NaH and PMBCl to afford the corresponding
PMB ether 24. As the Sharpless asymmetric dihydroxylation19
of 24 using AD-mix-b at 0?4 °C was found to be sluggish, the
reaction was carried out at 10 °C, which resulted in a moderate
diastereoselective (7:3). The cycloisomerization reaction of the
resulting alkynediol 17 was carried out under optimized condi-
tions (10 mol % of Pd[CH3CN]2Cl2/CH3CN, rt, 1 h) and the desired
bicyclic ketal was obtained in 51% yield (Scheme 2). The consti-
tution and the stereochemistry of the isolated bicyclic product
16 were established with the help of COSY and NOESY spectra.20
For example, in the 13C NMR spectrum of the 16, three methy-
lene carbons appeared at d 35.2, 40.9 and 37.6 ppm and were
comparable with the chemical shifts of the C13 (34.0 ppm),
C15 (41.0 ppm) and C17 (36.2 ppm), respectively, of the natural
product 1. As it was noticed with 1, there was no cross-peak be-
tween H–C(3) and H–C(2) in the COSY of 16, indicating a dihe-
dral angle of 90° between them.1 The other spectral data were
in accordance with the assigned structure.
Supplementary data (The NMR spectra of the bicyclic ketals 13,
15 and 16) associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2009.06.023.
References and notes
1. Mitchell, S. S.; Rhodes, D.; Bushman, F. D.; Faulkner, D. J. Org. Lett. 2000, 2,
1605–1607.
2. For recent reviews on synthesis of bridged bicyclic ketals see: (a) Mori, K.
Tetrahedron 1989, 45, 3233–3298; (b) Kotsuki, H. Synlett 1991, 97–106; (c)
Francke, W.; Schröder, W. Curr. Org. Chem. 1999, 3, 407–443; (d) Jun, J.-G.
Synlett 2003, 1759–1777; (e) Kiyota, H. Top. Heterocycl. Chem. 2006, 5, 65–95.
3. (a) Ramana, C. V.; Mallik, R.; Gonnade, R. G.; Gurjar, M. K. Tetrahedron Lett.
2006, 47, 3649–3652; (b) Ramana, C. V.; Patel, P.; Gonnade, R. G. Tetrahedron
Lett. 2007, 48, 4771–4774; (c) Ramana, C. V.; Mallik, R.; Gonnade, R. G.
Tetrahedron 2008, 64, 219–233.
4. (a) Ramana, C. V.; Reddy, C. N.; Gonnade, R. G. Chem. Commun. 2008, 3151–
3153; (b) Ramana, C. V.; Induvadana, B. Tetrahedron Lett. 2009, 50, 271–273; (c)
Ramana, C. V.; Suryawanshi, S. B.; Gonnade, R. G. J. Org. Chem. 2009, 74, 2842–
2845.
5. For selected reviews on the alkynol cycloisomerizations see: (a) Zeni, G.;
Larock, R. C. Chem. Rev. 2004, 104, 2285–2309; (b) Alonso, F.; Beletskaya, I. P.;
Yus, M. Chem. Rev. 2004, 104, 3079–3159; (c) Muzart, J. Tetrahedron 2005, 61,
5955–6008; (d) Hintermann, L.; Labonne, A. Synthesis 2007, 1121–1150; (e)
Larrosa, I.; Romea, P.; Urpí, F. Tetrahedron 2008, 64, 2683–2723.
6. For representative total synthesis employing Pd-mediated alkynediol
cycloisomerizations see: (a) Trost, B. M.; Horne, D. B.; Woltering, M. J. Angew.
Chem., Int. Ed. 2003, 42, 5987–5990; (b) Trost, B. M.; Weiss, A. H. Angew. Chem.,
Int. Ed. 2007, 46, 7664–7666; (c) Refs. 4b,c.
7. For isolation of 2 see: (a) González, N.; Rodríguez, J.; Jiménez, C. J. Org. Chem.
1999, 64, 5705–5707; For synthesis of 2 see: (b) Kiyota, H.; Dixon, D. J.;
Luscombe, C. K.; Hettstedt, S.; Ley, S. V. Org. Lett. 2002, 4, 3223–3226; (c)
Marvin, C. C.; Voight, E. A.; Burke, S. D. Org. Lett. 2007, 9, 5357–5359.
8. (a) Frantz, D. E.; Fässler, R.; Tomooka, C. S.; Carreira, E. M. Acc. Chem. Res. 2000,
33, 373–381; (b) Gao, G.; Moore, D.; Xie, Ru-G.; Pu, L. Org. Lett. 2002, 4, 4143–
4146; (c) Trost, B. M.; Weiss, A. H. Adv. Synth. Catal. 2009 (DOI No. 10.1002/
adsc.200800776).
