Stereoselective total synthesis of microcarpalide

Article abstract of DOI:10.1016/j.tetasy.2006.03.024

A stereoselective total synthesis of microcarpalide using ring-closing metathesis (RCM) as a key step is reported. l-Ascorbic acid was used as a chiral pool material for the construction of the olefinic alcohol and an asymmetric aldol reaction provided the chiral precursor for the synthesis of olefinic acid.

Full text of DOI:10.1016/j.tetasy.2006.03.024

Tetrahedron: Asymmetry 17 (2006) 1081–1088
Stereoselective total synthesis of microcarpalideq
G. V. M. Sharma and Govardhan R. Cherukupalli*
D-211, Discovery Laboratory, Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500 00, India
Received 6 March 2006; accepted 27 March 2006
Available online 6 May 2006
Abstract—A stereoselective total synthesis of microcarpalide using ring-closing metathesis (RCM) as a key step is reported. L-Ascorbic
acid was used as a chiral pool material for the construction of the olefinic alcohol and an asymmetric aldol reaction provided the chiral
precursor for the synthesis of olefinic acid.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
alkene group suitable for RCM macrocyclization. Frag-
ment 3 could be prepared from L-ascorbic acid, whereas
fragment 4 was prepared from 1,4-butanediol using Evan’s
aldol reaction as the key step.
Medium ring compounds1 are important in organic chem-
istry, as they are contained in an ever growing number of
natural products. Microcarpalide 1, a 10-membered lac-
tone was isolated and characterized by Hemscheidt et al.2
from the bark of the tropical tree Ficus microcarpa L.
Microcarpalide was found to disrupt actin microfilaments.
Moreover, it displayed a weak cytotoxicity to mammalian
cells. Owing to its biological activity, a few total syntheses
have appeared.3 In continuation of our interest on the syn-
thesis of natural lactones,4 we herein, report the stereo-
selective synthesis of microcarpalide 1 (Fig. 1).
2. Results and discussions
Accordingly, 3,4-O-isopropylidene-L-threitol5 7 derived
from L-ascorbic acid was treated with p-TsCl and Et3N
in CH2Cl2 at room temperature (Scheme 2) to furnish
monotosylate 8 as the major product, which on treatment
with K2CO3 in MeOH gave epoxide 5. The regioselective
opening of the epoxide with n-pentylmagnesium bromide
in the presence of cuprous iodide in dry THF provided
compound 9. The secondary alcohol in 9 was protected
using BnBr and NaH in THF to furnish 10, which on ace-
tonide hydrolysis with 60% aq AcOH afforded diol 11.
Tosylation of 11 with p-TsCl and Et3N in CH2Cl2 gave
12 as the major product, which on treatment with K2CO3
in MeOH gave epoxide 13. The regioselective opening of
this epoxide ring with vinylmagnesium bromide, in the
presence of cuprous iodide in dry THF, gave the desired
alcohol 3 with S,S-absolute configuration, thus releasing
the free hydroxy required for the coupling reaction with
fragment 4.
OH
OH
O
O
OH
1
Figure 1.
The synthetic strategy for microcarpalide 1 (Scheme 1) was
designed to explore two pivotal tactical issues. First, we
envisioned a convergent disconnection of the microcarpa-
lide by exploiting esterification and ring-closing metathesis.
Second, we designed each of the fragments 3 and 4 to con-
tain two stereogenic carbon atoms and bear a terminal
The acidic segment 4 was prepared from commercially
available 1,4-butanediol. Accordingly, treatment of 1,4-
butanediol with BnBr in the presence of NaH gave 14
(Scheme 2), which on oxidation under Swern conditions
furnished aldehyde 15. To introduce the two adjacent ste-
reocenters with the required absolute (R)-configuration in
a threo fashion, aldehyde 15 was subjected to the Evans
q IICT Communication No. 060216.
Corresponding author. E-mail: govardhanreddy@ucla.edu
*
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.03.024

1082
G. V. M. Sharma, G. R. Cherukupalli / Tetrahedron: Asymmetry 17 (2006) 1081–1088
OH
O
OH
O
O
O
+
O
O
2
OH
OBn
1
O
O
OH
HOOC
OBn
4
3
O
O
OH
O
OBN
O
N
O
OPMB
O
6
Bn
5
L-Ascorbic acid
1,4 Butane diol
Scheme 1.
O
a
O
c, d
O
b
OTs
5
a) L-Ascorbic acid
O
OH
OH
OH
RO
8 (62%)
7
HO
O
f
O
b
e, a
n-C6H13
3 (57%)
n-C6H13
OBn
n-C6H13
O
OBn
13 (71%)
OR
11 R = H (84%)
12 R = Ts (68%)
9 R = H (83%)
10 R = Bn (78%)
O
O
OPMB
O
N
d, g
b) 1,4-butane diol
BnO
R
Bn
6 (66%)
h
14 R = CH2OH (70%)
15 R = CHO (92%)
OH
OH
j, k
i
l
OHC
OBn
OBn
OPMB
16 (73%)
OR
17 R = PMB (60%)
18 R = H (91%)
O
O
n
O
O
m, g
4 (90%)
OBn
R
20 R = CH2OH (89%)
21 R = CHO (94%)
19 (84%)
Scheme 2. Reagents and conditions: (a) p-TsCl, Et3N, CH2Cl2, rt, 12 h; (b) K2CO3, MeOH, rt, 1 h; (c) n-C5H11MgBr, CuI, THF, ꢀ30 ꢁC, 1 h; (d) BnBr,
NaH, rt, 3 h; (e) 60% aq AcOH, rt, 12 h; (f) vinylmagnesium bromide, CuI, THF, ꢀ30 ꢁC, 1 h; (g) (COCl)2, DMSO, Et3N, ꢀ78 ꢁC, 3 h; (h) Bu2BOTf,
N-ethyldiisopropyl amine, CH2Cl2, 0 ꢁC ꢀ78 ꢁC, 5 h; (i) DIBAL-H, CH2Cl2, ꢀ78 ꢁC, 2 h; (j) Ph3PCH3I, n-BuLi, 0 ꢁC, 3 h; (k) ZrCl4, CH3CN, 1 h; (l) 2,2-
DMP, PTSA (cat.), DMSO, rt, 5 h; (m) DDQ, CH2Cl2/H2O (19:1), reflux, 3 h; (n) NaClO2, 30% H2O2, t-BuOH, rt, 6 h.
aldol reaction.6 The oxazolidinone auxiliary was treated
with dibutylboron triflate in the presence of N-ethyldiiso-
propyl amine at ꢀ78 to 0 ꢁC in CH2Cl2, followed by alde-
hyde 15, to furnish aldol product 6, which on reduction

G. V. M. Sharma, G. R. Cherukupalli / Tetrahedron: Asymmetry 17 (2006) 1081–1088
1083
with DIBAL-H in dry CH2Cl2 at ꢀ78 ꢁC gave aldehyde 16.
