A carbohydrate approach for the synthesis of tetrahydropyran containing C16-C29 fragment of sorangicin A

Article abstract of DOI:10.1016/j.tet.2009.06.035

A carbohydrate derived synthesis of C16-C29 fragment of sorangicin A is described utilizing regioselective epoxide opening, segment-coupled Prins cyclization reaction and cross metathesis as the key steps.

Full text of DOI:10.1016/j.tet.2009.06.035

Tetrahedron 65 (2009) 6304–6309
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A carbohydrate approach for the synthesis of tetrahydropyran containing
C16–C29 fragment of sorangicin A
*
P. Srihari , B. Kumaraswamy, J.S. Yadav
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad-500607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 April 2009
Received in revised form 9 June 2009
Accepted 11 June 2009
Available online 17 June 2009
A carbohydrate derived synthesis of C16–C29 fragment of sorangicin A is described utilizing re-
gioselective epoxide opening, segment-coupled Prins cyclization reaction and cross metathesis as the key
steps.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
The increasing multi-resistance in bacteria has been a major
demand for the discovery of new and novel antibiotic compounds.
The polyether and polyene macrolides, sorangicins are potent an-
tibiotic compounds which were isolated from gliding bacteria Sor-
angium cellulosum1 in 1985 and their structures were determined by
Hofle and Reichenbach in 1989.2 Sorangicin A was found to exhibit
extraordinary antibiotic activity against both Gram-positive (MIC
Our retrosynthetic analysis revealed three key intermediate
fragments 2, 3 and 4 (Scheme 1). Our initial focus was on the
synthesis of fragment 2 with 6 chiral centers and a tetrahydropyran
ring. We envisioned that the fragment 2 could be achieved by
segment coupled Prins cyclization of the compound 5 followed by
selective manipulations and cross metathesis reaction. Compound
5 in turn could be obtained by coupling homoallyl alcohol 7 and 3-
benzyloxy propionic acid 6 followed by two step manipulations.
<0.01w2 mg/mL) and Gram-negative bacteria (MIC 2 w>32 mg/
mL).3 Mechanistic studies revealed that the sorangicins inhibit DNA
dependent RNA polymerase in both Escherichia coli and Staphylo-
coccus aureus similar to rifampicin. Albeit the chemical structures of
both rifampicin and sorangicin are different, the similarity in be-
haviour was expected due to the conformational flexibility of sor-
angicin molecule which can undergo amino acid modifications
within the binding pocket of the subunit.4
The novel architecture of sorangicin, with a 31-membered
macrolide ring, dioxabicyclo[3.2.1]octane moiety, the cis,cis,trans-tri-
enoate, dihydropyran and tetrahydropyran units combined together
with the significant biological activity has featured sorangicin A as
an challenging target for the synthetic organic chemists. Even
though there are no reports for the total synthesis, significant efforts
from Amos Smith III et al.5 and other groups6 have resulted in the
synthesis of advanced key intermediate fragments of sorangicin A.
In continuation to the synthesis of biologically active natural
products targeting macrolides7 with potent antibiotic and anti tu-
mor activities, we herein describe an efficient synthesis of C16 to
C29 fragment of sorangicin A starting from the readily available
The homoallyl alcohol 7 can be easily synthesized from D-ribose in 6
steps.
O
O
38
O
29
O
9
H
O
O
OH
19
H
HO
OP
15
HO2C
sorangicin A 1
HO
OP
O
OH
9
O
O
TBSO
+
O
+
OP
H
H
6
37
16
OBn
OP
15
29
Ph
29
HO2C
2
3
4
AcO
OBn
O
OH
O
O
O
O
+
BnO
OH
chiral substrate D-ribose.
5
7
O
6
(D)-Ribose
* Corresponding author. Tel.: þ91 40 27191490; fax: þ91 40 27160512.
E-mail address: srihari@iict.res.in (P. Srihari).
Scheme 1. Retrosynthesis.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.035

P. Srihari et al. / Tetrahedron 65 (2009) 6304–6309
6305
The synthesis began with isopropylidination of
acetone in presence of catalytic amount of concd H2SO4 to get
compound 8.8 1C-Wittig reaction of lactol
with methyl-
triphenylphosphonium bromide in the presence of potassium tert
butoxide yielded olefin 9.9 Selective mono tosylation of diol 9 fol-
lowed by treatment with NaH provided epoxide 10. Regioselective
epoxide opening10 with lithiated propyne afforded homo prop-
argylic alcohol 11, which was partially reduced to homo allylic
alcohol 7 under Lindlar’s condition (Scheme 2) in 98% yield.
D
-ribose with
the only option left for us was to proceed further by the regular
oxidation and stereoselective reduction. PCC oxidation of com-
pound 14 afforded ketone 15 (Scheme 4) which was subjected to
stereoselective reduction. Several reducing agents such as
NaCNBH3, NaBH(OAc)3, Zn(BH4)2, Red Al, NaBH4 and LialH4 were
investigated and found to result in undesired product 14 (>90%
yields),14 whereas, reduction with N-Selectride and K-Selectride
gave 30% of the desired product 16.
8
OH
O
O
O
OH
O
O
OH
a
c
b
HO
O
(D)-Ribose
HO
e
O
b
a
13
O
14
O
O 8
9
O
O
OBn
OBn
15
OH
O
O
O
OH
O
d
O
Scheme 4. Synthesis of ketone 15. Reagents and conditions: NaOMe, MeOH, rt, 2 h,
89%. (b) PCC, Celite, DCM, 0 ꢁC to rt, 2 h, 96%.
O
O
10
7
11
Scheme 2. Synthesis of homoallyl alcohol 7. Reagents and conditions: (a) cat. H2SO4,
acetone, rt, 2.5 h, 93%. (b) Ph3PCH3Br, KOtBu, THF, 0 ꢁC–rt, 13 h. (c) (i) Et3N, Bu2SnO,
TsCl, 0 ꢁC–rt, 5 h, (ii) NaH, THF, 0 ꢁC–rt, 4 h, overall yield for 3 steps 61%. (d) CH3CCH,
n-BuLi, HMPA, ꢀ78 ꢁC to 0 ꢁC, 18 h, 99%. (e) Pd/CaCO3, MeOH, 10 min rt, 98%.
Finally, the transformation turned out to be the best with DIBAL-
H
5c (46% yield) which gave desired alcohol 16. Thus after reduction
with DIBAL-H, the alcohol 16 was protected with chloro-
methylmethyl ether to afford the MOM-ether 17. Selective deben-
zylation of 17 with lithium napthalenide yielded 18. With the
C19–C29 fragment 17 in hand it remained to effect cross metathesis
to extend the chain from C16 to C19. Thus, a cross metathesis re-
action between compound 17 and TBS protected 4-pentene-1-ol 19
employing Grubbs’ 2nd generation catalyst was attempted. The
reaction did not succeed to our expectations and resulted in an
unidentified by product15 which may be attributed to the presence
of acetonide moiety. Hence the metathesis reaction was attempted
once again with the free diol. Thus, isopropylidene group in 17 was
unmasked using 70% AcOH to get the free diol 20 in 90% yield.
