Formal total synthesis of (-)-5,6-dihydrocineromycine B

Article abstract of DOI:10.1055/s-0032-1317346

An efficient and highly convergent formal total synthesis of the 14-membered macrolide (-)-5,6-dihydrocineromycine B is achieved. Key reaction sequences include a Sharpless asymmetric epoxidation followed by esterification for the formation of a fully functionalized acyclic precursor, Corey-Bakshi-Shibata reduction, and ring-closing metathesis, respectively. Georg Thieme Verlag KG Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317346

LETTER
▌2677
letter
Formal Total Synthesis of (–)-5,6-Dihydrocineromycine B
(–)-5,6-Dihydrocineromycine B
G. Venkateswar Reddy, R. Sateesh Chandra Kumar, B. Siva, K. Suresh Babu, J. Madhusudana Rao*
Division of Natural Product Chemistry, CSIR - Indian Institute of Chemical Technology, Hyderabad – 500007, India
Fax +91(40)27160512; E-mail: suresh@iict.res.in
Received: 13.07.2012; Accepted after revision: 11.09.2012
The unique structures of these macrolides, in conjunction
with their potent biological activities, have made them at-
tractive synthetic targets.3 To date two total syntheses4 of
5,6-dihydrocineromycine B (1) have appeared in the liter-
Abstract: An efficient and highly convergent formal total synthesis
of the 14-membered macrolide (–)-5,6-dihydrocineromycine B is
achieved. Key reaction sequences include a Sharpless asymmetric
epoxidation followed by esterification for the formation of a fully
functionalized acyclic precursor, Corey–Bakshi–Shibata reduction, ature.
and ring-closing metathesis, respectively.
As part of our continuous endeavors in the synthesis of
bioactive macrolides,5 we were attracted to the structural
features and antibiotic activity of (–)-5,6-dihydrocinero-
mycine B (1). Herein, we report the formal total synthesis
of 1, utilizing Sharpless asymmetric epoxidation, Yama-
guchi esterification, Corey–Bakshi–Shibata (CBS) reduc-
tion, and ring-closing metathesis (RCM) as key steps.
Key words: antibiotic macrolide, (–)-5,6-dihydrocineromycine B,
Sharpless asymmetric epoxidation, CBS reduction, ring-closing
metathesis
Macrolide antibiotics belong to a class of polyketide nat-
ural products that exhibit a wide range of biological activ-
ities.1 These antibiotics are usually produced by certain
species of Streptomyces and possess a macrolactone ring
and double bonds. The cineromycins and 5,6-dihydro-
cineromycine B are perhaps the best examples of these in-
teresting macrolides that have been isolated from
Streptomyces sp. (strain Gö 40/10).2 The cineromycins
and albocyclins-18 are structurally related antibiotic natu-
ral products which display potent antibiotic activity
against Staphylococci. As shown in Figure 1, structural
features of (–)-5,6-dihydrocineromycine B (1) encom-
passes four stereogenic centers, two hydroxyls and two
carbon–carbon double bonds which are embedded in a
14-membered lactone ring.
Our retrosynthetic analysis of 1 is shown in Scheme 1. As
indicated, the cyclic framework could be constructed by
RCM of 5, which in turn could be obtained by the Yama-
guchi esterification of the building blocks – alkenes 6 and
7. Fragment 6 could be derived from ester 18 via oxida-
tion followed by Grignard reaction, which is conceived to
be obtained through a four-step sequence starting from the
inexpensive propane-1,3-diol (10). Similarly, we envi-
sioned that fragment 7 can be obtained from but-2-yne-
1,4-diol (12) through Sharpless asymmetric epoxidation
and other functional-group transformations.
As outlined retrosynthetically in Scheme 1, the synthesis
of fragment 6 commenced from commercially available
propane-1,3-diol (10) which was converted into the α,β-
unsaturated ester 13 by following a known procedure
(Scheme 2).6 Treatment of α,β-unsaturated ester 13 with
DIBAL-H at 0 °C yielded allyl alcohol 14 in 95% yield.
