Studies directed toward the synthesis of caylobolide A: Convergent synthesis of C21-C40 subunit

Article abstract of DOI:10.1016/j.tetlet.2013.12.091

Stereoselective synthesis of the C21-C40 core segment of caylobolide A has been achieved following a highly efficient convergent strategy. The key reactions featured in the synthesis are Prins cyclization, reductive radical cyclization, Sharpless asymmetric epoxidation and olefin cross metathesis.

Full text of DOI:10.1016/j.tetlet.2013.12.091

Tetrahedron Letters 55 (2014) 1164–1167
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Studies directed toward the synthesis of caylobolide A: convergent
synthesis of C21–C40 subunit
⇑
J. S. Yadav , N. Swapnil, M. Venkatesh, A. R. Prasad
Centre for SemioChemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 July 2013
Revised 23 December 2013
Accepted 25 December 2013
Available online 3 January 2014
Stereoselective synthesis of the C21–C40 core segment of caylobolide A has been achieved following a
highly efficient convergent strategy. The key reactions featured in the synthesis are Prins cyclization,
reductive radical cyclization, Sharpless asymmetric epoxidation and olefin cross metathesis.
Ó 2014 Published by Elsevier Ltd.
Keywords:
Caylobolide A
Prins cyclisation
Reductive radical cyclization
Olefin cross metathesis
Sharpless asymmetric epoxidation
Marine natural products have become a major source of new
OH
OH
OH
O
chemical entities in the discovery of potential anticancer agents
that potently suppress various molecular targets.1 These entities
O
give the synthetic chemist, a challenge in the area of the total syn-
thesis of natural products viz., the exponential probability of num-
HO
OH OH OH
OH
ber of diastereomers.
A new 36 membered macrolactone
caylobolide A (1) was one of such natural products which was iso-
HO
lated via bioassay-guided purification from the Bahamian cyano-
2
bacterium Lyngbya majuscule by Molinski and MacMillan. It
Caylobolide A (1)
exhibits potent cytotoxicity toward the human colon tumor cell
line HCT-116 (IC50 9.9 lM). As shown in Figure 1, caylobolide A
Figure 1. Structure of caylobolide A.
contains eight undefined stereogenic centers, thus giving several
structural diastereomeric possibilities with repeating 1,5-diol mo-
tif. Undoubtedly, this scarce natural product has attracted top
schools of synthesis to embark on its synthesis.3 Our group is en-
strategy in mind, the target fragment 2 could be synthesized via
cross metathesis of olefin 3 and allylic alcohol 4, having arbitrarily
chosen the R-configuration at C36. With this strategy we can build
directly syn and anti 1,5-diol motif.
4
gaged in the synthesis of biologically active natural products
and was attracted to the fascinating biological profile of caylobo-
lide. In this Letter, we report our preliminary studies that resulted
in the synthesis of the southern (C21–C40) domain of caylobolide
A.
As shown in Scheme 1, our overall retrosynthetic strategy for
the target fragment 2 involved disconnection at the C20–C21 and
the ester bonds, affording two subtargets 3 and 4, respectively.
The subtarget 3 as represented was derived from 5 obtainable by
Prins cyclization from homoallylic alcohol 7, whereas subtarget 4
was realized from 6, obtainable by radical cyclization. With this
The synthesis of fragment 3, the core intermediate is outlined in
Scheme 2. This is initiated from the known aldehyde 8 using a two-
5
step sequence. Aldehyde 8 is engaged in allylation under Keck’s
conditions6 to produce homo-allylic alcohol 9 in 87% yield.7 The
resulting alcohol 9 is then converted to benzyl ether 10 in 89%
yield. Ozonolytic cleavage of the olefinic bond of the compound
1
0 afforded the required aldehyde 11, which on Prins cyclization
with 7 in the presence of TFA followed by hydrolysis of the
resulting trifluoroacetate gave trisubstituted pyran 12 in 52%
8
yield. The primary hydroxyl group in 12 is transformed to its
corresponding tosylate using p-TsCl and triethylamine followed
by protection of the secondary hydroxyl group as its silyl ether
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: yadavpub@iict.res.in (J.S. Yadav).