Gratifyingly, cross metathesis reaction of diol 20 and TBS protected
4-pentene-1-ol 19 gave the desired product 21 as the only product
in 65% yield.16 The diol was reprotected as acetonide 2 and then
treated with lithium napthanelide to yield the known fragment5c
22 (Scheme 5) which can be utilized further for the total synthesis
of sorangicin A.
Initially, with the homoallyl alcohol 7 in hand, we investigated
the Prins cyclization with 3-benzyloxy propionaldehyde. Several
attempts with Prins cyclization produced no fruitful results.11 This
prompted us to alter our strategy for the segment coupled Prins
cyclization. The alcohol 7 was esterified with 3-benzyloxy prop-
anoic acid 6 employing DCC, DMAP to get the ester 12 in 95% yield.
The ester on treatment with DIBAL-H gave lactol, which was further
masked as acetate 5 upon treatment with acetic anhydride and
pyridine in 98% overall yield. The substrate 5 was subjected to the
segment-coupled Prins cyclization12 employing BF3$Et2O, AcOH at
ꢀ20 ꢁC to get the mixtures of easily separable tetrahydropyran
acetates 13 and 13a in 9:1 ratio (Scheme 3 and Fig. 1).
O
OBn
O
O
a
b
7
O
OBn
12
AcO
OMOM
OMOM
OH
O
O
O
c
O
OH
OH
O
b
a
d
+
15
14
5
O
O
O
O
O
OBn
OP
c
OAc
O
OBn
OAc
O
20
16
17 P = Bn
O
O
+
OBn
(9:1)
18 P = H
O
O
OMOM
O
OBn
OMOM
O
13
13a
O
OH
OH
g
e
f
Scheme 3. Synthesis of 13. Reagents and conditions: (a) 6, DCC, DMAP, DCM, 0 ꢁC to rt,
5 h, 95%. (b) (i) DIBAL-H, DCM, ꢀ78 ꢁC, (ii) Ac2O, pyridine, DMAP, 15 h, overall yield
98%. (c) BF3$Et2O, AcOH, hexane, 30 min 70%.
TBSO
TBSO
3
3
O
OBn
OBn
2
21
OMOM
O
CH3
R'
CH3
OAc
CH3
OAc
-
O
TBSO
3
O
OH
R
R
R'
R
O
O
22
R'
O
+
+
H
Scheme 5. Synthesis of 22. Reagents and conditions: (a) DIBAL-H, DCM, ꢀ78 ꢁC, 1.5 h,
46% for 16, 50% for 14. (b) MOMCl, 2,6-lutidine, CH3CN, rt, 12 h, 98%, (c) Li napthalene,
THF, 96%. (d) 70% AcOH, 45 ꢁC, 4 h, 90%. (e) 19, 2nd generation Grubbs catalyst, DCM, rt,
12 h, 65%. (f) 2,2-DMP, DCM, rt, 1 h, 98%. (g) Li, napthalene, THF, ꢀ20 ꢁC, 97%.
H
H
13
H
H
H
O
R =
CH3
OAc
O
OBn
R' =
R
R'
O
δ 4.95
3. Conclusions
H
13
δ 3.40
H
δ 3.54
H
In conclusion, we have synthesized a key intermediate, C16–C29
fragment required for the total synthesis of sorangicin A utilizing,
segment-coupled Prins reaction, regioselective epoxide opening
Figure 1. Chair like transition state for segment coupled Prins cyclization and signif-
icant NOE correlations observed confirming 2,4,6-syn substitution for compound 13.
reaction as the key steps starting from the chiral precursor D-ribose
The compound 13 was treated with sodium methoxide in
methanol to get the alcohol 14. Inversion of C25 hydroxyl under
Mitsunobu conditions did not succeed to our expectations.13 Thus
in total of 17 steps with an overall yield of 7.7%. Studies towards the
synthesis of other key intermediate fragments and the total syn-
thesis of sorangicin A are currently being investigated.

6306
P. Srihari et al. / Tetrahedron 65 (2009) 6304–6309
4. Experimental section
4.1.3. (4R,5S)-2,2-Dimethyl-4-((R)-oxiran-2-yl)-5-vinyl-1,3-
dioxolane 10
A stirred solution of the diol (9.9 g, 52.6 mmol) and dibutyltin
4.1. General information
oxide (2.6 g, 10.5 mmol) in anhydrous dichloromethane (100 mL)
was added dropwise tryethylamine (11 mL, 79 mmol) at 0 ꢁC, then
the reaction mixture was allowed to warm to room temperature.
After 15 min at room temperature, the reaction mixture was cooled
to 0 ꢁC then p-toluenesulfonylchloride (10.3 g, 52.6 mmol) was
added portion wise and stirred at rt for 5 h. The reaction was
monitered by TLC and filtered through sintered funnel on Celite
bed; the organic layer was dried over anhydrous sodium sulphate,
filtered, and evaporated. The resulting colorless oil was directly
used for the next reaction without any further purification. To the
suspension of NaH (1.9 g, 78.9 mmol) in dry THF (70 mL) was
cooled to 0 ꢁC and added monotosylate compound (18.0 g,
52.6 mmol) in THF (100 mL) in a drop wise manner. The reaction
was left to room temperature and stirred for 4 h, quenched at 0 ꢁC
using saturated aqueous NH4Cl solution (20 mL). Then diethyl ether
(150 mL) and water (100 mL) were added, the organic layer was
separated and the aqueous layer was extracted with diethyl ether
(3ꢂ100 mL). The combined organic extracts were washed with
brine, dried over anhydrous sodium sulphate and concentrated at
reduced pressure. Column chromatography of crude product
afforded 10 (5.4 g, 61% over three steps) as a colourless oil. Rf (50%
All the reagents employed were obtained commercially from
M/s. Aldrich and used without further purifications unless oth-
erwise stated. For anhydrous reactions, solvents were dried fol-
lowing known literature and removal of solvent was performed
under reduced pressure using a rotary evaporator. All reactions
requiring anhydrous conditions were carried out in oven-dried
glassware under a nitrogen atmosphere. The 1H NMR spectra
were recorded at 300 or 400 MHz, and the 13C NMR spectra were
recorded at 75 MHz/100 MHz at ambient temperature. Chemical
shifts of the 1H NMR spectra are expressed in ppm relative to the
solvent residual signal 7.26 in CDCl3 or to tetramethylsilane
(
d
¼0.00). Chemical shifts of the 13C NMR spectra are expressed
in ppm relative to the solvent signal 77.00 in CDCl3 unless oth-
erwise noted. One or more of the following methods were used
for visualization: UV absorption by fluorescence quenching;
iodine staining; anisaldehyde stain (ethanol (135 mL)/H2SO4
(5 mL)/AcOH (1.5 mL)/p-anisaldehyde 3.7 mL). Column chroma-
tography was performed using 60–120 mesh silica gel. Ethyl
acetate and hexane were the common eluents used unless
specified.