Aldehyde 16 was immediately homologated with (methyl-
ene)triphenyl phosphorane in THF at ꢀ20 ꢁC to provide
17. Deprotection of the PMB group in 17 using 20 mol %
of ZrCl4 in acetonitrile gave diol 18, which was treated with
2,2-dimethoxypropane (DMP) and p-toluenesulfonic acid
(PTSA) (cat.) in dry DMSO at room temperature for 5 h
to furnish 19. Oxidative deprotection of the benzyl group
in 19 using DDQ in aq CH2Cl2 (1:19) at reflux furnished
alcohol 20, which upon oxidation under Swern conditions
gave aldehyde 21. Further, oxidation of 21 using NaClO2
and 30% H2O2 in t-BuOH/H2O (2:1) gave acid 4.
ing metathesis (RCM) of a suitable diene ester, which
was assembled by coupling the two advanced fragments 3
and 4. Fragment 3 has been synthesized by a chiral pool
approach from L-ascorbic acid, while fragment 4 from
1,4-butanediol. The required C7 backbone of 4 has been
constructed from the C4-starting synthon using Evans aldol
reaction as a key step, which allowed the introduction of
the two asymmetric centers with the final absolute (R)-con-
figuration. Completion of the total synthesis used a Yama-
guchi-mediated coupling between partners 3 and 4,
followed by RCM using Grubbs’ catalyst I, providing the
desired 10-membered macrocyclic framework with good
stereoselectivity (67:33 E–Z) and in excellent yield. Finally,
cleavage of the protecting groups afforded a single product
whose spectroscopic properties were identical to those of
the natural compound 1.
The union of the two advanced fragments 3 and 4 was suc-
cessfully carried out using Yamaguchi’s7 protocol (2,4,6-
trichlorobenzoyl chloride, Et3N, THF, DMAP, toluene)
to give the coupling product 2 in 73% yield. A highly di-
luted solution of diene 2 in anhydrous CH2Cl2 was heated
at reflux for 48 h in the presence of Grubbs’ catalyst I8 and
resulted in an efficient closure to afford the 10-membered
lactone 22 as a mixture of two geometric isomers in a
67:33 E:Z-ratio. The desired trans-oxecin (E)-22 was sepa-
rated by column chromatography from the cis-analogue
(Z)-22. Treatment of (E)-22 with titanium tetrachloride in
CH2Cl2 at 0 ꢁC resulted in the simultaneous removal of
all protecting groups, affording a single product 1, whose
spectral data matched perfectly with that reported for the
natural compound 12 (Scheme 3).
4. Experimental
4.1. General
All moisture sensitive reactions were performed under a
nitrogen atmosphere using flame-dried glasswares. Solvents
were dried over standard drying agents and freshly distilled
prior to use. NMR spectra were recorded on Varian Gem-
ini FT-200 MHz, Unity-400 MHz (21 ꢁC) and Inova-
500 MHz (30 ꢁC) spectrometers, with 7–10 mM solutions
in appropriate solvents using TMS as the internal standard.
13C NMR spectra were recorded with complete proton
decoupling. Optical rotations were measured with a JAS-
CO DIP-370 instrument, and [a]D-values are in units of
10ꢀ1 deg cm2 gꢀ1. IR spectra were taken with a Perkin–
Elmer 1310 spectrometer. Mass spectra were recorded on
CEC-21-11013 or Finnigan Mat 1210 double focusing mass
spectrometers operating at a direct inlet system, and FAB
MS were measured using VG AUTOSPEC mass spectro-
meters at 5 or 7 K resolution, using perfluorokerosene as
an internal reference. Nomenclature mentioned in Section
3 was adopted from ACD/Name Version 1.0b, Advanced
Chemistry Development Inc., Toronto, Canada. Organic
solutions were dried over anhydrous Na2SO4 and concen-
trated below 40 ꢁC in vacuo.
+
3
4
a
O
O
n-C6H13
O
O
OBn
2 (73%)
b
O
O
O
O
O
+
4.1.1. (2S,3S)-2-Hydroxy-3,4-isopropylidenedioxy-1-(p-tolu-
enesulfonyloxy)-butane (8). To a cooled (0 ꢁC) solution of
diol 7 (15.00 g, 92.60 mmol) and Et3N (38.60 mL, 2.77 mol)
in CH2Cl2 (150 mL), p-TsCl (19.40 g, 101.8 mmol) was
added portionwise and stirred at room temperature for
8 h. The solvent was evaporated and the obtained residue
was purified by column chromatography (Silica gel 60–120
mesh, EtOAc/hexane, 1:4) to afford (2S,3S)-2-hydroxy-
3,4-isopropylidenedioxy-1-(p-toluenesulfonyloxy)-butane 8
(18.10 g) in 62% yield as a yellow syrup. [a]D = ꢀ8.6 (c
1.5, CHCl31); IR (neat): 580, 820, 1090, 1170, 2950,
3420 cmꢀ1; H NMR (200 MHz, CDCl3): d 1.29, 1.35 (2s,
6H, –CH3), 2.44 (s, 3H, Ar–CH3), 3.66–3.86 (m, 2H, H-
4a0), 3.92–4.17 (m, 4H, H-1, 2, 3), 7.32, 7.78 (2d, 4H,
J = 7.80 Hz, Ar–H).
O
n-C6H13
O
O
OBn
n-C6H13
OBn
E-22 (52%)
Z-22 (26%)
c
1 (59%)
Scheme 3. Reagents and conditions: (a) 2,4,6-trichlorobenzoyl chloride,
Et3N, THF, DMAP, toluene, rt, 24 h; (b) Grubb’s catalyst I, CH2Cl2,
reflux, 48 h; (c) TiCl4, CH2Cl2, 0 ꢁC, 1 h.
3. Conclusion
A new stereoselective total synthesis of microcarpalide 1
has been accomplished. The formation of the required
10-membered lactone was achieved by means of ring-clos-
4.1.2.
(2S,3S)-1,2-Epoxy-3,4-isopropylidenedioxy-butane
5. A solution of compound 8 (18.00 g, 56.96 mmol) in

1084
G. V. M. Sharma, G. R. Cherukupalli / Tetrahedron: Asymmetry 17 (2006) 1081–1088
MeOH (100 mL) was treated with K2CO3 (19.60 g,
142.40 mmol) and stirred for 1 h at room temperature.
The reaction mixture was further treated with aqueous
NH4Cl solution (20 mL). MeOH was evaporated at 25 ꢁC
under reduced pressure, and the residue was extracted with
solvent ether (3 · 100 mL). The organic layer was washed
with water (1 · 75 mL), brine (1 · 75 mL), dried over
Na2SO4, and evaporated. The obtained residue was puri-
fied by column chromatography (Silica gel 60–120 mesh,
EtOAc/hexane, 1:4) to afford 5 (5.98 g) in 73% yield as a
(M+ꢀ1, 9), 199 (4), 157 (2), 101 (12), 91 (100). Analysis
calcd for C19H30O3 (306): C, 74.47; H, 9.87. Found: C,
74.45; H, 9.85.