Sharpless asymmetric epoxidation7 of 14 using (+)-diiso-
propyl L-tartrate, titanium isopropoxide, and TBHP at –
20 °C furnished 15 in 95% yield with an excellent enanti-
oselectivity of 98% ee. Regioselective opening of epoxide
15 using LAH provided the corresponding8 1,2-diol 9 in
92% yield. The primary hydroxyl group in 9 was oxidized
using 2-iodoxybenzoic acid (IBX)9 to afford an aldehyde,
which was immediately subjected to Horner–Wadsworth–
Emmons olefination10 to give 16 exclusively as the E-iso-
mer (J = 15.6 Hz) in 90% yield.
OH
OH
6
OH
OH
5
10
3
13
1
O
O
O
O
1: (–)-5,6-dihydrocineromycin B
2: cineromycin B
OH
OH
8
9
OH
OH
3
The tertiary hydroxyl group in 16 was protected as a TES
ether by using TESCl and triethylamine in dichlorometh-
ane to give compound 8 in 94% yield and subsequent ox-
idative removal11 of the PMB group by using DDQ in
dichloromethane, pH buffer (9:1 ratio) afforded 17 in 90%
yield. Oxidation of primary alcohol 17 by Dess–Martin
periodinane12 in dichloromethane gave an aldehyde in
quantitative yield which was treated with isopropenyl-
magnesium bromide in THF to afford the secondary alco-
hol in a 1:1 diastereomeric mixture and further Dess–
2
O
O
O
O
4: 2,3,8,9-tetrahydrocineromycin B
3: 2,3-dihydrocineromycin B
Figure 1 Structures of cineromycin B and its derivatives
SYNLETT 2012, 23, 2677–2681
Advanced online publication: 18.10.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317346; Art ID: ST-2012-D0589-L
© Georg Thieme Verlag Stuttgart · New York

2678
G. V. Reddy et al.
LETTER
CBS reduction
O
OH
RCM
6
HO
OH
OTES
+
OH
5
OTES
7
2
1
HO
O
O
O
O
O
esterification
6
5
O
1: (–)-5,6-dihydrocineromycine B
O
TsO
11
O
OTES
OH
PMBO
OEt
PMBO
OH
OH
9
8
12
HO
OH
OH
10
Scheme 1 Retrosynthetic analysis of (–)-5,6-dihydrocineromycine B (1) leading to the key building blocks 5–7
Martin oxidation of the secondary alcohol yielded ketone a known procedure.14 Sharpless asymmetric epoxidation7
18 in 97% yield.
of allylic alcohol 19 using (–)-DIPT resulted in pure epox-
ide 20 in 95% yield with 98% ee. Ring opening of the ep-
oxide was carried out by following Tius15 protocol using
MeLi and CuI in Et2O, which yielded the mixture of 1,3-
diol and undesired 1,2-diol (6:1). Subsequently, the minor
isomer was readily removed by treating the mixture with
sodium periodate to yield 1,3-diol 21 in 71% yield. After
debenzylation of 21 by H2, 10% Pd/C and MeOH at 25 °C
for twelve hours afforded triol 2216 in 95% yield, the 1,2-
hydroxyl groups were protected using 2,2-
dimethoxypropane17 and PTSA in CH2Cl2 at 25 °C to give
23 in 90% yield. Tosylation of the primary alcohol in 23
followed by the Grignard reaction with allylmagnesium
bromide in the presence of stoichiometric18 CuI led to the
formation of allylated product 24 in 84% yield. Acid hy-
Finally, compound 18 was subjected to ester hydrolysis
using LiOH in THF–MeOH–H2O (4:4:2) and THF–H2O
(1:1) at 0 °C to room temperature to give the correspond-
ing acid 6 with low yields. The reaction was sluggish and
resulted in multiple spots by TLC. At this stage, we opted
for the Me3SnOH-mediated nonacidolytic and non-
nucleophilic hydrolysis13 conditions in dichloroethane at
80 °C. As anticipated, the hydrolysis proceeded smoothly
to afford the expected acid 3 in 98% yield. We believe this
could be a general mild method for the benign cleavage of
esters within labile substrates.
