A convenient synthesis of carbohydrate derived furo/pyrano[2,3-b]pyrans from 2-hydroxymethyl glycals

Article abstract of DOI:10.1016/j.tet.2017.05.069

An efficient method for the stereoselective synthesis of various linearly fused bicyclic acetals using 2-hydroxymethyl glycals, involving Ferrier type rearrangement and ring-closing metathesis as the key steps, is revealed. The methodology was shown to be very general by applying it to various sugar substrates which lead to the formation of various bicyclic furo/pyrano[2,3-b]pyran ring systems.

Full text of DOI:10.1016/j.tet.2017.05.069

Accepted Manuscript
A convenient synthesis of carbohydrate derived furo/pyrano[2,3-b]pyrans from 2-
hydroxymethyl glycals
Sudharani Chalapala, Ramakrishna Bandi, Bhumireddy Chinnachennaiahgari
Venkatesh, Ramu Sridhar Perali
PII:
S0040-4020(17)30570-7
10.1016/j.tet.2017.05.069
TET 28735
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 6 February 2017
Revised Date: 19 April 2017
Accepted Date: 19 May 2017
Please cite this article as: Chalapala S, Bandi R, Venkatesh BC, Perali RS, A convenient synthesis of
carbohydrate derived furo/pyrano[2,3-b]pyrans from 2-hydroxymethyl glycals, Tetrahedron (2017), doi:
10.1016/j.tet.2017.05.069.
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ACCEPTED MANUSCRIPT
Graphical Abstract
A Convenient Synthesis of Carbohydrate
Derived Furo/Pyrano[2,3-b]pyrans from 2-
hydroxymethyl Glycals
Leave this area blank for abstract info.
Sudharani Chalapala, Ramakrishna Bandi, Venkatesh Bhumireddy Chinnachennaiahgari and
Ramu Sridhar Perali∗
School of Chemistry, University of Hyderabad, Hyderabad-500 046, India
O
O
O
2
steps
OH
n
BnO
BnO
OBn
OBn
n = 1 furo[2,3-b]pyrans
n = 2 pyrano[2,3-b]pyrans
2-hydroxymethyl glycal

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
A Convenient Synthesis of Carbohydrate Derived Furo/Pyrano[2,3-b]pyrans
from 2-hydroxymethyl Glycals
Sudharani Chalapala, Ramakrishna Bandi, Venkatesh Bhumireddy Chinnachennaiahgari and Ramu Sridhar
Perali∗
School of Chemistry, University of Hyderabad, Hyderabad-500 046, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient method for the stereoselective synthesis of various linearly fused bicyclic acetals
using 2-hydroxymethyl glycals, involving Ferrier type rearrangement and ring-closing
metathesis as the key steps, is revealed. The methodology was shown to be very general by
applying it to various sugar substrates which lead to the formation of various bicyclic
furo/pyrano[2,3-b]pyran ring systems.
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords:
Carbohydrates
Bicyclic acetals
Fused rings
Glycals
Ring-closing metathesis
1
. Introduction
(Figure 1). On the other hand, pyrano[2,3-b]pyran containing
compound 1 is an important precursor in the total synthesis of
ansamycins whereas compound 2 is a natural product produced
Linearly fused bicyclic acetals are ubiquitously present as
9
1
subunits in a number of bio-active natural products. A major
portion of these bicyclic acetals exists either as furo[2,3-b]pyrans
or pyrano[2,3-b]pyrans. For instance, Benesudon (antibacterial
by a rare bacterial strain Actinoalloteichus nanshanensis sp.
10
Nov. The glycofused benzopyran 3 was recently identified as a
novel ligand for amyloid β peptidase in the development of novel
2
and cytotoxic with IC values of 1-2 µg/mL), Euplotin A, B,
11
90
therapeutics for Alzheimer’s disease (Figure 2).
3
4
5
and C (cytotoxic), Novaxenicin A and B (induces apoptosis),
–)-Penifulvin (potent insecticides),
(
A
a6nd
B
7
Tetrahydroaplysulfurin-1, Cadlinolides A, B and C, and
Neopeapyran possess the furo[2,3-b]pyran framework
8
Figure 2: Representative natural and synthetic products
containing the pyrano[2,3-b]pyran structure.
Very often, the presence of the bicyclic acetal system in bio-
active molecules is vital for acquiring the appropriate molecular
conformation that helps in eliciting the biological response. In
general, the formation of these bicyclic acetal motifs involves the
halo etherification of cyclic vinyl ethers, using NBS or NIS and
allyl or propargyl alcohol, followed by a radical cyclization to
12
produce the corresponding bicyclic acetals. Various radical
13
14
15
16
initiators like Vitamin B , AIBN, Et B, Co(salen), etc.,
12
3
have been studied for the radical cyclization reactions.
Carbohydrate derived vinyl ethers, generally called as glycals,
have been one of the highly studied precursors in radical
Figure 1: Representative natural products possessing furo[2,3-
b]pyran framework.
17
cyclization reactions. Apart from these, we previously reported
—
——
∗
Corresponding author. Tel.: +91-40-2313-4823; fax: +91-40-2301-2460; e-mail: prssc@uohyd.ernet.in

2
Tetrahedron
ed MANUSCRIPT
1
A
8
the application of 2-C-branched sugars
,
C
3-C-bran
C
E
P
TED
ch
19
20
glycals and 1,2-cyclopropanated sugar derivatives for the
stereoselective preparation of a variety of furo/pyrano[2,3-
b]furans/pyrans. Very recently, Vankar et al. reported a distinct
method involving Grignard addition of allyl and vinyl
magnesium halides on allyl-2-oxo-glycosides followed by ring-
21a
closing metathesis to produce pyrano[2,3-b]pyran/oxepines.
A
similar protocol was also described to synthesize 1,2-annulated
21b
sugars with β-mannose configuration. In addition to the above
methods, very few approaches were available for the synthesis of
furo/pyrano[2,3-b]pyran ring systems encompassing acid-
2
2
catalyzed2 cyclization of hydroxyacetals,
cycloaddition
3
24
reactions,
intramolecular dehydration reactions
and
25
ketalization of acyclic dihydroxyaldehydes.
