A facile approach towards synthesis of verbalactone and biologically active δ-lactones using d-glucose

Article abstract of DOI:10.1016/j.tet.2009.08.054

A general synthetic approach has been developed for the asymmetric synthesis of chiral δ-lactones and verbalactone using d-glucose. The key intermediate used in this approach was α-diazoketone.

Full text of DOI:10.1016/j.tet.2009.08.054

Tetrahedron 65 (2009) 8677–8682
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A facile approach towards synthesis of verbalactone and biologically active
d-lactones using
D-glucose
*
Ashish Garg, Vinod K. Singh
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 June 2009
Received in revised form 20 August 2009
Accepted 21 August 2009
Available online 26 August 2009
A general synthetic approach has been developed for the asymmetric synthesis of chiral d-lactones and
verbalactone using D-glucose. The key intermediate used in this approach was a-diazoketone.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Verbalactone
Diazoketone
Lactone
D
-Glucose
The biological activity of compounds having lactonic function-
OH
O
ality is highly dependent on their configuration and optical purity,
therefore, there have been considerable efforts towards the syn-
thesis of lactones in enantiomerically pure form.1 In general
biologically active lactones are prepared by the microbial reduction
of the corresponding ketoester2 or by the enzymatic resolution3 of
the hydroxyl-acid precursor. However, these methods often suffer
from serious drawbacks. Enzymatic resolution or microbial re-
duction is substrate specific and the use of chiral reagents often
results in low enantioselectivity. Therefore, it was of interest to
investigate the use of chiral synthon in the asymmetric synthesis of
these compounds. We have been working in the area of natural
product synthesis for the past one and a half decades, and, have
synthesized many of the naturally occurring biologically active
natural products utilizing the chiron source.4 Out of the several
O
O
O
OH
verbalactone
OH
O
O
O
O
O
O
2
4
(R)-massoialactone
valerolactone
(R)-decalactone 3
Figure 1. Verbalactone and chiral
d
-lactones.
of MIC¼62.5
m
g/mL and five Gram-negative bacteria with optimum
activity of MIC¼125
m
g/mL.5,6 The structure and absolute stereo-
available carbohydrate sources, we herein report
a general
chemistry of this lactone 1, as 4R,6R,10R,12R,4,10-dihydroxy-2,8-
dioxo-6,12-dipentyl-1,7- dioxacyclododecane, were determined by
spectral methods and chemical correlations. The NMR profile is
very similar to the monomeric lactone of (3R,5R)-dihydroxy-
decanoic acid. Till date, four total synthesis of the verbalactone
have been reported.7 (R)-Massoialactone 2 is the allomone of two
species of formmicine ants of genus Camponotus, collected in
Western Australia.8 It was first isolated from the bark of Cryptocaria
massoia, by Abe9 in 1937 and later from jasmine flower10 and cane
molasses11 where it acts as flavour component. It is also present in
Hierochloe odorata and Hierochloe australis both being used in
vodka production.12 It also acts as a powerful skin irritant and
produces systolic standstill in frog heart muscles.13 (R)-Decalactone
3 was first observed in cashew apple product produced from
approach where -glucose can be crafted in a desired way to give
D
a common diazoketone intermediate, which can be utilized further
for the synthesis of naturally occurring verbalactone 1, and other
bioactive chiral d-lactones 2–4 (Fig. 1).
Verbalactone5 1 is the first example where 1,7-dioxacyclodo-
decane moiety was reported as the ring system of a natural product.
It is obtained from roots of Verbascum undulatum a biennial plant of
genus Verbascum that belongs to Schrophulariaceae family. The
lactone has a novel macrocyclic dimeric structure and shows ac-
tivity against three Gram-positive bacteria with optimum activity
* Corresponding author. Tel.: þ91 512 259 7291; fax: þ91 512 259 7436.
E-mail address: vinodks@iitk.ac.in (V.K. Singh).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.08.054

8678
A. Garg, V.K. Singh / Tetrahedron 65 (2009) 8677–8682
cashew tree, Anacardium occidentale L. an indigenous Brazilian tree
found in northeastern coastal region. It is an important constituent
in cheese, butter having sweet, creamy and milky odour.14 Low
threshold concentration and specific odour makes this highly im-
portant subunit to be crucial for simple synthetic approach.
(þ)-Valerolactone 4, more commonly known as 3-hydroxy-5-dec-
anolide is identical to lactone subunits present in mevinolin and
compactin15 and acts a potent inhibitor of enzyme HMG-CoA
reductase. Various groups have reported both racemic as well as
enantioselective synthesis of these lactones.16,17 Although several
reports for the synthesis of 6-substituted hydropyran-2-one de-
rivatives have been reported, there is no efficient general route to
these derivatives. We herein, therefore report a new route to 6-
substituted hydropyran-2-one derivatives along with verbalactone.
The common retrosynthetic pathway is shown in Scheme 1. It
OPMB
O
HO
C5H9
C5H11
O
a
b
9
O
O
H
H
O
O
11
10
S
O
SMe
c
d
C5H11
C5H11
O
O
O
O
H
H
O
O
13
12
C5H11
C5H11
O
f
e
O
OMe
OH
OBn
H
H
OH
14
8
PMB = p-Methoxybenzyl
was conceived that the dimeric lactone 1 and d-lactones 2–4 can be
Scheme 2. Reagents and conditions: (a) Ph3PC4H9Br, n-BuLi, THF, 0 ꢁC to rt, 95%; (b) (i)
DDQ, DCM/H2O (10:1); (ii) H2, 10% Pd/C, EtOH, rt (92% for two steps); (c) NaH, CS2, MeI,
THF, 0 ꢁC to rt, 12 h, 95%; (d) n-Bu3SnH, AIBN, toluene, 110 ꢁC, 16 h, 82%; (e) MeOH,
AcCl, 60 ꢁC, 6 h, 77%; (f) (i) NaH, BnBr, THF, 0 ꢁC to rt, 6 h; (ii) 60% AcOH, Hþ, 60 ꢁC, 4 h
(83% for two steps).
obtained from esters 5 and 6, which were obtained by Arndt–Eis-
tert homologation of diazoketone 7, a common intermediate. Fur-
ther this diazoketone can be derived from a hemiacetal 8, which
can be obtained from an aldehyde 9.18 The aldehyde 918 can easily
be synthesized from
chirality at C-4 and C-6 in the natural product 1 would be directly
translated from -glucose.