Et2O/hexane) 0.70; IR (neat) nmax: 2990, 2925, 2854, 1459, 1378,
28
4.1.1. 2,3-O-Isopropylidene-
D
-ribose 8
1216 cmꢀ1; [
d
a
]
D
þ16.1 (c 0.75, CHCl3); 1H NMR (300 MHz, CDCl3):
To a stirred suspension of
D
-ribose (20.0 g, 133.3 mmol) in ace-
5.96 (ddd, J¼16.6, 10.6, 6.8 Hz, 1H), 5.46 (td, J¼17.3, 1.5 Hz, 1H),
tone (200 mL) was added drop wise concd H2SO4 (0.6 mL) at room
temperature and the reaction mixture was stirred at room tem-
perature for 2.5 h. The mixture was neutralized with solid NaHCO3,
filtered and evaporated under reduced pressure to give colorless
syrup. The residue was purified by silica gel column chromatogra-
phy (50% EtOAc/hexane) to afford 8 as a colorless syrup (23.5 g,
93%). Rf (50% EtOAc/hexane) 0.40; IR (neat) nmax: 3400, 2986, 2941,
5.32 (td, J¼10.6, 1.5 Hz, 1H), 4.69 (tt, J¼6.0, 1.5 Hz, 1H), 3.63 (dd,
J¼7.5, 6.8 Hz, 1H), 2.90–2.85 (m, 1H), 2.78 (dt, J¼3.8, 1.5 Hz, 1H),
2.60 (dd, J¼5.3, 2.3 Hz, 1H), 1.50 (s, 3H), 1.36 (s, 3H); 13C NMR
(75 MHz, CDCl3):
d 132.4, 118.6, 109.0, 78.8, 78.5, 49.7, 45.5, 27.5,
25.0; MS (ES): m/z 171 (MþHþ); HRMS (ESI): m/z calcd for
C9H14O3Na 193.0840, found 193.0838.
34
25
1376, 1211, 1068 cmꢀ1; [
a]
ꢀ37.4 (c 1.1, acetone); Lit.8 [
a
]
ꢀ37 (c
4.1.4. (R)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)pent-
3-yn-1-ol 11
D
D
53, acetone); 1H NMR (300 MHz, CDCl3):
d 5.39 (s, 1H), 4.81 (d,
J¼6.0 Hz,1H), 4.56 (d, J¼6.0 Hz,1H), 4.39 (br t, J¼2.6 Hz,1H), 3.71 (t,
A solution of n-butyl lithium in hexane (18.7 mL, 30 mmol, 1.6 M
solution in hexane) was added to a solution of propyne (2.27 g,
40 mmol) in THF (40 mL) at ꢀ78 ꢁC and the mixture was stirred for
15 min under nitrogen atmosphere. The reaction mixture was
warmed to ꢀ10 ꢁC over 30 min and then cooled to ꢀ78 ꢁC. Dry
HMPA (10 mL) was added, followed by dropwise addition, over
15 min, of epoxide (3.4 g, 20 mmol) in HMPA (15 mL). The reaction
was stirred at ꢀ20 ꢁC for 30 min, warmed to 20 ꢁC over 4 h, and
stirred for an additional 12 h. The mixture was then poured into ice
water (100 mL) and extracted with ether (3ꢂ100 mL). The com-
bined organic extracts were washed with brine, dried over anhy-
drous sodium sulphate and concentrated at reduced pressure. The
resulting syrup was purified by silica gel column chromatography
(15% EtOAc/hexane) to give pale yellow color alcohol 11 (4.15 g,
J¼2.6 Hz, 2H), 1.47 (s, 3H), 1.30 (s, 3H); 13C NMR (75 MHz, CD3OD):
d
113.1, 103.9, 88.5, 87.9, 83.4, 64.3, 26.7, 24.9; MS (ES): m/z 213
(MþþNa); HRMS (ESI) m/z calcd for C8H14O5Na 213.0738, found
213.0736.
4.1.2. (R)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-
ethane-1,2-diol 9
To a stirred suspension of methyl triphenylphosphonium bro-
mide (65.7 g, 184 mmol) in THF (200 mL) was added potassium
tert-butoxide (17.7 g, 157 mmol) at 0 ꢁC and the reaction mixture
was stirred for 20 min at same temperature and then at room
temperature for 1 h. After the mixture was cooled to 0 ꢁC, a solution
of 8 (10 g, 52.6 mmol) in THF (60 mL) was added and the reaction
mixture was stirred at room temperature for 12 h and poured into
water carefully. The mixture was extracted with ethyl acetate and
the organic layer was dried over anhydrous sodium sulphate, fil-
tered, and evaporated. The resulting syrup was purified by silica gel
column chromatography (60% EtOAc/hexane) to give diol 9 as
a colorless liquid with a little contamination of triphenylphosphine
oxide. Analytical sample of diol was obtained by preparative TLC. Rf
99%). Rf (10% EtOAc/hexane) 0.20; IR (neat) nmax: 3458, 2987, 2923,
28
1376, 1216, 1167, 1058 cmꢀ1; [
a]
ꢀ2.2 (c 1.40, CHCl3); 1H NMR
D
(300 MHz, CDCl3):
d
5.99 (ddd, J¼17.3, 10.6, 6.0 Hz, 1H), 5.40 (td,
J¼17.3, 1.5 Hz, 1H), 5.23 (tt, J¼10.6, 1.5 Hz, 1H), 4.65 (tt, J¼6.8, 1.5 Hz,
1H), 3.96 (dd, J¼9.0, 6.8 Hz, 1H), 3.80–3.58 (m, 1H), 2.61–2.48 (m,
1H), 2.43–2.29 (m, 1H), 1.83–1.78 (m, 3H), 1.44 (s, 3H), 1.35 (s, 3H);
13C NMR (75 MHz, CDCl3):
d 133.9, 117.8, 108.6, 79.3, 78.7, 78.5, 74.4,
(50% EtOAc/hexane) 0.40; IR (neat) nmax: 3415, 2987, 2928, 2856,
68.1, 27.6, 25.3, 24.5, 3.5; MS (ESI) m/z 233 (MþþNa); HRMS (ESI):
m/z calcd for C12H18O3Na 233.1153, found 233.1148.
