A cross-metathesis approach for the synthesis of tedanolide and 13-deoxytedanolide: stereoselective synthesis of the C3-C16 segment

Article abstract of DOI:10.1016/j.tetlet.2007.07.156

A unified synthetic strategy has been devised for the synthesis of both tedanolide and 13-deoxytedanolide, which involves a cross-metathesis reaction as the key step. We report herein the stereoselective synthesis of the C3-C16 segment (+)-5b and subseque

Full text of DOI:10.1016/j.tetlet.2007.07.156

Tetrahedron Letters 48 (2007) 6905–6911
A cross-metathesis approach for the synthesis of tedanolide
and 13-deoxytedanolide: stereoselective synthesis
of the C3–C16 segmentI
Vijay Kumar Nyavanandi,a,b Prabhakar Nadipalli,a Srinivas Nanduri,a
Andra Naidub and Javed Iqbala,*
aDiscovery Chemistry, Discovery Research, Dr. Reddy’s Laboratories Ltd., Miyapur, Hyderabad 500 049, India
bJawaharlal Nehru Technological University, Kukatpally, Hyderabad 500 072, India
Received 26 June 2007; revised 18 July 2007; accepted 25 July 2007
Available online 28 July 2007
Abstract—A unified synthetic strategy has been devised for the synthesis of both tedanolide and 13-deoxytedanolide, which involves
a cross-metathesis reaction as the key step. We report herein the stereoselective synthesis of the C3–C16 segment (+)-5b and sub-
sequent manipulation of the C12–C13 double bond leading to the preparation of both tedanolides.
Ó 2007 Elsevier Ltd. All rights reserved.
Tedanolide (1), an antitumour macrolide was isolated
from a prevalent Caribbean sponge Tedania ignis by
Schmitz et al.1 in 1984. In 1991, a closely related macro-
lide 13-deoxytedanolide (2) was discovered from the
Japanese sponge Mycale adhaerens, by Fusetani et al.2
These two polyketides exhibit remarkable cytotoxic-
ity against P388 murine leukemia cells at pico to nano-
molar ranges, and Fusetani et al. were able to identify
the 60S large ribosomal subunit as the molecular target
of (+)-13-deoxytedanolide (2).3 Recently, tedanolide
C (3) was reported by Ireland et al.,4 which differs in
the oxygenation and methylation pattern. The challeng-
ing structural complexity of the tedanolides in combina-
tion with their promising biological profile has
prompted several research groups to investigate the
synthesis of these natural products,5 resulting in a vari-
ety of fragment syntheses as well as fundamental studies.
Consequently, two total syntheses of (+)-13-deoxyted-
anolide (2) were reported in 2003 and 2005 by Smith
and Roush, respectively.6 The first total synthesis of
(+)-tedanolide was reported by Kalesse et al.7 (see
Fig. 1).
OH
O
OH
O
OH
1
O
OMe O
13
O
O
OH
O
23
HO
O
O
OH
O
R
O
OH
OH OH
(+)-tedanolide C (3)
R = OH (+)-tedanolide (1)
R = H (+)-13-deoxytedanolide ( )
2
Figure 1. Structures of tedanolides.
Keywords: Tedanolide; Stereoselective; Aldol; Cross-metathesis.
q DRL Publication number 641.
*
Corresponding author. Tel.: +91 40 23045439; fax: +91 40 2304 5438; e-mail: javediqbaldrf@hotmail.com
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.156

6906
V. K. Nyavanandi et al. / Tetrahedron Letters 48 (2007) 6905–6911
glycolate aldol
OH
Yamaguchi
3
TBSO
OTBS
1
O
OH
7
OTBDPS OPMB
23
O
OMe O
21
OP
13
R
11
O
16
O
OP
PMB
O
R
OPMB
OH
O
Wittig olefination
R = OH (+)-tedanolide (1)
R = H (+)-13-deoxytedanolide (2)
R = OH (4a)
R = H (4b)
13
OTBS
3
TBSO
OTBDPS OPMB
OTBS
OH
TBSO
OPMB
6
R'
OTBDPS
OTBDPS
OPMB
OH
16
12
21
OP
12
16
OPMB
OP OPMB
Olefin cross-metathesis
8
7
5a
R' =
OP
OP
R' =
H
5b
Scheme 1. Retrosynthesis of tedanolides 1 and 2.