D-glucose using literature procedure. The
yield. Further protection of secondary hydroxyl in 16 as TBDPS
ether using TBDPSCl gave 17. The acetate group in 17 was hydro-
lyzed using K2CO3/MeOH to give 18, which upon oxidation using
Swern conditions gave an aldehyde 19. The aldehyde 19 on further
oxidation using NaClO2 and NaH2PO4 in t-BuOH/H2O (2:1) gave an
acid 20 (Scheme 3). As per this stratagem, we needed one more
carbon and it was achieved using Arndt–Eistert homologation
protocol. The acid 20 so formed was transformed into corre-
D
n-C5H11
OMe
OMe
1-4
TBDPSO
OBn O
5
O
N2
n-C5H11
TBDPSO
OBn
7
n-C5H11
TBDPSO
6
sponding
a
-diazoketone 7 via reaction of diazomethane with
a mixed anhydride 21. Wolff rearrangement20 of
a
-diazoketone 7
3
O
using silver benzoate afforded a mixture of homologated ester 5
and a homologated unsaturated ester 6 as side product (Scheme 4).
O
OH
H
8
OBn
C5H11
C5H11
b
a
8
OAc
OH
OH OBn
16
OH OBn
15
O
OHC
O
O
D-glucose
H
PMBO
9
C5H11
C5H11
TBDPSO
OH
OAc
d
c
Scheme 1. Retrosynthetic scheme.
TBDPSO
OBn
OBn
18
17
The synthesis of verbalactone 1 and chiral
(R)-massoialactone 2, (R)-decalactone 3 and valerolactone 4 in-
volved -pentodialdose 5, which was easily synthesized from
-glucose using literature procedures.18 The aldehyde 9 was con-
d-lactones such as
a-D
D
C5H11
CHO
OBn
C5H11
COOH
OBn
f
e
verted into 10 using Wittig chemistry with a phosphonium salt
prepared from butyl bromide and triphenylphosphine. Further
oxidative cleavage of PMB ether in 10 using DDQ in aqueous DCM
followed by hydrogenation of the double bond by Pd/C in MeOH
gave 11 as a solid product. The C3 hydroxyl xanthate functionality
in 11 was now converted to corresponding 12 by treatment with
CS2 and MeI. The xanthate 12 so obtained when exposed to
n-Bu3SnH in toluene under reflux conditions led to Barton–
McCombie deoxygenation19 at C3 thereby giving 13. At this stage
we decided to deprotect internal acetonide in 13 with simultaneous
protection of lactal hydroxy group. Exposure of 13 to a catalytic
amount of acetyl chloride in methanol afforded the methyl acetal
TBDPSO
19
TBDPSO
20
Scheme 3. Reagents and conditions: (a) NaBH4, MeOH, 0 ꢁC to rt, 6 h, 96%; (b) AcCl,
collidine, DCM, ꢀ78 ꢁC, 3 h, ꢀ40 ꢁC, 6 h, 95%; (c) TBDPSCl, imidazole, DCM, 0 ꢁC to rt,
4 h, 93%; (d) K2CO3, MeOH, 0 ꢁC to rt, 2 h, 90%; (e) (COCl)2, DMSO, DCM, Et3N, ꢀ78 ꢁC,
99%; (f) NaClO2, NaH2PO4$H2O, 2-methyl-2-butene, t-BuOH/H2O, rt, 12 h, 92%.
With the required homologated ester 5 in hand, we first
deprotected the TBDPS ether using 70% HF/Py in THF, to obtain the
six-membered lactone having C-5 hydroxy protected as corre-
sponding benzyl ether 22 (Scheme 5). The lactone upon treatment
with Pd/C in ethanol led to the debenzylation as well as opening of
lactone to give an ester 23. The ester 23 was then hydrolyzed to
a corresponding seco-acid 24, which is a well known precursor for
the synthesis of the natural product 1. Since the conversion of seco-
acid into verbalactone 1 is well established, this completed its
formal total synthesis.7a,c
14, which was successively protected as benzyl ether at a-position
yielding an anomeric mixture. It was then decided to deprotect the
methyl acetal and it was achieved using 60% AcOH and catalytic
amount of concd HCl affording hemiacetal 8 (Scheme 2).
The hemiacetal 8 was then reduced with sodium borohydride to
provide diol 15. Selective protection of terminal hydroxyl in 15 was
done using AcCl/collidine at ꢀ78 ꢁC, to provide acetate 16 in good
Further, the Arndt–Eistert products 5 and 6 obtained after Wolf
rearrangement were found to be key intermediates in the synthesis

A. Garg, V.K. Singh / Tetrahedron 65 (2009) 8677–8682
8679
using silica gel (Acme’s, 100–200 mesh). Petroleum ether used was
of boiling range 60–80 ꢁC. Melting points were determined by us-
ing Perfit apparatus and are uncorrected.
O
O
C5H11
COOH
a
C5H11
O
TBDPSO
OBn
TBDPSO
OBn
1.1.1. (3aR,5R,6R,6aS)-6-(4-Methoxybenzyloxy)-2,2-dimethyl-5-((E)-
pent-1-enyl)tetrahydrofuro[2,3-d][1,3]dioxole (10). n-BuLi (1.6 M
soln in n-Hexane, 19.95 mL) was added dropwise to a solution of
triphenylphosphonium butyl bromide (12.78 g, 31.95 mmol) in
anhydrous THF (90.0 mL) at 0 ꢁC and allowed to stir for 15 min.
Then, a solution of the aldehyde 9 (8.2 g, 26.6 mmol) in anhydrous
THF (50.0 mL) was added and the mixture was stirred at room
temperature for 6 h. The reaction mixture was quenched with
water and filtered through Celite. The filtrate was concentrated by
evaporation and taken into ethyl acetate. It was washed with water,
brine and dried over Na2SO4. After concentration on rotavapor, the
20
21
b
c
6 (22%)
+
7
5 (64%)
Scheme 4. Reagents and conditions: (a) (i) Et3N, ClCOOEt, THF, 0 ꢁC to rt, 2 h; (b)
CH2N2, Et2O, rt, 2 h (68% for two steps); (c) PhCOOAg, Et3N, MeOH, ꢀ10 ꢁC to rt,
1.5 h, 86%.
