Stereoselective synthesis of (+)-pericosine B and (+)-pericosine C using ring closing metathesis approach

Article abstract of DOI:10.1016/j.tetasy.2012.01.002

Stereoselective synthesis of (+)-pericosine B and (+)-pericosine C were achieved from d-ribose using RCM and RCEYM as key steps.

Full text of DOI:10.1016/j.tetasy.2012.01.002

Tetrahedron: Asymmetry 23 (2012) 86–93
Contents lists available at SciVerse ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective synthesis of (+)-pericosine B and (+)-pericosine C using ring
closing metathesis approach
⇑
Ch. MuniRaju, J. Prasada Rao, B. Venkateswara Rao
Organic Division III, Indian Institute of Chemical Technology, Hyderabad 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Stereoselective synthesis of (+)-pericosine B and (+)-pericosine C were achieved from
and RCEYM as key steps.
D-ribose using RCM
Received 13 December 2011
Accepted 5 January 2012
Available online 31 January 2012
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
duction at C-5 will give the RCM precursors 6 or 7 respectively
which can be elongated to the cyclohexene cores of (+)-pericosine
B 8 and (+)-pericosine C 9. In our previous communication, we
have studied and compared the stereoselectivities between the
addition of organo chromium and organo magnesium nucleophiles
Carbasugars1 are the mimics of monosaccharides in biological
systems in which the ring oxygen is replaced with a methylene
group2 and they have attracted considerable attention from biolo-
gists and chemists because of glycosidase inhibitory activity. Gly-
cosidase enzymes are involved in numerous biological processes
and their inhibition has enormous potential for the treatment of
many diseases. Some of the carbasugar related compounds have
been isolated from natural sources.3 One among them is the peric-
osine family, pericosines A–E 1–5 have been isolated from Periconia
byssoides OUPS-N133 fungus that was originally isolated from the
sea hare, Aplysia kurodai (Fig 1).4
onto a
-alkoxy aldehydes,9b where organo chromium addition takes
place via a Felkin–Anh model, in non-chelation mode. In the case of
organo lithiums, the addition takes place in chelation mode, thus
giving a reversal of stereochemistry at the newly generated stereo-
centre. Herein we have developed a common strategy for the syn-
thesis of epimers 2 and 3 based on the above approach from D-
ribose by the addition of appropriate nucleophiles onto C-5 of
ribose.
These compounds show interesting biological activities such as
cytotoxicity against P388 lymphocytic leukemia cells, antitumor
activity against murine P388 cells and selective growth inhibition
against human cancer cell lines HBC-5 and SNB-75.4,5 Hence vari-
ous synthetic approaches to pericosine A–D,6,7 have been devel-
oped and most of these syntheses start from shikimic acid or
quinic acid. Shikimic acid and quinic acids are relatively expensive
and are of limited availability,8 therefore non-dependent shikimic
acid or quinic acid routes are desirable for the synthesis of these
natural products. As a part of ongoing program in our group on
the synthesis of carbasugars we have developed a NHK-RCM strat-
egy for the construction of carbocycles;9 herein we are presenting
the application of this approach to the synthesis of (+)-pericosine B
2 and an enyne metathesis strategy (RCEYM) for (+)-pericosine C 3
Based on our retrosynthetic analysis, we have chosen
as a starting material and the compound 10 required for the syn-
D-ribose
thesis is prepared from
procedure.9b
D-ribose in six steps by using our earlier
2. Results and discussion
Nucleophilic addition onto
a-alkoxy aldehyde 10 with iodo
compound 11 under Nozaki–Hiyama–Kishi (NHK) conditions10 in
DMF gave anti alcohol 12 as the major product along with syn 13
in the ratio of 3:1. The major isomer 12 was separated and sub-
jected to ring closing metathesis using Grubbs 2nd generation cat-
alyst in toluene at reflux to give cyclohexene derivative 14.11 The
allylic alcohol in compound 14 was converted into a methyl ether
15 using NaH/MeI, which on treatment with PPTS in MeOH yielded
16 (Scheme 2).
from the inexpensive starting material D-ribose (Scheme 1).
The (+)-pericosine C 3 is nothing but a C6 epimer of (+)-perico-
sine B 2. Therefore, it is logical to envisage a common strategy for
their synthesis by appropriately tuning the reaction conditions to
get both epimers at C6. The chiral hydroxyl groups at C3, C4 and
The primary alcohol within compound 16 was oxidized using
TEMPO/BAIB to give
a,b-unsaturated aldehyde 17. The aldehyde
17 was subjected to Pinnick oxidation12 to give an acid, which on
esterification with MeI and K2CO3 gave compound 18. Global
deprotection of the MOM and isopropylidene in compound 18
was achieved with TFA in methanol to give (+)-pericosine B 2 as
a white solid whose physical and spectroscopic data were identical
with the reported values.7b,e
C5 of 2 and 3 can be obtained from D-ribose. For instance, one car-
bon homologation at C-1, and a vinyl group or ethynyl group intro-
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: venky@iict.res.in (B.V. Rao).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2012.01.002

Ch. MuniRaju et al. / Tetrahedron: Asymmetry 23 (2012) 86–93
87
COOMe
Cl
OH
COOMe
COOMe
COOMe
O
COOMe
OH
OH
Cl
MeO
HO
MeO
HO
MeOOC
Cl
HO
OH
OH
OH
OH
HO
OH
OH
OH
OH
OH
OH
(+)-pericosine A 1
(+)-pericosine B 2
(+)-pericosine C 3
(+)-pericosine E 5
(+)-pericosine D 4
Figure 1. Structures of (+) pericosines A, B, C, D and E.
TMS
OTHP
OMe
O
THPO
OP
1
MeO
PO
RCM
MeO
HO
6
2
3
MeO
OP
OP
PO
OP
1
O
5
OH
OH
4
5
OP
4
one carbon
OH
2
homologation
3
6
8
PO
2
OP
THPO
O
OMe
OP
ENYNE RCM
MeO
HO
MeO
O
OH
MeO
OH
PO
OP
OP
PO
OH
OP
HO
OH
7
3
OH
D-ribose
9
Scheme 1. Retrosynthetic analysis of (+) pericosine B and C.