Almost every group chose to disconnect the natural
product at the C12–C13 bond, with the plan of eventu-
ally using some type of aldol coupling to form this bond
once the synthesis of the two fragments had been com-
pleted. In continuation of our efforts5v towards the total
synthesis of tedanolides, we have devised a unified syn-
thetic strategy, our retrosynthesis of tedanolides 1 and
2 is shown in Scheme 1.
The synthesis began with a Crimmins asymmetric
aldol reaction8 between 9 and imide 10 to afford the
Evans’ syn aldol product (ꢀ)-11 with high diastereo-
selectivity9 (Scheme 2). This was converted into a cyclic
acetal 12 by reductive removal of chiral auxiliary
(NaBH4)10 followed by cyclic acetal formation (p-anis-
aldehyde dimethylacetal/CSA) on the resulting diol.
Selective unmasking of the primary alcohol with DI-
BAL-H11 followed by TEMPO oxidation12 gave alde-
hyde 13 in good yield, which was subjected to a Wittig
olefination13 resulting in (+)-14 in 92% yield (24:1 E/
Z). The a,b-unsaturated ester was reduced with DI-
BAL-H14 to the allylic alcohol and then oxidized with
Our retrosynthetic strategy for tedanolides 1 and 2
involves disconnections leading to two fragments 6
(C3–C13), and 7 (C12–C21) as shown in Scheme 1.
Fragments 6 and 7 were designed to be connected by
olefin cross-metathesis to give 5a. Subsequently, the
C12–C13 double bond in 5a is planned to be manipu-
lated utilizing the C11 allylic alcohol to afford the C3–
C21 segments 4a and 4b of both the tedanolides. Later,
an asymmetric glycolate aldol reaction to install the
remaining two stereocentres at C2 and C3, followed by
a Wittig olefination at C21 are expected to give the car-
bon back-bone of the tedanolides. In order to establish
our synthetic strategy, we report herein the stereoselec-
tive synthesis of the C3–C16 segment 5b and subsequent
manipulation of the C12–C13 double bond to afford the
C3–C16 segments of both the tedanolides. We have uti-
lized Crimmins asymmetric aldol protocol as the main
tool to synthesize fragments 6 and 8.
15
MnO2 to the corresponding aldehyde 15 in excellent
yield.
A second Crimmins asymmetric aldol9 protocol with
imide 10 followed by a silyl protection of the secondary
hydroxyl group afforded (ꢀ)-16.
Subsequently, (ꢀ)-16 was reduced with NaBH4 and the
resulting primary alcohol was oxidized with TEMPO to
afford aldehyde 17. Another iterative Crimmins asym-
metric aldol protocol9 with imide 10 and subsequent
reduction (NaBH4) gave diol (+)-18 in very good yield
and diastereoselectivity. The C5 hydroxyl group was
protected as OPMB ether (ꢀ)-19 by converting the diol

V. K. Nyavanandi et al. / Tetrahedron Letters 48 (2007) 6905–6911
6907
Bn
10,TiCl4, (-)-Sparteine
0 ºC, CH2Cl2, 95%
i) NaBH4
THF-H2O, 90%
O
O
N
ii) CSA, CH2Cl2, 96%
OH
O
O
OMe
MeO
OMe
9
(-)-11
OEt
i) DIBAL-H, CH2Cl2
0 ºC, 80%
Ph3P
O
O
O
O
ii) TEMPO, IBDA
CH2Cl2, 95%
CH2Cl2, 92%
(24:1, E/Z)
OPMB
13
12
OMe
i) DIBAL-H,
CH2Cl2 -78 °C, 93%
OEt
OPMB
O
ii) MnO2, CH2Cl2,
95%
OPMB
O
15
(+)-14
Bn
O
10 =
N
i)10,TiCl4, (-)-Sparteine
0 ºC, CH2Cl2, 92%
Aux
O
O
Bn
ii) TBSCl, Imidazole
DMF, 90%
OPMB TBSO
O
O
N
Aux =
(-)-16
O
Scheme 2.
into a cyclic acetal (p-anisaldehyde dimethylacetal/CSA)
followed by DIBAL-H reduction. Protection of the
primary alcohol as an OTBS ether and oxidative
removal (DDQ) of the allylic OPMB ether selectively
resulted in the desired fragment (+)-616 along with
15% of diol (ꢀ)-2017 (Scheme 3).
product. Starting material 6 was also recovered in small
amounts. On the other hand, we carried out a cross-
metathesis reaction between fragments 8 and (ꢀ)-20 (a
minor product obtained in the DDQ step), and to our
delight we obtained the desired product (+)-2622 in
60% yield along with a small amount of homo-dimer
(+)-25. Based on these results, we converted allylic alco-
hol (ꢀ)-6 into (ꢀ)-20 with DDQ in 92% yield and subse-
quent cross-metathesis reaction with 8 gave (+)-26 in
good yield (Scheme 5).