OBn
b
a
crude reaction mixture was purified over silica gel to obtain pure
5
25
C5H11
O
22
O
alkene 10 (8.3 g) as a colourless liquid; [
a]
ꢀ34.5 (c 0.60, CHCl3);
D
IR (thin film, cmꢀ1) 2934, 2890, 1173; 1H NMR (CDCl3, 500 MHz):
d
0.84 (t, J¼5.9 Hz, 3H), 1.31 (s, 3H), 1.32–1.42 (m, 2H), 1.51 (s, 3H),
C5H11
c
C5H11
COOH
1.98–2.11 (m, 2H), 3.73 (m, 4H), 4.52 (ABq, J¼9.4 Hz, Dn¼34.5 Hz,
2H), 4.59 (d, J¼3.0 Hz, 1H), 4.92 (dd, J¼5.5, 5.9 Hz, 1H), 5.62–5.70
(m, 2H), 5.94 (d, J¼2.9 Hz, 1H), 6.82–6.89 (m, 2H), 7.21–7.25
COOEt
OH OH
24
OH OH
23
(m, 2H); 13C NMR (CDCl3, 125 MHz):
d 13.8, 22.7, 26.3, 26.9, 30.2,
30.4, 55.3, 71.9, 75.9, 83.1, 104.8, 111.4, 113.9, 123.9, 128.6, 129.5,
135.1, 159.4. HRMS (ESI): exact mass calcd for C20H28O5: [MþH]þ:
349.1945. Found: 349.1947. Anal. Calcd for C20H28O5: C, 68.94; H,
8.10. Found: C, 68.86; H, 8.19.
ref 7a, 7c
1
Scheme 5. Reagents and conditions: (a) 70% HF/Py, pyridine, THF, rt, 24 h, 82%; (b) H2,
Pd/C, EtOH, 40 psi, 12 h, 89%; (c) LiOH$H2O, MeOH/H2O (4:1), 0 ꢁC to rt, 4 h, 94%.
of d-lactones. We first carried out the TBDPS cleavage in 5 using
1.1.2. (3aR,5R,6R,6aS)-2,2-Dimethyl-5-pentyltetrahydrofuro[2,3-
d][1,3]dioxol-6-ol (11). A solution of 10 (5.41 g, 15.24 mmol) was
treated with DDQ (5.19 mg, 22.86 mmol) in CH2Cl2/H2O (10:1,
60 mL) at room temperature. The reaction mixture was stirred
vigorously for 4 h and quenched with an aqueous saturated so-
dium hydrogen carbonate. The aqueous layer was extracted with
CH2Cl2. The organic phase was washed with brine and dried over
anhydrous Na2SO4. The solvent was removed on a rotary evapo-
rator and the crude mixture was chromatographed over silica gel
to give 3.26 g (92% yield) of alkene, which was subjected to hy-
CBr4/MeOH, which surprisingly gave the lactonized product (R)-
massoialactone 2, which upon hydrogenation gave (R)-decalactone
3. Similarly, TBDPS deprotection in 6 with CBr4/MeOH, followed by
hydrogenation of double bond using Pd/C in MeOH gave (R)-dec-
alactone 3 (Scheme 6).
b
a
3
6
5
2
Scheme 6. Reagents and conditions: (a) CBr4, MeOH, 60 ꢁC, 12 h; (b) H2, Pd/C, MeOH,
1 atm, 12 h; (c) (i) CBr4, MeOH, 60 ꢁC, 12 h; (ii) H2, Pd/C, MeOH, 1 atm, 12 h.
drogenation using 10% Pd/C (300 mg) in anhydrous MeOH, which
25
afforded the 11 3.2 g (99%) as a white solid; [
a
]
ꢀ49.4 (c 6.4,
D
The massoialactone 2 so obtained can easily be converted into
valerolactone 4 via a literature known procedure.21
In conclusion we have demonstrated a facile approach towards
the synthesis of verbalactone 1, (R)-massoialactone 2, (R)-deca-
lactone 3 and valerolactone 4 using D-glucose as a readily avail-
able chiral synthon in a simple and straight-forward manner.
Infact the strategy is useful for synthesis of several other 6-
CHCl3); IR (thin film, cmꢀ1) 3150, 2934, 2890, 1173; 1H NMR (CDCl3,
400 MHz):
0.89 (t, J¼1.2 Hz, 3H), 1.30 (s, 3H), 1.32–1.44 (m, 5H),
d
1.47 (s, 3H), 1.49–1.72 (m, 3H), 4.04–4.13 (m, 3H), 4.51 (d, J¼3.4 Hz,
1H), 5.88 (d, J¼3.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz):
d 13.9, 22.5,
25.7, 26.1, 26.5, 27.5, 31.8, 75.3, 80.3, 85.2, 104.1, 111.3. HRMS (ESI):
exact mass calcd for C12H22O4: [MþH]þ: 231.1526. Found:
231.1529. Anal. Calcd for C12H22O4: C, 62.58; H, 9.63. Found: C,
62.67; H, 9.56.
substituted chiral
natural products.
d-lactones present in various biologically active
1.1.3. O-(3aR,5R,6R,6aS)-2,2-Dimethyl-5-pentyltetrahydrofuro-[2,3-
d][1,3]dioxol-6-yl S-methyl carbono-dithioate (12). To a suspension
of NaH (3 g, 74.84 mmol) in anhydrous THF (80 mL), 11 (8.72 g,
37.42 mmol) in anhydrous THF (40 mL) was slowly added at 0 ꢁC,
stirred for 30 min followed by addition of CS2 (3.39 mL,
56.14 mmol) and further stirred for 15 min at 0 ꢁC. To this reaction
mixture MeI (3.51 mL, 56.14 mmol) was added and left for stirring
for 12 h and was quenched with acetic acid. The aqueous layer was
extracted with ethyl acetate. The organic phase was washed with
brine and dried over anhydrous Na2SO4. The solvent was removed
1. Experimental
1.1. General methods
All reactions were carried out under an atmosphere of nitrogen
in oven dried glassware with magnetic stirring. 1H and 13C NMR
spectra were recorded on Joel (400 MHz) NMR or Jeol (500 MHz)
spectrometer in CDCl3. Chemical shifts are reported in delta (d)
units, in parts per million (ppm). Tetramethylsilane and CDCl3 were
used as internal standard for 1H and 13C NMR, respectively. Cou-
pling constants were reported in hertz. Splitting patterns are des-
ignated as s for singlet; d for doublet; t for triplet; q for quartet; m
for multiplet and br s for broad singlet. IR spectra were measured
with Bruker FT/IR Vector 22 spectrometer. Routine monitoring of
reactions was performed using precoated silica gel TLC plates from
E-Merck. All the chromatographic separations were carried out by
on a rotary evaporator and the crude mixture was chromato-
25
graphed over silica gel to give 11.52 g of xanthate 12; [
a]
þ6.4
D
(c 5.0, CHCl3); IR (thin film, cmꢀ1) 2954, 1713, 1208; 1H NMR (CDCl3,
500 MHz):
d
0.86 (t, J¼5.3 Hz, 3H), 1.24–1.30 (m, 4H), 1.32 (s, 3H),
1.41–1.49 (m, 1H), 1.52 (s, 3H), 1.60–1.74 (m, 3H), 2.59 (s, 3H), 4.32
(dt, J¼2.2, 5.4 Hz, 1H), 4.61 (d, J¼3.1 Hz, 1H), 5.85 (d, J¼2.4 Hz, 1H),
5.90 (d, J¼3.1 Hz, 1H); 13C NMR (CDCl3, 125 MHz):
d 14.0, 19.3, 22.5,

8680
A. Garg, V.K. Singh / Tetrahedron 65 (2009) 8677–8682
25.8, 26.3, 26.6, 27.8, 31.8, 79.5, 83.2, 84.9, 104.5, 111.9, 215.4. Anal.