0
040-4039/$ - see front matter Ó 2014 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2013.12.091

J. S. Yadav et al. / Tetrahedron Letters 55 (2014) 1164–1167
1165
OH
OH
OH
O
using TBSCl, and imidazole to obtain silyl ether 13 in 80% yield in
two steps. Substitution of the tosyl group in 13 using NaI in ace-
tone followed by reductive opening produced alcohol 3 in 83%
O
3
6
8
b,d
overall yield (two steps).
4
0
The synthesis of fragment 4 commenced from alcohol 14
Scheme 3). Compound 14 is subsequently reacted with ethyl vi-
HO
20
OH OH OH
OH
9
(
HO 21
nyl ether and NBS, which resulted in bromoacetal 15 as a 1:1 mix-
Caylobolide A (1)
10
OTBS
OH
ture of diastereomers. It was converted into cyclic ethyl acetal 15
(
80% for two steps) with a preferential trans geometry of the new
stereogenic center via a radical cyclization using n-Bu SnH in
3
OBn OH OTBS
11
refluxing benzene with catalytic AIBN as a radical initiator. The
hydrolysis of ethyl acetal 16 using 60% acetic acid under reflux
conditions afforded the lactol 17, which on two carbon Wittig olef-
ination furnished the hydroxy derivative 18 as mixture of diaste-
reomers in 64% yield in two steps. The resulting alcohol 18 is
protected as its silyl ether followed by simultaneous reduction of
olefin and benzyl group furnished primary alcohol 19 in 86% yield.
Subsequently, oxidation of the alcohol 20 followed by two-carbon
BnO
2
OH OTBS
OBn OH OTBS
+
BnO
3
4
OH
Wittig olefination gave the a,b-unsaturated ester 21 in 74% yield in
OBn
BnO
overall two steps. The ester 21 is reduced with DIBAL-H at ꢀ20 °C
to afford allylic alcohol 22 in 92% yield. The requisite chiral epoxide
was introduced at this stage via a Sharpless asymmetric epoxida-
OH
OH
BnO
O
O
5
6
OBn
12
tion reaction, using (ꢀ)-diisopropyl tartrate to yield epoxide 23
O
BnO
O
+
OH
in 88% yield. Furthermore, titanocene induced regioselective deox-
BnO
11
13
7
ygenation of epoxy alcohol 23 afforded allylic alcohol 4 in 80%
OH
yield.
Scheme 1. Retrosynthetic analysis of caylobolide A.
OH
OBn
a
b
BnO
O
BnO
BnO
8
9
10
OH
O
OBn
OBn
12
e, f
c
d
OH
BnO
O
BnO
1
1
OTBS
O
OBn OH OTBS
OBn
g, h
OTs
BnO
BnO
1
3
3
i
Scheme 2. Reagents and conditions: (a) R-BINOL, Ti(O Pr)
4
, allyltributylstannane, 4° MS, ꢀ78 °C, ꢀ20 °C, 72 h, 87%; (b) NaH, BnBr, cat. TBAI, THF, 0 °C to rt, 89%; (c) O
3
, CH
2
Cl
Cl
2
,
,
o
TPP, ꢀ78 C, 1 h, 84%; (d) 7, TFA, CH
2
Cl
2
, 0 °C to rt, 3 h then K
°C to rt, 2 h, 91%; (g) NaI, acetone, reflux, 24 h, 90%; (h) Zn, EtOH, reflux, 2 h, 92%.
2
CO , MeOH, rt, 30 min, 52%; (e) p-TsCl, Et N, CH Cl , 0 °C to rt, 3 h, 88%; (f) TBDMSCl, imidazole, DMAP, CH
3
3
2
2
2
2
0
Br
OH
a
b
OEt
c
BnO
BnO
O
OEt
BnO
O
14
15
16
OTBS
OH
d
e
OH
BnO
BnO
f
O
BnO
1
7
18
19
OTBS
OTBS
g
h
EtO C
2
HO
20
21
OTBS
OTBS
O
i
j
HO
HO
4
22
23
Scheme 3. Reagents and conditions: (a) ethyl vinyl ether, NBS, CH
2
Cl
2
, 0 °C to rt, 5 h, 88%; (b) n-Bu
3
SnH, AIBN (cat.), benzene, reflux, 2 h, 90%; (c) 60% AcOH, reflux, 2 h, 85%;
, 0 °C to rt, 90%; (f) H , Pd/c, EtOAc, rt, 96%; (g) (i) IBX, DMSO, CH Cl , 0 °C to rt, 2 h; (ii)
, TBHP, 4 Å MS, CH Cl TiCl , Zn, ZnCl , THF, rt,
, ꢀ20 °C, 12 h, 88%; (j) (C
þ
ꢀ
(
d) C
Ph
0 min, 80%.