29
1646, 1377, 1217, 1059 cmꢀ1; [
a
]
þ5.3 (c 5.40, CHCl3); 1H NMR
D
(300 MHz, CDCl3):
d
5.99 (ddd, J¼17.6, 10.4, 6.8 Hz, 1H), 5.45 (td,
J¼17.6, 1.6 Hz, 1H), 5.32 (td, J¼10.4, 1.2 Hz, 1H), 4.69 (tt, J¼6.4,
1.3 Hz, 1H), 4.09 (dd, J¼8.4, 6.4 Hz, 1H), 3.83–3.59 (m, 3H), 2.88 (br
4.1.5. (R,Z)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-
pent-3-en-1-ol 7
To a solution of 11 (0.5 g, 2 mmol) in 5 mL of methanol/quin-
oline (10:0.3) was added Lindlar’s catalyst (10 mg). The reaction
mixture was stirred for 10 min under atmosphere of H2 at room
temperature and filtered through a Celite pad. The filtrate was
s, 2H), 1.45 (s, 3H), 1.35 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
133.5,
117.8, 108.7, 78.3, 77.5, 69.8, 64.0, 27.5, 25.1; MS (ES): m/z 188
(MþHþ); HRMS (ESI) m/z calcd for C9H16O4Na 211.0946, found
211.0938.

P. Srihari et al. / Tetrahedron 65 (2009) 6304–6309
6307
concentrated, and the residue was purified by silica gel column
chromatography using (10% EtOAc/hexane) to give olefin 7 (0.49 g,
98%) as a colorless liquid. Rf (10% EtOAc/hexane) 0.30; IR (neat)
4.1.8. (2R,3S,4R,6R)-2-(2-(Benzyloxy)ethyl)-6-((4R,5R)-2,2-
dimethyl-5-vinyl-1,3-dioxolan-4-yl)-3-methyltetrahydro-2H-
pyran-4-yl acetate 13
A premixed solution of BF3$OEt2 (1.82 mL, 31.5 mmol) and AcOH
(2.6 mL, 20 mmol) in hexane (15 mL) was added the solution of a-
acetoxy ether 5 (4.4 g, 10 mmol) in hexane (40 mL) by cannula at
ꢀ20 ꢁC. The reaction mixture was stirred for 30 min at ꢀ20 ꢁC and
then warmed to 0 ꢁC, whereupon saturated aqueous NaHCO3
(20 mL) was added. The reaction mixture was diluted with hexane
(30 mL), washed with brine (20 mL), filtered, dried over anhydrous
sodium sulphate and concentrated in vacuum. The resulting orange
oil was purified by flash chromatography on silica gel (10% EtOAc/
hexane) to afford more polar tetrahydropyran 13 (3.07 g, 70%) as
27
nmax: 3448, 2986, 2927, 1375, 1217, 1057 cmꢀ1; [
a
]
ꢀ2.3 (c 0.90,
D
CHCl3); 1H NMR (300 MHz, CDCl3):
d
6.02 (ddd, J¼17.3, 10.5,
6.8 Hz, 1H), 5.76–5.60 (m, 1H), 5.51–5.36 (m, 2H), 5.27 (d,
J¼10.6 Hz, 1H), 4.61 (t, J¼6.8 Hz, 1H), 3.94 (dd, J¼9.0, 6.8 Hz, 1H),
3.70–3.54 (m, 1H), 2.49–2.35 (m, 1H), 2.33–2.19 (m, 1H), 1.66 (d,
J¼6.8 Hz, 3H), 1.46 (s, 3H), 1.35 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
134.5, 127.7, 125.3, 118.0, 108.6, 80.1, 78.8, 69.5, 31.3, 27.7, 25.3,
12.9; MS (ES): m/z 235 (MþþNa); HRMS (ESI) m/z calcd for
C12H20O3Na 235.1310, found 235.1304.
4.1.6. (R,Z)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-
pent-3-enyl 3-(benzyloxy)propanoate 12
a major diastereomer. Rf (10% EtOAc/hexane) 0.4; IR (neat) nmax
2983, 2929, 2861, 1740, 1373, 1241, 1103 cmꢀ1 1H NMR (300 MHz,
CDCl3):
:
;
A solution of 3-O-benzyl propionic acid-6 (3.05 g, 16.9 mmol) in
30 mL dichloromethane was cooled to 0 ꢁC. A sample of DCC (4.3 g,
20 mmol) was added in several portions and a white precipitate
formed quickly. After 15 min stirring, alcohol 7 (3.0 g, 14.1 mmol)
was added as a solution in 15 mL dichloromethane along with
a small amount of DMAP. The cooling bath was removed and stir-
ring was continued for 5 h. The solution was filtered and the solvent
was removed under reduced pressure. The resulting oil purified by
column chromatography (5% EtOAc/hexane) to obtain 12 (4.97 g,
d
7.39–7.19 (m, 5H), 5.82 (ddd, J¼17.4, 10.5, 6.8 Hz, 1H), 5.30
(d, J¼17.4 Hz, 1H), 5.10 (d, J¼10.6 Hz, 1H), 5.02–4.89 (m, 1H), 4.61 (t,
J¼6.8 Hz, 1H), 4.47 (d, J¼3.0 Hz, 2H), 3.95 (d, J¼8.3, 6.0 Hz, 1H), 3.54
(td, J¼9.0, 2.2 Hz, 1H), 3.48 (dt, J¼6.8, 1.5 Hz, 2H), 3.38 (dt, J¼10.6,
1.5 Hz, 1H), 2.04 (s, 3H), 2.02–1.85 (m, 2H), 1.84–1.71 (m, 1H), 1.67–
1.51 (m, 2H), 1.46 (s, 3H), 1.36 (s, 3H), 0.91 (d, J¼6.8 Hz, 3H); 13C
NMR (75 MHz, CDCl3): d 170.2, 138.4, 136.4, 133.7, 128.4, 127.6, 117.3,
108.6, 79.4, 78.7, 75.1, 74.1, 73.0, 72.9, 67.1, 35.8, 33.1, 28.8, 27.7, 25.3,
21.1, 5.8; MS (ES): m/z 441 (MþþNa); HRMS (ESI) m/z calcd for
C24H34O6Na 441.2253, found 441.2235.