To conclude, synthesis of the bicyclic ketal core of the cyclodi-
demniserniol trisulfate was executed by employing a Pd-mediated
intramolecular ketalization of an alkynediol. Contrary to our
expectations, the initial design projecting a 6-endo-dig mode of
cyclization resulted in an exclusive 5-exo-dig cyclization. By posi-
tioning the central alkyne for a 6-exo-dig mode, the required
[3.2.1]-bicyclic ketal could be realized with the desired constitu-
tion. Application of this methodology to the synthesis of cyclodi-
demniserinol is progressing in our laboratory.
9. Bessodes, M.; Boukarim, C. Synlett 1996, 1119–1120.
10. (a) Ohira, S. Synth. Commun. 1989, 19, 561–564; (b) Muller, S.; Liepold, B.; Roth,
G. J.; Bestmann, H. J. Synlett 1996, 521–522.
11. Vlahov, I. R.; Vlahova, P. I.; Schmidt, R. R. Tetrahedron: Asymmetry 1993, 4, 293–
296.
12. Vijayasaradhi, S.; Beedimane, M. N.; Aidhen, I. S. Synthesis 2005, 2267–2269.
13. (a) Mori, Y.; Kuhara, M.; Takeuchi, A.; Suzuki, M. Tetrahedron Lett. 1988, 29,
5419–5422; (b) Mori, Y.; Suzuki, M. Tetrahedron Lett. 1989, 30, 4383–4386.
14. Spectral data of bicyclic ketal 13: Colorless oil. ½a D25
ꢁ
+26.5 (c 1.5, CHCl3); IR
(CHCl3) 3412, 3011, 2929, 2856,1645, 1496, 1454, 1401, 1363, 1027, 971, 912,
Acknowledgements
697, 667 cmꢀ1
;
1H NMR (400 MHz, CDCl3) d 1.30ꢀ1.45 (m, 10H), 1.58ꢀ1.63 (m,
We thank the Ministry of Science Technology for funding
through the Department of Science and Technology under the
Green Chemistry Programme (No. SR/S5/GC-20/2007). Financial
support from UGC (New Delhi) and CSIR (New Delhi) in the form
2H), 1.75 (ddd, J = 2.7, 5.5, 12.6 Hz, 1H), 1.86ꢀ1.94 (m, 1H), 1.96ꢀ2.01 (m, 2H),
3.37 (ddd, J = 1.9, 4.7, 9.0 Hz, 1H), 3.46 (t, J = 6.6 Hz, 2H), 3.53 (d, J = 9.2 Hz, 1H),
3.55 (dd, J = 4.7, 10.7 Hz, 1H), 3.67 (dd, J = 2.7, 6.6 Hz, 1H), 3.75 (dd, J = 1.9,
10.7 Hz, 1H), 4.38 (d, J = 12.1 Hz, 1H), 4.49ꢀ4.61 (m, 6H), 4.70ꢀ4.75 (m, 2H),
7.26ꢀ7.34 (m, 20H); 13C NMR (100 MHz, CDCl3) d 23.2 (t), 26.2 (t), 28.2 (t), 29.4
(t), 29.5 (t), 29.8 (t), 29.9 (t), 37.2 (t), 68.7 (t), 70.5 (t), 70.6 (t), 72.5 (t), 72.8 (t),
73.3 (t), 76.0 (d), 78.3 (d), 78.4 (d), 80.0 (d), 110.7 (s), 127.4 (d), 127.5 (d), 127.6
of
a research fellowship to R.M. and G.S. is gratefully
acknowledged.

C. V. Ramana et al. / Tetrahedron Letters 50 (2009) 4844–4847
4847
(d, 2C), 127.6 (d, 2C), 127.7 (d), 127.9 (d, 2C), 128.0 (d, 2C), 128.3 (d, 2C), 128.4
(d, 5C), 128.4 (d, 2C), 137.9 (s), 138.3 (s), 138.4 (s), 138.7 (s) ppm; ESI-MS: m/z
687.9 (100%, [M+Na]); Anal. Calcd for C43H52O6: C, 77.68; H, 7.88. Found: C,
77.39; H, 8.03.
17. (a) Meyers, A. I.; Lawson, J. P.; Walker, D. G.; Linderman, R. J. J. Org. Chem. 1986,
51, 5111–5123; (b) Lebar, M. D.; Baker, B. J. Tetrahedron Lett. 2007, 48, 8009–
8010.
