A concise approach for the synthesis of core fragment C7-C15 of (+)-migrastatin using desymmetrization strategy

Article abstract of DOI:10.1055/s-0029-1219785

The core fragment C7-C15 the (+)-migrastatin was constructed in a stereoconvergent manner utilizing desymmetrization approach. The strategy involved the generation of Z-configuration of trisubstituted double bond at C11-C12, epimerization at C10, ring opening of the pyran lactol with C2 Wittig ylide, and regioselective Sharpless dihydroxylation. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1219785

LETTER
1033
A Concise Approach for the Synthesis of Core Fragment C7–C15 of
(+)-Migrastatin Using Desymmetrization Strategy
A
pproach
.
for the Synth
S
e
sis of Core
F
.
ragment C7
Y
astatin dav,* P. Naga Lakshmi
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500607, India
Fax +91(40)27160387; E-mail: yadavpub@iict.res.in
Received 21 October 2009
The first total synthesis of migrastatin (1) was achieved by
Danishefsky and co-workers7 and recently an alternative
route has been described by Reymond and Cossy.8 A
semi-synthetic approach has been described from isomi-
Abstract: The core fragment C7–C15 the (+)-migrastatin was con-
structed in a stereoconvergent manner utilizing desymmetrization
approach. The strategy involved the generation of Z-configuration
of trisubstituted double bond at C11–C12, epimerization at C10,
ring opening of the pyran lactol with C2 Wittig ylide, and regiose- grastatin by Shen and co- workers.9
lective Sharpless dihydroxylation.
Our ongoing research on the synthesis of biologically ac-
Key words: (+)-migrastatin, desymmetrization, epimerization,
Sharpless asymmetric dihydroxylation
tive molecules by desymmetrization strategy, and the no-
table biological activity of (+)-migrastatin encouraged us
to select this molecule as a target for total synthesis. We
herein report the synthesis of core fragment C7–C15 frag-
ment of (+)-migrastatin (1).
Migrastatin (1, Figure 1) is a novel macrolide natural
product, isolated from a cultured broth of Streptomyces
sp. MK929-43F1 by Imoto and co-workers in 2000.1,2 It
was shown by Kosan Bioscience researchers that cultures
of Streptomyces platensis (strain NRRL 18993) also pro-
duce migrastatin.3 Migrastatin displays a remarkable in-
hibitory effect on the migration of human tumor cells and
also selectively inhibits the anchorage-independent
growth of human small cell lung carcinoma Ms-1 cells.4
More recently, it has been shown to inhibit P-glycoprotein
and consequently sensitizes drug-resistant P-glycopro-
tein-overexpressing cells to anticancer drugs like taxol,
vinblastine, and vincristine.5 The structure of migrastatin
was established unambiguously by X-ray analysis of a de-
rivative.6 This compound consists of a 14-membered lac-
tone linked to an alkylglutarimide side chain and contains
five stereogenic centers, two E-disubstituted double
bonds, and one Z-trisubstituted double bond.
The challenge in the construction of 2 was the proper po-
sitioning of the chiral centers (C8, C9, C10, C13, C14),
the Z-configuration of C11–C12 double bond and to pro-
vide functionalities for the proper attachment leading to
the C6–C7 double bond in 1.
We embarked on the synthesis of the (+)-migrastatin (1)
fragment by a retrosynthetic analysis starting with 231
which can be obtained by subjecting the compound 3 to
regioselective sharpless asymmetric dihydroxylation,
regioselective monomethylation of diol, and TBDMS
protection. The compound 3 is resulted from 4 by epimer-
ization at C10 and ring opening of pyran lactol with ethoxy-
carbonyl
methylene
triphenylphosphorane.
The
compound 4 in turn could be easily prepared from 5 by se-
lective protection of primary alcohol and generation of Z-
configured double bond. The compound 5 could be easily
prepared from 6 through acetal ester, its reduction and de-
benzylation. Compound 620 is obtained by regioselective
methylation of the known precursor 7 (Scheme 1).