2
H
5
PPh Br , n-BuLi, THF, ꢀ20 °C, 75%; (e) TBSOTf, 2,6-lutidine, CH
Cl
2 2
2
2
2
3
i
3
P@CHCO
2
Et, benzene, rt, 2 h, 92%; (h) DIBAL-H, CH
2
Cl
2
, ꢀ20 °C, 2 h, 92%; (i) (ꢀ)-DIPT, Ti(O Pr)
4
2
2
5
H
5
)
2
2
2
1

1
166
J. S. Yadav et al. / Tetrahedron Letters 55 (2014) 1164–1167
OTBS
OH
Gayathri, K. U.; Rao, N. V.; Prasad, A. R. Synthesis 2008, 3945; (f) Yadav, J. S.;
Venkatesh, M.; Thrimurtulu, N.; Prasad, A. R. Synlett 2010, 1255.
(a) Yadav, J. S.; Lakshmi, K. L.; Reddy, N. M.; Swapnil, N.; Prasad, A. R.
Tetrahedron: Asymmetry 2012, 23, 1155; (b) Srihari, P.; Kumaraswamy, B.;
Shankar, P.; Ravishashidhar, V.; Yadav, J. S. Tetrahedron Lett. 2010, 51, 6174.
9
.
OBn OH OTBS
1
0. Ueno, Y.; Chino, K. J. Chem. Soc., Perkin Trans. 1 1986, 1351.
a
b
3
+
4
BnO
2
11. (a) Yadav, J. S.; Gadgil, V. R. J. Chem. Soc., Chem. Commun. 1989, 23, 1824; (b)
Stork, G.; Mook, R., Jr. J. Am. Chem. Soc. 1983, 105, 3741; (c) Beckwith, A. L. J.;
Lawrence, T.; Serelis, A. K. J. Chem. Soc., Chem. Commun. 1980, 484; (d) Baldwin,
J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
2. (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974; (b) Gao, Y.;
Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am.
Chem. Soc. 1987, 109, 5765.
2
4
Scheme 4. Reagents and conditions: (a) Grubb’s-II catalyst, CH
b) Pd/CaCO , H , EtOAc, 3 h, 90%.
2 2
Cl , reflux, 6 h, 72%;
1
(
3
2
13. (a) Yadav, J. S.; Shakharam, T.; Gadgil, V. R. J. Chem. Soc., Chem. Commun 1990,
843; (b) RajanBabu, T. V.; Nugent, A. W. J. Am. Chem. Soc. 1994, 116, 986.
Having both the desired fragments 3 and 4 in hand, we pro-
ceeded to converge the required synthons via a Ru-catalyzed
cross-metathesis reaction and complete the C21–C40 segment of
14. (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953; (b)
Chatterjee, A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H. J. Am. Chem. Soc. 2000,
1
22, 3783; (c) Chatterjee, A. K.; Choi, T. L.; Sanders, D. P.; Grubbs, R. H. J. Am.
Chem. Soc. 2003, 125, 11360.