For the synthesis of (+)-pericosine C 3, we needed a reversal of
stereochemistry at the newly generated stereogenic centre ob-
tained during nucleophilic addition onto 10. For this we envisaged
The minor isomer 13 was separated and subjected to ring closing
metathesis using Grubbs 2nd generation catalyst in toluene at re-
flux to give cyclohexene derivative 25 (Scheme 4).11 The allylic alco-
hol within compound 25 was converted to methyl ether 26(a) using
NaH, MeI and followed by THP deprotection with PPTS in MeOH to
yield 26(b). The primary alcohol in compound 26(b) was oxidized
to carry out an alkynylation on the a, b-anti-dialkoxyaldehyde 10
under the chelation mode and we assumed that the MOM protect-
ing group in the alkoxy aldehyde should act as a bidentate ligand to
give 1,2-syn selectivity during nucleophilic addition.13
using TEMPO/BAIB to give a,b-unsaturated aldehyde 23 (Scheme 4).
When aldehyde 10 was treated with lithium trimethylsilylace-
talide in THF it gave syn propargylic alcohol 19 as the major isomer
along with anti propargylic alcohol 20 in a ratio of 4:1. Both iso-
mers were separated by column chromatography. The C-Silyl
group in major compound 19 was desilylated with K2CO3 in meth-
anol to give 21(a), which on methylation with NaH and MeI affor-
ded the required RCEYM precursor 21(b). The enyne 21(b) was
treated with 10 mol % Grubbs second generation catalyst in tolu-
ene at 80 °C under Mori’s conditions and gave the cyclohexene
derivative 22 in a 60% yield.14 Oxidative cleavage of the terminal
double bond in compound 22 was achieved with OsO4/NaIO4 to
The spectroscopic data of compound 23 were identical with the
compound obtained from alkenyl addition (Scheme 3).
3. Conclusion
In conclusion we successfully developed a common strategy
based on ring closing metathesis for the synthesis of (+)-pericosine
B and (+)-pericosine C. Our strategy may be useful to synthesize
other pericosines and related structures.
give a
,b-unsaturated aldehyde 23.15 Aldehyde 23 was oxidized to
4. Experimental
an acid using Pinnick’s protocol, followed by esterification with
K2CO3/MeI in acetone and yielded the protected form of (+)-peric-
osine C 24. Global deprotection of the isopropylidine and methoxy
methyl groups in compound 24 was achieved with TFA in metha-
nol to give (+)-pericosine C 3 (Scheme 3). The spectroscopic and
physical data of (+)-pericosine C 3 were identical with the reported
values.6e
To further confirm the stereochemistry of the newly generated
stereogenic centre the minor isomer 13 was converted to com-
pound 23 as shown in Scheme 4.
TLC was performed on Merck Kiesel gel 60, F254 plates (layer
thickness 0.25 mm). Column chromatography was performed on
silica gel (60–120 mesh) using ethyl acetate and hexane mixture
as an eluent. Melting points were determined on a Fisher John’s
melting point apparatus and are uncorrected. IR spectra were re-
corded on a Perkin–Elmer RX-1FT-IR system. 1H NMR and 13C
NMR spectra were recorded using Varian Gemini-200 MHz and
400 MHz or a Bruker Avance-300 MHz spectrometer. 1H NMR data
are expressed as chemical shifts in ppm followed by multiplicity

88
Ch. MuniRaju et al. / Tetrahedron: Asymmetry 23 (2012) 86–93
OTHP
I
OMOM
OMOM
O
O
ref 9b
11
b
THPO
R
D-ribose
R'
a
O
O
O
R = OH, R' = H, 12
R' = H, R = OH, 13
10
OH
OTHP
O
OTHP
MeO
MeO
HO
e
d
c
MOMO
MOMO
O
MOMO
O
O
O
O
14
16
15
O
OMe
O
OMe
CHO
MeO
HO
MeO
MeO
g
f
OH
MOMO
MOMO
O
O
OH
O
O
(+)-pericosine B 2
18
17
Scheme 2. Reagents and conditions: (a) CrCl2, NiCl2, DMF, 11, 24 h, 72%; (b) 10 mol % Grubbs 2nd gen. cat. toluene, reflux, 12 h, 80%; (c) NaH, MeI, THF, 0 °C to rt, 3 h, 70%; (d)
PPTS, MeOH, rt, 1 h, 65%; (e) BAIB, TEMPO (cat), DCM, 1 h, 62%; (f) (i) NaClO2, NaH2PO4, 2-methyl-2-butene, tBuOH, 0 °C to rt, 2 h; (ii) K2CO3, MeI, acetone, rt, 3 h, 80% (over 2
steps); (g) TFA, MeOH, 3 h, rt, 65%.
(s–singlet; d–doublet; t–triplet; q–quartet; m–multiplet), number
of proton (s) and coupling constant (s) J (Hz). 13C NMR data are ex-
pressed as chemical shifts in ppm. Optical rotations were
measured with JASCO digital polarimeter. Accurate mass measure-
ment was performed on Q STAR mass spectrometer (Applied Bio-
systems, USA). Doubling of peaks in NMR of compounds 12, 13,
14, 15, 25 and 26(a) is because of diastereomers due to THP
protection.
75 MHz): (19.3, 19.4)*, (25.3, 25.4)*, 27.9, 30.5, (56.4, 56.4)*,
(61.9, 62.1)*, (67.7, 67.9)*, (73.2, 73.5)*, 77.2, 79.0, (82.0, 82.2)*,
97.7, 98.0, (98.7, 98.8)*, 108.5, (114.5, 115.0)*, (117.6, 117.6)*,
(134.7, 134.8)*, (144.1, 144.3)*; ESI/MS (m/z): 395 (M+Na)+; HRMS
Calcd for C19H32O7Na (M+Na)+ 395.2045, found 395.2048.
4.1.1. Data for compound 13
½
a 2D4
ꢀ
¼ ꢁ14:3 (c 2.1, CHCl3): IR (neat)
mmax: 3471, 2938, 1377,
1214, 1030, 908, 762 cmꢁ1 1H NMR (CDCl3, 300 MHz): 1.36 (s,
;
4.1. (1R,2R)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-
1-(methoxymethoxy)-3-((tetrahydro-2H-pyran-2-yloxy)methyl)
but-3-en-2-ol 12, (1R,2S)-1-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-
dioxolan-4-yl)-1-(methoxymethoxy)-3-((tetrahydro-2H-pyran-
2-yloxy)methyl) but-3-en-2-ol 13
3H), 1.50 (s, 3H), 1.52–1.87 (m, 6H), 3.38 (s, 3H), 3.49 (m, 1H),
3.77–3.96 (m, 2H), 4.04 (m, 1H), 4.26–4.47 (m, 3H), 4.60–4.72
(m, 4H), 5.24–5.42 (m, 5H), 6.02 (m, 1H); 13C NMR (CDCl3,
75 MHz): (19.2, 19.2)*, (25.2, 25.4)*, (27.7, 27.9)*, 30.5, 56.3, 61.9,
(67.4, 67.6)*, 67.9, 72.1, 72.5, 78.4, 78.8, (97.5, 97.7)*, 98.3, 98.30,
108.4, 114.4, 114.554, 118.3, (134.6, 134.7)*, (145.0, 145.2)*; ESI/
MS (m/z): 395 (M+Na)+.