4.1.5. 3-Benzyloxy-(2S,3S)-nonane-1,2-diol 11. A mixture
of compound 10 (2.2 g, 8.27 mmol) in 60% aq AcOH
(20 mL) was stirred at room temperature for 12 h. The
reaction mixture was neutralized with solid NaHCO3
(pH 7) and extracted with EtOAc (3 · 30 mL). The com-
bined organic layers were evaporated, and the obtained
residue was purified by filtration through a small pad of
silica gel with a 1:1 EtOAc/hexane solvent system to afford
diol 11 (1.6 g) in 84% yield as a pale yellow syrup.
[a]D = +42.5 (c 0.6, CHCl3); IR (neat): 856, 1070, 1450,
colorless liquid. IR (neat): 1180, 1750, 2830, 2900 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 1.35, 1.40 (2s, 6H,
–CH3), 2.62 (dd, 1H, J = 2.30, 6.60 Hz, H-1), 2.74 (t, 1H,
J = 5.20 Hz, H-10), 2.92–3.00 (m, 1H, H-2), 3.79 (dd, 1H,
J = 0.47, 7.10 Hz, H-4), 3.91–4.11 (m, 2H, H-40, 3).
1
1610, 2855, 2931, 3060, 3462 cmꢀ1. H NMR (400 MHz,
CDCl3): d 0.91 (t, 3H, J = 4.76 Hz, –CH2CH3), 1.26–1.38
(m, 10H), 3.39 (m, 1H, H-3), 3.62 (dd, 1H, J = 7.10,
6.70 Hz, H-10), 3.82–3.89 (m, 2H, H-1, 2), 4.72 (s, 2H),
7.22–7.38 (m, 5H, Ar–H); FAB MS (m/z, %): 267
(M++1, 16), 181 (4), 159 (8), 107 (12), 91 (100).
4.1.3. 1-[2,2-Dimethyl-(4S)-1,3-dioxolan-4-yl]-(1S)-heptan-
1-ol 9. A suspension of magnesium (1 g, 41.66 mmol) in
THF (10 mL) was treated with n-pentyl bromide (6.29 g,
41.66 mmol) in THF (10 mL) over 1 h. The resulting mix-
ture was stirred for 30 min and copper(I) iodide (0.52 g,
2.77 mmol) was added and the mixture cooled to ꢀ30 ꢁC.
A solution of 5 (2 g, 13.88 mmol) in dry THF (10 mL)
was then added dropwise. After the addition was complete,
the mixture was stirred for 3 h and then quenched by pour-
ing it into cold saturated aqueous NH4Cl solution (30 mL).
The solution was extracted with ether (30 mL) and the
organic layers combined, dried over Na2SO4, and concen-
trated under reduced pressure. The crude product was
purified by column chromatography (Silica gel 60–120
mesh, EtOAc/hexane, 1:4) to afford 9 (2.5 g) in 83% yield
as a colorless liquid. [a]D = +3.3 (c 0.6, CHCl3); IR (neat):
4.1.6. 3-Benzyloxy-2-(4-methylphenylsulfonyloxy)-(2S,3S)-
nonyl4-methyl-1-benzenesulfonate 12. To a cooled (0 ꢁC)
solution of diol 11 (1.4 g, 5.26 mmol) and Et3N (1.47 mL,
10.52 mol) in CH2Cl2 (20 mL), p-TsCl (1.1 g, 5.78 mmol)
was added portionwise and stirred at room temperature
for 8 h. The solvent was evaporated, and the obtained residue
was purified by column chromatography (Silica gel 60–120
mesh, EtOAc/hexane, 1:9) to give benzyloxy-2-hydroxy-
(2S,3S)-nonyl4-methyl-1-benzenesulfonate 12 (1.5 g) in 68%
yield as a yellow syrup. [a]D = ꢀ4.7 (c 0.75, CHCl3); IR
(neat): 580, 820, 1090, 1120, 1610, 2855, 2950, 3060,
1
1
1070, 1455, 1603, 2858, 2931, 3060, 3445 cmꢀ1. H NMR
3420 cmꢀ1. H NMR (400 MHz, CDCl3): d 0.91 (t, 3H,
(200 MHz, CDCl3): d 0.91 (t, 3H, J = 4.76 Hz, –CH2CH3),
1.26–1.32 (m, 8H), 1.34 (s, 3H, CH3), 1.39 (s, 3H, CH3),
1.42–1.46 (m, 2H), 2.05 (br s, 1H, –OH), 3.45–3.49 (m,
1H, H-3), 3.71 (dd, 1H, J = 7.20, 6.70 Hz, H-10), 3.91–
4.02 (m, 2H, H-1, 2); FAB MS (m/z, %): 217 (M++1,
32), 181 (94), 151 (26), 127 (100), 91 (44).
J = 4.76 Hz, –CH2CH3), 1.26–1.42 (m, 10H), 2.44 (s, 3H,
Ar–CH3), 3.39 (m, 1H, H-3), 3.62 (dd, 1H, J = 7.22,
6.72 Hz, H-10), 3.94–3.96 (dd, 1H, J = 7.20, 6.70 Hz, H-1),
4.18 (dd, 1H, J = 6.71, 8.30 Hz, H-2), 4.61 (d, 1H,
J = 11.7 Hz, –OCH2Ph), 4.76 (d, 1H, J = 11.7 Hz,
–OCH2Ph), 7.22–7.42 (m, 7H, Ar–H), 7.78 (d, 2H,
J = 7.80 Hz, Ar–H); FAB MS (m/z, %): 421 (M++1, 3),
391 (9), 154 (22), 91 (100).
4.1.4.
4-[1-Benzyloxy-(1S)-heptyl]-2,2-dimethyl-(4S)-1,3-
dioxolane 10. To a cooled (0 ꢁC) suspension of NaH
(0.511 g, 21.29 mmol, 60% w/w dispersion in paraffin oil)
in THF (10 mL), a solution of 9 (1.82 g, 10.64 mmol) in
THF (10 mL) was added dropwise. After 15 min, BnBr
(1.20 g, 10.64 mmol) was added dropwise at 0 ꢁC and stir-
red for 4 h at room temperature. Saturated aqueous NH4Cl
solution (10 mL) was added dropwise at 0 ꢁC and extracted
with ether (50 mL). The organic layer was separated and
washed with water (25 mL), brine (25 mL), dried over
Na2SO4, and evaporated. The obtained residue was puri-
fied by column chromatography (Silica gel 60–120 mesh,
EtOAc/hexane, 1:5) to give 10 (2.5 g) in 78% yield as a light
yellow liquid. [a]D = ꢀ 18.8 (c 1.3, CHCl3); IR (neat): 856,
4.1.7. 1-Benzyloxy-1-[(2S)-oxiran-2-yl]-(1S)-heptane 13.