O
O
NH
15
Our synthesis started with the precursor 7, which was pre-
pared earlier in our group and utilized to make several nat-
ural products.10 The lactone 7 was subjected to
regioslective methylation using LDA and methyl iodide to
afford the methylated lactone 611 in 92% yield. The hy-
drolysis of the bicyclic lactone 6 with catalytic amount of
sulfuric acid in methanol afforded acetal ester 821 along
with a minor amount of the a-isomer (at C1 center) in 86%
yield.12 Reduction of 8 with LiAlH4 followed by debenzy-
lation with Li-napthanelide13 afforded diol 522 in 80%
yield. The primary alcohol in compound 5 was selectively
protected with TBDPSCl and imidazole in CH2Cl2 to the
corresponding TBDPS ether, and the secondary alcohol
was mesylated with methane sulfonyl chloride and Et3N
in CH2Cl2 to give the compound 923 in 90% yield
(Scheme 2).
O
O
O
15
7
OTBDPS
OH
6
TESO
OMe
(+)-migrastatin (1)
O
7
EtO
OTBS
OMe
C7–C15 fragment (2)
Figure 1
SYNLETT 2010, No. 7, pp 1033–1036
Advanced online publication: 23.03.2010
DOI: 10.1055/s-0029-1219785; Art ID: D29909ST
x
x.
x
x.
2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

1034
J. S. Yadav, P. N. Lakshmi
LETTER
15
OTBDPS
OTBDPS
TESO
HO
MeO
O
OTBDPS
9
O
15
7
EtO
OTBS
4
OMe
CO2Et
C7–C15 fragment (2)
3
O
O
O
MeO
O
OH
O
O
O
OBn
7
OBn
OH
5
6
Scheme 1 Retrosynthetic strategy
O
O
O
MeO
O
COOMe
b
a
O
O
O
OBn
OBn
OBn
7
6
8
MeO
O
OH
MeO
O
OTBDPS
c, d
e, f
OH
OMs
5
9
Scheme 2 Reagents and conditions: (a) LDA, MeI, THF, –78 °C, 92%; (b) MeOH, cat. H2SO4, 86%; (c) LiAlH4, THF, 0 °C to r.t.; (d) Li
naphthanelide, –23 °C, 3–4 h, (80%,overall yield for two steps); (e) TBDPSCl, imidazole, CH2Cl2, 0 °C, 0.5–1 h, 98%; (f) MsCl, Et3N, CH2Cl2,
0 °C to r.t.,16–20 h, 90%
Compound 9 was treated with DBU (neat) at the 70 °C for 11 in 45% yield.12 The epimerized lactone 1126 when re-
8–12 h to afford 424 in 40% yield.14 Hydrolysis using duced with DIBAL-H in anhydrous THF at –78 °C result-
AcOH–H2O–THF (6:3:1) at 50–55 °C afforded the ed in lactol 12. Exposure of crude lactol 12 to
lactol15 which was further oxidized with bis(acetoxy)iodo- ethoxycarbonylmethylene triphenylphosphorane in tolu-
benzene (BAIB) and 2,2,6,6-tetramethylpiperidine-N-ox- ene at reflux conditions resulted in ring opening of pyran
ide (TEMPO)16 to afford the lactone 10 in 60% (overall to aliphatic chain with secondary alcohol and a,b-unsatur-
yield for two steps). The lactone 1025 was treated with ated ester 317,27 in 92% overall yield for the two steps
DBU in dry THF at –10 °C to afford the required epimer (Scheme 3).
MeO
O
OTBDPS
O
O
OTBDPS
b, c
d
a
9
4
10
OTBDPS
O
O
OTBDPS
HO
O
OTBDPS
HO
f
e
11
12
3
CO2Et
Scheme 3 Reagents and conditions: (a) DBU (neat), –70 °C, 8–12 h, 40%; (b) AcOH–H2O–THF (6:3:1), 50–55 °C, 12 h; (c) BAIB, TEMPO,
CH2Cl2, 0 °C to r.t., 2–3 h, (60%, overall yield for two steps); d) DBU, THF, –10 °C, 0.5 h, 45%; (e) DIBAL-H, THF, –78 °C, 2 h; (f)
Ph3P=CHCO2Et, toluene, reflux, 2–4 h, (92%, overall yield for two steps).