2
5
1
as delineated in Scheme 4. Inspired by Grubb’s report on selective
Spectral data for (S)-8-(benzyloxy)oct-1-en-4-ol (9): ½
a
ꢁ
ꢀ2.75 (c 1.4, CHCl
3
); IR
D
ꢀ
1 1
1
4
(KBr)
CDCl
.70–3.59(m, 1H), 3.48(t, J = 6.7 Hz, 2H), 2.36–2.24(m, 1H), 2.19–2.07(m, 1H),
m
max
3414, 2935, 1640, 1455, 1101, 736, 698 cm ; H NMR (300 MHz,
cross-metathesis, olefin 3 is coupled with the allylic alcohol 4 in
3
): d 7.39–7.27 (m, 5H), 5.90–5.74(m, 1H), 5.18–5.08(m, 2H), 4.50(s, 2H),
the presence of second generation Grubbs catalyst to obtain alkene
4 (E/Z: 80:20) with 72% yield. Subsequent reduction of the result-
ing olefin using Lindlar’s catalyst afforded the all important C21–
3
13
2
1.73–1.59(m, 3H), 1.58–1.38 (m, 3H); C NMR (75 MHz, CDCl
3
): d 139.3, 134.7,
1
2
28.8, 127.5, 124.4, 117.9, 72.8, 70.4, 70.1, 41.8, 36.4, 29.5, 22.2; MS (ESI) m/z
57 [M+Na] ; HRMS Calcd for C15H O Na [M+Na] 257.1517, found 257.1512.
22 2
+
+
C40 segment 2 in 90% yield. The structure of 2 is fully characterized
(
2R,4R,6S)-2-((S)-2,6-Bis(benzyloxy)hexyl)-6-(hydroxymethyl)tetrahydro-2H-
1
13
25
by H NMR, C NMR, and mass spectral data.
pyran-4-ol (12): ½
a
ꢁ
+2.0 (c 1.75, CHCl ); IR (KBr) mmax 3401, 3030, 2932, 1453,
D
3
ꢀ
1 1
1
4
1
206, 1099, 1028, 611 cm
3
; H NMR (300 MHz, CDCl ) d 7.38–7.27(m, 10H),
Thus, a highly convergent stereoselective approach to complete
the synthesis of the C21–C40 segment 2 of caylobolide A is here-
with illustrated
.54–4.45(m, 4H), 3.95–3.65(m, 2H), 3.61–3.39 (m, 6H), 1.98–1.79(m, 2H),
13
3
.87–1.79(1H, m) 1.68–1.40(m,10H); C NMR (75 MHz, CDCl ) d 138.7, 138.5,
128.3, 127.8, 127.6, 127.4, 75.9, 75.3, 72.8, 72.5, 70.5, 70.2, 67.8, 65.8, 41.4,
+
By utilizing high-yielding chemical transformations, a highly
convergent and stereoselective synthesis of core fragment of cayl-
obolide A, a potent cytotoxic macrolide is accomplished. Prins
cyclization, reductive radical cyclization, and Sharpless asymmet-
ric epoxidation reactions, are efficiently used for the preparation
of key intermediates. The present strategy could be well utilized
to construct the repeating syn and anti-1,5 diol sub units effec-
tively. The salient features of the approach include an efficient
and scalable synthesis of two fragments 3 and 4 in a stereoselective
manner and the use of olefin cross metathesis for fastening these
fragments.
36.6, 33.6, 29.7, 21.8; MS (ESI) m/z 451 [M+Na] ; HRMS Calcd for C26
H
36
O
5
Na
+
[
M+Na] 451.2460, found 451.2455.
(
(2S,4R,6S)-6-((S)-2,6-Bis(benzyloxy)hexyl)-4-((tert-
butyldimethylsilyl)oxy)tetrahydro-2H-pyran-2-yl)methyl
4-
2
5
methylbenzenesulfonate (13): ½
936, 1599, 1363, 1177, 836, 773 cm
m, 2H), 7.37–7.23 (m, 12H), 4.50 (s, 2H),4.45 (s, 2H), 4.46–4.42 (m, 2H), 4.03–
.89 (m, 2H), 3.75–3.62(m, 1H), 3.55–3.32 (m, 5H), 2.41 (s, 3H), 1.90–1.67 (m,
aꢁ
+59 (c 0.3, CHCl
3
); IR (KBr)
mmax: 3064,
D
ꢀ
1 1
2
;
H NMR (300 MHz, CDCl ): d 7.81–7.74
3
(
3
13
2H), 1.66–1.33 (m, 8H), 1.30–1.04 (m, 2H), 0.86 (s, 9H), 0.03 (s, 6H); C NMR
75 MHz, CDCl ): d 129.7, 128.8, 127.9, 127.7, 127.5, 127.3, 75.5, 72.8, 71.9,
0.5, 70.2, 69.2, 68.0, 41.3, 39.3, 37.3, 33.6, 29.7, 25.7, 21.8, 21.5, ꢀ4.5, ꢀ4.9; MS
(
3
7
+
SSiNa [M+Na]+ 719.3414,
56 7
H O
(
ESI) m/z 719 [M+Na] ; HRMS Calcd for C39
found 719.3408.