95%) as colorless oil. Rf (10% EtOAc/hexane) 0.40; IR (neat) nmax
:
27
2925, 2857, 1741, 1455, 1374, 1177, 1069 cmꢀ1; [
a
]
ꢀ4.1 (c 2.05,
D
CHCl3); 1H NMR (300 MHz, CDCl3):
d
7.35–7.18 (m, 5H), 5.75 (ddd,
4.1.9. (2R,3R,4R,6R)-2-(2-(Benzyloxy)ethyl)-6-((4R,5R)-2,2-
dimethyl-5-vinyl-1,3-dioxolan-4-yl)-3-methyltetrahydro-2H-
pyran-4-ol 14
J¼17.3, 9.8, 6.8 Hz, 1H), 5.61–5.46 (m, 1H), 5.42–5.23 (m, 2H), 5.14
(d, J¼9.8 Hz, 1H), 4.95–4.85 (m, 1H), 4.55 (t, J¼6.8 Hz, 1H), 4.50 (s,
2H), 4.16 (dd, J¼8.3, 6.8 Hz, 1H), 3.67 (t, J¼6.0 Hz, 2H), 2.57–2.33 (m,
4H), 1.58 (d, J¼6.8 Hz, 3H), 1.47 (s, 3H), 1.34 (s, 3H); 13C NMR
To stirred solution of compound 13 (2.7 g, 6.0 mmol) in meth-
anol (30 mL) at 0 ꢁC was added sodium methoxide (1.0 g,
18.0 mmol) and stirred at room temperature for 2 h. The methanol
was then removed under reduced pressure and water (30 mL) was
added. The mixture was extracted with dichloromethane
(3ꢂ30 mL) and the combined organic layer was dried over anhy-
drous sodium sulphate and the solvent was removed under re-
duced pressure. Column chromatography (30% EtOAc/hexane) of
the crude mixture afforded pure 14 (2.0 g, 89%) as a colorless oil. Rf
(75 MHz, CDCl3):
d 170.3, 138.0, 135.7, 133.1, 128.3, 127.6, 127.0,
124.3, 118.3, 108.7, 78.7, 77.6, 73.0, 71.6, 65.5, 35.2, 28.5, 27.6, 25.2,
12.8; MS (ES): m/z 397 (MþþNa); HRMS (ESI): m/z calcd for
C22H30O5Na 397.1990, found 397.1999.
4.1.7. 3-(Benzyloxy)-1-((R,Z)-1-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-
dioxolan-4-yl)pent-3-enyloxy)propyl acetate 5
A sample of ester 12 (4.97 g, 13.2 mmol) was dissolved in 50 mL
dichloromethane and cooled to ꢀ78 ꢁC. Then 1.0 M solution of
DIBAL-H in toluene (18.87 mL, 26.5 mmol) were added dropwise
and stirring was continued for 45 min. TLC (9:1 hexane/ethyl ace-
tate) analysis indicated that all the starting material 12 was con-
sumed at this time. Then pyridine (3.2 mL, 39 mmol), DMAP (4.86 g,
39 mmol) and acetic anhydride (7.53 mL, 80 mmol) were added
and stirring was continued at ꢀ78 ꢁC for 14 h. The solution was
allowed to warmed 0 ꢁC and stirred for an additional hour. The
reaction was quenched with 20 mL satd aq NH4Cl solution and
20 mL saturated aq sodium potassium tartrate solution and the
solution was warmed to 23 ꢁC. The mixture was diluted with
dichloromethane and stirred vigorously for 1 h. After extraction
with dichloromethane (4ꢂ70 mL), the combined organic extracts
were washed with ice-cooled 1 M potassium bisulfate (2ꢂ20 mL),
saturated aq sodium bicarbonate (3ꢂ20 mL) and brine. After drying
over anhydrous sodium sulphate, the solvent was evaporated and
the residue was purified by silica gel column chromatography (10%
ethylacetate/hexane) to afford product 5 (5.4 g, 98%) as a colorless
oil. Rf (10% ethyl acetate/hexanes, TLC plate developed twice) 0.5; IR
(neat) nmax: 2928, 2859, 1739, 1374, 1240, 1109, 759 cmꢀ1; 1H NMR
(30% EtOAc/hexane) 0.35; IR (neat) nmax: 2926, 2825, 1655, 1457,
28
1382 cmꢀ1; [
a
]
þ28.2 (c 1.15, CHCl3); 1H NMR (300 MHz, CDCl3):
D
d
7.38–7.30 (m, 5H), 5.92–5.80 (m, 1H), 5.37–5.30 (d, J¼16.6 Hz, 1H),
5.14–5.10 (d, J¼10.5 Hz, 1H), 4.64 (t, J¼6.4 Hz, 1H), 4.50 (d, J¼3.8 Hz,
2H), 3.95 (dd, J¼8.3, 6.0 Hz, 1H), 3.93–3.85 (m, 1H), 3.54–3.41 (m,
3H), 3.38–3.27 (m, 1H), 1.93–1.75 (m, 3H), 1.70–1.55 (m, 1H), 1.43 (s,
3H), 1.48–1.36 (m, 1H), 1.34 (s, 3H), 0.9 (d, J¼6.8 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d 138.4, 136.4, 133.8, 128.3, 127.6, 117.2, 108.5, 79.5,
78.7, 75.3, 74.2, 73.0, 70.6, 67.2, 38.5, 33.2, 32.2, 27.7, 25.3, 4.9; MS
(ES): m/z 399 (MþþNa); HRMS (ESI): m/z calcd for C22H32O5Na
399.2147, found 399.2129.
4.1.10. (2R,3S,6R)-2-(2-(Benzyloxy)ethyl)-6-((4R,5R)-2,2-dimethyl-
5-vinyl-1,3-dioxolan-4-yl)-3-methyldihydro-2H-pyran-4(3H)-
one 15
To stirred solution of alcohol 14 (2.0 g, 5.31 mmol) in dichloro-
methane (60 mL) at 0 ꢁC was added pyridinium chlorochromate
(2.85 g, 13.2 mmol) and Celite (2.85 g) and stirred at room tem-
perature for 2 h. Diethyl ether (100 mL) was added and the reaction
mixture was filtered through a small pad of Celite and silica gel. The
filtered cake was washed thoroughly with ether (2ꢂ30 mL) and the
filtrate was concentrated under reduced pressure. After flash
chromatography (20% EtOAc/hexane), the residue afforded the
(300 MHz, CDCl3):
d
7.40–7.21 (m, 5H), 6.17 (t, J¼6.0 Hz, 1H), 6.02–
5.88 (m, 1H), 5.64–5.50 (m, 1H), 5.51–5.39 (m, 1H), 5.38–5.28 (m,
1H), 5.22–5.13 (m, 1H), 4.58 (t, 1H), 4.51–4.43 (m, 2H), 4.07 (dd,
J¼7.5, 1.51 Hz, 1H), 3.78–3.71 (m, 1H), 3.59–3.41 (m, 2H), 2.62–2.31
(m, 2H), 2.01 (s, 3H), 1.94 (m, 2H), 1.64 (d, J¼6.8 Hz, 3H), 1.47 (s, 3H),
1.34 (s, 3H); MS (ES): m/z 441 (MþþNa); HRMS (ESI): m/z calcd for
C24H34O6Na 441.2253, found 441.2242.