Calcd for C14H24O4S2: C, 52.47; H, 7.55. Found: C, 52.54; H, 7.47.
3H), 1.26–1.37 (m, 5H), 1.38–1.48 (m, 2H), 1.68–1.79 (m, 3H), 3.59
(dd, J¼9.3, 3.2 Hz, 1H), 3.73–3.83 (m, 3H), 4.61 (ABq, J¼9.1 Hz,
Dn¼23.4 Hz, 2H), 7.25–7.36 (m, 5H); 13C NMR (CDCl3, 100 MHz):
1.1.4. (3aR,5R,6aS)-2,2-Dimethyl-5-pentyltetrahydrofuro[2,3-d][1,3]-
dioxole (13). To a solution of n-Bu3SnH (14.79 mL, 56.86 mmol) in
anhydrous toluene 160 mL, 12 (11.52 g, 35.54 mmol) in anhydrous
toluene 90 mL was added. To this catalytic amount of AIBN was
added and the resulting reaction mixture was refluxed for 16 h. The
reaction mixture was cooled to room temperature and toluene was
evaporated on rotavapor to get the crude product. The crude
d 14.1, 22.7, 25.3, 31.9, 37.9, 38.3, 63.8, 70.1, 71.6, 78.9, 127.9, 128.1,
128.7, 137.9. HRMS (ESI): exact mass calcd for C16H26O3: [MþH]þ:
267.1890. Found: 267.1893. Anal. Calcd for C16H26O3: C, 72.14; H,
9.84. Found: C, 72.23; H, 9.78.
1.1.8. (2R,4R)-2-(Benzyloxy)-4-hydroxynonyl acetate (16). To a solu-
tion of diol 15 (280 mg, 1.04 mmol) in dry DCM (5.0 mL), collidine
product upon purification on silica gel gave 6.32 g of the required
(275
m
L, 2.08 mmol) was added at ꢀ78 ꢁC followed by acetyl chlo-
25
compound 13; [
a
]
ꢀ1.9 (c 2.6, CHCl3); IR (thin film, cmꢀ1) 3150,
ride (81.4 mL, 1.14 mmol) under N2 atmosphere and stirred for 3 h.
D
2934, 1173; 1H NMR (CDCl3, 400 MHz):
d
0.86–0.88 (m, 3H), 1.31 (s,
The reaction mixture was warmed to ꢀ40 ꢁC and again stirred for
6 h. The reaction mixture was quenched with saturated solution of
aqueous NH4Cl and was extracted with EtOAc. The organic layer
was washed with aqueous CuSO4 solution, brine and placed over
3H), 1.39–1.46 (m, 8H), 1.51 (s, 3H), 2.11 (dd, J¼3.8, 13.2 Hz, 2H),
4.16–4.18 (m, 1H), 4.70–4.72 (m, 1H), 5.79 (d, J¼3.9 Hz, 1H); 13C
NMR (CDCl3, 100 MHz): d 13.9, 22.5, 25.7, 26.1, 26.6, 31.9, 34.2, 38.9,
78.0, 80.5, 105.2, 110.7. HRMS (ESI): exact mass calcd for C12H22O3:
[MþH]þ: 215.1577. Found: 215.1572. Anal. Calcd for C12H22O3: C,
67.26; H, 10.35. Found: C, 67.35; H, 10.26.
anhydrous Na2SO4. The organic layer was concentrated under vacuo
25
and chromatographed to give acetate 16 (306 mg, 94.6%); [a]
þ19.3 (c 3.5, CHCl3); IR (thin film, cmꢀ1) 3461, 2929, 1741, 1237; 1DH
NMR (CDCl3, 400 MHz):
d
0.88 (t, J¼6.8 Hz, 3H), 1.28–1.77 (m, 10H),
1.1.5. (2S,3S,5R)-2-Methoxy-5-pentyltetrahydrofuran-3-ol (14). A solu-
tion of 13 (4.6 g, 21.19 mmol) in MeOH (60.0 mL) and catalytic amount
of acetyl chloride was refluxed for 6 h. The reaction mixture was
neutralized with solid Na2CO3 and then concentrated on rotary
evaporator. The residue was dissolved in EtOAc (50 mL), washed with
water, brine and dried over anhydrous Na2SO4. The organic layer was
concentrated and chromatographed over silica gel to give methyl
2.08 (s, 3H), 3.73–3.86 (m, 2H), 4.10 (dd, J¼4.8,11.9 Hz,1H), 4.29 (dd,
J¼3.6, 11.7 Hz, 1H), 4.64 (ABq, J¼11.4 Hz, Dn¼76.3 Hz, 2H), 7.31–7.25
(m, 5H); 13C NMR (CDCl3, 100 MHz):
d 13.9, 20.8, 22.5, 24.9, 31.8,
37.6, 38.7, 65.4, 70.5, 71.8,127.8,127.9,128.5,137.5,170.8. Anal. Calcd
for C18H28O4: C, 70.10; H, 9.15. Found: C, 70.16; H, 9.09.
1.1.9. (2R,4R)-2-(Benzyloxy)-4-(tert-butyldiphenylsilyl-oxy)nonyl ac-
etate (17). To a stirred solution of alcohol 16 (214 mg, 0.69 mmol) in
anhydrous DCM (3.0 mL), imidazole (284 mg, 1.03 mmol) and
TBDPSCl (93.7 mg, 1.37 mmol) were added and stirred at room
temperature for 6 h. The reaction mixture was poured into water
and extracted with ether. The organic layer was washed with water,
brine and dried over anhydrous Na2SO4. The organic layer was
concentrated under vacuo and chromatographed to give silyl ether
hemiacetal 14; 1H NMR (CDCl3, 400 MHz):
1.24–1.49 (m, 5H), 1.59–2.00 (m, 5H), 3.33 (s, 3H), 4.11–4.33 (m, 2H),
4.77 (s, 1H); 13C NMR (CDCl3, 100 MHz):
14.0, 14.1, 22.7, 25.9, 31.8,
d
0.89 (t, J¼6.6 Hz, 3H),
d
38.2, 76.3, 76.5, 79.8, 109.1. Anal. Calcd for C10H20O3: C, 63.80; H, 10.71.