In continuation of our efforts in the synthesis of fused bicyclic
26
acetals, herein we report the application of C-2-methylene
glycosides in the synthesis of furo/pyrano[2,3-b]pyrans in two
steps comprising Ferrier type rearrangement and ring closing
metathesis.
2
. Results and Discussion
Scheme 2: Synthesis of
D-arabinose derived furo/pyrano[2,3-
We intended the synthesis of furo/pyrano[2,3-b]pyran systems
b]pyran frameworks. Reagents and conditions: (a) G-II (20
mol%), toluene, 80 C. (b) G-I (20 mol%), toluene, 80 C.
o
o
starting from C-2-methylene O-alkenyl glycosides of various
27
length. Towards this, 2-hydroxymehtyl D-arabinal 7 was treated
28
Encouraged by these observations, we extended the
methodology to glucal and galactal derived 2-hydroxymethyl
with allyl alcohol 4 in the presence of catalytic InCl3 to provide
the C-2-methylene α- and β-glycosides 8 and 9. In a similar way
glycosides 10, 11 and 12, 13 were synthesized by the Ferrier type
rearrangement of 7 with 3-butenyl alcohol 5 and 4-pentenyl
30
derivatives 21 and 22 respectively. Thus, glucal derived C-2
28
31
methylene O-glycosides 23, 24 and 25 were prepared from 21,
28
31
29
galactose derived C-2-methylene O-glycosides 26, 27 and 28
alcohol 6, respectively (Scheme 1).
were obtained from 22 by following the procedure for the
preparation of compound 8. (Table 1). Unlike in the case of 2-
hydroxymethyl arabinal derivative 7, the Ferrier type
rearrangement of 21 and 22 with O-nucleophilic allyl alcohol 4,
3
-butenyl alcohol 5 and 4-pentenyl alcohol 6 provided the
corresponding C-2-methylene-α- -glycosides as the only
D
products. No isolable amounts of the C-2-methylene-β-D-
glycosides were obtained.
Scheme 1: Synthesis of
O-glycoside derivatives.
D-arabinose derived C-2-methylene
Having a series of D-arabinose derived glycoside dienes 8-13
in hand, we proceeded to synthesize various bicyclic acetals
using ring closing metathesis reaction. Thus, allyl
nd
arabinopyranosides 8 and 9 upon treatment with Grubb’s 2
generation catalyst (G-II) provided the furo[2,3-b]pyran
derivatives 14 and 15 as the only products respectively, in good
yield (Scheme 2). Similarly, 3-butenyl alcohol derived
arabinopyranoside derivatives 10 and 11 upon exposing to G-II
provided the corresponding pyrano[2,3-b]pyran derivatives 16
and 17 respectively, again as the only products. However,
subjecting the 4-pentenyl derived arabinopyranoside 12 to RCM
reaction using G-II provided the dimerization product 19 and no
detectable amount of the expected pyrano[2,3-b]oxepine 18 was
Table 1: Synthesis of
methylene O-glycosides.
D
-glucose and
D
-galactose derived C-2-
Subjecting C-2-methylene allyl α-
RCM provided the furo[2,3-b]pyran 29 along with the olefin
migrated furo[2,3-b]pyran 30 in 1:1 ratio in 61% yield. On the
D-glucopyranoside 23 to
other hand, C-2-methylene 3-butenyl α-D-glucopyranoside 24
upon RCM with G-II provided the expected pyrano[2,3-b]pyran
derivative 31 in 34% yield along with a mixture of furo[2,3-
b]pyran 30 and 2-C-branched glycal 32 in 34%. Whereas, RCM
of compound 25 using G-I or G-II gave the dimer 33 (cis, trans
st
observed. Carrying out the reaction using Grubbs 1 generation
catalyst (G-I) also did not show any change in the product
formation. Subjecting the β-isomer 13 to G-I or G-II mediated
RCM reaction also lead to the formation of dimer 20 as the only
isolable product (Scheme 2).
(
0.75:1) mixture) as the only isolable product (Scheme 3).

3
ACCEPTED MANUSCRIPT
OBn
O
OBn
OBn
a
O
O
2
6
BnO
BnO
O
4
9%
3
4
OBn
a
2
2
7
8
Complex mixture
OBn
O
OBn
OBn
a or b
6%
O
O
BnO
BnO
O
5
35
OBn
Scheme 5: RCM reaction of galactose derived C-2-methylene
D-galactopyranoside derivatives. Reagents and conditions: (a)
G-II (20 mol%), toluene, 80 C. (b) G-I (20 mol%), toluene, 80
α-
o
o
C.
Scheme 3: Synthesis of
D-glucose derived furo/pyrano[2,3-
b]pyran frameworks. Reagents and conditions: (a) G-II (20
o
o
mol%), toluene, 80 C. (b) G-I (20 mol%), toluene, 80 C.
The formation of the unexpected products 30 and 32 from 24
could be explained by considering the following possible
intermediates. It has been reported in the literature that terminal
olefins undergo olefin migration under the influence of Ru
32
catalysts. Thus, 24 in the presence of Grubs II might undergo
olefin migration producing the intermediates 24a and 24b. 24a
upon RCM would produce the furo[2,3-b]pyran 29 which could
undergo further olefin migration leading to the formation of 30.
On the other hand, intermediate 24b could result in the formation
Scheme 6: Synthesis of fully saturated linearly fused bicycles.
of 2-C-branched glycal 32 involving
rearrangement (Scheme 4).
a
3,3-sigmatropic
To further extend the scope of the reaction we planned to
synthesize substituted furo[2,3-b]pyran ring systems. Towards
this, 2-acetoxymethyl glucal derivative 38 upon reaction with
alcohol 39 in the presence of InCl gave the C-2-methylene
3
glycoside 40 (as a single diastereomer in 25% isolated yield)
along with a mixture of all the diastereomers. Subjecting the
glycoside 40 to G-II mediated ring-closing metathesis allowed
the isolation of phenyl substituted furo[2,3-b]pyran derivative 41
as a single diastereomer (Scheme 7).