The synthesis of building block 7 started from but-2-yne-
1,4-diol (12) which was converted to allylic alcohol 19 by
O
ref. 6
a
b
PMBO
OH
O
PMBO
PMBO
OEt
OH
HO
OH
10
13
14
OH
OH
O
c
d
e
PMBO
OEt
PMBO
OH
15
OTES
9
16
OTES
O
O
O
O
OTES
f
g
h
OEt
PMBO
O
OEt
HO
OEt
8
17
18
O
OTES
OH
6
Scheme 2 Reagents and conditions: (a) DIBAL-H, CH2Cl2, 0 °C, 30 min, 95%; (b) (+)-DIPT, Ti(Oi-Pr)4, t-BuOOH, CH2Cl2, –20 °C, 95%; (c)
LAH, THF, 0 °C, 30 min, 92%; (d) (i) IBX, DMSO, THF, r.t., 1 h; (ii) (EtO)2POCH2CO2Et, n-BuLi, THF, 0 °C, 30 min, 90%; (e) TESCl, Et3N,
CH2Cl2, 0 °C to r.t., 6 h, 94%; (f) DDQ, CH2Cl2–H2O (9:1), 30 min, 90%; (g) (i) DMP, CH2Cl2, 0 °C to r.t., 1 h; (ii) C3H5MgBr, THF, –40
°C, 30 min, 70%; (iii) DMP, CH2Cl2, 0 °C to r.t., 1 h, 97%; (h) Me3SnOH, DCE, 80 °C, 10 h, 98%.
Synlett 2012, 23, 2677–2681
© Georg Thieme Verlag Stuttgart · New York

LETTER
(–)-5,6-Dihydrocineromycine B
2679
HO
OH
ref. 14
a
b
OH
c
OH
BnO
O
BnO
O
BnO
O
OH
21
OH
12
19
20
O
d
e
f
g
O
OH
O
O
HO
HO
OH
OTs
OH
OH
22
24
23
11
OH
OH
h
i
TsO
25
26
7
Scheme 3 Reagents and conditions: (a) (–)-DIPT, Ti(Oi-Pr)4, t-BuOOH, CH2Cl2, –20 °C, 95%; (b) Me2CuLi, Et2O, –50 °C to 25 °C, 1,3-diol–
1,2-diol (6:1); NaIO4, H2O, 71%; (c) H2, Pd/C, MeOH, 12 h, 95%; (d) 2,2-dimethoxypropane, PTSA, CH2Cl2, 6 h, 90%; (e) TsCl, pyridine,
CH2Cl2, 12 h, 93%; (f) AllylMgBr, CuI, Et2O, 0 °C to r.t., 12 h, 82%; (g) AcOH–THF–H2O (1:1:1), 8 h, 60 °C, 92%; (h) TsCl, Bu2SnO, Et3N,
CH2Cl2, 10 h, 90%; (i) LAH, THF, 0 °C, 2 h, 85%.
drolysis followed by the tosylation of the primary hydrox- available for sterically crowded or functionalized dienes
yl group in 25 was accomplished 26 in 90% using the to undergo RCM,24 we next submitted the diene 5 to 25
Martinelli19 procedure (Bu2SnO, TsCl). Finally, reductive mol% of Grubbs’ second-generation catalyst in refluxing
cleavage of sulfonate 26 by LAH in THF afforded key dichloromethane. As expected, the RCM proceeded
fragment 7 in 85% yield.
smoothly to afford compound 32 in 40% yield. This late-
stage intermediate has been already converted into the tar-
get compound in one step.4b All the intermediate com-
pounds including macrolide 32 were fully characterized
by IR, 1H NMR, 13C NMR, and mass spectral data.25
The key fragment 7 can also be synthesized from 4-pent-
en-1-ol (27) shown in Scheme 4. Swern oxidation and
subsequent Wittig homologation of 27 yielded α,β-unsat-
urated ester 28 in 90% yield exclusively as the E-isomer
(J = 15.6 Hz). The ester was then subjected to reduction In summary, we have achieved an efficient and elegant
by DIBAL-H and afforded allylic alcohol 29, which was formal synthesis of (–)-5,6-dihydrocineromycine B. The
further subjected to Sharpless epoxidation using (–)-DIPT synthesis features key fragments which were constructed
and resulted in pure epoxide 30 in 75% yield with 95% ee. employing Sharpless asymmetric epoxidation and CBS
Regioselective ring opening of epoxide 30 with reduction followed by ring-closing metathesis. A Yama-
trimethylaluminium20 in dichloromethane gave 1,2-diol guchi esterification protocol was utilized to construct the
25, which was converted into key fragment 7 as shown in backbone of the natural product, in which the 14-mem-
Scheme 3.