Synlett 2010, No. 7, 1033–1036 © Thieme Stuttgart · New York

LETTER
Approach for the Synthesis of Core Fragment C7–C15 of (+)-Migrastatin
1035
(4) Takemoto, Y.; Nakae, K.; Kawatani, M.; Takahashi, Y.;
Naganawa, H.; Imoto, M. J. Antibiot. 2001, 54, 1104.
(5) Takemoto, Y.; Tashiro, E.; Imoto, M. J. Antibiot. 2006, 59,
435.
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Imoto, M.; Shiro, M.; Matsumura, K.; Watanabe, H.;
Kitahara, T. J. Antibiot. 2002, 55, 442.
Silylation of secondary alcohol in compound 3 using
TESCl, imidazole as the corresponding TES ether 1328
followed by regioselective Sharpless asymmetric
dihydroxylation18 using AD mix-a, MeSO2NH2 in t-
BuOH–H2O (1:1) gave diol 1429 (72% yield).
(7) Gaul, C.; Njardarson, J. T.; Danishefsky, S. J. J. Am. Chem.
Soc. 2003, 125, 6042.
(8) (a) Reymond, S.; Cossy, J. Eur. J. Org. Chem. 2006, 4800.
(b) Reymond, S.; Cossy, J. Tetrahedron 2007, 63, 5918.
(9) Ju, J.; Lim, S.-K.; Jiang, H.; Seo, J.-W.; Her, Y.; Shen, B.
Org. Lett. 2006, 8, 5865.
OTBDPS
OTBDPS
TESO
TESO
a
b
3
EtO2C
OH
(10) (a) Yadav, J. S.; Rao, C. S.; Chandrasekhar, S.; Ramarao,
A. V. Tetrahedron Lett. 1995, 36, 7717. (b) Yadav, J. S.;
Abraham, S.; Reddy, M. M.; Sabitha, G.; Sankar, A. R.;
Kunwar, A. C. Tetrahedron Lett. 2001, 42, 4713.
(c) Yadav, J. S.; Abraham, S.; Reddy, M. M.; Sabitha, G.;
Sankar, A. R.; Kunwar, A. C. Tetrahedron Lett. 2002, 43,
3453. (d) Yadav, J. S.; Ahmed, M. Md. Tetrahedron Lett.
2002, 43, 7147. (e) Yadav, J. S.; Reddy, K. B.; Sabitha, G.
Tetrahedron Lett. 2004, 45, 6475. (f) Yadav, J. S.; Srinivas,
R.; Sathiah, K. Tetrahedron Lett. 2006, 47, 1603.
(g) Yadav, J. S.; Venkatram Reddy, P.; Chandraiah, L.
Tetrahedron Lett. 2007, 48, 145. (h) Yadav, J. S.; Pratap,
T. V.; Rajender, V. J. Org. Chem. 2007, 72, 5882.
(i) Yadav, J. S.; Ravindar, K.; Reddy, B. V. S. Synlett 2007,
1957. (j) Yadav, J. S.; Venugopal, C. Synlett 2007, 2262.
(11) Hoffmann, H. M. R.; Clemens, K. E.; Smithers, R. H. J. Am.
Chem. Soc. 1972, 94, 3940.
OH
14
CO2Et
13
OTBDPS
OTBDPS
TESO
TESO
c
d
EtO2C
EtO2C
OTBS
OH
OMe
2
OMe
15
Scheme 4 Reagents and conditions: (a) TESCl, imidazole, CH2Cl2,
0 °C to r.t., 24 h, 94%; (b) AD mix-a, t-BuOH–H2O (1:1),
MeSO2NH2, 0 °C, 24–36 h, 72% (based on recovery of starting mate-
rial); (c) Ag2O, MeI, MS 4 Å, MeCN, r.t., 1–2 d, 80%; (d) TBSOTf,
2,6-lutidine, CH2Cl2, –23 °C to 0 °C, 2–3 h, 88%.