A mixture of CrCl2 (1.33 g, 8.69 mmol) and a catalytic amount of
NiCl2 (0.028 g, 0.217 mmol) in dry DMF (7 mL) was stirred at 25 °C
for 10 min under nitrogen atmosphere. To it a solution of aldehyde
10 (0.5 g, 2.17 mmol) in DMF (5 mL), 11 (0.76 mL, 8.69 mmol) was
added at 25 °C successively. After stirring at room temperature for
24 h, the reaction mixture was diluted with ether, poured into
water and extracted with ether repeatedly. The combined extracts
were dried (Na2SO4) and concentrated. Purification by silica gel
column chromatography using EtOAc/hexane (12:1) as an eluant
provided alcohol 12 as a yellow oil (0.36 g, 54%) and 13 also as a
yellow oil (0.06 g, 18%) in a ratio of 3:1 (0.42 g, 72%): Data for com-
4.2. (3aS,4R,5R,7aS)-4-(Methoxymethoxy)-2,2-dimethyl-6-
((tetrahydro-2H-pyran-2-yloxy)methyl)-3a,4,5,7a-tetrahydro-
benzo[d][1,3]dioxol-5-ol 14
To a solution of 12 (0.6 g, 1.7 mmol) in toluene (44 mL) Grubbs
second generation catalyst (0.13 g, 0.16 mmol) was added at room
temperature. The reaction mixture was refluxed for 12 h, toluene
was removed under vacuum and purified by column chromatogra-
phy using EtOAc/hexane (1:4) to provide cyclohexenol derivative
pound 12: ½a 2D4
ꢀ
¼ þ122:3 (c 0.3, CHCl3): IR (neat)
m
max: 3471, 2938,
14 as an oily compound (0.44 g, 80%). ½a D24
ꢀ
¼ ꢁ64:06 (c 2.1, CHCl3);
1377, 1214, 1030, 908, 762 cmꢁ1
;
1H NMR (CDCl3, 300 MHz): 1.34
IR (neat) m ;
max: 2933, 2355, 1201, 1119, 1030, 908, 762 cmꢁ1 1H
(s, 3H), 1.48 (s, 3H), 1.51–1.91 (m, 6H), 3.41 (s, 3H), 3.49 (m, 1H),
3.77–3.96 (m, 3H), 4.06–4.22 (m, 2H), 4.32–4.46 (m, 2H), 4.58–
4.73 (m, 4H), 5.20–5.42 (m, 4H), 5.95 (m, 1H); 13C NMR (CDCl3,
NMR (300 MHz): 1.36 (s, 3H), 1.43 (s, 3H), 1.48–1.91 (m, 6H),
3.14 (dd, 1H, J = 2.6, 10.7 Hz), 3.47 (s, 3H), 3.53 (br s, 1H), 3.75–
3.87 (m, 2H), 4.05 (m, 1H), 4.16 (m, 1H), 4.31 (m, 1H), 4.53–4.66

Ch. MuniRaju et al. / Tetrahedron: Asymmetry 23 (2012) 86–93
89
TMS
OMOM
OMOM
OMOM
O
a
b
R
R'
RO
O
O
O
O
O
O
10
R = OH, R' = H, 19
R = H, R' = OH, 20
R= H
21(a)
c
R=Me
21(b)
O
OMe
O
O
H
MeO
MeO
MeO
d
e
f
MOMO
MOMO
MOMO
O
O
O
O
O
24
23
22
g
O
OMe
MeO
HO
OH
OH
(+)-Pericosine C 3
Scheme 3. Reagents and conditions: (a) TMS–acetylene, n-BuLi, THF, ꢁ78 °C, 3 h, 85%; (b) K2CO3, MeOH, rt, 2 h, 85%; (c) NaH, MeI, THF, 0 °C to rt, 3 h, 70%; (d) 10 mol %
Grubbs 2nd gen. cat. toluene, ethylene gas, 80 °C, 12 h, 65%; (e) (i) OsO4, NMO, acetone/water, rt, 3 h; (ii) NaIO4, 1 h, rt, 50% (over 2 steps); (f) (i) NaClO2, NaH2PO4, 2-methyl-2-
butene, tBuOH, 0 °C to rt, 2 h; (ii) K2CO3, MeI, acetone, rt, 3 h, 80% (over 2 steps); (g) TFA, MeOH, rt, 3 h, 65%.
OR
OTHP
O
OMOM
MeO
HO
b
a
THPO
R
R'
MOMO
MOMO
O
O
O
O
O
R= H, R1 = OH, 13
26(a)
R = THP
R = H
c
25
26(b)
d
CHO
MeO
MOMO
O
O
23
Scheme 4. Reagents and conditions: (a) 10 mol % Grubbs 2nd gen. cat. toluene, reflux, 12 h, 80%; (b) NaH, MeI, THF, 0 °C to rt, 3 h, 70%; (c) PPTS, MeOH, rt, 1 h, 65%; (d) BAIB,
TEMPO (cat), DCM, 1 h, 65%.

90
Ch. MuniRaju et al. / Tetrahedron: Asymmetry 23 (2012) 86–93
(m, 3H), 4.78 (d, 1H, J = 6.9 Hz), 4.92 (d, 1H, J = 6.8 Hz), 5.67 (s, 1H);
13C (CDCl3, 75 MHz): (19.2, 19.4)*, 25.3, 26.4, 28.0, 30.4, 55.7, (62.0,
62.2)*, 64.7, 66.8, 67.9, 71.6, 73.6, 76.0, (95.0, 95.1)*, 97.6, 99.0,
110.8, (122.2, 122.3)*, (137.9, 137.0)*; ESI/MS (m/z): 367
(M+Na)+; HRMS Calcd for C17H28O7Na (M+Na)+ 367.1732, found
367.1737.
J = 0.7, 3.2 Hz), 9.59 (s, 1H); 13C NMR (CDCl3, 75 MHz): 25.9, 27.7,
55.8, 61.0, 69.2, 72.2, 72.7, 74.0, 95.0, 111.7, 139.3, 145.7, 192.9;
ESI/MS (m/z): 295 (M+Na)+; HRMS Calcd for C13H20O6Na (M+Na)+
295.1157, found 295.1154.