bered lactone moiety was constructed by the ring-closing
metathesis. We believe that the presented synthetic meth-
od could be of value in the development of novel 14-mem-
bered lactone ring analogues for 5,6-dihydro-
cineromycine B research.
With the two key fragments 6 and 7 in hand, the stage was
now set for their assembly and elaboration into (–)-5,6-di-
hydrocineromycine B (1) as shown in Scheme 5. Our frag-
ment assembly began with coupling of fragments 6 and 7.
Esterification of 6 and 7 under Yamaguchi conditions21
yielded 31 in 97% yield.
Acknowledgment
The α,β-unsaturated ketone 31 was then treated with (R)-
(+)-2-methyl-CBS oxazaborolidine22 and BH3·DMS at
–40 °C to furnish allyl alcohol 5 with an S-configuration
in 90% yield with 98% de.23 With a wealth of literature24
The authors gratefully acknowledge keen interest shown by Dr. J.
S. Yadav, Director, IICT, Hyderabad. G.V.R thanks UGC, New
Delhi for financial support.
OEt
a
b
c
OH
OH
O
27
28
29
OH
O
d
OH
OH
30
25
Scheme 4 Reagents and conditions: (a) (i) Swern oxidation; (ii) Ph3PCHCOOEt, CH2Cl2, r.t., 6 h, 90% (2 steps); (b) DIBAL-H, CH2Cl2, –
78 °C; (c) (–)-DIPT, Ti(Oi-Pr)4, t-BuOOH, CH2Cl2, –20 °C, 95%; (d) Me3Al, toluene, 0 °C to r.t., 6 h, 86%.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2677–2681

2680
G. V. Reddy et al.
LETTER
O
OH
O
HO
OTES
OTES
OTES
OTES
a
b
c
ref. 4b
+
HO
O
OH
O
O
O
5
O
32
O
O
7
6
31
OH
OH
Ph
H
N
Ph
O
N
N
Cl
Ru
B
Cl
O
O
Ph
PCy3
CH3
R-CBS catalyst
Grubbs II catalyst
1: (–)-5,6-dihydrocineromycin B
Scheme 5 Reagents and conditions: (a) benzene, 2,4,6-trichlorobenzoyl chloride, Et3N then 7, DMAP, 30 min, 97%; (b) (R)-2-methyl-CBS
oxazaborolidine, THF, 0 °C, BH3·DMS, 3 h, 90%, 98% de; (c) Grubbs II (25 mol%), CH2Cl2, reflux, 48 h, 40%.
(19) Martinelli, M. J.; Nayyar, N. K.; Moher, E. D.; Dhokte, U.
References and Notes
P.; Pawlak, J. M.; Vaidyanathan, R. Org. Lett. 1999, 1, 447.
(1) (a) Galm, U.; Hager, M. H.; Lanen, S. G. V.; Ju, J.; Thorson,
(20) Suzuki, T.; Saimoto, H.; Tomioka, H.; Oshima, K.; Nozaki,
J. S.; Shen, B. Chem. Rev. 2005, 105, 739. (b) Zhang, H.;
H. Tetrahedron Lett. 1982, 23, 3597.
Wang, Y.; Pfeifer, B. A. Mol. Pharm. 2008, 5, 212.
(21) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi,
(2) Schiewe, H. J.; Zeeck, A. J. Antibiot. 1999, 52, 635.
M. Bull. Chem. Soc. Jpn. 1979, 52, 1989.
(3) (a) Tanner, D.; Somfai, P. Tetrahedron 1987, 43, 4395.
(22) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc.
(b) Takahashi, T.; Watanabe, H.; Kitahara, T. Tetrahedron
1987, 109, 5551. (b) Corey, E. J.; Helal, C. J. Angew. Chem.