Scheme 4: Possible intermediates in the formation of furo[2,3-
b]pyran 30 and 2-C-branched glycal 32 from 24.
Unexpectedly, the C-2-methylene α-D-galactopyranoside
derivatives 26 and 28 upon exposing to G-II provided only the
dimerization products 34 and 35, respectively, whereas the 27
lead to the formation of a complex mixture of products (Scheme
Scheme 7: Synthesis of aryl substituted furo[2,3-b]pyran
framework.
5
).
3
. Conclusion
In view of synthesizing fully saturated furo[2,3-b]pyran and
pyrano[2,3-b]pyran derivatives, compounds 14 and 31 were
In conclusion, various C-2-methylene glycosides were
hydrogenated using Pd/C, in EtOH having a trace amount of Et N
3
synthesized involving Ferrier type rearrangement of 2-
hydroxymethyl glycals with different alkenols. The obtained
dienes were subjected to RCM reaction to provide a variety of
bicyclic acetal systems. These observations revealed that the
formation of furo[2,3-b]pyran and pyrano[2,3-b]pyran systems is
reasonably facile in the case of arabinose and glucose derived
to provide bicyclic acetals 36 and 37, as single diastereomers in
excellent yield (Scheme 6).

4
Tetrahedron
dienes. Whereas, the synthesis of pyrano[2,3-
A
b]o
C
xe
C
pi
E
ne
P
s
T
ys
E
tem
D
s
MA
Hz),
N
U
1
4.
S
36
C
-4
R
.3
I
7
P
(m, C4-H, 1H), 4.19-4.23 (m, C1'-H 1H), 4.03-
a,
T
was unsuccessful. Interestingly the galactose derived dienes were
highly resistant to undergo RCM indicating the influence of the
stereochemistry on pyranose ring. Further application of the
developed methodology in the total synthesis of natural products
is in progress.
4.07 (m, C1'-H 1H), 3.82-3.88 (m, C6-H , 2H), 3.76 (m, C5-H,
b
a,b
3
1H). C NMR (CDCl , 100 MHz): δ 140.7, 138.3, 138.2, 134.0,
3
128.3, 128.2, 127.8, 127.5, 127.5, 127.3, 117.2, 111.9, 100.1,
76.1, 74.6, 71.4, 70.8, 68.1, 61.8. HRMS (ESI): calcd for
C H O +Na 389.1729 found 389.1727. Compound (9): R = 0.5
23
26
4
f
(
10% EtOAc/hexanes).
+108.6 (c 0.65, CHCl ); IR (neat):
3
4
. Experimental section
-
3
097, 3059, 3027, 2919, 2870, 1736, 1649, 1600, 1498, 1444 cm
1
1
.
H NMR (CDCl , 500 MHz): δ 7.26-7.41 (m, Ar-H, 10H),
3
General methods: Chemicals and solvents were purchased
®
5.88-5.978 (m, C2'-H, 1H), 5.26-5.36 (m, C3-methylene H , C3'-
H , 2H), 5.16-5.12 (m, C3-methylene H , C3'-H , 2H), 4.98 (s,
a
from the local suppliers and Sigma-Aldrich chemical company.
Solvents were used in the reactions after distilled over the
dehydrating agents. All the reactions were carried out under N2
atmosphere and monitored by the thin layer chromatography
a
b
b
C2-H (anomeric), 1H), 4.74 (d, benzyl-CH, 1H, J = 12.5 Hz),
.63 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.5 (d, benzyl-CH, 1H, J
12.5 Hz), 4.40 (d, benzyl-CH, 1H, J = 12.5 Hz), 4.22-4.29 (m,
C4-H, C6-H , 3H), 4.00-4.04 (m, C5-H, 1H), 3.58-3.62 (m, C1'-
4
=
(
TLC) using silica gel on aluminum plates (GF254) by charring
a,b
with 5% (v/v) H SO in methanol or by phosphomolybdic acid
2
4
13
Ha, 1H), 3.52-3.55 (m, C1'-Hb, 1H).
MHz): δ 139.9, 138.5, 138.1, 134.3, 128.3, 128.2, 128.0, 127.6,
27.6, 127.3, 118.4, 116.5, 98.9, 75.4, 75.2, 70.3, 69.1, 67.9,
57.8. HRMS (ESI): calcd for C H O +Na 389.1729 found
C NMR (CDCl , 100
3
(
2
PMA) stain or by ultra violet (UV) detection. Silica-gel (100-
00 mesh) was used for column chromatography to purify all the
compounds. IR spectra were recorded on JASCO FT/IR-5300.
1
1
13
®
23
26
4
H, C, DEPT spectra were recorded on Bruker 400 and 500
1
389.1729.
Avance MHz spectrometer in CDCl . H NMR chemical shifts
3
were reported in parts per million (ppm) (δ) with TMS as an
internal standard (δ 0.00), and C NMR were reported in
4.4. (2S,4S,5R)-4,5-bis(benzyloxy)-2-(but-3-en-1-yloxy)-3-
methylenetetrahydro-2H-pyran (10) and (2R,4S,5R)-4,5-
bis(benzyloxy)-2-(but-3-en-1-yloxy)-3-methylenetetrahydro-2H-
pyran (11)
13
chemical shifts with solvent reference (CDCl , δ 77.00). High-
3
resolution mass spectra (HRMS) were recorded on Bruker maXis
ESI-TOF spectrometer.
Compound 10 and 11 were synthesized from glycal 7 by
following the general experimental procedure A. Yield 69% with
4
.1. General experimental procedure (A): Synthesis of C-2-
methylene-O-glycosides
8
=
5:15 ratio, respectively as a colourless gum. Compound (10): Rf
0.5 (10% EtOAc/hexanes). -44.5 (c 1.0, CHCl ); IR
3
A
solution of 2-hydroxymethyl glycal (1 mmol) in
-1 1
(neat): 2917, 2866, 1723, 1666, 1496, 1453, 1360 cm . H NMR
dichloromethane (10 mL) was treated with alkenol (1.2 mmol) in
(
CDCl , 400 MHz): δ 7.28-7.40 (m, Ar-H, 10H), 5.78-5.88 (m,
3
the presence of 5 mol % InCl . The reaction mixture was stirred
3
C3'-H, 1H), 5.37 (s, C3-methylene H , 1H), 5.32 (s, C3-
a
at room temperature under nitrogen atmosphere for 2 hr. After
completion of the reaction (monitored by TLC), the reaction was
quenched with water and extracted with chloroform (3x25 mL).