(12) Yadav, J. S.; Satyanaryana, M.; Srinivasulu, G.; Kunwar,
A. C. Synlett 2007, 1577.
(13) Liu, H. J.; Yip, J.; Shia, K. S. Tetrahedron Lett. 1997, 38,
2253.
(14) (a) Majetich, G.; Song, J.; Leigh, A. J.; Condon, S. M.
J. Org. Chem. 1993, 58, 1030. (b) The progress of reaction
and its completion was also invariably checked in different
solvents and at different temperatures.
(15) Snider, B. B.; Song, F. Org. Lett. 2001, 3, 1817.
(16) Mico, A. D.; Margarita, R.; Parlanti, L.; Vescovi, A.;
Piancatelli, G. J. Org. Chem. 1997, 62, 6974.
The a-OH in diol 14 was selectively protected as methyl
ether by using modified Gurjar’s protocol.19 Treatment of
diol with silver oxide, methyl iodide, and MS 4 Å in ace-
tonitrile at room temperature resulted in monoprotected
methyl ether 1530 selectively in 80% yield, and the free
secondary hydroxyl group was protected as tert-butyl
dimethylsilylether using 2,6-lutidine and tert-butyldime-
thylsilyl trifluoromethane sulfonate in dichloromethane in
90% yield (Scheme 4). Thus the core fragment C7–C15 of
(+)-migrastatin has been synthesized.
(17) Valverde, S.; Martin-Lomas, M.; Herradon, B.; Garcia-
Ochoa, S. Tetrahedron 1987, 43, 1895.
(18) Kolb, H. C.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483.
(19) Gurjar, M. K.; Mainkar, A. S.; Srinivas, P. Tetrahedron Lett.
1995, 36, 5967.
In conclusion, the synthesis of core fragment C7–C15 of
migrastatin has been accomplished wherein the required
stereogenic centers and the Z-configuration of trisubstitut-
ed double bond at C11–C12 have been achieved by using
desymmetrization approach. Further efforts for the total
synthesis of migrastatin are currenly under way in our lab-
oratory.
(20) Analytical Data for Compound 6
[a]D25 –54.7 (c 3.0, CHCl3). IR: nmax = 2928, 1742, 1455,
1073 cm–1. 1H NMR (200 MHz, CDCl3): d = 7.35–7.20 (m,
5 H), 5.38 (d, J = 2.7 Hz, 1 H), 4.70–4.40 (ABq, 2 H), 3.65
(d, J = 4.0 Hz, 1 H), 3.60–3.52 (m, 1 H), 2.75 (q, J = 7.0 Hz,
2 H), 2.30–2.10 (m, 1 H), 2.10–1.96 (m, 1 H), 1.42 (d,
J = 6.5 Hz, 3 H), 1.15 (d, J = 6.8 Hz, 3 H), 0.96 (d, J = 6.8
Hz, 3 H). MS: m/z = 290 [M+]. Anal. Calcd (%) for
C17H22O4: C, 70.32; H, 7.64. Found: C, 70.01; H, 7.32.
(21) Analytical Data for Compound 8
Acknowledgment
[a]D25 +77.6 (c 1.5, CHCl3). IR (neat): nmax = 2827, 1739,
1456, 1082 cm–1. 1H NMR (400 MHz, CDCl3): d = 7.36–
7.22 (m, 5 H), 4.54 (s, 2 H), 4.52 (s, 1 H), 4.00–3.95 (m, 1
H), 3.86 (t, J = 3.5 Hz, 1 H), 3.72 (s, 3 H), 3.28 (s, 3 H),
2.75–2.64 (m, 1 H), 2.25–2.10 (m, 2 H), 1.14–1.05 (m, 6 H),
1.02 (d, J = 6.6 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d =
176.0, 138.8, 128.2, 127.2, 127.1, 104.2, 74.9, 71.7, 69.4,
54.7, 51.5, 41.7, 36.4, 32.5, 13.1, 13.0, 7.5. MS: m/z = 307
[M+ + 1 – 30]. Anal. Calcd (%) for C19H28O5: C, 67.83; H,
8.39. Found: C, 67.13; H, 8.26.
P.N.L. thanks CSIR, New Delhi for the award of a fellowship.