Lett. 2003, 44, 9219.
Int. Ed. 1998, 37, 1986.
(4) (a) Tietze, L. F.; Völkel, L. Angew. Chem. Int. Ed. 2001, 40,
(23) The diastereomeric excess of the allylic alcohol 5 was
901. (b) Li, G.; Yang, X.; Zhai, H. J. Org. Chem. 2009, 74,
1356.
(5) (a) Reddy, G. V.; Kumar, R. S. C.; Babu, K. S.; Rao, J. M.
determined by HPLC [YMC CYNAO column, 250 × 4.6
mm, 5μ; eluent, MeCN–H2O (50:50), 10 μL injection
volume, flow rate 1.0 mL/min; tR = 15.50 and 17.09 min].
Tetrahedron Lett. 2009, 50, 4117. (b) Reddy, G. V.; Kumar,
(24) (a) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem.
R. S. C.; Sreedhar, E.; Babu, K. S.; Rao, J. M. Tetrahedron
Int. Ed. 2005, 44, 4490. (b) Jin, J.; Chen, Y.; Li, Y.; Wu, J.;
Lett. 2010, 51, 1723.
(6) Hayashi, Y.; Yamaguchi, H.; Toyoshima, M.; Okado, K.;
Toyo, T.; Shoji, M. Org. Lett. 2008, 10, 1405.
(7) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.;
Dai, W.-M. Org. Lett. 2007, 9, 2585. (c) Park, P. K.;
O’Mally, S. J.; Schmidt, D. R.; Leighton, J. L. J. Am. Chem.
Soc. 2006, 128, 2796. (d) Ko, K.-S.; Alexander, M. D.;
Fontaine, S. D.; Biggs-Houck, J. E.; Clair, J. J. L.; Burkart,
Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987,
M. D. Org. Biomol. Chem. 2010, 8, 5159.
109, 5765.
(25) Spectral Data for Representative New Compounds
Compound 9: colorless oil; [α]D25 –5.5 (c 1, CHCl3). IR
(KBr): 3399, 2933, 1612, 1513, 1248, 1035, 772 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 7.17 (d, 2 H, J = 8.30 Hz),
6.80 (d, 2 H, J = 9.00 Hz), 4.38 (s, 2 H), 3.74 (s, 3 H), 3.40
(t, 2 H, J = 5.20 Hz), 3.35–3.21 (m, 2 H), 1.70–1.39 (m, 4 H),
1.06 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 159.1, 129.2,
113.6, 72.5, 72.4, 70.4, 69.5, 54.8, 35.2, 24.0, 23.1. ESI-MS:
m/z = 277 [M + Na]+. ESI-HRMS: m/z calcd for
(8) Lee, A. W. M. J. Chem. Soc., Chem. Commun. 1984, 578.
(9) Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994, 35,
8019.
(10) Wadsworth, W. S. Jr.; Emmons, W. D. J. Am. Chem. Soc.
1961, 83, 1733.
(11) Oikawa, Y.; Yoshioka, T.; Yonemitsu, O. Tetrahedron Lett.
1982, 23, 885.
(12) (a) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277. (b) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1983,
105, 4155.
(13) Furlan, R. L. E.; Mata, E. G.; Mascaretti, O. A.; Pena, C.;
Coba, M. P. Tetrahedron 1998, 54, 13023.
(14) Sabitha, G.; Reddy, C. N.; Gopal, P.; Yadav, J. S.
Tetrahedron Lett. 2010, 51, 5736.
(15) Tius, M. A.; Fauq, A. H. J. Org. Chem. 1983, 48, 4131.
(16) (a) Mori, K.; Nomi, H.; Chuman, T.; Kohno, M.; Kato, K.;
Noguchi, M. Tetrahedron 1982, 38, 3705. (b) Shimizu, Y.;
Kiyota, H.; Oritani, T. Tetrahedron Lett. 2000, 41, 3141.
(17) Nicolaou, K. C.; Papahatjis, D. P.; Claremon, D. A.; Dolle,
R. E. J. Am. Chem. Soc. 1981, 103, 6967.
C14H22NaO4: 277.1416; found: 277.1410.