4.6. (3aS,6R,7R,7aS)-Methyl 6-methoxy-7-(methoxymethoxy)-
2,2-dimethyl-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxole-5-
carboxylate 18
4.3. (3aS,4R,5R,7aS)-5-Methoxy-4-(methoxymethoxy)-2,2-
dimethyl-6-((tetrahydro2H-pyran-2-yloxy)methyl)-3a,4,5,7a-
tetrahydrobenzo[d][1,3]dioxole 15
To an ice cooled stirred solution of compound 17 (0.06 g,
0.22 mmol) in t-BuOH (1.0 mL) were added (0.2 mL) of 2-methyl-
2-butene, NaClO2 (0.06 g, 0.68 mmol) and NaH2PO4 (0.10 g,
0.67 mmol) and then stirred for 2 h at room temperature. Then
the reaction mixture was treated with aq 1 M HCl and extracted
with EtOAc (2 ꢂ 50 mL). Organic layers were combined and
washed with water and brine then dried over Na2SO4 and concen-
trated in vacuum. The crude acid was dissolved in acetone (2 mL),
to it K2CO3 (0.09 g, 0.64 mmol) and methyl iodide (0.02 mL,
0.32 mmol) were added and then stirred for 3 h. Reaction mixture
was filtered through a celite pad and washed with ethyl acetate
and the filtrate was concentrated under vacuum. The residue was
dissolved in EtOAc (50 mL), washed with water, brine and dried
over Na2SO4. The solvent was removed on a rotary evaporator,
the crude ester 18 was submitted to column chromatography
and eluted using EtOAc/hexane (2:3) to give ester 18 (0.04 g) as a
To an ice-cooled, stirred solution of NaH (0.09 g, 60% w/v dis-
persion in mineral oil, 2.3 mmol) in THF (5 mL) were added com-
pound 14 (0.4 g, 1.11 mmol) in THF (5 mL) and methyl iodide
(0.1 mL, 1.7 mmol). The mixture was stirred at room temperature
for 3 h, quenched with saturated NH4Cl solution and extracted
with EtOAc (2 ꢂ 100 mL). The combined organic layers were
washed with water and brine, then dried over Na2SO4 and concen-
trated in vacuo. The crude material was purified by column chro-
matography on silica gel eluting with EtOAc/hexane (9:1) to give
compound 15 (0.29 g, 70%) as a syrup. ½a D24
ꢀ
¼ þ31:9 (c 0.6, CHCl3):
IR (neat) m ;
max: 2933, 2355, 1201, 1119, 1030, 908 cmꢁ1 1H NMR
(CDCl3, 300 MHz): 1.31 (s, 3H), 1.41 (s, 3H), 1.44–1.88 (m, 6H),
3.35 (s, 3H), 3.41(2s, 3H), 3.45 (m, 1H), 3.74–3.80 (m, 2H), 3.90–
4.01 (m, 2H), 4.13–4.30 (m, 2H), 4.51 (br s, 1H), 4.55 (m, 1H),
4.67 (d, 1H, J = 6.4 Hz), 4.75(d, 1H, J = 6.7 Hz), 5.80 (d, 1H,
J = 9.4 Hz); 13C NMR (CDCl3, 75 MHz): (19.3, 19.3)*, 25.4, 25.6,
26.8, 30.5, 30.8, 55.5, 58.7, 62.1, 64.1, 66.9, 67.9, (69.0, 69.4)*,
69.9, (71.1, 71.5)*, 74.0, 77.2, (96.3, 96.6)*, 98.0, 98.8, (110.3,
110.3)*, (120.4, 120.7)*, (137.6, 137.8)*; ESI/MS (m/z): 381
(M+Na)+: HRMS Calcd for C18H30O7Na (M+Na)+ 381.1889, found
381.1879.
syrup in an 80% yield (over 2 steps). ½a D24
¼ ꢁ39:8 (c 0.8, CHCl3):
ꢀ
IR (neat) m
max: 2921, 2363, 1693, 1516, 1025 cmꢁ1; 1H NMR (CDCl3,
300 MHz): 1.39 (s, 3H), 1.43 (s, 3H), 3.49 (s, 3H), 3.60 (s, 3H), 3.78
(s, 3H), 3.80 (m, 1H), 4.38 (d, 1H, J = 4.5 Hz), 4.59 (m, 1H), 4.67 (dd,
1H, J = 3.3, 5.4 Hz), 4.87 (s, 2H), 6.80 (dd, 1H, J = 0.7, 3.3 Hz); 13C
NMR (CDCl3, 75 MHz): 26.1, 27.7, 52.1, 55.8, 61.2, 71.7, 72.6,
72.8, 73.2, 95.0, 111.5, 130.2, 137.0, 166.5; ESI/MS (m/z): 325
(M+Na)+; HRMS Calcd for C15H24O7Na (M+Na)+ 325.1263, found
325.1255.
4.4. ((3aS,6R,7R,7aS)-6-Methoxy-7-(methoxymethoxy)-2,2-
dimethyl-3a,6,7,7a-tetra-hydrobenzo[d][1,3]dioxol-5-yl)
methanol 16
4.7. (+)-Pericosine B 2
To an ice cooled stirred solution of compound 15 (0.2 g,
0.55 mmol) in methanol (5 mL) catalytic amount of PPTS was
added. The mixture was stirred for 1 h at 0 °C, methanol was re-
moved under vacuo and purified by column chromatography using
EtOAc/hexane (3:2) to give compound 16 (0.09 g, 65%) as a syrup.
To a solution of compound 18 (0.04 g, 0.13 mmol) in methanol
(1 mL), TFA (0.5 mL) was added and stirred the reaction mixture
at room temperature for 3 h. Then the solvent was removed under
vacuum to afford crude pericosine B, which was purified by col-
umn chromatography using MeOH/CHCl3 (1:24) to give (+)-perico-
sine B 2 (0.018 g) as a white solid in a 65% yield, mp 85–87 °C.
½
a 2D4
ꢀ
¼ þ62:9 (c 0.5, CHCl3): IR (neat)
mmax: 3470, 2926, 1376, 1123,
1031, 975, 907, 863 cmꢁ1; 1H NMR (CDCl3, 300 MHz): 1.39 (s, 3H),
1.48 (s, 3H), 3.42 (s, 3H), 3.51 (s, 3H), 3.92 (br s, 1H), 4.17 (m, 1H),
4.24 (br s, 2H), 4.30 (m, 1H), 4.59 (m, 1H), 4.73 (d, 1H, J = 6.9 Hz),
4.88 (d, 1H, J = 6.9 Hz), 5.90 (s, 1H); 13C (CDCl3, 75 MHz): 25.4,
26.6, 55.4, 57.8, 64.2, 68.9, 71.1, 74.2, 77.9, 96.7, 110.4, 120.5,
139.7; ESI/MS (m/z): 297 (M+Na)+; HRMS Calcd for C13H22O6Na
(M+Na)+ 297.1314, found 297.1305.