References and Notes
(1) Nakae, K.; Yoshimoto, Y.; Sawa, T.; Homma, Y.; Hamada,
M.; Takeuchi, T.; Imoto, M. J. Antibiot. 2000, 53, 1130.
(2) Nakae, K.; Yoshimoto, Y.; Ueda, M.; Sawa, T.; Takahashi,
Y.; Naganawa, H.; Takeuchi, T.; Imoto, M. J. Antibiot. 2000,
53, 1228.
(3) Woo, E. J.; Starks, C. M.; Carney, J. R.; Arslanian, R.;
Cadapan, L.; Zavala, S.; Licari, P. J. Antibiot. 2002, 55, 141.
(22) Analytical Data for Compound 5
[a]D25 +35.4 (c 2.0, CHCl3). IR (KBr): nmax = 3489, 2924,
Synlett 2010, No. 7, 1033–1036 © Thieme Stuttgart · New York

1036
J. S. Yadav, P. N. Lakshmi
LETTER
135.6, 133.0, 133.0, 130.1, 130.0, 128.0, 127.9, 127.9,
127.8, 119.7, 74.0, 68.9, 60.3, 37.9, 34.3, 27.0, 27.0, 26.9,
20.0, 19.3, 17.9, 14.4, 13.3. ESI-MS: m/z = 517 [M + Na]+.
HRMS: m/z calcd for C30H42O4NaSi [M + Na]+: 517.2750;
found: 517.2757.
2855, 1724, 1460, 1377, 1130, 1073, 1029 cm–1. 1H NMR
(200 MHz, CDCl3): d = 4.50 (s, 1 H), 4.05 (t, J = 5.3 Hz, 1
H), 3.69–3.55 (m, 3 H), 3.35 (s, 3 H), 3.15–2.98 (br, 1 H),
2.07–1.90 (m, 3 H), 1.67–1.55 (br, 1 H), 1.04 (d, J = 6.8 Hz,
3 H), 0.97 (d, J = 6.8 Hz, 3 H), 0.81 (d, J = 6.8 Hz, 3 H), 13
C
NMR (50 MHz, CDCl3): d = 104.2, 75.7, 68.2, 67.6, 54.7,
38.6, 35.9, 35.7, 12.5, 12.5, 7.4. ESI-MS: m/z = 241.1 [M +
Na]+. HRMS: m/z calcd for C11H22O4Na [M + Na]+:
241.1410; found: 241.1415.
(28) Analytical Data for Compound 13
[a]D25 +19.7 (c 0.4, CHCl3). IR (KBr): nmax = 2959, 2877,
1722, 1650, 1463, 1426, 1385, 1262, 1108, 1065, 1014, 703
cm–1. 1H NMR (300 MHz, CDCl3): d = 7.63–7.53 (m, 4 H),
7.37–7.22 (m, 6 H), 6.87–6.74 (dd, J = 6.6, 15.9 Hz, 1 H),
5.72 (d, J = 15.9 Hz, 1 H), 4.96 (d, J = 9.2 Hz, 1 H), 4.28 (d,
J = 9.2 Hz, 1 H), 4.18–4.05 (q, J = 6.6 Hz, 2 H), 3.78–3.52
(dq, J = 3.6, 5.3, 10.2 Hz, 2 H), 3.40–3.28 (m, 1 H), 1.77–
1.61 (m, 1 H), 1.57 (s, 3 H), 1.27–1.15 (m, 6 H), 1.05–0.95
(m, 12 H), 0.75 (t, J = 7.9 Hz, 9 H), 0.44–0.30 (q, J = 6.6 Hz,
6 H). 13C NMR (75 MHz, CDCl3): d = 167.0, 152.4, 137.4,
135.9, 135.9, 134.2, 134.1, 129.7, 128.6, 127.7, 119.6, 71.2,
66.0, 60.4, 40.4, 34.7, 27.2, 20.7, 19.5, 14.4, 13.9, 7.06, 5.05.