Compound 16: colorless oil; [α]D25 +13.7 (c 1, CHCl3). IR
(KBr): 3446, 2926, 1722, 1655, 1513, 1219, 1035, 772
cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.19 (d, 2 H, J = 8.49
Hz), 6.92–6.77 (m, 3 H), 5.97 (d, 1 H, J = 15.67 Hz), 4.40 (s,
2 H), 4.16 (q, 2 H, J = 7.17, 14.16 Hz), 3.77 (s, 3 H), 3.47–
3.32 (m, 3 H), 1.75–1.56 (m, 4 H), 1.33–1.22 (m, 6 H). 13
C
NMR (75 MHz, CDCl3): δ = 166.3, 159.1, 154.4, 129.7,
129.1, 118.9, 113.6, 72.6, 72.1, 70.0, 59.9, 54.8, 39.5, 28.1,
24.3, 14.3. ESI-MS: m/z = 345 [M + Na]+. ESI-HRMS: m/z
calcd for C18H26NaO5: 345.1678; found: 345.1667.
Compound 17: colorless oil; [α]D25 +10.6 (c 1, CHCl3). IR
(KBr): 3424, 2955, 1720, 1656, 1459, 1299, 1061, 772 cm–1.
(18) Koert, U.; Wagner, H.; Pidun, U. Chem. Ber. 1994, 127,
1447.
Synlett 2012, 23, 2677–2681
© Georg Thieme Verlag Stuttgart · New York

LETTER
1H NMR (300 MHz, CDCl3): δ = 6.83 (d, 1 H, J = 15.1 Hz),
(–)-5,6-Dihydrocineromycine B
2681
(m, 2 H), 3.62 (pent, 1 H, J = 6.04, 12.08, 18.12 Hz), 2.27–
2.06 (m, 1 H), 2.05–1.86 (m, 2 H), 1.66–1.42 (m, 1 H), 1.23–
1.13 (m, 1 H), 1.10 (d, 3 H, J = 6.04 Hz), 0.87 (d, 3 H,
J = 6.79 Hz). 13C NMR (75 MHz, CDCl3): δ = 138.73,
114.53, 71.26, 39.41, 31.73, 31.50, 19.39, 14.50.
5.88 (d, 1 H, J = 15.1 Hz), 4.18 (q, 2 H, J = 6.79, 14.35 Hz),
3.59 (t, 2 H, J = 6.04 Hz), 1.67–1.52 (m, 4 H), 1.39 (s, 3 H),
1.31 (t, 3 H, J = 6.79 Hz) 0.97 (t, 9 H, J = 8.30, 15.86 Hz),
0.61 (q, 6 H, J = 7.55, 15.86 Hz). 13C NMR (75 MHz,
CDCl3): δ = 166.4, 154.4, 119.0, 75.1, 62.9, 60.2, 39.8, 27.9,
27.4, 14.4, 7.2, 6.8. ESI-MS: m/z = 339 [M + Na]+. ESI-
HRMS: m/z calcd for C16H32NaO4Si: 339.1968; found:
339.1961.
Compound 31: colorless oil; [α]D25 –17.2 (c 1, CHCl3). 1H
NMR (300 MHz, CDCl3): δ = 6.78 (d, 1 H, J = 15.70 Hz),
5.93–5.84 (m, 2 H), 5.77–5.69 (m, 2 H), 5.02–4.38 (m, 3 H),
2.80–2.69 (m, 1 H), 2.67–2.58 (m, 1 H), 2.21–2.09 (m, 1 H),
2.06–1.97 (m, 1 H), 1.91–1.83 (m, 5 H), 1.79–1.69 (m, 1 H),
1.56–1.45 (m, 1 H), 1.41 (s, 3 H), 1.27–1.23 (m, 1 H), 1.20
(d, 3 H, J = 6.87 Hz), 0.96 (t, 9 H, J = 7.85 Hz), 0.92 (d, 3 H,
J = 6.87 Hz), 0.61 (q, 6 H, J = 7.85, 15.70 Hz). 13C NMR (75
MHz, CDCl3): δ = 201.47, 166.14, 153.78, 144.47, 138.58,
124.34, 119.72, 114.63, 74.67, 74.17, 37.26, 36.80, 32.09,
31.78, 31.29, 28.09, 17.73, 16.07, 14.60, 7.12, 6.71. ESI-
MS: m/z = 459 [M + Na]+. ESI-HRMS: m/z calcd for
C25H44NaO4Si: 459.2907; found: 459.2910.