ketone 15 (1.90 g, 96%) as a colorless liquid. Rf (30% EtOAc/hexane)
27
0.70; IR (neat) nmax: 2928, 2859, 1716, 1378, 1102 cmꢀ1; [
a
]
þ56.2
D
(c 1.75, CHCl3); 1H NMR (300 MHz, CDCl3):
d 7.40–7.20 (m, 5H), 5.84
(ddd, J¼17.3, 10.6, 6.8 Hz, 1H), 5.36 (td, J¼17.3, 1.5 Hz, 1H), 5.14 (td,
J¼10.5, 1.5 Hz, 1H), 4.68 (t, J¼6.8 Hz, 1H), 4.49 (d, J¼1.5 Hz, 2H), 4.08

6308
P. Srihari et al. / Tetrahedron 65 (2009) 6304–6309
(dt, J¼6.8, 1.5 Hz, 1H), 3.77 (td, J¼9.0, 3.0 Hz, 1H), 3.63–3.48 (m, 3H),
2.62–2.24 (m, 3H), 1.88 (ddd, J¼18.9, 9.0, 4.5 Hz, 1H), 1.74–1.57 (m,
1H), 1.45 (s, 3H), 1.37 (s, 3H), 1.44 (d, J¼6.8 Hz, 3H); 13C NMR
under an argon atmosphere until lithium metal was completely
dissolved (3–4 h). The resulting dark green solution of lithium
naphthalenide was then cooled to ꢀ25 ꢁC, followed by addition of
a solution of compound 17 (0.10 g, 0.23 mmol) in THF (0.5 mL)
dropwise over 5 min. The resulting mixture was stirred at ꢀ25 ꢁC
for 30 min. saturated aqueous ammonium chloride (1 mL) and
water (1 mL) were then added. The resulting solution was
extracted with ether (3ꢂ10 mL). The combined extracts were
washed with water and brine, dried over anhydrous sodium sul-
phate and concentrated in vacuum The crude product was purified
by column chromatography (40% EtOAc/hexane) to afford 18
(0.073 g, 96%) as a yellow liquid. Rf (40% EtOAc/hexane) 0.30; IR
(75 MHz, CDCl3):
d 210.6, 138.2, 133.0, 128.4, 127.6, 127.5, 117.7,
108.8, 79.5, 78.4, 75.7, 75.2, 73.0, 66.6, 49.2, 40.8, 32.2, 27.5, 25.2,
10.8; MS (ES) m/z 397 (MþþNa); HRMS (ESI): m/z calcd for
C22H30O5Na 397.1990, found 397.2000.
4.1.11. (2R,3R,4S,6R)-2-(2-(Benzyloxy)ethyl)-6-((4R,5R)-2,2-
dimethyl-5-vinyl-1,3-dioxolan-4-yl)-3-methyltetrahydro-2H-
pyran-4-ol 16
To a stirring solution of (þ)-15 (3.0 g, 8.0 mmol) in dichloro-
methane (35 mL) at ꢀ78 ꢁC was added DIBAL (16.0 mL, 16 mmol,
1.0 M solution in toluene). The reaction was maintained at ꢀ78 ꢁC
until complete consumption of starting material occurred (judged
by TLC analysis) for 1.5 h. The reaction was quenched by the addi-
tion of a 1:2 mixture of Celite to Na2SO4$10H2O and then allowed to
warm to rt. Filtration and washing of the filter cake with 2ꢂ50 mL
dichloromethane was followed by concentration to yield mixture of
alcohols 16/14 (48:52 by HPLC) in 96% yield. This mixture was
separated using column chromatography (20% EtOAc/Hexane) to
yield the desired alcohol 16 (1.38 g, 46% yield) as a yellow liquid and
(neat) nmax: 3445, 2927, 1601, 1460, 1378, 1100, 1065, 1038 cmꢀ1
;
27
[
a
]
þ15.6 (c 0.9, CHCl3); 1H NMR (300 MHz, CDCl3):
d 5.95 (ddd,
D
J¼17.4, 10.0, 7.0 Hz, 1H), 5.40 (td, J¼17.0, 1.3 Hz, 1H), 5.28 (d,
J¼10.7 Hz, 1H), 4.68 (s, 2H), 4.63 (dt, J¼6.3, 0.7 Hz, 1H), 4.02–3.92
(m, 2H), 3.88–3.65 (m, 4H), 3.37 (s, 3H), 1.90–1.74 (m, 2H), 1.74–
1.55 (m, 3H), 1.46 (s, 3H), 1.36 (s, 3H), 0.95 (d, J¼7.2 Hz, 3H); 13C
NMR (75 MHz, CDCl3):
d 133.7, 118.2, 108.5, 94.8, 79.7, 79.0, 75.0,
74.0, 71.2, 61.4, 55.4, 36.5, 35.1, 28.4, 27.7, 25.4, 11.2; MS (ES): m/z
353 (MþNa)þ; HRMS (ESI): m/z calcd for C17H30O6Na 353.1940,
found 353.1956.
14 (1.5 g, 50% yield) as a colorless oil. Rf (30% EtOAc/hexane) 0.35; IR
27
(neat) nmax: 3455, 2926, 2857, 1455, 1376 cmꢀ1; [
a
]
D
þ11.7 (c 0.9,
4.1.14. (1S,2S)-1-((2R,4S,5S,6R)-6-(2-(Benzyloxy)ethyl)-4-
(methoxymethoxy)-5-methyltetrahydro-2H-pyran-2-yl)but-3-
ene-1,2-diol 20
Compound 17 (0.5 g, 1.20 mmol) was taken in 70% acetic acid
(10 mL) and stirred for 4 h at 45 ꢁC. After completion of reaction
(TLC), the acidic solution was concentrated under reduced pressure
to give a crude product which was purified by column chroma-
tography (40% EtOAc/Hexane) to yield compound 20 (0.41 g, 90%)
CHCl3); 1H NMR (300 MHz, CDCl3):
d 7.38–7.27 (m, 5H), 5.95–5.82
(m, 1H), 5.32 (td, J¼13, 17.18 Hz, 1H), 5.19–5.11 (m, 1H), 4.64 (t,
J¼6.4 Hz, 1H), 4.50 (d, J¼5.0 Hz, 2H), 4.03–3.90 (m, 3H), 3.86–3.72
(m, 1H), 3.60–3.45 (m, 2H), 1.88–1.49 (m, 5H), 1.45 (s, 3H), 1.35 (s,
3H), 0.90 (d, J¼7.17 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 138.5,
134.0, 128.4, 127.6, 127.5, 117.3, 108.5, 79.9, 78.9, 73.0, 70.7, 70.6,
70.3, 67.6, 38.8, 33.2, 31.2, 27.3, 25.4, 11.0; MS (ES): m/z 399
(MþþNa); HRMS (ESI): m/z calcd for C22H32O5Na 399.2147, found
399.2142.