A
solution of compound 12 (1.2 g, 2.85 mmol) in MeOH
(10 mL) was treated with K2CO3 (0.78 g, 5.71 mmol) and
stirred for 1 h at room temperature. The reaction mixture
was worked up as described for 5 and purified by column
chromatography (Silica gel 60–120 mesh, EtOAc/hexane,
1:9) to afford 13 (0.5 g) in 71% yield as a colorless liquid.
[a]D = ꢀ13.43 (c 0.8, CHCl3); IR (neat): 820, 1090, 1180,
1170, 1750, 2830, 2900 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d 0.91 (t, 3H, J = 4.76 Hz, –CH2CH3), 1.26–1.44 (m, 10H),
2.38–2.42 (m, 1H, H-2), 2.70–2.74 (m, 1H, H-1), 2.81–2.84
(m, 1H, H-10), 2.96 (m, 1H, H-3), 4.59 (d, 1H, J = 11.7 Hz,
–OCH2Ph), 4.76 (d, 1H, J = 11.7 Hz, –OCH2Ph), 7.22–
7.36 (m, 5H, Ar–H); FAB MS (m/z, %): 249 (M++1, 32),
181 (9), 154 (26), 127 (10), 91 (100).
1
1070, 1455, 1700, 2860, 2931, 3060, 3400 cmꢀ1. H NMR
(400 MHz, CDCl3): d 0.91 (t, 3H, J = 4.76 Hz, –CH2CH3),
1.26–1.32 (m, 10H), 1.38 (s, 3H, CH3), 1.42 (s, 3H, CH3),
3.39 (m, 1H, H-3), 3.62 (dd, 1H, J = 7.20, 6.70 Hz, H-10),
3.96 (dd, 1H, J = 7.20, 6.70 Hz, H-1), 4.18 (dd, 1H,
J = 6.71, 4.32 Hz, H-2), 4.61 (d, 1H, J = 11.7 Hz,
–OCH2Ph), 4.76 (d, 1H, J = 11.7 Hz, –OCH2Ph), 7.22–
7.38 (m, 5H, Ar–H); FAB MS (m/z, %): 306 (M+, 6), 305
4.1.8. 1-[1-Benzyloxy-(1S)-heptyl]-(1S)-3-butenyl alcohol
3. A suspension of magnesium (0.11 g, 4.83 mmol) in
THF (5 mL) was treated with vinyl bromide (0.51 g,
4.83 mmol) in THF (5 mL), which was added dropwise.

G. V. M. Sharma, G. R. Cherukupalli / Tetrahedron: Asymmetry 17 (2006) 1081–1088
1085
The resulting mixture was stirred for 30 min, and copper(I)
iodide (0.06 g, 0.32 mmol) was then added and the mixture
cooled to ꢀ30 ꢁC. A solution of 13 (0.4 g, 1.61 mmol) in
dry THF (5 mL) was then added dropwise. After 3 h, the
reaction mixture was worked up as described for 9 and puri-
fied by column chromatography (Silica gel 60–120 mesh,
EtOAc/hexane, 1:4) to give 3 (0.25 g) in 57% yield as a color-
less liquid. [a]D = +17.8 (c 1.5, CHCl3); IR (neat): 820, 1090,
1180, 1170, 1750, 2830, 2900 cmꢀ1; 1H NMR (300 MHz): d
0.90 (t, 3H, J = 6.7, H-11), 1.22–1.81 (m, 10H, H-6 to H-
10), 2.15–2.45 (m, 3H, OH and H-3), 3.34 (q, 1H, J = 5.5,
H-5), 3.56–3.72 (m, 1H, H-4), 4.52 (d, 1H, J = 11.3,
–OCH2Ph), 4.67 (d, 1H, J = 11.3, –OCH2Ph), 5.04–5.16
(dd, 2H, J = 17.6, 7.0 Hz, H-1, 10), 5.87–5.92 (m, 1H, H-2),
7.24–7.40 (m, 5H, Ar–H). 13C NMR (300 MHz, CDCl3): d
13.9, 22.5, 25.2, 29.5, 30.2, 32.7, 38.1, 72.1, 72.4, 81.5,
117.1, 127.7, 127.8, 128.4, 135.0, 138.5; FAB MS (m/z, %):
277 (M++1, 12), 181 (6), 154 (8), 127 (10), 107 (9), 91
(100). Analysis calcd for C18H28O2 (276): C, 78.21; H,
10.71. Found: C, 78.19; H, 10.69.
propyl amine (2.95 mL, 16.90 mmol) and dibutylboron tri-
flate (15.49 mL, 15.49 mmol, 1 M solution in toluene) were
added and stirred for 1 h at ꢀ78 ꢁC, then at 0 ꢁC for 45 min
and recooled to ꢀ78 ꢁC. A solution of aldehyde 15 (3.25 g,
18.30 mmol) in CH2Cl2 (10 mL) was added in one portion
and stirred at ꢀ78 ꢁC for 1 h, followed by 1 h at ꢀ45 ꢁC.
The reaction mixture was treated with MeOH (30 mL)
and 0.5 M pH 7 phosphate buffer (10 mL). After 1 h, 30%
aqueous H2O2 (5 mL) was added and stirred for 30 min
at 0 ꢁC, then at room temperature for 1 h. The reaction
mixture was diluted with CH2Cl2 (20 mL), washed with
water (20 mL), brine (10 mL), dried over Na2SO4, concen-
trated under reduced pressure, and the residue was purified
by column chromatography (Silica gel, 60–120 mesh,
EtOAc/hexane, 1:2) to give 6 (5 g) in 66% yield as a gummy
syrup. [a]D = +27.3 (c 0.75, CHCl3); IR (neat): 1172, 1245,
1513, 2859, 2931, 3064, 3446 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d 1.37–1.39 (m, 1H), 1.68–1.72 (m, 3H), 2.82
(dd, 1H, J = 4.7, 6.2 Hz), 3.34 (dd, 1H, J = 4.7, 6.3 Hz),
3.45 (t, 2H, J = 6.1 Hz), 3.63 (d, 2H, J = 5.7 Hz), 3.81 (s,
3H), 4.18–4.24 (m, 2H) 4.46 (s, 2H), 4.61–4.65 (m, 3H),
6.86 (d, 2H, J = 8.2 Hz, Ar–H), 7.18 ꢀ7.42 (m, 12H, Ar–
H); 13C NMR (300 MHz, CDCl3): d 25.9, 30.8, 35.0,
37.7, 41.5, 53.7, 55.2, 55.6, 66.9, 69.6, 70.0, 72.3, 72.7,
72.8, 79.1, 113.9, 127.2, 127.4, 127.5, 128.3, 128.9, 129.2,
129.3, 129.7, 130.1, 135.1, 135.9, 138.5, 153.3, 159.6,
170.8; FAB MS (m/z, %): 534 (M++1, 6), 391 (45), 307
(18), 154 (92), 121 (100). Analysis calcd for C31H35NO7
(533): C, 69.78; H, 6.61. Found: C, 69.74; H, 6.58.