On the other hand, the straightforward synthesis of
fragment 8 is illustrated in Scheme 4. Accordingly, 21
was subjected to Crimmins aldol reaction with imide
22 to furnish the Evans’ syn-aldol adduct,18,9b which
upon reduction with NaBH4 yielded diol (ꢀ)-23 in
excellent yield and diastereoselectivity. The C15-OPMB
protection was carried out by cyclic acetal formation
with anisaldehyde dimethyl acetal followed by regio-
selective opening with DIBAL-H (93%, two steps) to
give (+)-24. Oxidation of the primary alcohol with
TEMPO followed by a Wittig reaction on the result-
ing aldehyde with Ph3P@CH2ÆHBr and n-BuLi in
THF afforded the fragment (+)-819 in 85% yield
(Scheme 4).
The initial success in the olefin cross-metathesis reaction
encouraged us to transform fragment (+)-26 into the
C3–C16 segments of both the tedanolides. Accordingly,
the allylic alcohol group in (+)-26 was oxidized with
DMP and the resulting a,b-unsaturated double bond
was selectively reduced with NiCl2Æ6H2O/NaBH4 to
afford the C3–C16 segment of 13-deoxytedanolide (+)-
27.23 On the other hand, we converted (+)-26 into the
C3–C16 segment of tedanolide (ꢀ)-2824 by epoxidation
of allylic alcohol with mCPBA(Scheme 6).
With the two fragments 6 and 8 in hand, the stage was
set for the important cross-metathesis reaction. When
we carried out this reaction with 10 mol% of Grubb’s
2nd generation catalyst in refluxing dichloromethane,20
to our surprise, we only obtained the homo-dimer
product (+)-2521 of fragment 6 and none of the desired
In summary, we have successfully developed a conver-
gent synthetic route towards the tedanolides by synthe-
sizing the C3–C16 segments (+)-27 and (ꢀ)-28 from key
intermediate (+)-26. Efforts are currently being directed
towards the total syntheses of both the tedanolides, uti-
lizing the above strategy.

6908
V. K. Nyavanandi et al. / Tetrahedron Letters 48 (2007) 6905–6911
i) NaBH4
THF-H2O, 75%
Aux
ii) TEMPO, IBDA
CH2Cl2, 85%
OPMB TBSO
O
OPMB TBSO
16
O
(-)-
17
OMe
OMe
10
i) , TiCl4,
(-)-Sparteine 0°C,
CH2Cl2, 90%
MeO
i) CSA, CH2Cl2, 85%
ii) NaBH4
THF-H2O,
90%
OPMB TBSO
OH OH
ii) DIBAL-H, CH2Cl2
0 ºC, 90%
18
(+)-
i) TBSCl, Imidazole
DMF, 95%
OTBS
OTBS
OPMB
ii) DDQ, CH2Cl2-H2O
OH
PMBO
OH
PMBO
OTBS
19
(-)-
75%
6
(+)-
OTBS
OH
HO
OTBS
15%
20
(-)-
Scheme 3.
22,
i)
0
TiCl4, (-)-Sparteine
°C, CH2Cl2, 91%
H
ii) NaBH4
THF-H2O, 94%
TBDPSO
O
TBDPSO
OH OH
21
23
(-)-
OMe
OMe
i) TEMPO, IBDA
CH2Cl2, 86%
MeO
OH
i) CSA, CH2Cl2, 92%
TBDPSO
OPMB
ii) Ph3P=CH2.HBr
n-BuLi, THF, 85%
ii) DIBAL-H, CH2Cl2
0 °C, 95%
24
(+)-
Bn
N
O
22=
TBDPSO
OPMB
O
O
8
(+)-
Scheme 4.