(
(
7
4S,6S,8S)-8,12-Bis(benzyloxy)-4-((tert-butyldimethylsilyl)oxy)dodec-1-en-6-ol
25
3): ½
72 cm
5.06–5.01. (m, 2H), 4.60–4.43 (m, 4H), 4.05–3.97 (m, 2H), 3.68–3.61 (m, 2H),
.48 (t, J = 6.4 Hz, 2H), 2.29–2.25 (m, 2H), 1.77–1.25(m, 10H), 0.91 (s, 9H), 0.11
s, 3H), 0.09 (s, 3H); 13C NMR (75 MHz, CDCl
): d 138.5, 138.2, 134.1, 128.4,
28.3, 128.2, 117.1, 78.8, 72.9, 70.6, 70.2, 69.4, 67.1, 43.3, 42.0, 41.9, 33.2, 29.9,
a
ꢁ
ꢀ3.0 (c 0.55, CHCl
3
); IR (KBr)
mmax: 3500, 2930, 1455, 1299, 1081,
D
ꢀ
1 1
;
H NMR (300 MHz, CDCl ): d 7.35–7.26 (m, 10H), 5.81–5.72 (m, 1H),
3
Acknowledgements
3
(
1
3
N.S. and M.V. thank the Council of Scientific and Industrial
Research (CSIR), New Delhi, India, for financial assistance in the
form of research fellowships. J.S.Y. thanks CSIR for the award of
Bhatnagar Fellowship.
+
29.6, 25.8, 21.4, 18.0 ꢀ4.7, ꢀ4.6; MS (ESI) m/z 549 [M+Na] ; HRMS Calcd for
+
C
32
H
50
O
4
SiNa [M+Na] 549.33761, found 549.337.
(
(
3S)-3-(2-Bromo-1-ethoxyethoxy)pent-4-en-1-yl)oxy)methyl)benzene (15): IR
ꢀ1
1
KBr)
m
max: 3418, 2865, 1365, 1092, 924, 740, 698 cm
): d 7.38–7.23 (m, 5H), 5.85–5.65 (m, 1H), 5.27–5.13 (m, 2H), 4.72–4.61
m, 1H), 4.54–4.45 (m, 2H), 4.29–4.08 (m, 1H), 3.74–3.45 (m, 4H), 3.39–3.28
m, 2H), 1.99–1.86 (m, 1H), 1.85–1.76 (m, 1H), 1.27–1.16 (m, 3H); 13C NMR
75 MHz, CDCl ): d 139.7, 138.3, 138.2, 138.0, 128.3, 128.3, 127.8, 127.5, 116.8,
; H NMR (300 MHz,
CDCl
3
(
(
(
Supplementary data
3
+
Supplementary data associated with this article can be found, in
99.0, 75.5, 72.9, 66.2, 61.6, 35.6, 32.4, 15.2; MS (ESI) m/z 365 [M+Na] ; HRMS
Calcd for C16
+
23 3
H O BrNa [M+Na] 365.0728, found 365.0716.
the
online
version,
at
http://dx.doi.org/10.1016/
(
m
2S,3R)-2-(2-(Benzyloxy)ethyl)-5-ethoxy-3-methyltetrahydrofuran (16): IR(KBr)
j.tetlet.2013.12.091.