4.1.9. 4-Benzyloxy-butane-1-ol 14. To a stirred solution of
1,4-butanediol (5 g, 55.55 mmol) in dry THF (30 mL),
NaH (2.66 g, 111.11 mmol, 60% suspension) was added
in portions with constant stirring at 0 ꢁC. After 10 min,
BnBr (9.5 g, 55.55 mmol) was added through a syringe
and stirred at room temperature for 3 h. The excess of
NaH was quenched by slow and careful addition of MeOH
(5 mL), diluted with water (10 mL), and extracted into
ether (2 · 20 mL). The combined ether extracts were
washed with brine solution (10 mL), dried over Na2SO4,
and concentrated under reduced pressure, and the residue
was purified by column chromatography (Silica gel, 60–
120 mesh, EtOAc/hexane; 1:4) to afford 14 (7 g) in 70%
yield as a colorless syrup. IR (neat): 1024, 1240, 1455,
4.1.12.
6-Benzyloxy-3-hydroxy-2-(4-methoxybenzyloxy)-
(2S,3R)-hexanal 16. To a stirred solution of 6 (4.5 g,
8.44 mmol) in dry CH2Cl2 (40 mL), DIBAL-H (4.22 mL,
8.44 mmol, 2 M solution in toluene) was added at ꢀ78 ꢁC
and stirred at the same temperature for 1 h. Methanol
(15 mL) was added tothe reaction mixture at 0 ꢁC and stirred
for an additional 10 min. Saturated aq solution of sodium
potassium tartarate (15 mL) was added and stirred for
10 min. Methanol was evaporated, the residue diluted with
water (10 mL), and extracted with CH2Cl2 (2 · 50 mL).
The combined organic layers were washed with brine
(10 mL), dried (Na2SO4), concentrated, and the residue puri-
fied by column chromatography (Silica gel, 60–120 mesh,
EtOAc/hexane, 1:4) to afford 16 (2.2 g) in 73% yield as a
gummy syrup. IR (neat): 1510, 1586, 1705, 2062, 2906,
1612, 2939, 3440 cmꢀ1 1H NMR (200 MHz, CDCl3): d
.
1.26–1.34 (m, 4H), 3.68 (t, 2H, J = 6.4 Hz), 3.74 (t, 2H,
J = 6.2 Hz), 4.56 (s, 2H), 7.16–7.28 (m, 5H, Ar–H); EIMS
(m/z): 181 (M++1, 18), 131 (44), 117 (28), 69 (32).
4.1.10. 4-Benzyloxybutanal 15. To a stirred solution of
oxalyl chloride (5 mL, 41.66 mmol) in dry CH2Cl2
(10 mL), DMSO (5.91 mL, 83.33 mmol) was added at
ꢀ78 ꢁC and stirred at the same temperature for 30 min. A
solution of 14 (5 g, 27.77 mmol) in dry CH2Cl2 (20 mL)
was added at ꢀ78 ꢁC to the reaction mixture and stirred
for 2.5 h at the same temperature. Et3N (23.28 mL,
166.66 mmol) was added at 0 ꢁC and stirred for an addi-
tional 30 min. The reaction mixture was diluted with water
(30 mL) and extracted with dichloromethane (2 · 50 mL).
The combined organic layers were washed with brine
(20 mL), dried (Na2SO4), and concentrated to give 15
(4.5 g) in 92% yield as a pale yellow syrup. IR (neat): 1024,
1
3390 cmꢀ1; H NMR (300 MHz, CDCl3): d 1.38–1.68 (m,
4H), 3.38–3.54 (m, 4H), 3.78 (s, 3H), 4.27 (d, 1H,
J = 11.3 Hz, –OCH2Ph), 4.42 (s, 2H, –OCH2Ph), 4.54 (d,
1H, J = 11.3 Hz, –OCH2Ph), 6.84 (d, 2H, J = 8.2 Hz, Ar–
H), 7.19 ꢀ7.37 (m, 7H, Ar–H), 9.7 (s, 1H, –CHO).
4.1.13.
1-(3-Benzyloxypropyl)-2-(4-methoxybenzyloxy)-
(1R,2R)-3-butenyl alcohol 17. To a solution of (methyl)tri-
phenylphosphonium iodide (4.51 g, 11.17 mmol) in dry
THF (50 mL), n-BuLi (6.98 mL, 11.17 mmol, 1.6 M solution
in n-hexane) was added at ꢀ20 ꢁC and stirred for 30 min. A
solution of 16 (2 g, 5.58 mmol) in THF (10 mL) was added
dropwise and stirred for 5 h at room temperature. Saturated
aqueous NH4Cl solution (15 mL) was added and extracted
with EtOAc (3 · 50 mL). The organic layer was washed with
water (25 mL), brine (25 mL), dried (Na2SO4), evaporated,
andtheobtainedresiduepurifiedbycolumnchromatography
1
1247, 1463, 1705, 2859, 2933 cmꢀ1. H NMR (200 MHz,
CDCl3): d 1.26–1.42 (m, 2H), 2.67 (t, 2H, J = 4.7 Hz, H-2,
20), 3.58 (t, 2H, J = 6.2 Hz), 4.58 (s, 2H), 7.19–7.32 (m,
5H), 9.8 (s, 1H, –CHO).
4.1.11. 1-[4-Benzyl-2-oxo-(4S)-1,3-oxazolan-3-yl]-6-benzyl-
oxy-3-hydroxy-2-(4-methoxybenzyloxy)-(2S,3R)-hexan-1-
one 6. To a solution of the chiral auxiliary (5 g,
14.08 mmol) in CH2Cl2 (20 mL) at ꢀ78 ꢁC, N-ethyldiiso-

1086
G. V. M. Sharma, G. R. Cherukupalli / Tetrahedron: Asymmetry 17 (2006) 1081–1088
1
(Silica gel 60–120 mesh, EtOAc/hexane, 1:4) to furnish 17
(1.2 g) in 60% yield as a pale yellow liquid. [a]D = +9.7
(c 0.8, CHCl3); IR (neat): 1155, 1240, 1515, 2865, 2931,
3402 cmꢀ1; H NMR (200 MHz, CDCl3): d 1.39 (s, 3H,
CH3), 1.41 (s, 3H, CH3), 1.44–1.49 (m, 2H), 1.77–1.86
(m, 2H), 3.48–3.64 (m, 3H), 4.12 (dd, 1H, J = 8.1,
7.3 Hz), 5.28–5.38 (ddd, 2H, J = 1.1, 1.5, 10.2 Hz), 5.72–
5.77 (m, 1H); FAB MS (m/z, %): 187 (M++1, 4), 171
(24), 98 (100), 97 (69).