as a colorless oil. Rf (50% EtOAc/hexane) 0.3; IR (neat) nmax: 3442,
30
2887, 1453, 1101, 1037 cmꢀ1; [
a
]
þ20.9 (c 1.10, CHCl3); 1H NMR
D
(300 MHz, CDCl3):
d
7.39–7.27 (m, 5H), 5.94 (ddd, J¼17.2, 10.7,
4.1.12. (2R,3S,4S,6R)-2-(2-(Benzyloxy)ethyl)-6-((4R,5R)-2,2-
dimethyl-5-vinyl-1,3-dioxolan-4-yl)-4-(methoxymethoxy)-3-
methyltetrahydro-2H-pyran 17
6.6 Hz, 1H), 5.42–5.25 (m, 2H), 4.67 (s, 2H), 4.50 (s, 2H), 4.24 (br t,
J¼5.8 Hz, 1H), 4.03 (td, J¼9.4, 2.4 Hz, 1H), 3.84–3.71 (m, 2H), 3.59–
3.44 (m, 3H), 3.36 (s, 3H), 3.03 (d, J¼3.0 Hz, 1H), 2.07 (d, J¼4.1 Hz,
1H), 1.92–1.53 (m, 5H), 0.92 (d, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
To a solution of alcohol (þ)-16 (0.2 g, 0.53 mmol) in acetonitrile
(3.0 mL) was added 2,6-lutidine (0.24 mL, 2.12 mmol) followed by
MOMCl (0.12 mL, 1.60 mmol). The resulting reaction mixture was
then allowed to stir overnight at room temperature at which point
it was quenched by the addition of 5 mL of satd NaHCO3 and 30 mL
of EtOAc. The organic phase was then separated and the aqueous
phase was washed with EtOAc (2ꢂ30 mL). The combined organic
layer was dried over anhydrous sodium sulphate, filtered and
concentrated to yield a crude oil. Purification was accomplished by
column chromatography (10% EtOAc/hexane) to provide (þ)-17
(0.218 g, 98% yield) as a clear, colorless oil. Rf (10% EtOAc/hexane)
CDCl3): d 138.3, 136.8, 128.3, 127.6, 127.5, 117.6, 94.8, 75.2, 75.1, 75.0,
74.6, 73.0, 72.0, 67.3, 55.4, 36.2, 33.0, 28.0, 10.9; MS (ES): m/z 381
(Mþþ1); HRMS (ESI): m/z calcd for C21H32O6Na 403.2096, found
403.2089.
4.1.15. (1S,2S,E)-1-((2R,4S,5S,6R)-6-(2-(Benzyloxy)ethyl)-4-
(methoxymethoxy)-5-methyltetrahydro-2H-pyran-2-yl)-7-(tert-
butyldimethylsilyloxy)hept-3-ene-1,2-diol 21
Diol 20 (0.2 g, 0.52 mmol) and TBS protected 4-pentene-1-ol 19
(0.63 g, 3.15 mmol) were added via syringe to a stirring solution of
Grubbs 2nd generation catalyst (0.05 mmol, 5.0 mol %) in dichloro-
methane (2.5 mL). The flask was capped with a rubber septum,
flushed with dry nitrogen and stirred under nitrogen for 12 h at rt.
The reaction mixture was then reduced in volume to 0.5 mL and
purified directly by silica gel column chromatography (30% EtOAc/
hexane) to provide (þ)-21 (0.177 g, 65% yield) as a brown color oil.
0.40; IR (neat) nmax: 2925, 2857, 1376, 1215, 1068, 1037, 759 cmꢀ1
;
27
[
a]
þ19.7 (c 0.85, CHCl3); 1H NMR (300 MHz, CDCl3):
d 7.39–7.22
D
(m, 5H), 5.87 (ddd, J¼16.6, 10.6, 6.8 Hz, 1H), 5.32 (td, J¼16.6, 1.5 Hz,
1H), 5.12 (td, J¼10.6, 1.5 Hz, 1H), 4.66 (s, 2H), 4.62 (t, J¼6.8 Hz, 1H),
4.50 (d, J¼3.8 Hz, 2H), 3.98–3.85 (m, 2H), 3.78–3.64 (m, 2H), 3.57–
3.45 (m, 2H), 3.34 (s, 3H), 1.85–1.48 (m, 5H),1.44 (s, 3H),1.35 (s, 3H),
0.92 (d, J¼6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d
138.5, 134.0,
Rf (50% EtOAc in hexane) 0.40; IR (neat) nmax: 3445, 2926, 2856,
1736, 1460, 1255, 1101, 1038 cmꢀ1; [
a
]
þ17.5 (c 0.83, CHCl3); 1H
28
128.3, 127.6, 127.5, 117.2, 108.5, 94.8, 79.9, 78.9, 75.1, 73.0, 71.3, 71.1,
67.6, 55.3, 36.3, 33.2, 28.8, 27.7, 25.4, 11.0; MS (ES): m/z 443
(MþþNa); HRMS (ESI): m/z calcd for C24H36O6Na 443.2409, found
443.2396.
D
NMR (300 MHz, CDCl3):
d
7.38–7.27 (m, 5H), 5.79 (td, J¼15.5, 6.8 Hz,
1H), 5.53 (dd, J¼15.5, 7.4 Hz, 1H), 4.67 (s, 2H), 4.50 (s, 2H), 4.15 (t,
J¼6.8 Hz, 1H), 4.09–3.98 (m, 1H), 3.83–3.70 (m, 2H), 3.61 (t,
J¼6.4 Hz, 2H), 3.53 (t, J¼6.4 Hz, 2H), 3.45–3.37 (m, 1H), 3.36 (s, 3H),
2.13 (q, J¼6.8 Hz, 1H), 2.04 (br s, 1H), 1.94–1.52 (m, 7H), 0.92 (d,
J¼7.2 Hz, 3H), 0.89 (s, 9H), 0.04 (s, 6H); 13C NMR (75 MHz, CDCl3):
4.1.13. 2-((2R,3S,4S,6R)-6-((4R,5R)-2,2-Dimethyl-5-vinyl-1,3-
dioxolan-4-yl)-4-(methoxymethoxy)-3-methyltetrahydro-2H-
pyran-2-yl)ethanol 18
d
138.4, 135.0, 128.7, 128.3, 127.6, 127.5, 94.8, 75.5, 75.2, 75.1, 75.0,
To a stirred solution of naphthalene (0.24 g, 1.9 mmol) in THF
(4 mL), were added lithium metal (0.01 g, 1.4 mmol) in small
pieces. The reaction mixture was stirred at room temperature
73.0, 72.1, 67.4, 62.5, 55.4, 36.2, 33.0, 32.2, 28.8, 28.1, 25.9, 18.3, 10.9,
ꢀ5.3; MS (ES): m/z 553 (MþþH); HRMS (ESI): m/z calcd for
C30H52O7SiNa 575.3375, found 575.3399.