½
a 2D4
ꢀ
¼ þ29 (c 0.12, EtOH); (lit.7e
½
a 2D0
ꢀ
¼ þ22:3 (c 0.82, EtOH)); IR
(neat) m ;
max: 3620, 2924, 2362, 1740, 1462, 1080 cmꢁ1 1H NMR
(acetone-d6, 300 MHz): 3.58 (s, 3H), 3.75 (s, 3H), 3.79 (m, 1H),
3.81–3.96 (m, 2H), 4.15 (m, 1H), 4.25 (d, 1H, J = 4.1 Hz), 4.40 (d,
1H, J = 6.7 Hz), 6.70 (dd, 1H, J = 0.9, 2.4 Hz); 13C NMR (acetone-d6,
75 MHz): 51.9, 61.3, 69.3, 69.8, 72.5, 76.8, 130.3, 141.8, 166.7;
ESI/MS (m/z): 241 (M+Na)+; HRMS Calcd for C9H14O6Na (M+Na)+
241.0688, found 241.0682.
4.5. (3aS,6R,7R,7aS)-6-Methoxy-7-(methoxymethoxy)-2,2-
dimethyl-3a,6,7,7a-tetra-hydrobenzo[d][1,3]dioxole-5-
carbaldehyde 17
4.8. (1R,2S)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-
1-(methoxymethoxy)-4-(trimethylsilyl)but-3-yn-2-ol 19,
(1R,2R)-1-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)-1-
(methoxymethoxy)-4 (trimethylsilyl)but-3-yn-2-ol 20
To an ice cooled stirred solution of alcohol 16 (0.1 g, 0.36 mmol)
in CH2Cl2 (3 mL) TEMPO (0.005 g, 0.03 mmol) and BAIB (0.14 g,
0.43 mmol) were added. The reaction mixture was stirred at room
temperature for 1 h and extracted with DCM. The organic layer was
washed with brine, separated, dried over anhydrous Na2SO4 and
purified by column chromatography using EtOAc/hexane (3:7) to
To a solution of TMS-acetylene (1.8 mL, 13.04 mmol) in dry THF
(10 mL) was added n-BuLi (7.6 mL, 12.17 mmol, 1.6 M solution in
hexane) at 0 °C and the reaction mixture was stirred at 0 °C for
1 h. This reaction mixture was further cooled to ꢁ78 °C, to this
aldehyde 10 (1 g, 4.34 mmol) in THF was added over 10 min. After
stirring for 3 h, the reaction mixture was quenched with saturated
NH4Cl and extracted with EtOAc (2 ꢂ 100 mL). The combined or-
ganic extracts were washed with water, brine and dried over anhy-
drous Na2SO4. Concentration and purification by silica gel column
give compound 17 (0.06 g, 62%) as a syrup. ½a D24
¼ ꢁ52:1 (c 0.7,
ꢀ
CHCl3): IR (neat) m
max: 2923, 1742, 1459, 1258, 1019 cmꢁ1; 1HNMR
(CDCl3, 300 MHz): 1.38 (s, 3H), 1.41 (s, 3H), 3.46 (s, 3H), 3.52 (s,
3H), 3.74 (dd, 1H, J = 2.8, 4.5 Hz), 4.3 (d, 1H, J = 4.5 Hz), 4.60 (m,
1H), 4.72 (dd, 1H, J = 3.2, 5.6 Hz), 4.82 (s, 2H), 6.56 (dd, 1H,

Ch. MuniRaju et al. / Tetrahedron: Asymmetry 23 (2012) 86–93
91
chromatography using EtOAc/hexane (9:1) as eluent afforded
propargylic alcohol 19 (0.97 g, 68%) and 20 (0.24 g, 17%) as yellow
oils in the ratio 4:1 (1.21 g, 85%). Data for compound 19:
(m, 1H); 13C NMR (75 MHz, CDCl3): 25.4, 27.8, 56.3, 57.3, 71.0,
75.6, 76.5, 77.7, 78.5, 80.5, 97.4, 108.2, 117.8, 134.5; ESI/MS (m/
z): 293 (M+Na)+; HRMS Calcd for C14H22O5Na (M+Na)+ 293.1364,
found 293.1351.
½
a 2D4
ꢀ
¼ ꢁ16:5 (c 1.4, CHCl3); IR (neat)
mmax: 3529, 2956, 2173,
1643, 1034 cmꢁ1 1H NMR (300 MHz, CDCl3): 0.19 (s, 9H), 1.39 (s,
;
3H), 1.50 (s, 3H), 3.12 (d, 1H, –OH, J = 10.9 Hz), 3.38 (s, 3H), 3.54
(dd, 1H, J = 3.3, 9.0 Hz), 4.43 (dd, 1H, J = 6.0, 9.0 Hz), 4.61–4.67
(m, 4H), 5.23 (d, 1H, J = 10.5 Hz), 5.36 (d, 1H, J = 15.8 Hz), 5.89
(m, 1H); 13C NMR (75 MHz, CDCl3): ꢁ0.2, 25.1, 27.7, 56.1, 64.3,
77.2, 77.8, 78.8, 90.8, 97.7, 104.0, 109.1, 118.0, 133.8; ESI/MS (m/
z): 351 (M+Na)+; HRMS Calcd for C16H28O5NaSi (M+Na)+
351.1603, found 351.1588.
4.11. (3aS,4R,5S,7aS)-5-Methoxy-4-(methoxymethoxy)-2,2-
dimethyl-6-vinyl-3a,4,5,7a-tetrahydrobenzo[d][1,3]dioxole 22
To the solution of ene-yne 21 (b) (0.43 g, 1.6 mmol) in toluene
(44 mL), Grubbs’ second-generation catalyst (0.13 g, 0.16 mmol)
was added at room temperature and the reaction mixture refluxed
for 12 h under ethylene atmosphere. Toluene was removed under
vacuum, and the crude was purified by column chromatography
using EtOAc/hexane (1:9) to provide cyclohexene 22 (0.28 g, 65%)
4.8.1. Data for compound 20
½
a 2D4
ꢀ
¼ þ29:3 (c 2.2, CHCl3); IR (neat)
m
max: 3418, 2987, 2173,
as a syrup. ½a 2D4
ꢀ
¼ þ2:1 (c 0.9, CHCl3); IR (neat)
mmax: 2919, 2851,
1644, 1030 cmꢁ1 1H NMR (300 MHz, CDCl3): 0.18 (s, 9H), 1.40 (s,
;
1462, 1374, 1039 cmꢁ1 1H NMR (300 MHz, CDCl3); 1.40 (s, 3H),
;
3H), 1.50 (s, 3H), 3.53 (m, 1H), 3.55 (s, 3H), 4.21 (dd, 1H, J = 6.0,
9.6 Hz), 4.54–4.67 (m, 3H), 4.72 (t, 1H, J = 6.4 Hz), 4.90 (d, 1H,
J = 11.8 Hz), 5.24 (d, 1H, J = 10.3 Hz), 5.39 (d, 1H, J = 17.5 Hz), 5.87
(m, 1H); 13C NMR (75 MHz, CDCl3): ꢁ0.1, 25.2, 27.8, 56.2, 63.5,
76.3, 77.8, 78.4, 84.3, 90.8, 97.9, 103.2 108.8, 116.9, 133.6; ESI/
MS (m/z): 351 (M+Na)+; HRMS Calcd for C16H28O5NaSi (M+Na)+
351.1603, found 351.1590.