V. K. Nyavanandi et al. / Tetrahedron Letters 48 (2007) 6905–6911
6909
TBSO
OTBS
PMBO
TBDPSO
OPMB
OH
TBSO
OTBS
G-II
, 10 mol%
Desired
PMBO
+
CH2Cl2, reflux,
TBDPSO
OPMB
PMBO
OTBDPS
OH
(+)-8
(+)-6
TBDPSO
OPMB
Obtained,
70%
N
N
Mes
Mes
(+)-25
Cl
Cl
Ru
Ph
PCy3
G-II
TBSO
OTBS
TBSO
OPMB
OTBS
G-II
, 10 mol%
HO
HO
+
CH2Cl2, reflux,
60%
TBDPSO
OPMB
OH
TBDPSO
OH
(+)-8
(-)-20
(+)-26
Scheme 5.
TBSO
OTBS
TBSO
OTBS
TBSO
OTBS
i) Dess-Martin,
CH2Cl2,90%
mCPBA, CH2Cl2
HO
75%
HO
OH
O
ii) NiCl2.6H2O,
NaBH4, MeOH-THF,
0 ºC, 88%
O
TBDPSO
OPMB
OH
TBDPSO
OPMB
OH
TBDPSO
OPMB
(-)-28
(+)-26
(+)-27
Scheme 6.
T.; Mori, M.; Nakajima, N.; Maeda, H.; Uenishi, J.;
Yonemitsu, O. Chem. Pharm. Bull. 1998, 46, 1335; (c) Liu,
J. F.; Abiko, A.; Pei, Z.; Buske, D. C.; Masamune, S.
Tetrahedron Lett. 1998, 39, 1873; (d) Taylor, R. E.;
Ciavarri, J. P.; Hearn, B. R. Tetrahedron Lett. 1998, 39,
9361; (e) Roush, W. R.; Lane, G. C. Org. Lett. 1999, 1, 95;
(f) Matsushima, T.; Mori, M.; Zheng, B. Z.; Maeda, H.;
Nakajima, N.; Uenishi, J.; Yonemitsu, O. Chem. Pharm.
Bull. 1999, 47, 308; (g) Jung, M. E.; Karama, U.;
Marquez, R. J. Org. Chem. 1999, 64, 663; (h) Matsushima,
T.; Zheng, B. Z.; Maeda, H.; Nakajima, N.; Uenishi, J.;
Yonemitsu, O. Synlett 1999, 780; (i) Smith, A. B., III;
Lodise, S. A. Org. Lett. 1999, 1, 1249; (j) Zheng, B. Z.;
Maeda, H.; Mori, M.; Kusaka, S. i.; Yonemitsu, O.;
Matsushima, T.; Nakajima, N.; Uenishi, J. Chem. Pharm.
Bull. 1999, 47, 1288; (k) Jung, M. E.; Marquez, R.
Tetrahedron Lett. 1999, 40, 3129; (l) Matsushima, T.;
Nakajima, N.; Zheng, B. Z.; Yonemitsu, O. Chem. Pharm.
Bull. 2000, 48, 855; (m) Zheng, B. Z.; Yamauchi, M.; Dei,
H.; Kusaka, S. i.; Matsui, K.; Yonemitsu, O. Tetrahedron
Lett. 2000, 41, 6441; (n) Zheng, B. Z.; Yamauchi, H.; Dei,
H.; Yonemitsu, O. Chem. Pharm. Bull. 2000, 48, 1761; (o)
Jung, M. E.; Marquez, R. Org. Lett. 2000, 2, 1669; (p)
Jung, M. E.; Lee, C. P. Org. Lett. 2001, 3, 333; (q) Loh, T.
Acknowledgement
We thank Dr. Reddy’s Laboratories Ltd. for supporting
this research work.
References and notes
1. Schmitz, F. J.; Gunasekera, S. P.; Yalamanchili, G.;
Hossain, M. B.; Van der Helm, D. J. Am. Chem. Soc.
1984, 106, 7251.
2. Fusetani, N.; Sugawara, T.; Matsunaga, S.; Hirota, H. J.
Org. Chem. 1991, 56, 4971.
3. (a) Nishimura, S.; Matsunaga, S.; Yoshida, M.; Hirota,
H.; Yokoyama, S.; Fusetani, N. Bioorg. Med. Chem. 2005,
13, 449; (b) Nishimura, S.; Matsunaga, S.; Yoshida, M.;
Nakao, Y.; Hirota, H.; Fusetani, N. Bioorg. Med. Chem.