Found: C, 63.71; H, 10.82.
1.1.6. (2S,3S,5R)-3-(Benzyloxy)-5-pentyltetrahydrofuran-2-ol (8). To
a suspension of NaH (1.44 g, 36.12 mmol) in anhydrous THF
(40 mL), the methyl acetal 14 (2.76 g, 14.45 mmol) in anhydrous
THF was slowly added at 0 ꢁC and stirred for 30 min followed by
addition of benzyl bromide (2.06 mL, 17.34 mmol) and catalytic
amount of TBAI. The reaction mixture was stirred at room tem-
perature for 4 h, quenched with saturated NH4Cl and extracted
with ether. The organic layer was washed with brine and dried over
anhydrous Na2SO4, concentrated and on purification over column
chromatography gave benzyl ether. Then to a solution of benzyl
ether (3.92 g, 13.95 mmol) in 60% acetic acid (70.0 mL), catalytic
amount of concd HCl was added and refluxed at 80 ꢁC for 4 h. The
solution was quenched with solid NaHCO3 and extracted with ethyl
acetate. The organic layer was washed with water, brine and dried
over anhydrous Na2SO4. The organic layer was concentrated and
chromatographed over silica gel to give hemiacetal 8 (3.46 g, 93%);
IR (thin film, cmꢀ1) 3460, 3020, 1640; 1H NMR (CDCl3, 400 MHz):
17 (351 mg, 93%); 1H NMR (CDCl3, 400 MHz):
d
0.78 (t, J¼6.6 Hz,
3H), 1.02 (s, 9H), 1.09–1.16 (m, 3H), 1.33–1.37 (m, 3H), 1.64–1.67 (m,
1H), 1.80–1.85 (m, 3H), 2.00 (s, 3H), 3.67–3.69 (m, 2H), 3.79–3.89
(m, 2H), 4.45 (ABq, J¼9.4 Hz, Dn¼38 Hz, 2H), 7.19–7.71 (m, 15H); 13
C
NMR (CDCl3, 100 MHz):
d 14.1, 19.1, 19.4, 22.6, 24.5, 26.6, 26.7, 27.2,
31.7, 38.2, 70.4, 71.3, 73.8, 127.7, 127.9, 128.3, 128.5, 129.8, 134.3,
134.8, 134.9, 135.2, 135.9, 136.1, 138.4, 171.0. Anal. Calcd for
C34H46O4Si: C, 74.68; H, 8.48. Found: C, 74.76; H, 8.41.
1.1.10. (2R,4R)-2-(Benzyloxy)-4-(tert-butyldiphenylsilyl-oxy)nonan-
1-ol (18). Acetate 17 (351.2 mg, 0.64 mmol) was dissolved in MeOH
(5.0 mL) and finely powdered K2CO3 (132.3 mg, 0.96 mmol) at 0 ꢁC
was added. The reaction mixture was stirred for 2 h. MeOH was
evaporated on rotavapor, and solid residue so obtained was dis-
solved in water and extracted with ether. The combined organic
layers were washed with water, brine and dried over anhydrous
d
0.88 (t, J¼4.6 Hz, 3H), 1.24–2.14 (m, 10H), 3.99–4.30 (m, 2H), 4.53–
4.64 (m, 2H), 5.38–5.41 (m, 1H), 7.26–7.38 (m, 5H); 13C NMR (CDCl3,
100 MHz): 14.1, 22.7, 25.9, 31.9, 35.8, 37.7, 54.4, 71.3, 80.1, 83.4,
Na2SO4. The organic layer was concentrated under vacuo and
25
chromatographed to give alcohol 18 (291 mg, 90%); [
a
]
ꢀ11.9
D
d
(c 1.65, CHCl3); IR (thin film, cmꢀ1) 3435, 2930, 1110; 1H NMR
(CDCl3, 400 MHz):
106.8, 127.7, 127.8, 128.5, 138.1. Anal. Calcd for C16H24O3: C, 72.69; H,
9.15. Found: C, 72.78; H, 9.08.
d
0.71 (t, J¼7.6 Hz, 3H), 1.04 (s, 9H), 1.06–1.14 (m,
10H), 3.33 (dd, J¼1.2, 11.4 Hz, 1H), 3.52–3.60 (m, 2H), 3.80 (qn,
J¼5.3 Hz, 1H), 4.45 (ABq, J¼11.7 Hz, Dn¼20.5 Hz, 2H), 7.22–7.67 (m,
1.1.7. (2R,4R)-2-(Benzyloxy)nonane-1,4-diol (15). To a stirred solu-
tion of hemiacetal 8 (3.21 g, 12.02 mmol) in anhydrous MeOH was
added NaBH4 (1.14 g, 30.06 mmol) at 0 ꢁC and was stirred for 6 h.
The reaction mixture was quenched by addition of saturated NH4Cl
and MeOH was removed on rotary evaporator. The aqueous layer
was extracted with EtOAc, the combined organic layers were
washed with water, brine and dried over anhydrous Na2SO4, con-
centrated in vacuo and the residue was chromatographed over
silica gel to give the diol 15 (3.10 g, 96%); IR (thin film, cmꢀ1) 3400,
15H); 13C NMR (CDCl3, 100 MHz):
d 14.1, 19.4, 22.5, 24.6, 27.2, 31.8,
36.7, 37.6, 53.5, 64.2, 70.9, 71.1, 127.5, 127.6, 127.7, 127.8, 128.5, 129.8,
134.3, 136.0, 138.4. HRMS (ESI): exact mass calcd for C32H44O3Si:
[MþH]þ: 505.3068. Found: 505.306. Anal. Calcd for C32H44O3Si: C,
76.14; H, 8.79. Found: C, 76.19; H, 8.71.