The combined organic layers were washed with brine solution,
dried over anhydrous sodium sulfate, filtered and then
concentrated under reduced pressure. The crude product thus
obtained was further purified by column chromatography using
ethyl acetate: hexanes to give the C-2-methylene-O-glycosides in
good to moderate yield.
methylene H , 1H), 5.18 (s, C2-H (anomeric), 1H), 5.12 (d, C4'-
b
H ,1H, J = 17.2 Hz), 5.05 (d, C4'-H , 1H, J = 10.4 Hz), 4.74 (s,
a
b
benzyl-CH , 2H), 4.68 (d, benzyl-CH,1H, J = 12.0 Hz), 4.55 (dd,
2
benzyl-CH, 1H, J = 12.0 Hz), 4.35 (s, C4-H, 1H), 3.86 (bs, C6-
H , 2H), 3.75-3.86 (m, C1'-H , 2H), 3.52-3.58 (m, C5-H, 1H),
a,b
a,b
13
2
1
1
.38 (m, C2'-H , 2H). C NMR (CDCl , 100 MHz): δ 141.0,
a,b 3
38.2, 138.2, 134.9, 128.2, 128.2, 127.9, 127.4, 127.4, 127.3,
16.5, 111.8, 100.7, 76.1, 74.6, 71.3, 70.6, 66.8, 61.7, 33.9.
HRMS (ESI): calcd for C H O +Na 403.1885 found 403.1886.
24
28
4
4
.2. General Experimental procedure (B): Synthesis of
Compound (11): R
f
= 0.52 (10% EtOAc/hexanes).
+76.7 (c
-1
furo/pyrano[2,3-b]pyrans using ring closing metathesis reaction
1.0, CHCl ); IR (neat): 2986, 2926, 2850, 1495, 1454, 1330 cm .
3
1
H NMR (CDCl , 400 MHz): δ 7.26-7.42 (m, Ar-H, 10H), 5.82-
3
To a stirred solution of C-2-methylene-O-glycoside (0.15 mmol)
in anhydrous toluene (40 mL) at 80 °C under argon, Grubb’s
second generation catalyst 20 mol% was added, and the mixture
was stirred at 80 °C for 6-12 hr. The reaction mixture was bought
to room temperature and solvent was removed under reduced
pressure. The obtained residue was purified by column
chromatography on silica gel using ethyl acetate: hexanes as
eluent to provide the furo/pyrano[2,3-b]pyrans.
5
.92 (m, C3'-H, 1H), 5.31 (s, C3-methylene H , 1H), 5.14 (s, C3-
a
methylene H , 1H), 5.03-5.12 (m, C4'-H , 2H), 4.95 (s, C2-H
b
a,b
(anomeric), 1H), 4.74 (d, benzyl-CH, 1H, J = 12.4 Hz), 4.64 (d,
benzyl-CH, 1H, J = 12.0 Hz), 4.54 (d, benzyl-CH, 1H, J = 12.6
Hz), 4.39 (d, benzyl-CH, 1H, J = 12.4 Hz), 4.23-4.28 (m, C4-H,
C5-H, 2H), 3.78-3.84 (m, C6-H , 1H), 3.58-3.63 (m, C6-H , 1H),
a
b
3
.52-3.58 (m, C1'-H , 1H), 3.45-3.51 (m, C1'-H , 1H), 2.39-2.44
a b
13
(m, C2'-H , 2H). C NMR (CDCl , 100 MHz): δ 140.0, 138.5,
a
,
b
3
1
1
38.1, 135.3, 128.3, 128.1, 127.9, 127.6, 127.6, 127.3, 118.2,
16.2, 99.8, 75.4, 75.2, 70.3, 69.1, 67.1, 57.7, 34.1. HRMS (ESI):
4
.3. (2S,4S,5R)-2-(allyloxy)-4,5-bis(benzyloxy)-3-methylene
tetrahydro-2H-pyran (8) and (2R,4S,5R)-2-(allyloxy)-4,5-
bis(benzyloxy)-3-methylenetetrahydro-2H-pyran (9)
calcd for C24
H O +Na 403.1885 found 403.1887.
28 4
4
.5. (2S,4S,5R)-4,5-bis(benzyloxy)-3-methylene-2-(pent-4-en-1-
Compound 8 and 9 were synthesized from glycal 7 by following
the general experimental procedure A. Yield 76% with 90:10
yloxy)tetrahydro-2H-pyran (12) and (2R,4S,5R)-4,5-
bis(benzyloxy)-3-methylene-2-(pent-4-en-1-yloxy)tetrahydro-2H-
pyran (13)
ratio, respectively as a colourless gum. Compound (8): R = 0.48
f
(
10% EtOAc/hexanes).
-57.9 (c 1.0, CHCl ); IR (neat):
3
-
3
081, 3065, 3032, 2924, 2865, 1730, 1649, 1590, 1492, 1449 cm
Compound 12 and 13 were synthesized from glycal 7 by
following the general experimental procedure A. Yield 71% with
70:30 ratio, respectively as a colourless gum. Compound (12): Rf
= 0.52 (10% EtOAc/hexanes).
(neat): 3057, 3030, 2920, 2860, 2350, 1726, 1600, 1490, 1452,
1
1
.