2005, 13, 455.
4. Chevallier, C.; Bugni, T. S.; Feng, X.; Harper, M. K.;
Orendt, A. M.; Ireland, C. M. J. Org. Chem. 2006, 71,
2510.
5. (a) Matsushima, T.; Horita, K.; Nakajima, N.; Yonemi-
tsu, O. Tetrahedron Lett. 1996, 37, 385; (b) Matsushima,

6910
V. K. Nyavanandi et al. / Tetrahedron Letters 48 (2007) 6905–6911
P.; Feng, L. C. Tetrahedron Lett. 2001, 42, 6001; (r) Loh,
18. Smith, A. B., III; Minbiole, K. P.; Verhoest, P. R.;
T. P.; Feng, L. C. Tetrahedron Lett. 2001, 42, 3223; (s)
Matsui, K.; Zheng, B. Z.; Kusaka, S. i.; Kuroda, M.;
Yoshimoto, K.; Yamada, H.; Yonemitsu, O. Eur. J. Org.
Chem. 2001, 3615; (t) Hearn, B. R.; Ciavarri, J. P.; Taylor,
R. E. Org. Lett. 2002, 4, 2953; (u) Wong, C. M.; Loh, T. P.
Tetrahedron Lett. 2006, 47, 4485; (v) Iqbal, J.; Nyava-
nandi, V. K.; Nanduri, S.; Vasudev, R.; Naidu, A.
Tetrahedron Lett. 2006, 47, 6667.
Schelhaas, M. J. Am. Chem. Soc. 2001, 123, 10942.
25
19. Spectral data for (+)-8: ½aꢁ 29.8 (c 0.5, CHCl3); 1H
NMR (400 MHz, CDCl3) d D7.65 (m, 4H), 7.43–7.33 (m,
6H), 7.17 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 8.8 Hz, 2H),
5.84 (ddd, J = 16.8 Hz, 10.4 Hz, 6.8 Hz, 1H), 5.02 (ddd,
J = 5.2 Hz, 3.2 Hz, 2.0 Hz, 1H), 4.99 (d, J = 0.8 Hz, 1H),
4.47 (d, J = 10.8 Hz, 1H), 4.37 (d, J = 10.8 Hz, 1H), 3.77
(s, 3H), 3.76 (m, 2H), 3.52 (m, 1H), 2.47 (m, 1H), 1.77 (m,
1H), 1.63 (m, 1H), 1.05 (s, 9H), 1.02 (d, J = 6.8 Hz, 3H);
13C NMR (50 MHz, CDCl3) d 159.0, 140.7, 135.5, 133.9,
133.9, 131.0, 129.5, 129.3, 127.6, 114.4, 113.6, 79.3, 71.6,
6. (a) Smith, A. B., III; Adams, C. M.; Barbosa, S. A. L.;
Degnan, P. J. Am. Chem. Soc. 2003, 125, 350; (b) Smith,
A. B., III; Adams, C. M.; Barbosa, S. A. L.; Degnan, P.
Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 12042; (c) Julian,
L. D.; Newcom, J. S.; Roush, W. R. J. Am. Chem. Soc.
2005, 127, 6186.
7. Ehrlich, G.; Hassfeld, J.; Eggert, U.; Kalesse, M. J. Am.
Chem. Soc. 2006, 128, 14038.
8. Crimmins, M. T.; King, B. W.; Tabet, E. A.; Chaudhary,
K. J. Org. Chem. 2001, 66, 894.
9. (a) Evans, D. A.; Gage, J. R.; Leighton, J. L. J. Am. Chem.
Soc. 1992, 114, 9434; (b) The other diastereomer was not
observed in the crude NMR.
10. Prashad, M.; Har, D.; Kim, H. Y.; Repic, O. Tetrahedron
Lett. 1998, 39, 7067–7070.
11. Takano, S.; Akiyama, M.; Sato, S.; Ogasawara, K. Chem.
Lett. 1983, 1593.
12. De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.;
Piancatelli, G. J. Org. Chem. 1997, 62, 6974–6977.
13. Li, D. R.; Tu, Y. Q.; Lin, G. Q.; Zhou, W. S. Tetrahedron
Lett. 2003, 44, 8729.