1.41 (s, 3H), 3.42 (s, 3H), 3.47 (s, 3H), 4.04 (dd, 1H, J = 3.02,
6.6 Hz), 4.25 (d, 1H, J = 6.6 Hz), 4.53 (dd, 1H, J = 3.02, 5.85 Hz),
4.67 (dd, 1H, J = 3.2, 5.85 Hz), 4.80 (d, 1H, J = 6.8 Hz), 4.86 (d, 1H,
J = 6.8 Hz), 5.18 (d, 1H, J = 10.9 Hz), 5.48 (d, 1H, J = 17.5 Hz), 5.86
(d, 1H, J = 3.2 Hz), 6.38 (dd, 1H, J = 10.9, 17.5 Hz); 13C NMR
(75 MHz, CDCl3): 26.1, 27.1, 55.5, 57.9, 72.2, 73.8, 74.2, 75.9,
97.0, 109.8, 115.4, 125.7, 135.8, 137.3; ESI/MS (m/z): 293 (M+Na)+.
4.9. (1R,2S)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-
1-(methoxymethoxy)-but-3-yn-2-ol 21a
4.12. (3aS,6S,7R,7aS)-6-Methoxy-7-(methoxymethoxy)-2,2-
dimethyl-3a,6,7,7a-tetra-hydrobenzo[d][1,3]dioxole-5-
carbaldehyde 23
To a stirred solution of silyl derivative 19 (0.95 g, 2.9 mmol) in
dry MeOH (5 mL) was added K2CO3 (1.2 g, 8.6 mmol) under nitro-
gen atmosphere. After being stirred for 2 h at room temperature,
the reaction mixture was filtered through a Celite pad and washed
with ethyl acetate. Then MeOH was evaporated under reduced
pressure. The residue was extracted with CHCl3 (3 ꢂ 50 mL), and
the organic extract was washed with water, brine, dried over anhy-
drous Na2SO4, concentrated under reduced pressure and purified
by silica gel column chromatography using EtOAc/hexane (5:1)
4.12.1. Method A
To an ice cooled stirred solution of compound 22 (0.2 g,
0.74 mmol) in acetone/water (4:1), (5 mL) were added NMO
(0.2 g, 1.48 mmol) and OsO4 (in toluene) (0.003 g, 0.0.15 mmol),
stirred for 3 h at 0 °C. To this reaction mixture NaIO4 (0.31 g,
1.48 mmol) was added at 0 °C and stirred for 1 h. The solvent
was removed and the residue was taken in EtOAc (75 mL) and
washed with water and brine. The solvent was removed on a rotary
evaporator, the crude aldehyde 23 was submitted to column chro-
matography and eluted using EtOAc/hexane (1:1) to give aldehyde
23 (0.1 g, 50%) as a syrup.
to give 21(a) (0.63 g, 85%) as a liquid. ½a D24
ꢀ
¼ þ11:0 (c 2.2, CHCl3);
IR (neat)
m ;
max: 3516, 2926, 2173, 1377, 1033 cmꢁ1 1H NMR
(300 MHz, CDCl3): 1.41 (s, 3H), 1.52 (s, 3H), 2.52 (d, 1H,
J = 1.98 Hz), 3.41 (s, 3H), 3.55 (d, 1H, J = 11 Hz, –OH), 3.63 (dd,
1H, J = 3.3, 8.8 Hz), 4.55 (dd, 1H, J = 6.3, 8.8 Hz), 4.66 (d, 1H,
J = 6.7 Hz), 4.72 (d, 1H, J = 6.7 Hz), 4.68–4.80 (m, 2H), 5.27 (d, 1H,
J = 10.4 Hz), 5.40 (d, 1H, J = 17.1 Hz), 5.92 (m, 1H); 13C NMR
(75 MHz, CDCl3): 25.2, 27.6, 56.1, 64.2, 73.9, 77.4, 77.4, 78.6,
82.3, 97.9, 109.2, 117.8, 133.4; ESI/MS (m/z): 293 (M+Na)+; HRMS
Calcd for C14H22O5Na (M+Na)+ 279.1208, found 279.1208.
4.12.2. Method B
To an ice cooled stirred solution of alcohol 26(b) (0.30 g,
0.7 mmol) in DCM (3 mL) TEMPO (0.001 g, 0.01 mmol) and BAIB
(0.042 g, 0.13 mmol) were added. The reaction mixture was stirred
at room temperature for 1 h extracted with DCM. The organic layer
was washed with brine, separated, and dried over anhydrous
Na2SO4, purification by column chromatography using EtOAc/hex-
ane (3:7) gave compound 23 (0.026, 65%) as a syrup.
4.10. (4S,5S)-4-((1R,2S)-2-Methoxy-1-(methoxymethoxy)but-3-
ynyl)-2,2-dimethyl-5-vinyl-1,3-dioxolane 21b
½
a 2D4
ꢀ
¼ þ78:2 (c 1.5, CHCl3); IR (neat)
mmax: 2923, 1742, 1459,
1258, 1019 cmꢁ1 1H NMR (300 MHz, CDCl3): 1.41 (s, 3H), 1.43
;
To an ice-cooled, stirred solution of NaH (0.18 g, 60% w/v dis-
persion in mineral oil, 4.68 mmol) in THF (5 mL) were added com-
pound 21(a) (0.65 g, 2.34 mmol) in THF (5 mL) and methyl iodide
(0.25 mL, 3.8 mmol). The mixture was stirred at room temperature
for 3 h. It was quenched with saturated aqueous NH4Cl solution
and extracted with EtOAc (2 ꢂ 75 mL). The combined organic lay-
ers were washed with water and brine, then dried over Na2SO4
and concentrated in vacuo. The crude material was purified by col-
umn chromatography on silica gel using EtOAc/hexane (9:1) to
(s, 3H), 3.35 (s, 3H), 3.46 (s, 3H), 4.08 (dd, 1H, J = 3.3, 5.2 Hz),
4.37 (d, 1H, J = 5.2 Hz), 4.60 (dd, 1H, J = 3.3, 6.4 Hz), 4.69 (d, 1H,
J = 6.8 Hz), 4.80 (m, 1H), 4.81 (d, 1H, J = 6.8 Hz), 6.83 (d, 1H,
J = 2.8 Hz), 9.64 (s, 1H); 13C NMR (75 MHz, CDCl3): 25.4, 26.6,
55.6, 59.2, 71.1, 72.5, 72.5, 74.1, 97.1, 110.4, 140.0, 145.4, 192.3;
ESI/MS (m/z): 295 (M+Na)+; HRMS Calcd for C13H20O6Na (M+Na)+
295.1157, found 295.1162.