P. Srihari et al. / Tetrahedron 65 (2009) 6304–6309
6309
4.1.16. ((E)-5-((4R,5R)-5-((2R,4S,5S,6R)-6-(2-(Benzyloxy)ethyl)-4-
(methoxymethoxy)-5-methyltetrahydro-2H-pyran-2-yl)-2,2-
dimethyl-1,3-dioxolan-4-yl)pent-4-enyloxy)(tert-butyl)-
3.78–3.68 (m, 3H), 3.64 (t, J¼6.2 Hz, 2H), 3.37 (s, 3H), 2.21–2.10 (m,
2H), 1.84–1.73 (m, 2H), 1.72–1.55 (m, 5H), 1.44 (s, 3H), 1.44–1.43 (m,
1H), 1.34 (s, 3H), 0.94 (d, J¼7.1 Hz, 3H), 0.89 (s, 9H), 0.05 (s, 6H); 13C
dimethylsilane 2
NMR (75 MHz, CDCl3): d 135.3, 125.3, 108.0, 94.7, 79.7, 79.0, 74.9,
To a solution of diol 21 (0.12 g, 0.23 mmol) in dry dichloro-
methane (3 mL) was added 2,2-dimethoxy propane (0.08 mL,
0.69 mmol) and a catalytic amount of pyridinium p-toluenesulfo-
nate. The homogeneous solution was stirred for 1 h. Dichloro-
methane (10 mL) and saturated NaHCO3 (100 mL) were added and
the mixture was extracted with dichloromethane (2ꢂ20 mL). The
combined organic layers was dried over anhydrous sodium sul-
phate and evaporated. Purification by silica gel column chroma-
tography (10% EtOAc/hexane) yielded white color acetal 2 (0.13 g,
73.9, 71.2, 62.8, 61.1, 55.0, 36.5, 35.1, 31.9, 28.8, 28.3, 27.7, 25.9, 25.3,
18.3, 11.2, ꢀ5.3; MS (ES): m/z 502 (MþH)þ; HRMS (ESI) m/z calcd for
C26H50O7Si 502.3325, found 502.3347.
Acknowledgements
B.K. thank CSIR, New Delhi for financial assistance in the form of
fellowship.
98%). Rf (10% EtOAc/hexane) 0.6; IR (neat) nmax: 2929, 2858, 1374,
Supplementary data
25
1251, 1099, 838 cmꢀ1; [
a]
þ15.0 (c 0.75, CHCl3); 1H NMR
D
(300 MHz, CDCl3): d 7.38–7.27 (m, 5H), 5.87–5.65 (m, 1H), 5.52 (dd,
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.06.035.
J¼15.5, 7.7.1 Hz, 1H), 4.67 (s, 2H), 4.58 (t, J¼6.8 Hz, 1H), 4.50 (s, 2H),
3.97–3.82 (m, 2H), 3.79–3.67 (m, 2H), 3.58 (t, J¼6.2 Hz, 2H), 3.56–
3.44 (m, 2H), 3.35 (s, 3H), 2.17–1.96 (m, 2H), 1.89–1.49 (m, 7H), 1.43
(s, 3H), 1.34 (s, 3H), 0.92 (d, J¼7.2 Hz, 3H), 0.88 (s, 9H), 0.03 (s, 6H);
References and notes
13C NMR (75 MHz, CDCl3):
d 138.5, 134.5, 128.3, 127.5, 125.6, 125.0,
1. Jansen, R.; Wray, V.; Irschik, H.; Reichenbach, H.; Hofle, G. Tetrahedron Lett.
1985, 26, 6031–6034.
2. Jansen, R.; Irschik, H.; Reichenbach, H.; Schomburg, D.; Wray, V.; Hofle, G.
Liebigs Ann. Chem. 1989, 111–119.
3. Rommele, G.; Wirz, G.; Solf, R.; Vosbeck, K.; Gruner, J.; Wehrli, W. J. Antibiot.
1990, 43, 88–91.
108.1, 94.6, 79.9, 78.9, 75.0, 72.8, 71.5, 71.3, 67.8, 62.6, 55.3, 36.2,
33.1, 32.3, 28.8, 28.5, 27.7, 25.9, 25.4, 18.3, 11.0, ꢀ5.3; MS (ES): m/z
615 (MþþNa); HRMS (ESI): m/z calcd for C33H56O7SiNa 615.3688,
found 615.3693.
4. Campbell, E. A.; Pavlova, O.; Zenkin, N.; Leon, F.; Irschik, H.; Jansen, R.;
Severinov, K.; Darst, S. A. EMBO J. 2005, 24, 674–682.
5. (a) Smith, A. B., III; Dong, S. Org. Lett. 2009. doi:10.1021/ol802942j; (b) Smith,
A. B., III; Fox, R. J. Org. Lett. 2004, 6, 1477–1480; (c) Smith, A. B., III; Fox, R. J.;
Vanecko, J. A. Org. Lett. 2005, 7, 3099–3102.
4.1.17. 2-((2R,3S,4S,6R)-6-((4R,5R)-5-((E)-5-(tert-Butyldimethyl-
silyloxy)pent-1-enyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-
(methoxymethoxy)-3-methyltetrahydro-2H-pyran-2-yl)-
6. (a) Schinzer, D.; Schulz, C.; Krug, O. Synlett 2004, 2689–2692; (b) Crimmins, M.
T.; Haley, M. W. Org. Lett. 2006, 8, 4223–4225; (c) Park, S. H.; Lee, H. W. Bull.
Korean Chem. Soc. 2008, 29, 1661–1662.
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Yadav, J. S.; Srihari, P. Tetrahedron: Asymmetry 2004, 15, 81–89; (c) Yadav, J. S.;
Reddy, S. R. Synthesis 2007, 1070–1076; (d) Yadav, J. S.; Kumar, N. N.; Prasad,
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aldehyde.
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12216–12217. Also attempts to esterify the alcohol with inversion using
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ethanol 22
To a stirred solution of naphthalene (0.038 g, 0.304 mmol) in
THF (2 mL), was added lithium metal (0.0014 g, 0.20 mmol). The
reaction mixture was stirred at room temperature under an argon
atmosphere until lithium metal was completely dissolved (3–4 h).
The resulting dark green solution of lithium naphthalenide was
then cooled to ꢀ25 ꢁC, followed by addition of a solution of com-
pound 2 (0.015 g, 0.025 mmol) in THF (0.5 mL) dropwise over
5 min. The resulting mixture was stirred at ꢀ25 ꢁC for 30 min sat-
urated aqueous ammonium chloride (1 mL) and water (1 mL) were
then added. The resulting solution was extracted with diethyl ether
(3ꢂ10 mL). The combined extracts were washed with water and
brine, dried over anhydrous sodium sulphate and concentrated in
vacuum. The crude product was purified by column chromatogra-
phy (40% EtOAc/hexane) to afford 22 (0.012 g, 97%) as a yellow
liquid. Rf (40% EtOAc/hexane) 0.35; IR (neat) nmax: 3448, 2925, 2855,
27
1736, 1463, 1377, 1251, 1216, 1092, 1040 cmꢀ1; [
a]
þ9.5 (c 0.6,
D
20
CHCl3); Lit.5c
[a
]
þ8.8 (c 0.35, CHCl3); 1H NMR (300 MHz, CDCl3):
D
d
5.90–5.78 (m, 1H), 5.56 (dd, J¼15.2, 8.0 Hz, 1H), 4.68 (br s, 2H),
4.59 (dd, J¼8.0, 6.3 Hz, 1H), 4.04–3.89 (m, 2H), 3.89–3.78 (m, 1H),