18. Yamaguchi, M.; Hirao, I. Tetrahedron Lett. 1983, 24, 391–394.
19. Kolb, H. C.; Sharpless, K. B.; VanNieuwenhze, M. S. Chem. Rev. 1994, 94, 2483–2547.
15. Spectral data of triacetate 15: Colorless liquid. ½a D25
ꢁ
+61.0 (c 1, CHCl3); IR (CHCl3)
3391, 2931, 2851, 1745, 1648, 1402, 1231, 1045, 755, 602 cmꢀ1
;
1H NMR
20. Spectral data of bicyclic ketal 16: Colorless oil. ½a D25
ꢁ
+11.4 (c 0.7, CHCl3); IR
(CHCl3) 3445, 3251, 3020, 2941, 1603, 1386, 1166, 1107, 1072, 1017, 874,
(500 MHz, CDCl3) d 1.29ꢀ1.40 (m, 9H), 1.44ꢀ1.52 (m, 1H), 1.59ꢀ1.62 (m, 2H),
1.71ꢀ1.79 (m, 2H), 1.84 (ddd, J = 3.1, 7.5, 14.4 Hz, 1H), 2.06 (s, 3H), 2.08 (s, 6H),
2.61 (dd, J = 7.5, 14.4 Hz, 1H), 3.46 (t, J = 6.6 Hz, 2H), 3.78 (ddd, J = 2.6, 5.0,
9.5 Hz, 1H), 4.05 (dd, J = 5.0, 12.1 Hz, 1H), 4.20 (dd, J = 2.5, 12.1 Hz, 1H), 4.50 (s,
2H), 4.60 (dd, J = 4.0, 7.5 Hz, 1H), 4.82 (dd, J = 4.0, 9.5 Hz, 1H), 5.22 (dd, J = 3.1,
7.5 Hz, 1H), 7.27ꢀ7.34 (m, 5H); 13C NMR (125 MHz, CDCl3) d 20.8 (q, 2C), 21.0
(q), 23.0 (t), 26.2 (t), 29.4 (t), 29.4 (t), 29.8 (t, 2C), 32.4 (t), 33.5 (t), 63.4 (t), 65.0
(d), 70.0 (d), 70.5 (t), 72.8 (t), 73.6 (d), 75.7 (d), 107.1 (s), 127.4 (d), 127.6 (d,
2C), 128.3 (d, 2C), 138.7 (s), 169.5 (s), 170.0 (s), 170.8 (s) ppm; ESI-MS: m/z
543.1 (100%, [M+Na]); Anal. Calcd for C28H40O9: C, 64.60; H, 7.74. Found: C,
64.86; H, 7.35.
669 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.28–1.36 (m, 10H), 1.53 (dd, J = 10.3,
;
12.5 Hz, 1H), 1.62–1.76 (m, 5H), 2.05 (dd, J = 5.8, 13.0 Hz, 1H), 2.20 (dd, J = 6.1,
12.5 Hz, 1H), 3.28 (t, J = 8.6 Hz, 1H), 3.37 (dd, J = 5.5, 9.1 Hz, 1H), 3.46 (t,
J = 6.6 Hz, 2H), 3.80 (s, 3H), 3.86–3.94 (m, 1H), 3.98 (dd, J = 5.7, 7.6 Hz, 1H), 4.40
(br s, 1H), 4.44 (s, 2H), 4.50 (s, 2H), 4.52 (s, 2H), 6.86 (d, J = 8.4 Hz, 2H), 7.23 (d,
J = 8.4 Hz, 2H), 7.28–7.34 (m, 10H); 13C NMR (100 MHz, CDCl3) d 23.1 (t), 26.2
(t), 29.4 (t), 29.5 (t), 29.6 (t), 29.7 (t), 35.2 (t), 37.6 (t), 40.9 (t), 55.3 (q), 69.7 (t),
70.0 (d), 70.5 (t), 71.4 (t), 72.8 (t), 73.4 (t), 75.7 (d), 77.6 (d), 109.1 (s), 113.7 (d),
113.8 (d), 127.4 (d), 127.6 (d, 2C), 127.7 (d, 2C), 128.3 (d, 2C), 128.4 (d, 2C),
129.0 (d), 129.2 (d, 2C), 130.5 (s), 138.0 (s), 138.7 (s), 159.2 (s) ppm; ESI-MS: m/
z 611.7 (100%, [M+Na]); Anal. Calcd for C37H48O6: C, 75.48; H, 8.22. Found: C,
75.29; H, 8.36.
16. Xu, M.; Miao, Z.; Bernet, B.; Vasella, A. Helv. Chim. Acta 2005, 88, 2918–
2937.