ESI-MS: m/z = 631.3 [M + Na]+. HRMS: m/z calcd for
C36H56O4NaSi2 [M + Na]+: 631.3614; found: 631.3619.
(29) Analytical Data for Compound 14
(23) Analytical Data for Compound 9
[a]D25 +3.0 (c 1, CHCl3). IR (KBr): nmax = 2926, 2856, 1464,
1360, 1177, 1079, 1019, 954 cm–1.1H NMR (300 MHz,
CDCl3): d = 7.61 (d, J = 7.7 Hz, 4 H), 7.43–7.28 (m, 6 H),
5.1 (t, J = 5.6 Hz, 1 H), 4.40 (s, 1 H), 3.83–3.60 (m, 3 H),
3.09 (s, 3 H), 2.98 (s, 3 H), 2.24–2.12 (m, 2 H), 1.89–1.73
(m, 1 H), 1.15–1.02 (m, 12 H), 0.97 (d, J = 6.8 Hz, 3 H), 0.91
(d, J = 7.5 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 136.0,
135.8, 134.1, 133.9, 129.7, 129.7, 127.7, 103.7, 80.4, 69.8,
65.5, 60.5, 54.9, 38.8, 37.9, 36.9, 35.0, 27.2, 19.5, 14.4, 13.4,
13.0, 8.15. ESI-MS: m/z = 557.2 [M + Na]+. HRMS: m/z
calcd for C28H42O6NaSi [M + Na]+: 557.2366; found:
557.2369.
[a]D25 –6.0 (c 0.3, CHCl3). IR (KBr): nmax = 3440, 2959,
2877, 1722, 1650, 1463, 1426, 1385, 1262, 1108, 1065,
1014, 703 cm–1. 1H NMR (300 MHz, CDCl3): d = 7.73–7.56
(m, 4 H), 7.48–7.28 (m, 6 H), 5.08 (d, J = 10.2 Hz, 1 H), 4.32
(d, J = 9.3 Hz, 1 H), 4.23–4.20 (m, 2 H), 3.88–3.75 (m, 1 H),
3.69–3.47 (m, 2 H), 3.01–2.84 (m, 2 H), 1.89–1.71 (m, 2 H),
1.70–1.59 (m, 3 H), 1.43–1.21 (m, 3 H), 1.08 (s, 9 H), 0.99
(d, J = 6.6 Hz, 3 H), 0.93–0.74 (m, 12 H), 0.57–0.37 (q,
J = 6.6 Hz, 6 H). 13C NMR (75 MHz, CDCl3): d = 173.9,
140.6, 135.9, 134.2, 129.6, 128.9, 127.7, 80.0, 71.7, 71.3,
70.5, 66.3, 62.1, 61.3, 59.0, 40.8, 34.9, 32.1, 31.1, 31.1, 29.9,
29.5, 27.2, 22.9, 29.5, 27.2, 22.9, 19.5, 18.5, 17.8, 17.4,
14.4, 14.3, 7.1, 5.5, 5.1, 0.20. ESI-MS: m/z = 665.0 [M +
Na]+. HRMS: m/z calcd for C36H58O6NaSi2 [M + Na]+:
665.3669; found: 665.3672.