1.1.11. (2R,4R)-2-(Benzyloxy)-4-(tert-butyldiphenylsilyl-oxy)-nona-
nal (19). A solution of oxalyl chloride (254
mL, 2.96 mmol) was
cautiously treated with DMSO (419.5
mL, 5.91 mmol) in CH2Cl2
2929, 1495, 1049; 1H NMR (CDCl3, 500 MHz):
d
0.88 (t, J¼5.5 Hz,
(11.0 mL) at ꢀ78 ꢁC under a nitrogen atmosphere. To this solution

A. Garg, V.K. Singh / Tetrahedron 65 (2009) 8677–8682
8681
was added a solution of the alcohol 18 (1.0 g, 1.97 mmol) in CH2Cl2
(3.0 mL). After the reaction mixture was stirred for 2 h at ꢀ78 ꢁC,
Et3N (1.36 mL) was added and the resulting reaction mixture was
allowed to come to 0 ꢁC. The reaction mixture was diluted with
phosphate buffer and then extracted with Et2O. The organic layer
was washed with brine, dried over anhydrous Na2SO4 and con-
1.04–1.95 (m, 10H), 2.31–2.43 (m, 2H), 3.63 (s, 3H), 3.79 (t, J¼5.6 Hz,
1H), 3.97–4.00 (m, 1H), 4.54–4.55 (m, 2H), 7.18–7.47 (m, 15H); 13C
NMR (CDCl3, 100 MHz):
d 14.1, 19.4, 22.6, 24.4, 26.6, 27.1, 31.8, 36.6,
39.8, 41.0, 70.6, 71.2, 73.4, 122.9, 127.5, 127.6, 127.8, 128.3, 129.7,
134.9, 136.1, 138.5, 172.1. Anal. Calcd for C34H46O4Si: C, 74.68; H,
8.48. Found: C, 74.77; H, 8.39.
25
centrated. The crude mixture was chromatographed over silica gel
For 6: [
a]
þ11.8 (c 2.25, CHCl3); IR (thin film, cmꢀ1) 2924, 1727,
D
25
to give aldehyde 19 (989 mg, 99%); [
a
]
D
ꢀ3.7 (c 1.87, CHCl3); IR
1110; 1H NMR (CDCl3, 400 MHz):
9H), 1.08–1.75 (m, 8H), 2.21–2.43 (m, 2H), 3.53 (s, 3H), 3.97–4.00
d
0.88 (t, J¼7.3 Hz, 3H), 1.04 (s,
(thin film, cmꢀ1) 2930,1734, 1111; 1H NMR (CDCl3, 400 MHz):
d
0.76
(t, J¼7.3 Hz, 3H), 1.03 (s, 9H), 1.05–1.87 (m, 10H), 3.90–3.96 (m, 2H),
(m, 1H), 5.76 (d, J¼15.1 Hz, 1H), 6.92 (d, J¼15.4 Hz, 1H), 7.28–7.77
4.51 (ABq, J¼11.4 Hz, Dn¼72.7 Hz, 2H), 7.23–7.3 (m, 10H), 7.65–7.72
(m, 10H); 13C NMR (CDCl3, 100 MHz):
d 14.2, 19.3, 22.6, 24.4, 26.6,
(m, 5H), 9.52 (s, 1H); 13C NMR (CDCl3, 100 MHz):
d
13.9, 19.3, 22.4,
27.1, 39.8, 41.0, 70.6, 71.2, 73.4, 101.4, 104.3, 122.9, 125.5, 125.6,
126.8, 128.1, 129.7, 133.9, 136.7, 138.2, 171.1. Anal. Calcd for
C27H38O3Si: C, 73.92; H, 8.73. Found: C, 73.86; H, 8.82.
24.4, 27.0, 31.6, 36.1, 36.4, 69.9, 72.2, 80.4, 127.5, 127.6, 127.7, 128.4,
129.6, 134.0, 134.8, 135.2, 137.3, 202.9. Anal. Calcd for C32H42O3Si: C,
76.45; H, 8.42. Found: C, 76.38; H, 8.49.
1.1.15. (4R,6R)-4-(Benzyloxy)-6-pentyltetrahydro-2H-pyran-2-one
22. To a solution of ester 5 (136 mg, 0.33 mmol) in THF (20.0 mL) at
ambient temperature in a plastic vial was added 70% HF/Py (5.0 mL)
dropwise and the yellow mixture was stirred for 24 h. The reaction
mixture was quenched by the addition of saturated NaHCO3 solu-
tion. The biphasic mixture was extracted with ethyl acetate. The
combined organic layers were dried over anhydrous Na2SO4. The
solvent was evaporated and the residue was purified by column
1.1.12. (2R,4R)-2-(Benzyloxy)-4-(tert-butyldiphenylsilyl-oxy)-
nonanoic acid (20). To a solution of aldehyde 19 (1 g, 2.02 mmol) in
t-BuOH (13.0 mL), NaClO2 (3.8 g, 20.2 mmol) and NaH2PO4$2H2O
(2.2 g, 14.14 mmol) in H2O (7.0 mL) was added. To this stirred so-
lution 2-methyl-2-butene (2.0 mL) was added and left for stirring
for 6 h. The reaction mixture was acidified with 1 N HCl and
extracted with diethyl ether. The combined organic layers were
washed with water, brine and dried over anhydrous Na2SO4. The
chromatography to give the lactonized product 22 (53 mg, 82%);
25
organic layer was concentrated under vacuo and chromatographed
[a
]
þ14.2 (c 0.8, CHCl3); IR (thin film, cmꢀ1) 3171, 3031, 2107,1698,
D
25
to give acid 20 (972 mg, 92.3%); [
a]
10.6 (c 7.3, CHCl3); IR (thin
1071; 1H NMR (CDCl3, 400 MHz):
(m, 10H), 2.69–2.75 (m, 2H), 3.63–3.74 (m, 1H), 3.98–4.00 (m, 1H),
4.52–4.63 (m, 2H), 7.26–7.37 (m, 5H). Anal. Calcd for C17H24O3: C,
73.88; H, 8.75. Found: C, 73.81; H, 8.81.
d
0.89 (t, J¼6.8 Hz, 3H), 1.25–2.17
D
film, cmꢀ1) 3371, 3031, 2107, 1637, 1071; 1H NMR (CDCl3, 400 MHz):
0.75 (t, J¼7.3 Hz, 3H), 1.03 (s, 9H), 1.05–2.04 (m, 10H), 3.90–3.93
(m, 2H), 4.50 (ABq, J¼11.2 Hz, Dn¼112.4 Hz, 2H), 7.23–7.43 (m, 11H),
7.63–7.70 (m, 4H); 13C NMR (CDCl3, 125 MHz):
14.0, 19.4, 22.5,
d
d
24.5, 27.1, 31.7, 35.8, 38.9, 68.6, 70.3, 72.5, 127.5, 127.6, 128.2, 128.5,
129.7, 134.3, 136.0, 136.9, 154.2. Anal. Calcd for C32H42O4Si: C, 74.09;
H, 8.16. Found: C, 74.17; H, 8.09.