H NMR (CDCl , 500 MHz): δ 7.26-7.38 (m, Ar-H, 10H),
3
5
.89-5.97 (m, C2'-H, 1H), 5.37 (d, C3-methylene H , 1H, J = 1.5
a
Hz), 5.27-5.31 (m, C3-methylene H , C2-H (anomeric), 2H),
b
-57.9 (c 1.0, CHCl ); IR
3
5
.18-5.21 (m, C3'-H , 2H), 4.73 (s, benzyl-CH , 2H), 4.67 (d,
a
,
b
2
-
1 1
benzyl-CH, 1H, J = 12.0 Hz), 4.54 (d, benzyl-CH, 1H, J = 12.0
1
397 cm . H NMR (CDCl , 500 MHz): δ 7.26-7.39 (m, Ar-H,
3

5
1
5
4
0H), 5.78-5.87 (m, C4'-H, 1H), 5.36 (s, C3-m
A
et
C
hy
C
len
E
e
P
H
T
,
E
1H
D
), MACo
N
m
U
po
general experimental procedure B. Yield 71%, as a colourless
gum. R = 0.5 (20% EtOAc/hexanes). -13.5 (c 1.0, CHCl );
S
un
C
d
R
1
I
6
PTwas synthesized from 10 by following the
a
.31 (s, C3-methylene H , 1H), 5.14 (s, C2-H (anomeric), 1H),
b
.98-5.08 (m, C5'-H , 2H), 4.73 (s, benzyl-CH , 2H), 4.68 (d,
a,b
2
f
3
-
1
benzyl-CH, 1H, J = 12.5 Hz), 4.55 (d, benzyl-CH, 1H, J = 12.5
Hz), 4.35 (s, C4-H, 1H), 3.85 (d, C6-H , 2H, J = 3.0 Hz), 3.77
IR (neat): 2917, 2863, 1729, 1609, 1501, 1444, 1419, 1387 cm .
1
H NMR (CDCl , 400 MHz): δ 7.27-7.38 (m, Ar-H, 10H), 5.89
a,b
3
(
9
d, C5-H, 1H, J = 3.0 Hz), 3.76 (dt, C1'-H , 1H, J = 6.5 Hz, J =
(d, C5-H, 1H, J = 4.4 Hz), 5.17 (s, C8a-H, 1H), 4.69 (d, benzyl-
CH, 1H, J = 12.4 Hz), 4.55 (d, benzyl-CH, 1H, J = 12.0 Hz),
4.48 (d, benzyl-CH, 1H, J = 12.8 Hz), 4.45 (d, benzyl-CH, 1H, J
a
.5 Hz), 3.50 (dt, C1'-H , 1H, J = 6.5 Hz, J = 9.5 Hz), 2.11-2.16
b
13
(m, C3'-H , 2H) 1.69-1.75 (m, C2'-H , 2H). C NMR (CDCl3,
a,b a,b
1
1
6
25 MHz): δ 141.0, 138.3, 138.3, 138.0, 128.2, 128.2, 127.7,
27.4, 127.3, 114.7, 111.7, 100.9, 76.3, 74.8, 71.3, 70.7, 67.1,
1.8, 30.2, 28.7. HRMS (ESI): calcd for C H O +Na 417.2042
= 12.8 Hz), 4.17 (d, C4-H, 1H, J = 2.8 Hz), 4.02 (t, C2-H , 1H, J
a
= 10.8 Hz), 3.89 (dd, C7-H , 1H, J = 5.2 Hz, J = 11.2 Hz), 3.84
a
(dd, C7-H , 1H, J = 4.8 Hz, J = 11.2 Hz), 3.73-3.79 (dt, C2-H ,
25
30
4
b
b
found 417.2038. Compound (13): Rf
EtOAc/hexanes). +81.1 (c 1.0, CHCl ); IR (neat): 2931,
865, 1638, 1490, 1452, 1205 cm . H NMR (CDCl , 500 MHz):
=
0.54 (10%
1H, J = 3.2 Hz, J = 10.8 Hz), 3.55 (ddd, C3-H, 1H, J = 3.2 Hz, J
= 4.8 Hz, J = 10.4 Hz), 2.27-2.40 (m, C6-H , 1H), 1.89-1.96 (m,
3
a
-
1
1
13
2
C6-H , 1H). C NMR (CDCl , 100 MHz): δ 138.0, 132.7, 128.3,
3
b
3
δ 7.26-7.41 (m, Ar-H, 10H), 5.77-5.85 (m, C4'-H, 1H), 5.30 (s,
128.3, 127.9, 127.7, 1276, 127.5, 126.2, 92.1, 76.4, 76.0, 70.6,
69.4, 63.3, 59.8, 24.3. HRMS (ESI): calcd for C H O +Na
C3-methylene H , 1H), 5.11 (s, C3-methylene H , 1H), 5.01 (dd,
a
b
22 24
4
C5'-H , 1H, J = 1.0 Hz, J = 17.0 Hz), 4.95 (dd, C5'-H , 1H, J =
375.1572 found 375.1571.
a
b
1
.0 Hz, J = 10. Hz), 4.93 (s, C2-H (anomeric), 1H), 4.74 (d, 1H,
benzyl-CH, J = 12.5 Hz), 4.64 (d, benzyl-CH, 1H, J = 12.0 Hz),
.54 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.40 (d, benzyl-CH, 1H, J
12.0 Hz), 4.20-4.24 (m, C4-H, C5-H, 2H), 3.75-3.80 (m, C1'-
H , 1H), 3.59-3.62 (m, C6-H ,1H), 3.53 (dd, C6-H , 1H, J = 5.0
4
.9. (3R,4S,8aR)-3,4-bis(benzyloxy)-2,3,4,6,7,8a-hexahydro
pyrano[2,3-b]pyran (17)
4
=
Compound 17 was synthesized from 11 by following the general
experimental procedure B. Yield 68%, as a colourless gum. R =
a
a
b
f
Hz, J = 11.0 Hz), 3.41-3.45 (m, C1'-H ,1H), 2.09-2.20 (m, C3'-
H , 2H), 1.68-1.75 (m, C2'-H , 2H). C NMR (CDCl , 125
MHz): δ 140.3, 138.6, 138.3, 138.2, 128.3, 128.2, 127.9, 127.6,
1
b
0. 5 (30% EtOAc/hexanes).