Compound 6: colorless oil; [α]D25 –13.5 (c 1, CHCl3). IR
(KBr): 3414, 2924, 1706, 1454, 1219, 1018, 770 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 6.92 (d, 1 H, J = 15.86 Hz),
5.95 (d, 1 H, J = 15.10 Hz), 5.91 (s, 1 H), 5.73 (s, 1 H), 2.83–
2.69 (m, 1 H), 2.66–2.52 (m, 1 H), 1.95–1.81 (m, 5 H), 1.43
(s, 3 H), 0.97 (t, 9 H, J = 8.30 Hz), 0.61 (q, 6 H, J = 7.55,
15.86 Hz). 13C NMR (75 MHz, CDCl3): δ = 200.6, 172.0,
156.7, 144.6, 124.1, 118.8, 74.8, 37.0, 31.9, 28.2, 17.8, 7.2,
6.7. ESI-MS: m/z = 349 [M + Na]+. ESI-HRMS: m/z calcd
for C17H30NaO4Si: 349.1811; found: 349.1820.
Compound 5: colorless oil; [α]D25 –21.7 (c 1, CHCl3). 1H
NMR (300 MHz, CDCl3): δ = 6.86 (d, 1 H, J = 15.48 Hz),
5.93–5.84 (m, 2 H), 5.91 (d, 1 H, J = 15.48 Hz), 5.87–5.69
(m, 1 H), 5.07–4.81 (m, 5 H), 4.02 (t, 1 H, J = 5.28 Hz),
2.30–2.30 (m, 1 H), 2.23–1.93(m, 2 H), 1.69 (s, 3 H), 1.64–
1.44 (m, 4 H), 1.38 (s, 3 H), 1.30–1.23 (m, 2 H), 1.19 (d, 3
H, J = 6.7 Hz), 0.96 (t, 9 H, J = 7.55 Hz), 0.92 (d, 3 H,
J = 6.79 Hz), 0.61 (q, 6 H, J = 7.55, 15.86 Hz). 13C NMR (75
MHz, CDCl3): δ = 166.17, 154.27, 147.27, 128.58, 127.58,
126.56, 114.75, 111.27, 75.81, 74.96, 74.10, 39.02 36.83,
31.81, 31.34, 29.79, 29.11, 27.71, 17.64, 16.12, 14.68, 7.16,
6.79. ESI-MS: m/z 461 [M + Na]+. ESI-HRMS: m/z calcd for
C25H46NaO4Si: 461.3063; found: 461.3044.
Compound 11: colorless oil, [α]D25 –2.5 (c 1, CHCl3). 1H
NMR (300 MHz, CDCl3): δ = 7.79 (d, 2 H, J = 7.90 Hz),
7.34 (d, J = 7.90 Hz), 4.19–4.13 (m, 1 H), 4.03–3.96 (m, 2
H), 3.84 (q, 1 H, J = 6.30, 14.30 Hz), 3.58 (t, 1 H, J = 7.10
Hz), 2.45 (s, 3 H), 1.96–1.87 (m, 1 H), 1.31 (s, 3 H), 1.27 (s,
3 H), 0.90 (d, 3 H, J = 7.10 Hz). 13C NMR (75 MHz, CDCl3):
δ = 144.6, 132.9, 129.7, 127.8, 109.0, 76.3, 72.2, 67.6, 37.0,
26.5, 25.3, 21.5, 12.8. ESI-MS: m/z = 337 [M + Na]+. ESI-
HRMS: m/z calcd for C15H22NaO5S: 337.1086; found:
337.1091.
Compound 7: colorless oil; [α]D25 –12.8 (c 1, CHCl3). 1H
NMR (300 MHz, CDCl3): δ = 5.85–5.65 (m, 1 H), 5.05–4.85
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2677–2681

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