3064, 3446 cmꢀ1 1H NMR (200 MHz, CDCl3): d 1.38–
;
1.68 (m, 4H), 3.38–3.52 (m, 4H), 3.79 (s, 3H), 4.26 (d, 1H,
J = 11.3 Hz, –OCH2Ph), 4.42 (s, 2H, –OCH2Ph), 4.52 (d,
1H, J = 11.3 Hz, –OCH2Ph), 5.34 (dd, 2H, J = 4.6,
10.2 Hz), 5.71–5.74 (m, 1H), 6.84 (d, 2H, J = 8.2 Hz, Ar–
H), 7.18 ꢀ7.37 (m, 7H, Ar–H); FAB MS (m/z, %): 355
(M+ ꢀ 1, 6), 326 (4), 281 (16), 147 (41), 73 (100).
4.1.17. 3-[2,2-Dimethyl-5-vinyl-(4R,5R)-1,3-dioxolan-4-yl]-
propanal 21. To a stirred solution of oxalyl chloride
(0.29 mL, 2.41 mmol) in dry CH2Cl2 (10 mL), DMSO
(0.34 mL, 4.83 mmol) was added at ꢀ78 ꢁC and stirred at
the same temperature for 30 min. A solution of 20 (0.3 g,
1.61 mmol) in dichloromethane (5 mL) was added at
ꢀ78 ꢁC and stirred for 3 h at the same temperature. The
reaction mixture was cooled to 0 ꢁC, treated with Et3N
(1.35 mL, 9.67 mmol) and stirred for 15 min. The reaction
mixture was then worked up as described for 15 to afford
21 (0.28 g) in 94% yield as a pale yellow syrup. IR (neat):
4.1.14. 7-Benzyloxy-(3R,4R)-1-heptene-3,4-diol 18. To a
stirred solution of 17 (1 g, 2.08 mmol) in dry acetonitrile,
ZrCl4 (0.130 g, 0.561 mmol) was added and stirred at room
temperature for 1 h. The solvent was removed under reduced
pressure and the residue treated with EtOAc (20 mL). It was
then washed with water (15 mL), brine (15 mL), dried over
Na2SO4, and evaporated under reduced pressure. The resi-
due purified by column chromatography (Silica gel, 60–120
mesh, EtOAc/hexane, 1:2) to furnish 18 (0.6 g) in 91% yield
as a colorless syrup. [a]D = +5.2 (c 0.5, CHCl3); IR (neat):
1170, 1458, 1705, 2855, 2935 cmꢀ1; H NMR (200 MHz,
1
CDCl3): d 1.39 (s, 3H, CH3), 1.41 (s, 3H, CH3), 1.77–1.86
(m, 2H), 2.67 (t, 2H, J = 4.7 Hz), 3.62–3.65 (m, 1H), 3.98
(dd, 1H, J = 8.1, 7.3 Hz), 5.27–5.36 (ddd, 2H, J = 1.1,
1.5, 10.2 Hz), 5.72–5.77 (m, 1H), 9.7 (s, 1H, –CHO).
1
1255, 1450, 1605, 2596, 3034, 3580 cmꢀ1. H NMR (200
MHz, CDCl3): d 1.38–1.68 (m, 4H), 3.38–3.52 (m, 4H),
4.24 (d, 1H, J = 11.3 Hz, –OCH2Ph), 4.51 (d, 1H, J =
11.3 Hz, –OCH2Ph), 5.34 (dd, 2H, J = 4.6, 10.2 Hz), 5.72
(m, 1H), 7.17–7.39 (m, 5H, Ar–H); FAB MS (m/z, %): 237
(M++1, 6), 181 (28), 157 (24), 121 (100).
4.1.18. 3-[2,2-Dimethyl-5-vinyl-(4R,5R)-1,3-dioxolan-4-yl]-
propanoic acid 4. To a stirred solution of 21 (0.28 g,
1.52 mmol) in tert-butanol/water (7:3, 10 mL), sodium
chlorite (0.20 g, 2.28 mmol), and H2O2 (1 mL, 7.60 mmol,
30% aq soln) were added and stirred at room temperature
for 10 h. The reaction mixture was concentrated, the resi-
due dissolved in ethyl acetate (10 mL), washed with water
(5 mL) and brine (5 mL), dried over Na2SO4, and concen-
trated under reduced pressure. The crude product was puri-
fied by column chromatography (Silica gel, 60–120 mesh,
EtOAc/hexane, 1:3) to afford 4 (0.27 g) in 90% yield as a
pale yellow syrup. [a]D = +25.6 (c 0.8, CHCl3); IR (neat):
4.1.15. 3-[2,2-Dimethyl-5-vinyl-(4R,5R)-1,3-dioxolan-4-yl]-
1-benzyloxy-propane 19. To a solution of 18 (0.5 g,
2.11 mmol) and 2,2-dimethoxypropane (0.44 g, 4.22 mmol)
in dry DMSO (20 mL), PTSA (0.05 mg) was added and
stirred for 5 h at room temperature. The reaction mixture
was treated with saturated aqueous NaHCO3 solution
(20 mL) and extracted with 30% EtOAc in a hexane solvent
system (3 · 75 mL). The organic layer was washed with
water (50 mL), brine (50 mL), dried over Na2SO4, evapo-
rated, and the residue purified by column chromatography
(Silica gel, 60–120 mesh, EtOAc/hexane, 1:4) to afford 19
(0.5 g) in 84% yield as a gummy syrup. [a]D = ꢀ27.2 (c
0.5, CHCl3); IR (neat): 873, 1057, 1239, 1376, 2937,
1165, 1220, 1427, 1607, 1714, 2878, 2987, 3085 cmꢀ1. H
1
NMR (200 MHz, CDCl3): d 1.39 (s, 6H, 2CH3), 1.77–
1.96 (m, 2H), 2.44–2.58 (m, 2H, H-2, 20), 3.61–3.66 (m,
1H, H-4), 3.98 (dd, 1H, J = 7.3, 8.1 Hz, H-5), 5.27–5.36
(ddd, 2H, J = 1.1, 1.5, 10.2 Hz, H-7, 70), 5.72–5.77 (m,
1H, H-6); FAB MS (m/z, %): 200 (M+, 4), 185 (64), 167
(4), 144 (5), 98 (93). Analysis calcd for C10H16O4 (200):
C, 59.98; H, 8.05. Found: C, 59.94; H, 8.01.
1
2986 cmꢀ1; H NMR (200 MHz, CDCl3): d 1.40 (s, 3H,
CH3), 1.41 (s, 3H, CH3), 1.45–1.49 (m, 2H), 1.77–1.84
(m, 2H), 3.44–3.56 (m, 3H), 4.18 (dd, 1H, J = 8.1,
7.3 Hz), 4.44 (s, 2H, –OCH2Ph), 5.27–5.36 (ddd, 2H,
J = 1.1, 1.5, 10.2 Hz), 5.72–5.77 (m, 1H), 7.18–7.35 (m,
5H, Ar–H); FAB MS (m/z, %): 277 (M++1, 8), 184 (24),
121 (100), 91 (52). Analysis calcd for C17H24O3 (276): C,
73.88; H, 8.75. Found: C, 73.84; H, 8.71.