(neat): 2922, 2852, 1718, 1496, 1453, 1397, 1353 cm . H NMR
CDCl , 400 MHz): δ 7.26-7.41 (m, Ar-H, 10H), 6.20 (d, C5-H,
+60.2 (c 1.0, CHCl ); IR
3
-1 1
13
a,b
a,b
3
(
1
3
27.6, 127.2, 117.9, 114.6, 99.9, 75.7, 75.4, 70.4, 69.2, 67.0,
7.8, 30.3, 20.8. HRMS (ESI): calcd for C H O +Na 417.2042
H, J = 6.0 Hz), 4.83 (d, benzyl-CH, 1H, J = 12.8 Hz), 4.82 (s,
5
25
30
4
C8a-H, 1H), 4.76 (d, benzyl-CH, 1H, J = 11.2 Hz), 4.61 (d,
benzyl-CH, 1H, J = 12.4 Hz), 4.56 (d, benzyl-CH, 1H, J = 12.4
found 417.2044.
Hz), 4.12 (dd, C2-H , 1H, J = 1.6 Hz, J = 13.2 Hz), 4.00 (s, C4-
a
4
.6. (4S,5R,7aS)-4,5-bis(benzyloxy)-4,5,6,7a-tetrahydro-2H-
H, 1H), 3.95 (dd, 1H, C7-H , J = 2.8 Hz, J = 10.8 Hz), 3.89 (dd,
a
furo[2,3-b]pyran (14)
C7-H , 1H, J = 4.8 Hz, J = 10.8 Hz), 3.69 (s, C3-H, 1H), 3.42 (d,
b
Compound 14 was synthesized from 8 by following the general
C2-H , 1H, J = 13.2 Hz), 2.30-2.37 (m, C6-H , 1H), 2.04-2.10
b
a
13
experimental procedure B. Yield 77%, as a colourless gum. R =
(m, C6-H , 1H). C NMR (CDCl , 100 MHz): δ 138.4, 138.0,
f
b
3
0
1
1
5
4
5
.48 (30% EtOAc/hexanes). IR (neat): 2908, 2866, 1600, 1473,
132.1, 128.4, 128.2, 127.8, 127.6, 127.5, 127.2, 119.7, 94.6, 78.1,
73.2, 71.0, 70.9, 64.1, 60.7, 24.2. HRMS (ESI): calcd for
C H O +Na 375.1572 found 375.1572.
-
1 1
362 cm . H NMR (CDCl , 500 MHz): δ 7.28-7.35 (m, Ar-H,
3
0H), 5.98 (s, C7a-H, 1H), 5.83 (d, C3-H, 1H, J = 2.0 Hz), 5.80-
22
24
4
.81 (m, C2-H , 2H), 4.74 (d, benzyl-CH, 1H, J = 12.5 Hz),
a,b
4
.10. (E)-1,8-bis(((2S,4S,5R)-4,5-bis(benzyloxy)-3-
.59 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.57 (d, C6-H , 1H, J =
a
methylenetetrahydro-2H-pyran-2-yl)oxy)oct-4-ene (19)
.0 Hz), 4.50 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.89 (d, benzyl-
CH, 1H, J = 12.5 Hz), 4.02 (t, C5-H, 1H, J = 11.0 Hz), 3.85 (dd,
C6-H , 1H, J = 5.0 Hz, J = 11.5 Hz), 3.56-3.60 (m, C5-H, 1H).
Compound 19 was synthesized from 12 by following the general
b
experimental procedure B. Yield 56%, as a colourless gum. R =
f
13
C NMR (CDCl , 125 MHz): δ 137.8, 137.7, 136.2, 128.4,
3
0.4 (20% EtOAc/hexanes).
neat): 2915, 2843, 1731, 1654, 1446, 1358 cm . H NMR
(CDCl , 500 MHz): δ 7.29-7.39 (m, Ar-H, 20H), 5.41 (t, C4'-H,
-40.0 (c 0.66, CHCl ); IR
3
-1 1
1
7
3
28.0, 127.8, 127.8, 127.7, 126.4, 105.0, 76.6, 76.2, 70.9, 70.8,
(
0.2, 62.3. HRMS (ESI): calcd for C H O +Na 361.1416 found
21
24
4
3
61.1418.
2
H, J = 3.5 Hz), 5.34 (s, C3-methylene H , 2H), 5.30 (s, C3-
a
methylene H , 2H), 5.13 (s, C2-H (anomeric), 2H), 4.72 (s,
b
4
.7. (4S,5R,7aR)-4,5-bis(benzyloxy)-4,5,6,7a-tetrahydro-2H-
benzyl-CH , 4H), 4.67 (d, benzyl-CH, 2H, J = 12.0 Hz), 4.54 (d,
2
furo[2,3-b]pyran (15)
benzyl-CH, 2H, J = 12.0 Hz), 4.33 (s, C4-H, 2H), 3.84 (bs, C6-
Compound 15 was synthesized from 9 by following the general
H , 4H), 3.75-3,78 (m, C5-H, 2H), 3.68-3.72 (m, C1'-H , 2H),
a,b
a
experimental procedure B. Yield 81%, as a colourless gum. R =
3.45-3.48 (m, C1'-H , 2H), 2.04-2.06 (m, C3'-H , 4H), 1.63-1.69
b a,b
13
f
0
2
.4 (30% EtOAc/hexanes).
923, 2849, 1597, 1501, 1352 cm . H NMR (CDCl , 400 MHz):
+27.6 (c 0.5, CHCl ); IR (neat):
(m, C2'-H , 4H). C NMR (CDCl , 125 MHz): δ 141.1, 138.4,
a,b 3
3
-
1 1
138.3, 130.0, 128.3, 128.3, 127.8, 127.5, 127.5, 127.4, 111.8,
100.9, 76.3, 74.9, 71.4, 70.7, 67.3, 61.9, 29.6, 29.1. HRMS
(ESI): calcd for C H O +Na 783.3873 found 783.3873.