(24) Analytical Data for Compound 4
[a]D25 +100.9 (c 0.8, CHCl3). IR (KBr): nmax = 2960, 2926,
2856, 2827, 1465, 1384, 1108, 1086, 1030, 954 cm–1. 1H
NMR (300 MHz, CDCl3): d = 7.66 (d, J = 7.5 Hz, 4 H),
7.43–7.31 (m, 6 H), 5.31 (d, J = 5.2 Hz, 1 H), 4.38 (s, 1 H),
3.93 (s, 1 H), 3.66–3.48 (qd, J = 4.5, 9.8 Hz, 2 H), 3.37 (s, 3
H), 2.21–1.92 (m, 2 H), 1.46 (s, 3 H), 1.21 (d, J = 6.7 Hz, 3
H).1.08 (s, 12 H), 0.85 (d, J = 7.5 Hz, 3 H). 13C NMR (75
MHz, CDCl3): d = 135.5, 129.4, 129.4, 127.5, 123.7, 101.8,
73.1, 64.6, 54.9, 36.9, 34.0, 26.8, 19.1, 18.6, 14.9. ESI-MS:
m/z = 461.2 [M + Na]+. HRMS: m/z calcd for C27H38O3NaSi
[M + Na]+: 461.2494; found: 461.2487.
(25) Analytical Data for Compound 10
[a]D25 –14.3 (c 0.5, CHCl3). IR (KBr): nmax = 2927, 2856,
1739, 1465, 1427, 1364, 1109 cm–1. 1H NMR (300 MHz,
CDCl3): d = 7.69–7.58 (m, 4 H), 7.44–7.31 (m, 6 H), 5.33 (d,
J = 5.2 Hz, 1 H), 4.76 (s, 1 H), 3.66–3.55 (m, 1 H), 3.54–3.41
(m, 1 H), 3.05–2.85 (m, 1 H), 2.21–2.01 (m, 1 H), 1.62 (s, 3
H), 1.17 (d, J = 7.3 Hz, 6 H), 1.04 (s, 9 H). 13C NMR (75
MHz, CDCl3): d = 176.0, 135.5, 134.7, 129.4, 129.4, 127.7,
127.5, 123.1, 94.9, 77.4, 76.5, 73.6, 64.8, 37.0, 34.8, 26.9,
26.5, 19.2, 18.4, 15.1. ESI-MS: m/z = 445.2 [M + Na]+.
HRMS: m/z calcd for C26H34O3NaSi [M + Na]+: 445.2174;
found: 445.2173.
(30) Analytical Data for Compound 15
[a]D25 –3.0 (c 0.4, CHCl3). IR (KBr): nmax = 3513, 2960,
2874, 1721, 1650,1462, 1426, 1386, 1260, 1109, 1064, 1014
cm–1. 1H NMR (300 MHz, CDCl3): d = 7.70–7.62 (m, 4 H),
7.44–7.32 (m, 6 H), 5.14 (d, J = 10.0 Hz, 1 H), 4.39 (d,
J = 9.2 Hz, 1 H), 4.32–4.22 (m, 2 H), 3.87–3.81 (dd, J = 3.3,
9.4 Hz, 1 H), 3.68–3.61 (dd, J = 6.4, 9.4 Hz, 3 H), 3.39–3.32
(m, 1 H), 3.35 (s, 3 H), 3.12–2.97 (m, 1 H), 2.86 (d, J = 9.2
Hz, 1 H), 1.87–1.73 (m, 1 H), 1.65 (s, 3 H), 1.31 (t, J = 7.1
Hz, 3 H), 1.08 (s, 9 H), 1.00 (d, J = 6.9 Hz, 3 H), 0.89–0.79
(m, 12 H), 0.59–0.45 (q, J = 6.6 Hz, 6 H). 13C NMR (75
MHz, CDCl3): d = 173.8, 137.3, 135.6, 134.1, 127.4, 134.1,
129.4, 127.4, 85.4, 77.4, 77.1, 77.1, 76.9, 76.5, 71.2, 70.6,
66.0, 61.4, 59.2, 40.5, 33.2, 29.6, 26.9, 19.3, 18.2, 16.7, 14.2,
14.0, 6.9, 4.7. ESI-MS: m/z = 679.0 [M + Na]+. HRMS: m/z
calcd for C37H60O6NaSi2 [M + Na]+: 679.3826; found:
679.3837.