4.13. (3aS,6S,7R,7aS)-Methyl-6-methoxy-7-(methoxymethoxy)-
2,2-dimethyl-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxole-5-
carboxylate 24
give compound 21(b) (0.48 g, 70%) as a syrup. ½a D24
ꢀ
¼ ꢁ8:9 (c 1.1,
CHCl3); IR (neat)
m ;
max: 3257, 2926, 2854, 1375, 1039 cmꢁ1 1H
NMR (300 MHz, CDCl3): 1.35 (s, 3H), 1.46 (s, 3H), 2.45 (d, 1H,
J = 1.8 Hz), 3.38 (s, 3H), 3.44 (s, 3H), 3.75 (dd, 1H, J = 3.02, 7.5 Hz),
4.20 (dd, 1H, J = 2.26, 3.02 Hz), 4.34 (dd, 1H, J = 6.4, 7.5 Hz), 4.61
(dd, 1H, J = 6.04, 6.4 Hz), 4.77 (d, 1H, J = 6.4 Hz), 4.88 (d, 1H,
J = 6.4 Hz), 5.22 (d, 1H, J = 10.2 Hz), 5.35 (d, 1H, J = 16.9 Hz), 6.06
To an ice cooled stirred solution of compound 23 (0.1 g,
0.36 mmol) in t-BuOH (1.5 mL) were added 2-methyl-2-butene
(0.4 mL), NaClO2 (0.1 g, 1.1 mmol) and NaH2PO4 (0.17 g, 1.1 mmol)
were added and stirred for 2 h at room temperature. Then the

92
Ch. MuniRaju et al. / Tetrahedron: Asymmetry 23 (2012) 86–93
reaction mixture was neutralized with aqueous 1 M HCl and ex-
tracted with EtOAc (2 ꢂ 50 mL). The organic layers were combined
and washed with water and brine, then dried over Na2SO4 and con-
centrated in vacuum. The crude acid was dissolved in acetone
(2 mL) to it were added K2CO3 (0.1 g, 0.72 mmol) and methyl io-
dide (0.03 mL, 0.44 mmol) and stirred for 3 h. The reaction mixture
was filtered through a Celite pad and washed with EtOAc; the fil-
trate was concentrated under vacuum, the residue was dissolved
in (50 mL) of EtOAc, washed with water, brine and dried over
Na2SO4. The solvent was removed on a rotary evaporator; the
crude ester 24 was purified by column chromatography using
EtOAc/hexane (2:3) to give ester 24 (0.04 g) as a syrup in an 80%
extracted with EtOAc (2 ꢂ 50 mL). The combined organic layers
were washed with water and brine, then dried over Na2SO4 and
concentrated in vacuo. The crude material was purified by column
chromatography on silica gel by using EtOAc/hexane (1:9) to give
compound 26(a) (0.1 g, 70%) as a syrup. ½a D24
¼ ꢁ7:3 (c 1.17,
ꢀ
CHCl3); IR (neat) m ;
max: 2933, 2355, 1201, 1119, 1030, 908 cmꢁ1
1H NMR (CDCl3, 300 MHz): 1.39 (s, 3H), 1.40 (s, 3H), 1.44–1.90
(m, 6H), 3.46 (s, 3H), 3.57 (2s, 3H), 3.80–3.90 (m, 2H), 3.95–4.13
(m, 3H), 4.30 (m, 1H), 4.51 (br s, 1H), 4.58–4.69 (m, 3H), 4.82–
4.91 (m, 2H), 5.69 (br s, 1H); 13C NMR (CDCl3, 75 MHz): (19.1,
19.3)*, 25.4, (26.5, 26.6)*, (27.6, 27.7)*, (30.5, 30.6)*, 55.5, 60.5,
60.7, 61.8, 62.1, 66.0, 66.6, 73.1, (75.3, 75.4)*, 77.09, (77.7, 77.8)*,
(96.7, 96.8)*, 97.1, 98.3, 109.6, 109.7, 122.5, 123.4, 137.0, 137.4;
ESI/MS (m/z); 381 (M+Na)+.
yield (over 2 steps). ½a D24
ꢀ
¼ þ45:6 (c 0.8, CHCl3); IR (neat) mmax
:
2921, 2363, 1693, 1516, 1025 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
1.42 (s, 3H), 1.43 (s, 3H), 3.43 (s, 3H), 3.54 (s, 3H), 3.82 (s, 3H),
4.04 (dd, 1H, J = 3.3, 6.04 Hz), 4.4 (d, 1H, J = 6.04 Hz), 4.57 (dd,
1H, J = 3.02, 5.6 Hz), 4.72 (m, 1H), 4.78 (d, 1H, J = 6.79 Hz), 4.86
(d, 1H, J = 6.79 Hz), 6.82 (d, 1H, J = 3.02); 13C NMR (75 MHz, CDCl3);
25.7, 26.9, 52.0, 55.6, 59.6, 71.5, 74.0, 74.0, 75.0, 97.0, 110.2, 132.2,
136.0, 166.6; ESI/MS (m/z): 325 (M+Na)+; HRMS Calcd for
4.17. ((3aS,6S,7R,7aS)-6-Methoxy-7-(methoxymethoxy)-2,2-
dimethyl-3a,6,7,7a-tetra-hydrobenzo[d][1,3]dioxol-5-
yl)methanol 26(b)
To compound 26(a) (0.1 g, 0.36 mmol) in methanol (5 mL) at
0 °C, a catalytic amount of PPTS was added. The mixture was stir-
red for 1 h at 0 °C, the methanol was removed under vacuo and
purified by column chromatography using EtOAc/hexane (3:2) to
C
15H24O7Na (M+Na)+ 325.1263, found 325.1257.