3
δ 7.28-7.41 (m, Ar-H, 10H), 6.12 (s, C7a-H, 1H), 5.53 (d, C3-H,
1
1
H, J = 4.4 Hz), 4.94-4.97 (m, C2-H , 1H), 4.82 (d, benzyl-CH,
a
48 56
8
H, J = 12.8 Hz), 4.79 (d, C2-H , 1H, J = 8.4 Hz), 4.76 (d,
b
4
.11. (E)-1,8-bis(((2R,4S,5R)-4,5-bis(benzyloxy)-3-
benzyl-CH, 1H, J = 12.8 Hz), 4.68 (d, benzyl-CH, 1H, J = 12.4
Hz), 4.63 (d, benzyl-CH, 1H, J = 12.4 Hz), 4.22 (s, C4-H, 1H),
methylenetetrahydro-2H-pyran-2-yl)oxy)oct-4-ene (20)
4
1
.09 (dd, C6-H , 1H, J = 1.6 Hz, J = 13.2 Hz), 3.74 (s, C5-H,
a
13
Compound 20 was synthesized from 13 by following the general
H), 3.41 (d, C6-H , 1H, J = 13.2). C NMR (CDCl , 100 MHz):
b
3
experimental procedure B. Yield 45%, as a colourless gum. R =
f
δ 138.2, 137.8, 136.1, 128.4, 128.3, 128.0, 127.7, 127.6, 127.3,
21.6, 107.3, 76.0, 73.6, 71.3, 70.7, 63.7. HRMS (ESI): calcd for
C H O +Na 361.1416 found 361.1419.
0
1
.45 (20% EtOAc/hexanes). IR (neat): 3043, 2921, 2700, 2551,
-1 1
1
651, 1593 cm . H NMR (CDCl , 400 MHz): δ 7.30-7.42 (m,
3
21
22
4
Ar-H, 20H), 5.37 (t, C4'-H, 2H, J = 3.6 Hz), 5.30 (d, C3-
methylene CH , 2H, J = 4.0 Hz ), 5.12 (s, C3-methylene CH ,
2
1
a
b
4
.8. (3R,4S,8aS)-3,4-bis(benzyloxy)-2,3,4,6,7,8a-hexahydro
H), 4.92 (s, C2-H (anomeric), 2H), 4.75 (d, benzyl-CH, 2H, J =
2.0 Hz), 4.64 (d, benzyl-CH, 2H, J = 12.0 Hz), 4.54 (d, benzyl-
pyrano[2,3-b]pyran (16)

6
Tetrahedron
CH, 2H, J = 12.0 Hz), 4.40 (d, benzyl-CH, 2
A
H
C
, J
C
=
E
1
P
2
T
.4
E
H
D
z), MACH
NU
C
l )
S
;
C
IR
R
(nIPea
T
t): 3024, 2958, 2926, 2865, 1720, 1638, 1490,
3
-
1
1
4
.18-4.24 (m, C4-H, C5-H, 4H), 3.76 (dt, C1'-H , 2H, J = 6.8 Hz,
1446, 1358 cm . H NMR (CDCl , 400 MHz): δ 7.26-7.47 (m,
a
3
J = 13.2 Hz), 3.58-3.63 (m, C6-H , 2H), 3.53 (dd, C6-H , 2H, J =
Ar-H, 15H), 5.84-5.94 (m, C4'-H, 1H), 5.38 (s, C3-methylene Ha,
a
b
4
.0 Hz, J = 10.0 Hz), 3.41 (dt, C1'-H , 2H, J = 6.4 Hz, J = 12.4
1H), 5.25 (s, C3-methylene H , 1H), 5.23 (s, C2-H (anomeric),
b
b
1
3
Hz), 2.04-2.13 (m, C3'-H , 4H), 1.65-1.70 (m, C2'-H , 4H).
C
1H), 5.06-5.16 (m, C5'-H , 2H), 4.96 (d, benzyl-CH, 1H, J =
a,b
a,b
a,b
NMR (CDCl , 100 MHz): δ 140.2, 138.6, 138.3, 130.0, 128.3,
10.8 Hz), 4.87 (d, benzyl-CH, 1H, J = 11.2 Hz), 4.81 (d, benzyl-
CH, 1H, J = 11.2 Hz), 4.72 (d, benzyl-CH, 1H, J = 12.0 Hz),
3
1
6
7
28.2, 127.9, 127.7, 127.6, 127.3, 118.1, 99.9, 75.6, 75.3, 70.3,
9.1, 67.1, 57.8, 29.5, 29.2. HRMS (ESI): calcd for C H O +Na
83.3873 found 783.3871.
4.58 (d, benzyl-CH , 2H, J = 11.6 Hz), 4.55 (d, C4-H, 1H, J =
48
56
8
2
6.8 Hz), 4.04-4.06 (m, C6-H, 1H), 3.72-3.89 (m, C6-methylene
H , C1'-H , C5-H, 4H) 3.51-3.56 (m, C1'-H , 1H), 2.21 (m, C3'-
a,b
a
b
4
.12. (2S,4R,5S,6R)-2-(allyloxy)-4,5-bis(benzyloxy)-6-
13
H , 2H), 1.77-1.80 (m, C2'-H , 2H). C NMR (CDCl , 100
a,b
a,b
3
((benzyloxy)methyl)-3-methylenetetrahydro-2H-pyran (23)
MHz): δ 142.4, 138.2, 138.1, 138.0, 137.9, 128.3, 128.2, 128.1,
1
7
27.8, 127.7, 127.6, 127.5, 127.4, 114.7, 110.2, 101.2, 81.1, 79.9,
4.8, 73.3, 71.4, 68.6, 66.5, 30.2, 28.5. HRMS (ESI): calcd for
Compound 23 was synthesized from glycal 21 by following the
general experimental procedure A. Yield 78% as a colourless
C H O +Na 537.2617 found 537.2619.
gum. R = 0.45 (10% EtOAc/hexanes).