4.1.19. 1-[1-Benzyloxy-(1S)-heptyl]-(1S)-3-butenyl 3-[2,2-
dimethyl-5-vinyl-(4R,5R)-1,3-dioxolan-4-yl]propanoate 2. To
a stirred solution of 4 (0.12 g, 0.60 mmol) in dry THF
(5 mL), was added Et3N (0.16 mL, 1.20 mmol) at room
temperature and stirred for 30 min. A solution of 2,4,6-tri-
chlorobenzoyl chloride (0.148 mL, 0.60 mmol) in dry THF
(2 mL) was added to the reaction mixture and stirred for
5 h at room temperature. The solvent was evaporated, res-
idue diluted with toluene (20 mL) and treated with DMAP
(0.146 g, 1.20 mmol) and 3 (0.156 g, 0.60 mmol). After
14 h, toluene was evaporated; the crude residue was puri-
fied by column chromatography (Silica gel, 60–120 mesh,
EtOAc/hexane, 1:3) to afford 2 (0.2 g) in 73% yield as a col-
orless syrup. [a]D = ꢀ1.9 (c 4.2, CHCl3); IR (neat): 1150,
4.1.16. 3-[2,2-Dimethyl-5-vinyl-(4R,5R)-1,3-dioxolan-4-yl]-
1-propanol 20. To a stirred solution of 19 (0.5 g,
1.81 mmol) in CH2Cl2 (5 mL), DDQ (1.64 g, 7.24 mmol)
was added and stirred at reflux for 4 h. Saturated aq NaH-
CO3 solution (10 mL) was added to the reaction mixture
and extracted with CH2Cl2 (3 · 10 mL). The combined
organic layers were washed with water (15 mL), brine
(10 mL), dried over Na2SO4, and concentrated. The crude
residue was purified by column chromatography (Silica
gel, 60–120 mesh, EtOAc/hexane, 1:4) to afford 20 (0.3 g)
in 89% yield as a colorless syrup. [a]D = ꢀ8.6 (c 1.6,
CHCl3); IR (neat): 878, 1055, 1235, 1378, 2935, 2986,
1255, 1350, 1455, 1605, 1710, 2590, 3035 cmꢀ1. H NMR
1
(400 MHz, CDCl3): d 0.89 (t, 3H, J = 6.5 Hz, 3 · H-700),
1.26 (br m, 8H, H-300 to H-600), 1.39 (s, 3H, Me2C), 1.41

G. V. M. Sharma, G. R. Cherukupalli / Tetrahedron: Asymmetry 17 (2006) 1081–1088
1087
(s, 3H, Me2C), 1.44–1.62 (m, 2H, 2 · H-200), 1.72–1.96 (m,
2H, 2 · H-3), 2.23–2.54 (m, 4H, 2 · H-2 and 2 · H-20),
3.42 (dt, 1H, J = 7.1, 4.5 Hz, H-100), 3.64 (dt, 1H, J = 8.1,
3.9 Hz, H-4), 3.97 (dd, 1H, J = 8.1, 7.2 Hz, H-5), 4.60 (s,
2H, CH2Ph), 4.97–5.18 (m, 3H, H-10 and 2 · H-40), 5.25
(ddd, 1H, J = 10.2, 1.5, 0.8 Hz, H-7), 5.38 (ddd, 1H,
J = 17.1, 1.5, 0.9 Hz, H-7), 5.63–5.79 (m, 2H, H-30, 6),
7.23–7.40 (m, 5H, Ar–H). 13C NMR (300 MHz, CDCl3):
d 14.0, 22.5, 25.5, 26.8, 27.2, 29.3, 29.9, 30.7, 31.6, 34.3,
72.3, 73.5, 79.0, 82.4, 108.7, 117.5, 118.9, 127.6, 127.8,
128.3, 134.1, 135.1, 138.5, 172.6. FAB MS (m/z, %): 458
(M+, 0.4%), 443 (0.8), 361 (0.8), 294 (11), 275 (3.5), 259
(5.6), 223 (3.8), 205 (11), 183 (6.8), 143 (9.7), 125 (70), 98
(35), 91 (100), 83 (10), 69 (9.2), 55 (9.0), 43 (12). Analysis
calcd for C28H42O5 (458): C 73.3, H 9.2. Found: C 73.1,
H 9.1.
J = 11.6 Hz, CH2Ph), 4.66 (d, 1H, J = 11.6 Hz, CH2Ph),
5.10 (ddd, 1H, J = 11.8, 4.4, 2.2 Hz, H-10), 5.50 (t, 1H,
J = 10.3 Hz, H-7), 5.74 (dt, 1H, J = 0.3, 7.0 Hz, H-8),
7.28–7.44 (m, 5H, Ar–H). 13C NMR: 14.0, 22.5, 25.4,
26.8, 27.0, 29.3, 29.6, 30.5, 31.7, 32.1, 72.6, 72.8, 77.1,
79.7, 81.5, 107.6, 127.7, 128.4, 130.3, 130.9, 138.0, 176.6.
FAB MS (m/z, %): 430 (M+, 0.69%), 415 (2.3), 373
(0.30), 328 (1.1), 298 (0.60), 265 (1.7), 237 (3.0), 220 (1.7),
205 (3.9), 203 (6.3), 123 (5.1), 113 (13), 91 (100), 85 (16),
79 (6.6).
4.1.21. (5R,6R,7E,10S)-5,6-Dihydroxy-10-[(1S)-1-hydroxy-
heptyl]-3,4,5,6,9,10-hexahydro-2H-oxecin-2-one, microcar-
palide, 1. Titanium tetrachloride (0.044 g, 0.232 mmol)
in anhydrous CH2Cl2 (1 mL) was slowly added dropwise
over 10 min to a stirred solution of trans derivative E-22
(0.050 g, 0.116 mmol) in dry CH2Cl2 (2.5 mL) and cooled
to 0 ꢁC. After 1.5 h, the ochre-yellow cloudy mixture was
poured into water (5 mL), diluted with CH2Cl2 (4 mL),
and treated with satd NaHCO3 (8 mL), brine (5 mL), and
EtOAc (15 mL) in a separating funnel. After settling, the
upper milky layer was discarded, whereas the clear lower
phase was separated, dried over Na2SO4, filtered, and
concentrated under reduced pressure; silica gel chro-
matography of the crude residue using ethyl acetate as
eluent, afforded 1 as a beige oil (0.020 g) in 59% yield.