60.7, 55.2, 40.7, 34.3, 26.8, 19.1, 15.4; IR (neat, cmꢀ1
2956, 2929, 2856, 1612, 1514, 1427, 1247, 1111, 1087, 821;
HRMS (ESI-TOF) m/z (M+Na)+ calcd for C31H40O3S-
iNa, 511.2644; obsd 511.2662.
)
20. Nolen, E. G.; Kurish, A. J.; Potter, J. M.; Donahue, L. A.;
Orlando, M. D. Org. Lett. 2005, 7, 3383.
25
21. Spectral data for (+)-25: ½aꢁD 26.2 (c 1.0, CHCl3); 1H
NMR (400 MHz, CDCl3) d 7.64 (m, 8H), 7.41–7.32 (m,
12 H), 7.15 (d, J = 8.4 Hz, 4H), 6.79 (d, J = 8.8 Hz, 4H),
5.45 (dd, J = 4.0 Hz, 1.6 Hz, 2H), 4.46 (d, J = 11.2 Hz,
2H), 4.34 (d, J = 11.2 Hz, 2H), 3.76 (s, 6H), 3.74 (m, 4H),
3.49 (m, 2H), 2.44 (m, 2H), 1.75 (m, 2H), 1.64 (m, 2H),
1.03 (s, 18H), 0.99 (d, J = 6.8 Hz, 6H); 13C NMR
(50 MHz, CDCl3) d 158.9, 135.5, 133.99, 133.93, 132.1,
131.1, 129.5, 129.2, 127.5, 113.6, 79.7, 71.6, 60.7, 55.1,
39.6, 34.4, 26.8, 19.1, 15.9; IR (neat, cmꢀ1) 2958, 2931,
2858, 1612, 1514, 1467, 1427, 1247, 1109, 1087, 1037, 823;
HRMS (ESI-TOF) m/z (M+H)+ calcd for C60H77O6Si2,
949.5259; obsd 949.5255.
14. Kiyooka, S. I.; Hena, M. A. J. Org. Chem. 1999, 64,
5511.
25
22. Spectral data for (+)-26: ½aꢁD 19.4 (c 0.5, CHCl3); 1H
15. Shishido, K.; Takahashi, K.; Fukumoto, K.; Kametani,
T.; Honda, T. J. Org. Chem. 1987, 52, 5704.
NMR (400 MHz, CDCl3) d 7.64 (m, 4H), 7.43–7.33 (m,
6H), 7.16 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 8.4 Hz, 2H),
5.68 (dd, J = 15.2 Hz, 7.2 Hz, 1H), 5.49 (dd, J = 15.6 Hz,
6.4 Hz, 1H), 5.27 (d, J = 9.6 Hz, 1 H), 4.46 (d,
J = 10.8 Hz, 1H), 4.36 (d, J = 10.8 Hz, 1H), 3.95 (m,
2H), 3.77 (s, 3H), 3.75 (m, 2H), 3.54 (d, J = 4.4, 2H), 3.49
(m, 2H), 2.60 (m, 1H), 2.50 (m, 1H), 2.40 (br s, 1H), 1.76
(m, 2H), 1.60 (m, 2H), 1.58 (d, J = 0.8 Hz, 3H), 1.04 (s,
9H), 1.01 (d, J = 6.8 Hz, 3H), 0.97 (d, J = 6.4 Hz, 3H),
0.93 (d, J = 6.8 Hz, 3H), 0.92 (d, J = 6.8 Hz, 3H), 0.89 (s,
9H), 0.88 (s, 9H), 0.03 (s, 9H), ꢀ0.01 (s, 3H); 13C NMR
(50 MHz, CDCl3) d 159.0, 137.2, 135.5, 134.3, 133.9,
130.9, 130.6, 129.5, 129.3, 128.4, 127.6, 113.6, 81.4, 79.3,
74.4, 71.5, 66.4, 60.6, 55.2, 39.3, 39.2, 38.3, 37.9, 34.1, 26.8,
25.8, 19.1, 18.2, 18.1, 15.8, 15.6, 13.3, 12.4, 9.0, ꢀ4.2, ꢀ4.9,
ꢀ5.52, ꢀ5.55; IR (neat, cmꢀ1) 3028, 2922, 2862, 1778,
1699, 1476, 1454, 1390, 1352, 1217, 1107, 1076, 1051, 1051,
975; HRMS (ESI-TOF) m/z (M+Na)+ calcd for
C56H92O7Si3Na, 983.6049; obsd 983.6087.