1.1.16. (3R,5R)-Ethyl-3,5-dihydroxydecanoate 23. To a solution of
benzyl protected lactone 22 (53 mg, 0.19 mmol) in anhydrous
ethanol (3.0 mL), Pd/C (15 mg) was added and left for hydrogena-
tion at 40 psi pressure for 12 h. The reaction mixture was filtered
1.1.13. (3R,5R)-3-(Benzyloxy)-5-(tert-butyldiphenylsilyl-oxy)-1-di-
through Celite and concentrated to give the ester 23 (34.9 mg, 89%);
25
azodecan-2-one (7). To acid 20 (500 mg, 0.96 mmol) in THF (4.0 mL)
[a
]
þ9.4 (c 0.6, CHCl3); IR (thin film, cmꢀ1) 3171, 3031, 2107, 1698,
D
at 0 ꢁC triethylamine (400
mL, 2.88 mmol) and ethylchloroformate
1071; 1H NMR (CDCl3, 400 MHz):
d
0.89 (t, J¼6.6 Hz, 3H), 1.26–1.62
(183.4
mL, 1.92 mmol) were added one after the other. After 15 min,
(m,13H), 2.48 (m, 2H), 3.24 (s,1H, OH), 3.72–3.88 (m, 2H), 4.15–4.29
the reaction mixture was brought to room temperature for 30 min
and was filtered over Celite. To this filtrate a freshly prepared
solution of diazomethane in diethyl ether [prepared from N-nitro-
somethyl urea (800 mg) and KOH (1.6 g)] was added dropwise over
a period of 30 min. The mixture was stirred for 1.5 h, at room
temperature. The solvent was evaporated under reduced pressure,
(m, 2H), 4.34 (s, 1H, OH); 13C NMR (CDCl3, 100 MHz):
d
14.3, 22.7,
25.1, 31.9, 37.9, 41.7, 42.3, 60.9, 69.3, 72.4, 172.7. HRMS (ESI): exact
mass calcd for C12H24O4: [MþH]þ: 233.1683. Found: 233.1687. Anal.
Calcd for C12H24O4: C, 62.04; H, 10.41. Found: C, 62.11; H, 10.36.
1.1.17. (3R,5R)-3,5-Dihydroxydecanoic acid 24. To an ice cooled so-
lution of 23 (50 mg, 0.24 mmol) in methanol/water (3.0 mL, 4:1)
was added lithium hydroxide monohydrate (30 mg) at 0 ꢁC. The
mixture was brought to 25 ꢁC and was further stirred for 2 h. The pH
of the solution was adjusted to 7.0 by addition of aqueous NH4Cl, the
and the residue was purified by column chromatography to give 7
25
(353.7 mg, 68%); [
a
]
þ8.4 (c 3.4, CHCl3); IR (thin film, cmꢀ1) 3150,
D
2734, 1173; 1H NMR (CDCl3, 400 MHz):
(s, 9H),1.06–1.43 (m, 8H),1.81–1.83 (m, 2H), 3.90 (m, 2H), 4.40 (ABq,
d
0.78 (t, J¼7.3 Hz, 3H), 1.04
J¼11.4 Hz, Dn¼78.3 Hz, 2H), 5.52–5.31 (m, 1H), 7.15–7.68 (m, 15H);
solvent was evaporated and the residue so obtained was extracted
25
13C NMR (CDCl3, 100 MHz):
d
13.9, 19.3, 22.4, 24.1, 26.9, 31.7, 35.9,
with chloroform to give seco-acid 24 (40 mg, 94%); [
a
]
þ14.3 (c
D
39.8, 70.1, 72.1, 81.0, 88.5,127.3,127.4,127.5,127.7,128.3,129.4,134.3,
134.7, 135.9, 137.2. HRMS (ESI): exact mass calcd for C33H42N2O3Si:
[MþH]þ: 543.2973. Found: 543.2971. Anal. Calcd for C33H42N2O3Si:
C, 73.02; H, 7.80; N, 5.16. Found: C, 73.10; H, 7.73; N, 5.19.
0.23, CHCl3); IR (thin film, cmꢀ1) 3371, 3031, 2107, 1637, 1071; 1H
NMR (CDCl3, 400 MHz): 0.72–1.52 (m, 13H), 2.16–2.28 (m, 2H),
3.51–3.67 (m, 1H), 3.96–4.00 (m, 1H); 13C NMR (CDCl3, 100 MHz):
d
d
13.4, 21.9, 24.2, 31.1, 36.0, 42.9, 44.9, 69.7, 180.4. HRMS (ESI): exact
mass calcd for C10H20O4: [MꢀH]þ: 203.1283. Found: 203.1283. Anal.
1.1.14. (3R,5R)-Methyl-3-(benzyloxy)-5-(tert-butyl-diphenylsilyl-
Calcd for C10H20O4: C, 58.80; H, 9.87. Found: C, 58.89; H, 9.81.
oxy) decanoate 5 and (R,E)-methyl 5-(tert-butyl-diphenylsilyl-oxy)
dec-3-enoate 6. To
a
solution of
a
-diazoketone
7
(618 mg,
1.1.18. (R)-6-Pentyl-5,6-dihydro-2H-pyran-2-one 2. A solution of
the ester 5 (100 mg, 0.182 mmol) and CBr4 (24 mg, 0.073 mmol) in
anhydrous MeOH (2.5 mL) was refluxed for 12 h. After completion
of the reaction, the solvent was removed and the residue was pu-
rified by column chromatography to obtain the (R)-massoialactone
1.14 mmol) in anhydrous MeOH (10.0 mL) was added, dropwise,
a solution of silver benzoate (89 mg, 0.36 mmol) in triethylamine
(786
m
L, 5.7 mmol) under dry N2 at ꢀ10 ꢁC. The reaction mixture
was further stirred for 1.5 h. The solvent was evaporated and the
residue was purified by column chromatography to give homolo-
2 (19.2 mg, 52.2%); 1H NMR (CDCl3, 400 MHz):
d 0.89–0.91 (m, 3H),
gated ester 5 (401 mg, 64%) and unsaturated ester 6 (115 mg, 22%).
1.00–1.04 (m, 1H), 1.32–1.42 (m, 4H), 1.52–1.81 (m, 3H), 2.32–2.34
25
For 5: [
a
]
D
þ3.6 (c, 1.15 CHCl3); IR (thin film, cmꢀ1) 2930, 1738,
(m, 2H), 4.42–4.44 (m, 1H), 6.03 (dd, J¼1.4, 9.7 Hz, 1H), 6.87–6.90
1111; 1H NMR (CDCl3, 400 MHz):
d
0.78 (t, J¼7.3 Hz, 3H),1.02 (s, 9H),
(m, 1H); 13C NMR (CDCl3, 125 MHz):
d 14.1, 22.6, 24.6, 25.8, 29.5,

8682
A. Garg, V.K. Singh / Tetrahedron 65 (2009) 8677–8682
Gopalan, A.; Lucero, R.; Jacobs, H.; Berryman, K. Synth. Commun. 1991, 21,
1321.