(26) Analytical Data for Compound 11
[a]D25 –10.6 (c 1.0, CHCl3). IR (KBr): nmax = 3000, 2851,
1750, 1432, 1380, 1210 cm–1. 1H NMR (300 MHz, CDCl3):
d = 7.69–7.57 (m, 4 H), 7.44–7.31 (m, 6 H), 5.33 (d, J = 5.2
Hz, 1 H), 4.60 (s, 1 H), 3.61–3.45 (m, 2 H), 2.86–2.76 (m, 1
H), 2.19–1.91 (m, 1 H), 1.62 (s, 3 H), 1.10–0.90 (m, 15 H).
13C NMR (75 MHz, CDCl3): d = 176.0, 135.5, 134.7, 129.4,
129.4, 127.7, 127.5, 123.1, 94.9, 77.4, 76.5, 73.6, 64.8, 37.0,
34.8, 26.9, 26.5, 19.2, 18.4, 15.1. ESI-MS: m/z = 445.2 [M +
Na]+. HRMS: m/z calcd for C26H34O3NaSi [M + Na]+:
445.2174; found: 445.2173.
(31) Analytical Data for Compound 2
[a]D25 –3.0 (c 0.4, CHCl3). IR (KBr) nmax = 2959, 2877, 1722,
1650, 1463, 1426, 1385, 1262, 1108, 1065, 1014, 703 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.70–7.63 (m, 4 H), 7.45–
7.31 (m, 6 H), 5.13 (d, J = 10.1 Hz, 1 H), 4.33 (d, J = 3.2 Hz,
1 H), 4.28–4.15 (m, 3 H), 3.95–3.89 (dd, J = 3.3, 9.4 Hz, 1
H), 3.53–3.40 (m, 2 H), 3.31 (s, 3 H), 2.95–2.82 (m, 1
H),1.89–1.78 (m, 1 H), 1.65 (s, 3 H), 1.32–1.24 (m, 3 H),
1.09 (s, 9 H), 0.97–0.78 (m, 24 H), 0.56–0.45 (m, 6 H), 0.12
(s, 3 H), 0.06 (s, 3 H). 13C NMR (75 MHz, CDCl3): d =
136.9, 135.6, 134.1, 127.4, 127.4, 129.3, 86.6, 73.0, 71.9,
66.4, 60.7, 59.5, 40.9, 33.2, 31.9, 31.4, 29.6, 26.9, 25.8, 22.6,
19.3, 18.3, 17.2, 14.2, 6.9, 4.6, –4.4, –5.0. ESI-MS: m/z =
793.6 [M + Na]+. HRMS: m/z calcd for C43H74O6NaSi3 [M +
Na]+: 793.6826; found: 793.6837.
(27) Analytical Data for Compound 3
[a]D25 +44.3 (c 0.6, CHCl3). IR (KBr): nmax = 3420, 2960,
2929, 2858, 1716, 1464, 1428, 1385, 1109, 1035, 703 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.61 (d, J = 6.0 Hz, 4 H),
7.38–7.27 (m, 6 H), 6.87–6.77 (dd, J = 6.0, 15.1 Hz, 1 H),
5.72 (d, J = 15.1 Hz, 1 H), 5.03 (d, J = 9.8 Hz, 1 H), 4.36 (d,
J = 9.0 Hz, 1 H), 4.14–4.04 (q, J = 6.7 Hz, 2 H), 3.80–3.60
(dq, J = 3.7, 7.5, 10.5 Hz, 2 H), 3.40–3.28 (m, 2 H), 1.92–
1.76 (m, 1 H), 1.65 (s, 3 H), 1.19 (t, J = 6.7 Hz, 3 H), 1.02–
0.99 (m, 12 H), 0.60 (d, J = 6.8 Hz, 3 H). 13C NMR (75 MHz,
CDCl3): d = 167.0, 152.6, 136.6, 135.8, 135.8, 135.7, 135.7,
Synlett 2010, No. 7, 1033–1036 © Thieme Stuttgart · New York

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