ꢀ1
1
max: 3030 2870, 1453, 1099, 992, 772, 698 cm
;
H NMR (300 MHz, CDCl
3
): d
7
(
.35–7.25 (m, 5H), 5.10–5.0 (m, 1H), 4.47 (s, 2H), 3.76–3.58 (m, 4H), 3.46–3.36
m, 1H), 2.28–1.32 (m, 1H), 1.04 (t, J = 6.9 Hz, 3H), 0.92 (d, J = 6.9 Hz, 3H); 13
C
References and notes
3
NMR (75 MHz, CDCl ): d 138.5, 128.3, 127.6, 127.4, 103.3, 103.2, 83.6, 80.9,
7
3.0, 67.8, 62.9, 62.2, 41.8, 41.3, 38.6, 37.0, 36.1, 34.0, 17.1, 16.8, 15.3; MS (ESI)
1
.
(a) Noolvi, N. M.; Sharma, R.; Bhanot, A. Int. J. Phytomedicine 2011, 3, 09; (b)
Simmons, T. L.; Andrianasolo, E.; McPhail, K.; Flatt, P.; Gerwick, W. H. Mol.
Cancer Ther. 2005, 4, 333.
Molinski, T. F.; MacMillan, J. B. Org. Lett. 2002, 9, 1535.
Joarder, D. D.; Jennings, M. P. Tetrahedron Lett. 2011, 52, 5124.
(a) Yadav, J. S.; Pattanayak, Manas R.; Das, Pragna P.; Mohapatra, D. K. Org. Lett.
+
+
m/z 287 [M+Na] ; HRMS Calcd for C16
87.1617.
3S,4R,E)-1-(Benzyloxy)-4-methyloct-6-en-3-ol (18): ½
KBr)
H
24
O
3
Na [M+Na] 287.1623, found
2
25
(
(
aꢁ
D
3
+3.3 (c 1.1, CHCl ); IR
1
2
3
4
.
.
.
m
max: 3456, 2934, 2857, 1454, 1092, 772 cmꢀ1; H NMR (300 MHz,
): d 7.39–7.25 (m, 5H), 5.58–5.35 (m, 2H), 4.53 (s, 2H), 3.81–3.60 (m, 3H),
.98 (br, 1H), 2.29–2.12 (m, 1H) 2.02–1.88 (m, 1H), 1.80–1.70 (m, 2H), 1.68–
.55 (m, 4H), 0.88 (d, J = 6.6 Hz, 3H); C NMR (75 MHz, CDCl ): d 137.8, 129.7,
3
29.0, 128.3, 127.5, 127.6, 126.2, 124.4, 75.2, 73.3, 69.6, 39.2, 35.5, 32.7, 17.9,
CDCl
3
2
1
1
1
2
011, 13, 1710; (b) Yadav, J. S.; Suresh Reddy, Ch. Org. Lett. 2009, 11, 1705; (c)
13
Yadav, J. S.; Chetia, L. Org. Lett. 2007, 9, 4587; (d) Yadav, J. S.; Reddy, Y. J.; Reddy,
P. A. N.; Reddy, B. V. S. Org. Lett. 2013, 15, 546.
Yadav, J. S.; Raju, A.; Ravindar, K.; Reddy, B. V. S.; Ghamdi, A. K. A. Synthesis
+
2.8; MS (ESI) m/z 271 [M+Na] .
5
.
25
(
3S,4R)-3-((tert-Butyldimethylsilyl)oxy)-4-methyloctan-1-ol (20):
½aꢁ
ꢀ14 (c
ꢀ1 1
D
2
012, 44, 585.
0.3, CHCl
3
); IR (KBr)
m
max: 3408, 2956, 2929, 1453, 1098, 987, 772 cm
; H
6
7
.
.
Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467.
Tony, A. K.; Dabideen, D.; Jialiang, Li; Dıaz-Hern andez, M. D.; Barbero, J. J.;
Mootoo, D. R. J. Org. Chem. 2009, 74, 7774.
NMR (300 MHz, CDCl
H), 1.14–0.99 (m, 1H), 0.93–0.83 (m, 15H) 0.09 (s, 3H), 0.07 (s, 3H); C NMR
3
): d 3.82–3.70 (m, 3H), 1.73–1.55 (m, 4H), 1.38–1.20 (m,
13
5
(
75 MHz, CDCl
3
): d 75.1, 61.0, 38.6, 33.0, 32.9, 29.7, 25.8, 22.9, 14.0, 13.6, ꢀ4.3,
8
.