4.14. (+)-Pericosine C 3
give compound 26(b) (0.05 g, 65%) as a syrup. ½a D24
¼ þ22:5 (c
ꢀ
To a solution of compound 24 (0.04 g, 0.13 mmol) in methanol
(1 mL) TFA (0.5 mL) was added and the reaction mixture stirred
at room temperature for 3 h. Then the solvent was removed under
vacuum to afford crude (+)-pericosine C, which was subjected to
column chromatography and eluted using MeOH/CHCl3 (1:24) to
0.17, CHCl3): IR (neat) mmax: 3470, 2926, 1376, 1123, 1031, 975,
907, 863 cmꢁ1 1H NMR (CDCl3, 300 MHz); 1.37 (s, 6H), 3.46 (s,
;
3H), 3.64 (s, 3H), 3.86 (dd, 1H, J = 2.4, 8.3 Hz), 4.04–4.28 (m, 4H),
4.51–4.64 (m, 2H), 4.86 (s, 2H), 5.63 (br s, 1H); 13C (CDCl3,
75 MHz): 26.4, 27.7, 55.6, 61.1, 64.4, 73.1, 75.1, 78.4, 78.7, 96.7,
109.6 124.0, 138.9; ESI/MS (m/z): 297 (M+Na)+.
give (+)-pericosine
C
3
as an oil (0.018 g) in
a
65% yield.
¼ þ69:9 (c 0.17, EtOH)); IR
1H NMR
½
a 2D4
ꢀ
¼ þ72:1 (c 0.9, EtOH); (lit.6e
½ ꢀ
a 2D0
(neat)
m
max: 3620, 2924, 2362, 1740, 1462, 1080 cmꢁ1
;
Acknowledgements
(acetone-d6, 300 MHz): 3.49 (s, 3H), 3.77 (s, 3H), 3.87–3.93 (m,
2H), 3.94–4.02 (m, 2H, 1 -OH), 4.20 (d, 1H, J = 4.5 Hz), 4.27 (m,
1H), 4.43 (d, 1H J = 6.0 Hz, OH), 6.75 (1H, d, J = 3.7 Hz); 13C NMR
(acetone-d6, 75 MHz): 52.00, 59.4, 67.4, 70.1, 73.3, 79.1,131.5,
140.4, 166.7; ESI/MS (m/z): 241 (M+Na)+; HRMS Calcd for
C9H14O6Na (M+Na)+ 241.0688, found 241.0678.
CH.M.R and J.P.R thank CSIR-New Delhi for research fellowship.
The authors also thank Dr. J.S. Yadav and Dr. G.V.M. Sharma for
their constant support and encouragement. We also thank DST
(SR/S1/OC-14/2007), New Delhi for financial assistance.
References
4.15. (3aS,4R,5S,7aS)-4-(Methoxymethoxy)-2,2-dimethyl-6-
((tetrahydro-2H-pyran-2-yloxy)methyl)-3a,4,5,7a-
tetrahydrobenzo[d][1,3]dioxol-5-ol 25
1. (a) Arjona, O.; Gomez, A. M.; Lopez, J. C.; Plumet, J. Chem. Rev. 2007, 107, 1919;
(b) Plumet, J.; Gomez, A. M.; Lopez, J. C. Min. Rev. Org. Chem. 2007, 4, 201.
2. (a) McCasland, G. E.; Furuta, S.; Durham, L. J. J. Org. Chem. 1966, 31, 1516; (b)
Suami, T.; Ogawa, S. Adv. Carbohydr. Chem. Biochem. 1990, 48, 21.
3. (a) Asano, N. Glycobiology 2003, 13, 10; (b) de Melo, E. B.; Gomes, A. S.;
Carvalho, I. Tetrahedron 2006, 62, 10277; (c) Cipolla, L.; Araujo, A.; Bini, D.;
Gabrielli, L.; Russo, L.; Shaikh, N. Expert. Opin. Drug Discov. 2010, 5, 721; (d)
Cipolla, L.; Ferla, B. L.; Airoldi, C.; Zona, C.; Orsato, A.; Shaikh, N.; Russo, L.;
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4. (a) Numata, A.; Iritani, M.; Yamada, T.; Minoura, K.; Matsumura, E.; Yamori, T.;
Tsuruo, T. Tetrahedron Lett. 1997, 38, 8215; (b) Yamada, T.; Iritani, M.; Ohishi,
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3979.
To a solution of 13 (0.2 g, 0.7 mmol) in toluene (44 mL), Grubbs
second generation catalyst (0.062 g, 0.07 mmol) was added at
room temperature and refluxed for 12 h. Toluene was removed un-
der vacuo and purified by column chromatography using EtOAc/
hexane (1:4) to provide cyclohexenol 25 as an oily compound
(0.14 g, 80%). ½a D24
ꢀ
¼ þ76:31 (c 0.56, CHCl3): IR (neat)
mmax: 2933,
2355, 1201, 1119, 1030, 908, 762 cmꢁ1
;
1H NMR (300 MHz); 1.39
5. Review on Pericosines synthesis Usami, Y.; Ichikawa, H.; Arimoto, M. Int. J. Mol.
Sci. 2008, 9, 401.
(s, 6H), 1.42–1.67 (m, 6H), 3.43–3.56 (m, 4H), 3.64–3.94 (m, 2H),
4.15 (m, 1H), 4.31–4.70 (m, 5H), 4.78–4.99 (m, 2H), 5.66 (d, 1H,
J = 9.0 Hz); 13C (CDCl3, 75 MHz); (19.3, 19.9)*, (25.2, 25.3)*, 26.6,
27.7, 30.4, 30.7, 55.8, 62.2, 63.1 66.9, 67.2, 67.5, 68.2, 73.6, (75.4,
75.5)*, 80.7, 81.5, (97.6, 97.6)*, 98.3, 98.5, 109.84, 116.2, 122.6,
123.3, (136.9, 137.1); ESI/MS (m/z): 367 (M+Na)+.
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dimethyl-6-((tetrahydro-2H-pyran-2-yloxy)methyl)-3a,4,5,7a-
tetrahydrobenzo[d][1,3]dioxole 26(a)
To an ice-cooled, stirred solution of NaH (0.03 g, 60% w/v dis-
persion in mineral oil, 0.88 mmol) in THF (5 mL) were added com-
pound 25 (0.14 g, 0.41 mmol) in THF (5 mL) and methyl iodide
(0.03 mL, 0.6 mmol). The mixture was stirred at room temperature
for 3 h and then quenched with saturated NH4Cl solution and

Ch. MuniRaju et al. / Tetrahedron: Asymmetry 23 (2012) 86–93
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