25
16. Spectral data for (+)-6: ½aꢁD 20.0 (c 0.5, CHCl3); 1H
NMR (400 MHz, CDCl3) d 7.24 (d, J = 8.4 Hz, 2H), 6.86
(d, J = 8.4 Hz, 2H), 5.67 (ddd, J = 17.2 Hz, 10.4 Hz,
8.0 Hz, 1H), 5.23 (dd, J = 10.4 Hz, 1.6 Hz, 1H), 5.18
(dd, J = 17.2 Hz, 1.6 Hz, 1H), 5.09 (d, J = 10.0 Hz, 1H),
4.51 (d, J = 11.6 Hz, 1H), 4.24 (d, J = 11.6 Hz, 1H), 3.84
(d, J = 8.0 Hz, 1H), 3.80 (s, 3H), 3.50 (d, J = 4.4 Hz, 2H),
3.44 (t, J = 8.0 Hz, 1H), 3.36 (m, 1H), 2.62 (m, 1H), 1.94
(d, J = 4.8 Hz, 1H), 1.73 (m, 2H), 1.55 (d, J = 1.2 Hz, 3H),
1.00 (d, J = 6.8 Hz, 3H), 0.95 (d, J = 6.4 Hz, 3H), 0.92 (d,
J = 6.4 Hz, 3H), 0.89 (s, 9H), 0.87 (s, 9H), 0.037 (s, 3H),
0.034 (s, 3H), 0.02 (s, 3H), ꢀ0.04 (s, 3H); 13C NMR (50
MHz, CDCl3) d 159.0, 137.8, 136.8, 130.7, 129.3, 128.9,
118.0, 113.7, 84.3, 82.2, 73.3, 69.7, 65.9, 55.2, 39.2, 38.3,
37.2, 29.6, 25.8, 18.2, 18.1, 16.8, 13.8, 11.7, 9.3, ꢀ4.3, ꢀ4.9,
ꢀ5.4, ꢀ5.5; IR (neat, cmꢀ1) 3604, 3523, 2953, 2929, 1612,
1514, 1465, 1249, 1066, 1043, 837; HRMS (ESI-TOF) m/z
(M+Na)+ calcd for C35H64O5Si2Na, 643.4190; obsd
643.4213.
25
23. Spectral data for (+)-27: ½aꢁD 56.7 (c 0.8, CHCl3); 1H
NMR (400 MHz, CDCl3) d 7.65 (m, 4H), 7.43–7.33 (m,
6H), 7.16 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 8.4 Hz, 2H),
5.28 (d, J = 10.0 Hz, 1H), 4.44 (d, J = 10.8 Hz, 1H), 4.34
(d, J = 11.2 Hz, 1H), 3.97 (d, J = 5.6 Hz, 1H), 3.78 (s,
3H), 3.74 (m, 1H), 3.56 (t, J = 4.0 Hz, 2H), 3.54–3.45 (m,
2H), 3.38 (m, 1H), 2.45 (m, 2H), 2.35 (m, 1H), 1.80 (m,
4H), 1.70 (m, 3H), 1.61 (d, J = 1.2 Hz, 3H), 1.12 (d,
J = 6.8 Hz, 3H), 1.04 (s, 9H), 0.97 (d, J = 6.8 Hz, 3H),
0.91 (d, J = 6.4 Hz, 3H), 0.89 (s, 9H), 0.88 (s, 9H), 0.85 (d,
J = 7.2 Hz, 3H), 0.04 (s, 6H), 0.03 (s, 3H), ꢀ0.05 (s, 3H);
13C NMR (50 MHz, CDCl3) d 211.7, 158.9, 138.5, 135.5,
133.9, 133.8, 131.1, 129.5, 129.2, 127.5, 126.0, 113.6, 80.4,
79.3, 74.8, 71.4, 66.6, 60.8, 55.1, 45.7, 39.1, 38.1, 35.2, 33.5,
31.8, 29.6, 29.3, 26.8, 25.9, 25.8, 22.6, 19.1, 18.19, 18.1,
16.2, 15.2, 14.0, 13.0, 12.7, 8.6, 0.9, ꢀ4.3, ꢀ5.0, ꢀ5.54,
ꢀ5.58; IR (neat, cmꢀ1) 3504, 2929, 2856, 1712, 1612, 1512,
1465, 1249, 1109, 1072, 1039, 837; HRMS (ESI-TOF) m/z
25