(a) Yadav, J. S.; Reddy, M. S.; Rao, P. P.; Prasad, A. R. Tetrahedron Lett. 2006, 47,
+
Si [M+H]+ 275.2406,
ꢀ
4.6; MS (ESI) m/z 297 [M+Na] ; HRMS Calcd for C15H O
35 2
4
397; (b) Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2006, 47,
found 275.2400.
4
937; (c) Yadav, J. S.; Rao, P. P.; Reddy, M. S.; Rao, N. V.; Prasad, A. R.
25
(
5S,6R,E)-5-((tert-Butyldimethylsilyl)oxy)-6-methyldec-2-en-1-ol (22): ½
a
ꢁ
+3.3
D
1
Tetrahedron Lett. 2007, 48, 1469; (d) Rao, A. V. R.; Reddy, E. R.; Joshi, B. V.;
Yadav, J. S. Tetrahedron Lett. 1987, 28, 6497; (e) Yadav, J. S.; Hissana, A.;
ꢀ1
(c 1.45, CHCl ); IR (KBr) mmax: 3332, 2957, 1465, 1253, 1066, 773, 667 cm : H
3

J. S. Yadav et al. / Tetrahedron Letters 55 (2014) 1164–1167
1167
NMR (500 MHz, CDCl
3
): d 5.75–5.61 (m, 2H), 4.12–4.07 (m, 2H), 3.57–3.51 (m,
[M+Na]+ 323.2382, found 323.2376.
1
1
H), 2.17–2.12 (m, 2H), 1.57–1.50 (m, 1H), 1.41–1.13 (m, 5H), 1.10–1.00 (m,
(5S,7S,9S,13R,15S,16R,E)-1,5-Bis(benzyloxy)-9,15-bis((tert-
1
3
25
D
H), 0.89 (t, J = 7.1 Hz, 3H), 0.88 (s, 9H), 0.02 (s, 6H); C NMR (75 MHz, CDCl
3
):
butyldimethylsilyl)oxy)-16-methylicos-11-ene-7,13-diol (24): ½
aꢁ
ꢀ0.5 (c 0.9,
ꢀ
1
d 130.6, 75.5, 63.8, 38.2, 35.5, 32.0, 29.6, 25.8, 23.0, 14.6, 14.0, ꢀ4.2, ꢀ4.5; MS
3
CHCl ); IR (KBr) mmax: 3457, 2925, 2855, 1462, 1219, 1073, 969, 836, 772 cm ;
+
+
1
(
3
(
ESI) m/z 323 [M+Na] ; HRMS Calcd for C17
23.2377.
(2R,3R)-3-((2S,3R)-2-((tert-Butyldimethylsilyl)oxy)-3-methylheptyl)oxiran-2-
H
36
O
2
NaSi [M+Na] 323.2382, found
3
H NMR (500 MHz, CDCl ): d 7.35–7.25 (m, 10H), 5.76–5.42 (m, 2H), 4.61–4.54
(m, 1H), 4.5(m, 2H), 4.33–4.10 (m, 1H), 4.08–3.96 (m, 1H), 3.95–3.79 (m, 1H),
3.77–3.59 (m, 1H), 3.43 (t, J = 6.4 Hz, 2H), 2.36–2.13 (m,2H), 1.87–1.38 (m,
12H), 1.36–1.03 (m, 6H), 0.98–0.82 (m, 28H), 0.22–0.02 (m, 12H); C NMR
3
(75 MHz, CDCl ): d 138.5, 135.2, 128.5, 128.4, 128.3, 127.8, 127.6, 127.4, 72.9,
2
5
13
yl)methanol (23): ½
a
ꢁ
+0.7 (c 1.5, CHCl
H NMR (500 MHz, CDCl ): d 3.96–3.90 (m, 1H), 3.72–
3
); IR (KBr)
m
max: 3440, 2926,1463, 1219,
D
ꢀ
1
1
1
3
1
0
070, 772, 672 cm
;
3
.68(m, 1H), 3.64–3.58(m, 1H), 3.11–3.06 (m, 1H), 2.92–2.88 (m, 1H), 1.89–
.82 (m, 1H), 1.66–1.60 (m, 1H), 1.51–1.45(m, 1H), 1.38–1.16 (m, 6H), 1.10–
72.0, 71.3, 70.5, 70.2, 67.1, 38.9, 37.1, 37.0, 33.3, 33.2, 29.9, 29.6, 25.9, 22.9,
+
21.4, 17.9, 14.0, 13.1, ꢀ3.9, ꢀ4.6; MS (ESI) m/z 821 [M+Na] ; HRMS Calcd for
1
3
+
.99 (m, 1H), 0.93–0.87 (m, 15H), 0.05 (s, 3H), 0.04 (s, 3H); C NMR (75 MHz,
C
47
H
82
O
6
NaSi
2
[M+Na] 821.5548, found 821.5542.