[a]D = ꢀ23.6 (c 1.0, MeOH) (lit., ꢀ22.0). NMR analysis
clearly showed the presence of two slowly interconverting
conformers in a 76:24 ratio (in CD3CN), which is identical
to the value described in the literature for the natural com-
pound in the same solvent. IR (neat): 1150, 1255, 1350,
4.1.20. (5R,6R,7E,10S)- and (5R,6R,7Z,10S)-10-[(1S)-1-
Benzyloxyheptyl]-5,6-isopropylidenedioxy-3,4,5,6,9,10-hexa-
hydro-2H-oxecin-2-one, E-22 and Z-22. Ester 2 (0.150 g,
0.327 mmol) was dissolved in freshly distilled degassed
anhydrous CH2Cl2 (230 mL), treated with Grubbs’ catalyst
I (0.048 g, 0.0589 mmol) and heated at reflux for 2 days
under an Ar flow until TLC (hexane/EtOAc; 80:0) showed
complete disappearance of the starting material. Most of
the solvent was then distilled off and the concentrated solu-
tion left to stir at room temperature for 2 h under air bub-
bling, in order to decompose the catalyst. The reaction
mixture was evaporated to dryness to give a brown residue,
which was purified by column chromatography (Silica gel,
60–120 mesh, EtOAc/hexane, 3:97 to 20:80) to allow the
separation of the desired trans-stereoisomer (E)-22
(75 mg) from cis derivative (Z)-22 (35 mg) (combined
78% yield).
1
1450, 1602, 1710, 2590, 3035 cmꢀ1. H NMR (300 MHz,
CDCl3): d 0.91 (t, 3H, J = 6.8 Hz, 3 · H-70), 1.26–1.38
(br envelope, 8H, H-30 to H-60), 1.41–1.47 (br m, 2H,
2 · H-20), 1.80 (br dddd, 1H, H-4), 2.02 (br ddd, 1H, H-4
minor conformer), 2.11–2.23 (br m, 3H, H-3, H-4 and H-
9), 2.27–2.34 (br m, 1H, H-9), 2.36 (ddd, 1H, J = 5.2,
2.7, 1.1 Hz, H-9 minor), 2.47–2.58 (m, 1H, H-3), 3.28 (br
dt, 1H, H-5 minor), 3.54–3.60 (br m, 1H, H-10), 3.64 (dt,
1H, J = 3.1, 9.1 Hz, H-6 minor), 3.80 (br m, 1H, H-5),
4.13 (br m, 1H, H-6), 4.63 (ddd, 1H, J = 8.4, 4.5, 2.7 Hz,
H-10 minor), 4.84 (ddd, 1H, J = 11.3, 4.9, 3.3 Hz, H-10),
5.08 (dd, 1H, J = 15.7, 9.4 Hz, H-7 minor), 5.53 (dddd,
1H, J = 15.8, 10.3, 5.3, 2.2 Hz, H-8), 5.69 (m, 1H, H-8
minor), 5.73 (dd, 1H, J = 15.8, 2.5 Hz, H-7). 13C NMR
(CDCl3, 300 MHz): d 14.4 (C-7), 23.3 (C-6), 26.1 (C-3),
26.5 (C-4), 29.3 (C-3), 30.0 (C-4), 32.2 (C-9, minor con-
former), 32.3 (C-5, minor), 32.6 (C-5), 33.9 (C-2, minor),
34.3 (C-2), 35.9 (C-3, minor), 36.7 (C-9), 72.5 (C-6), 72.9
(C-1), 73.5 (C-5), 73.8 (C-1, minor), 76.4 (C-10, minor),
77.0 (C-5, minor), 79.5 (C-6, minor), 79.7 (C-10), 126.7
(C-8), 130.0 (C-8, minor), 133.8 (C-7, minor), 134.6 (C-7),
173.5 (C-2, minor), 176.4 (C-2); FAB MS (m/z, %): 301
(M++1, 1.4), 283 (0.55), 265 (0.78), 198 (6.2), 180 (55),
141 (10), 129 (30), 113 (13), 110 (16), 95 (39), 84 (100), 73
(44), 70 (80), 55 (64).
4.1.20.1. trans-(5R,6R,7E,10S)-2. [a]D = ꢀ37.9 (c 3.0,
CHCl3); IR (neat): 1155, 1255, 1330, 1450, 1602, 1715,
1
2590 cmꢀ1. H NMR (400 MHz, CDCl3): d 0.90 (t, 3H,
J = 6.5, 3 · H-70), 1.27 (br envelope, 8H, H-30 to H-60),
1.41 (s, 6H, 2 · Me2C), 1.51–1.65 (m, 2H, 2 · H-20), 1.87–
2.71 (m, 6H, 2 · H-3, H-4 and H-9), 3.47 (m, 1H, H-10),
3.61 (m, 1H, H-5), 3.89 (t, 1H, J = 9.2 Hz, H-6), 4.56 (d,
1H, J = 11.6 Hz, CH2Ph), 4.62 (d, 1H, J = 11.6, CH2Ph),
4.92 (m, 1H, H-10), 5.29 (dd, 1H, J = 15.6, 9.2 Hz, H-7),
5.72 (ddd, 1H, J = 15.6, 11.0, 4.7 Hz, H-8), 7.29–7.40 (m,
5H, Ar–H). 13C NMR: 14.0, 22.5, 25.4, 25.6, 26.9, 27.1,
29.4, 29.7, 31.7, 34.2, 72.5, 73.4, 79.8, 80.4, 84.4, 108.8,
127.8, 127.9, 128.4, 129.2, 130.3, 138.2, 171.8. FAB MS
(m/z, %): 430 (M+, 0.22), 415 (0.33), 373 (0.60), 328 (1.1),
298 (0.71), 237 (3.3), 220 (1.8), 205 (4.3), 203 (7.0), 179
(1.8), 123 (6.2), 113 (14), 91 (100), 85 (23), 79 (6.2). Analysis
calcd for C26H38O5 (430): C 72.5, H 8.9. Found: C 72.3, H
8.71.
4.1.20.2. cis-(5R,6R,7Z,10S)-22. [a]D = +4.5 (c 1.6,
CHCl3); IR (neat): 1155, 1255, 1330, 1450, 1602, 1715,
1
2590 cmꢀ1. H NMR (200 MHz, CDCl3): d 0.89 (t, 3H,
J = 6.5 Hz, 3 · H-70), 1.27 (br envelope, 8H, H-30 to H-
60), 1.40 (s, 3H, Me2C), 1.42 (s, 3H, Me2C), 1.50–1.77 (m,
2H, 2 · H-20), 2.01–2.77 (m, 6H, 2 · H-3, H-4 and H-9),
3.49 (m, 1H, H-10), 3.66 (ddd, 1H, J = 10.2, 9.5, 2.3 Hz,
H-5), 4.52 (dd, 1H, J = 9.5, 8.0 Hz, H-6), 4.58 (d, 1H,
Acknowledgement
Ch.G.R. thanks UGC, New Delhi, for the award of a
fellowship.

1088
G. V. M. Sharma, G. R. Cherukupalli / Tetrahedron: Asymmetry 17 (2006) 1081–1088
Rao, R.; Shashidhar, J. Tetrahedron Lett. 2005, 46, 5479–
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