17. Spectral data for (ꢀ)-20: ½aꢁD ꢀ3.6 (c 0.5, CHCl3); 1H
NMR (400 MHz, CDCl3) d 5.87 (ddd, J = 16.8 Hz,
10.4 Hz, 6.4 Hz, 1H), 5.23 (td, J = 17.2 Hz, 1.6 Hz, 1H),
5.17 (d, J = 10.4 Hz, 1H), 5.13 (td, J = 10.8 Hz, 1.2 Hz,
1H), 3.92 (m, 2H), 3.53 (dd, J = 4.8 Hz, 2.0 Hz, 2H), 3.42
(dd, J = 7.6 Hz, 2.8 Hz, 1H), 2.60 (m, 1H), 2.15 (br s, 1H),
1.74 (m, 2H), 1.62 (br s, 1H), 1.57 (d, J = 1.6 Hz, 3H), 1.00
(d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.8 Hz, 3H), 0.92 (d,
J = 6.4 Hz, 3H), 0.88 (s, 18H), 0.03 (s, 6H), ꢀ0.007 (s,
3H), ꢀ0.03 (s, 3H); 13C NMR (50 MHz, CDCl3) d 159.0,
137.8, 136.8, 130.7, 129.3, 128.9, 118.0, 113.7, 84.3, 82.2,
73.3, 69.7, 65.9, 55.2, 39.2, 38.3, 37.2, 29.6, 25.8, 18.2, 18.1,
16.8, 13.8, 11.7, 9.3, ꢀ4.3, ꢀ4.9, ꢀ5.4, ꢀ5.5; IR (neat,
cmꢀ1) 3604, 3523, 2953, 2929, 1612, 1514, 1465, 1249,
1066, 1043, 837; HRMS (ESI-TOF) m/z (M+Na)+ calcd
for C27H56O4Si2Na, 523.3615; obsd 523.3614.

V. K. Nyavanandi et al. / Tetrahedron Letters 48 (2007) 6905–6911
6911
(M+Na)+ calcd for C56H92O7Si3Na, 983.6049; obsd
983.6088.
J = 7.2 Hz, 3H), 1.05 (s, 9H), 0.99–0.82 (m, 30 H), 0.07 (s,
3H), 0.05 (s, 3H), ꢀ0.01 (s, 3H); 13C NMR (50 MHz,
CDCl3) d 159.0, 138.2, 135.5, 133.78, 133.74, 130.9,
129.5, 129.3, 129.2, 129.1, 127.9, 127.6, 113.6, 81.8, 74.0,
72.2, 72.0, 66.0, 60.7, 57.3, 56.8, 55.1, 39.5, 38.8, 38.3, 37.5,
34.8, 31.8, 29.6, 29.3, 26.8, 25.8, 22.6, 19.1, 18.2, 18.1, 16.3,
14.0, 13.8, 11.9, 10.4, 9.0, 0.9, ꢀ4.3, ꢀ4.9, ꢀ5.5; IR
(neat, cmꢀ1) 3462, 2956, 2856, 1612, 1512, 1465, 1427,
1388, 1251, 1109, 1074, 1041, 837; HRMS (ESI-TOF) m/z
(M+Na)+ calcd for C56H92O8Si3Na, 999.5998; obsd
999.6030.
25
24. Spectral data for (ꢀ)-28: ½aꢁD ꢀ3.8 (c 0.5, CHCl3); 1H
NMR (400 MHz, CDCl3) d 7.65 (m, 4H), 7.44–7.34 (m,
6H), 7.16 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 8.8 Hz, 2H),
5.29 (d, J = 10.0 Hz, 1H), 4.46 (d, J = 11.2 Hz, 1H), 4.43
(d, J = 11.2 Hz, 1H), 3.99 (d, J = 7.6 Hz, 1H), 3.78 (s,
3H), 3.75 (m, 4H), 3.59–3.50 (m, 3H), 3.36 (dd, J = 7.6,
2.8 Hz, 1H), 3.02 (dd, J = 7.6 Hz, 2.0 Hz, 1H), 2.91 (t,
J = 2.0 Hz, 1H), 2.85 (br s, 1H), 2.77 (m, 1H), 1.80 (m,
3H), 1.60 (d, J = 0.8 Hz, 3H), 1.58 (m, 2H), 1.07 (d,