3. (a) Jacobs, H. K.; Muller, B. H.; Gopalan, A. Tetrahedron 1992, 48, 8891; (b) Sibi,
M. P.; Gaboury, J. A. Tetrahedron Lett. 1992, 33, 5681; (c) Sugai, T.; Ohsawa, S.;
Yamada, H.; Ohta, H. Synthesis 1990, 1112; (d) Taylor, S. K.; Chmiel, N. K.;
Simons, L. J.; Vyvyan, J. R. J. Org. Chem. 1996, 61, 9084.
31.6, 34.9, 121.5, 145.2, 164.8. HRMS (ESI): exact mass calcd for
C10H16O2 [MþH]þ: 169.1229. Found: 169.1227. Anal. Calcd for
C10H16O2: C, 71.39; H, 9.59. Found: C, 71.48; H, 9.53.
1.1.19. (R)-6-Pentyltetrahydro-2H-pyran-2-one 3. A solution of the
ester 6 (130 mg, 0.283 mmol) and CBr4 (37.5 mg, 0.113 mmol) in
anhydrous MeOH (3.0 mL) was refluxed for 12 h. After completion
of the reaction, the solvent was removed and the residue was pu-
rified by column chromatography to obtain the 33 mg of alcohol.
Now to a solution of alcohol (29 mg, 0.145 mmol) in anhydrous
MeOH (3.0 mL), 10% Pd/C (15 mg) and few drops of HCl were added
and hydrogenated for 6 h at 1 atm pressure under H2 atmosphere.
The solvent was filtered over Celite and filtrate was evaporated. The
crude product so obtained after purification by column chroma-
4. (a) Raina, S.; Singh, V. K. Tetrahedron 1996, 52, 4479; (b) Chandrasekhar, M.;
Raina, S.; Singh, V. K. Tetrahedron Lett. 2000, 41, 4969; (c) Chandrasekhar, M.;
Chandra, K. L.; Singh, V. K. J. Org. Chem. 2003, 68, 4039; (d) Raina, S.; Prasad, B.
A. B.; Singh, V. K. Arkivoc 2003, vi, 16; (e) Singh, R. P.; Singh, V. K. J. Org. Chem.
2004, 69, 3425; (f) Baktharaman, S.; Selvakumar, S.; Singh, V. K. Tetrahedron
Lett. 2005, 46, 7527; (g) Chandra, K. L.; Chandrasekhar, M.; Singh, V. K. J. Org.
Chem. 2002, 67, 4630; (h) Garg, A.; Singh, R. P.; Singh, V. K. Tetrahedron 2006,
62, 11240.
5. Magiatis, P.; Spanakis, D.; Mitaku, S.; Tsitsa, E.; Mentis, A.; Harvala, C. J. Nat.
Prod. 2001, 64, 1093.
6. Doshida, J.; Hasegawa, H.; Onuki, H.; Shimidzu, N. J. Antibiot. 1996, 49, 1105.
7. (a) Gogoi, S.; Barua, N. C.; Kalita, B. Tetrahedron Lett. 2004, 45, 5577; (b) Sharma,
G. V. M.; Reddy, Ch. G. Tetrahedron Lett. 2004, 45, 7483; (c) Florent, A.; Marie-
Cecile, L.; Janine, C. Synlett 2007, 451; (d) Gurjar, M. K.; Shivakumar, I.; Salunke,
G. B. Tetrahedron Lett. 2009, 50, 2048.
8. Cavill, G. W. K.; Clark, D. V.; Whitfield, F. B. Aust. J. Chem. 1968, 21, 2819.
9. Abe, S. J. Chem. Soc. Jpn. 1937, 58, 246.
10. Kaiser, R.; Lamparsky, D. Tetrahedron Lett. 1976, 17, 1659.
11. Hashizumi, T.; Kikuchi, N.; Sasaki, Y.; Sakata, I. Agric. Biol. Chem. 1968, 32,
1306.
tography gave (R)-decalactone
400 MHz):
0.89 (t, J¼0.56 Hz, 3H), 1.25–1.31 (m, 12H), 2.46–2.56
(m, 2H), 4.14–4.29 (m, 1H); 13C NMR (CDCl3, 125 MHz):
14.1, 18.6,
3
(21 mg); 1H NMR (CDCl3,
d
d
22.6, 24.7, 27.9, 29.6, 31.7, 35.9, 80.7, 172.1. HRMS (ESI): exact mass
calcd for C10H18O2 [MþH]þ: 171.1386. Found: 171.1388. Anal. Calcd
for C10H18O2: C, 70.55; H, 10.66. Found: C, 70.61; H, 10.59.
12. Bernreuther, A.; Ladder, V.; Huffer, M.; Scherier, P. Flavour Fragrance J. 1990,
5, 71.
13. Meijer, T. M. Recl. Trav. Chim. Pays-Bas 1940, 59, 191.
Acknowledgements
14. Valim, M. F.; Rouseff, R. L.; Lin, J. J. Agric. Food Chem. 2003, 51, 1010.
15. (a) For reviews, see: Endo, A. J. Med. Chem. 1985, 28, 401; (b) Vega, L.; Grundy, S.
J. Am. Med. Assoc. 1987, 257, 33.
V.K.S. thanks the Department of Science and Technology, India
for a grant through J.C. Bose fellowship. A.G. thanks the Council of
Scientific and Industrial Research, New Delhi for a senior research
fellowship.
16. Crombie, L. J. Chem. Soc. 1955, 1007–1025, 2535.
17. (a) Nobuhara, A. J. Agric. Biol. Chem. 1968, 32, 1016; (b) Abe, S.; Sato, K. Bull.
Chem. Soc. Jpn. 1956, 29, 88; (c) Sabitha, G.; Bhaskar, V.; Yadav, J. S. Tetrahedron
Lett. 2006, 47, 8179.
18. (a) Lemieux, R. U.; Howard, J. Can. J. Chem. 1963, 41, 308; (b) Stevens, J. D. In
Methods Carbohydr. Chem.; Whistler, R. L., BeMiller, J. N., Eds.; Academic Press:
New York, NY, 1972; Vol. VI, p 123; (c) Tronchet, J. M. J.; Grivet, C.; Grand, E.;
Seman, M.; Dilda, P. Carbohydr. Lett. 2000, 4, 5.
References and notes
19. Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans. 1 1975, 1574.
20. Patil, N. T.; Tilekar, J. N.; Dhavale, D. D. J. Org. Chem. 2001, 66, 1065.
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