CDCl
4.5, ꢀ4.6; MS (ESI) m/z 339 [M+Na] ; HRMS Calcd for C17
39.2331, found 339.2325.
3R,5S,6R)-5-((tert-Butyldimethylsilyl)oxy)-6-methyldec-1-en-3-ol (4): ½
0.8, CHCl ); IR (KBr)
3
): d 74.0, 61.7, 58.3, 54.0, 38.5, 34.6, 32.3, 29.7, 29.6, 25.7, 22.9, 14.3, 14.0,
5S,7S,9S,13S,15S,16R)-1,5-Bis(benzyloxy)-9,15-bis((tertbutyldimethylsilyl)oxy)-
+
+
25
ꢀ
H
36
O
3
SiNa [M+Na]
16-methylicosane-7,13-diol (2): ½
a
ꢁ
ꢀ6.0 (c 0.15, CHCl
3
); IR (KBr)
m
max: 3449,
): d
D
1
3
2929, 2856, 1740, 1462, 1254, 1066, 835, 773; H NMR (500 MHz, CDCl
3
2
5
(
aꢁ
ꢀ6.0
7.35–7.25 (m, 10H), 4.56–4.43 (m, 4H),4.05–3.91 (m, 2H), 3.90–3.59 (m, 1H),
D
(c
3
m
max: 3429, 2956, 2929, 1464, 1253, 1065, 835,
3.78–3.60 (m, 2H), 3.47 (t, J = 6.4 Hz, 2H), 1.75–1.40 (m, 18H), 1.38–1.11 (m,
ꢀ
1
1
13
7
1
2
0
73 cm
;
H NMR (300 MHz, CDCl
3
): d 5.96–5.83 (m, 1H), 5.25 (dt, J = 17.1,
3
6H), 0.91–0.88 (m, 24H), 0.10–0.01 (m, 12H); C NMR (75 MHz, CDCl ): d
.5 Hz, 1H), 5.08 (dt, J = 17.1, 1.5 Hz, 1H), 4.40–4.30 (m, 1H), 3.89–3.82 (m, 1H),
.55 (br, 1H), 1.75–1.58 (m, 3H), 1.52–1.41 (m, 1H), 1.39–1.18 (m, 4H), 1.09–
138.5, 138.2, 128.3,128.3, 127.7, 127.5, 127.4, 78.6, 72.8, 71.3, 70.5, 70.2, 67.1,
43.3, 41.8, 39.0, 37.6, 37.3, 36.1, 33.3, 29.8, 25.9, 25.8, 22.8, 21.4, 21.1, 18.0,
1
3
+
.98 (m, 1H), 0.95–0.81 (m, 15H), 0.10 (s, 3H), 0.07 (s, 3H); C NMR (75 MHz,
): d 141.7, 113.5, 73.4, 69.8, 38.4, 38.0, 33.0, 29.7, 29.6, 25.9, 22.9, 14.0,
17.9, 14.0, 12.9, ꢀ3.9, ꢀ4.4, ꢀ4.6, ꢀ4.7; MS (ESI) m/z 467 [M+Na] ; HRMS Calcd
+
CDCl
3.9, ꢀ4.2, ꢀ4.5; MS (ESI) m/z 323 [M+Na] ; HRMS Calcd for C17
3
for C47
H
84
O
6
NaSi
2
[M+Na] 823.5704, found 823.5698.
+
1
36 2
H O NaSi