+31.4 (c 1.0,
33 38
5
f
-
1 1
CHCl ); IR (neat): 2910, 2863, 1647, 1552, 1492, 1448 cm . H-
3
4
.15. (2S,4R,5R,6R)-2-(allyloxy)-4,5-bis(benzyloxy)-6-
NMR (CDCl , 500 MHz): δ 7.18-7.43 (m, Ar-H, 15H), 5.91-6.01
3
((benzyloxy)methyl)-3-methylenetetrahydro-2H-pyran (26)
(
m, C2'-H, 1H), 5.31-5.36 (m, C3-methylene CH , C3'-H , 2H),
a a
5
.26 (s, C3-methylene CH , 1H), 5.26 (d, C3'-H , 1H, J = 10.5
Compound 26 was synthesized from glycal 22 by following the
b
b
Hz), 5.20 (s, C2-H (anomeric), 1H), 4.92 (d, benzyl-CH, 1H, J =
0.8 Hz), 4.81 (d, benzyl-CH, 1H, J = 11.6 Hz), 4.75 (d, benzyl-
CH, 1H, J = 11.2 Hz), 4.68 (d, benzyl-CH, 1H, J = 12.4 Hz),
.54 (d, benzyl-CH, 1H, J = 12.4 Hz), 4.53 (d, benzyl-CH, 1H, J
10.4 Hz), 4.51 (dt, C4-H, 1H, J = 2.0 Hz, 9.2 Hz), 4.21 (ddt,
general experimental procedure A. Yield 71% as a colourless
1
gum. R = 0.62 (20% EtOAc/hexanes).
+9.4 (c 1.0, CHCl3);
f
IR (neat): 2907, 2863, 1644, 1558, 1533, 1501, 1451, 1416, 1365
-
1 1
4
=
cm . H NMR (CDCl , 500 MHz): δ 7.26-7.43 (m, Ar-H, 15H),
3
5.93-6.00 (m, C2'-H, 1H), 5.47 (t, C3-methylene H , 1H, J = 2.0
a
C1'-H , 1H, J = 2.8 Hz, J = 5.2 Hz, J = 13.2 Hz), 4.06 (ddt, C1'-
Hz), 5.29-5.34 (m, C3'-H , C3-methylene H , C2-H (anomeric),
a
a
b
H , 1H, J = 1.2 Hz, J = 4.8 Hz, J = 12.8 Hz), 4.02 (ddd, C6-H,
b
3H), 5.22 (dd, C3'-H , 1H, J = 1.5 Hz, J = 10.5 Hz), 4.96 (d,
b
1
H, J = 2.0 Hz, J = 4.0 Hz, J = 10.0 Hz), 3.81 (dd, C6-
benzyl-CH, 1H, J = 12.0 Hz), 4.76 (d, benzyl-CH, 1H, J = 12.0
Hz), 4.70 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.66 (d, benzyl-CH,
1H, J = 12.0 Hz), 4.53 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.49 (d,
C4-H, 1H, 2.0 Hz), 4.45 (d, benzyl-CH, 1H, J = 11.5 Hz), 4.25
methylene H , 1H, J = 4.4 Hz, J = 10.8 Hz), 3.72 (dd, C6-
methylene H , 1H, J = 2.0 Hz, J = 10.4 Hz), 3.66 (dd, C5-H, 1H,
J = 9.2 Hz, J = 9.6 Hz). C NMR (CDCl , 100 MHz): δ 142.2,
b
a
13
3
1
1
7
5
38.2, 138.0, 133.8, 128.3, 128.2, 127.8, 127.7, 127.6, 127.6,
27.5, 127.5, 117.3, 110.5, 100.4, 81.1, 79.9, 74.9, 73.4, 73.3,
(ddt, C1'-H , 1H, J = 1.5 Hz, J = 5.5 Hz, J = 11.5 Hz), 4.20 (t,
a
C6-H, 1H, J = 6.5 Hz), 4.09 (ddt, C1'-H , 1H, J = 1.5 Hz, J = 6.0
b
+
1.5, 68.7, 67.6. HRMS (ESI): calcd. for C H O +NH4
Hz, J = 11.5 Hz), 4.05 (d, C5-H, 1H, J = 2.0 Hz), 3.62 (dd, C6-
31
34
5
13
04.2750; found 504.2755.
methylene H , 2H, J = 3.0 Hz, J = 6.0 Hz). C NMR (CDCl3,
a,b
1
1
7
25 MHz): δ 140.7, 138.6, 138.3, 138.0, 134.0, 128.3, 128.2,
28.0, 127.6, 127.5, 127.4, 127.4, 127.0, 117.2, 111.4, 100.6,
8.1, 75.4, 73.9, 73.3, 71.6, 70.7, 69.3, 67.7. HRMS (ESI): calcd
4
.13. (2S,4R,5S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-2-
(but-3-en-1-yloxy)-3-methylenetetrahydro-2H-pyran (24)
for C H O +Na 509.2304 found 509.2304.
Compound 24 was synthesized from glycal 21 by following the
31 34
5
general experimental procedure A. Yield 75% as a colourless
4
.16. (2S,4R,5R,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-2-
gum. R = 0.5 (10%, EtOAc/hexanes).
+25.0 (c 1.0,
f
(but-3-en-1-yloxy)-3-methylenetetrahydro-2H-pyran (27)
-
CHCl ); IR (neat): 2910, 2863, 1647, 1552, 1492, 1448, 1353 cm
3
1
1
.
H-NMR (CDCl , 500 MHz ): δ 7.20-7.44 (m, Ar-H, 15H),
Compound 27 was synthesized from glycal 22 by following the
3
5
.82-5.90 (m, C3'-H, 1H), 5.34 (s, C3-methylene CH , 1H), 5.22
general experimental procedure A. Yield 77% as a colourless
a
(
s, C2-H (anomeric), 1H), 5.19 (s, C3-methylene CH , 1H), 5.14
gum. R = 0.52 (20% EtOAc/hexanes).
+12.1 (c 1.0,
b
f
-1 1
(dd, C4'-H , 1H, J = 1.5 Hz, J = 4.5 Hz), 5.08-5.10 (m, C4'-H ,
CHCl ); IR (neat): 2920, 2866, 1641, 1492, 1451, 1353 cm . H
a
b
3
1
1
H), 4.92 (d, benzyl-CH, 1H, J = 10.5 Hz), 4.82 (d, benzyl-CH,
H, J = 11.5 Hz), 4.76 (d, benzyl-CH, 1H, J = 11.5 Hz), 4.68 (d,
NMR (CDCl , 500 MHz): δ 7.27-7042 (m, Ar-H, 15H), 5.80-5.88
3
(m, C3'-H, 1H), 5.45 (s, C3-methylene H , 1H), 5.29 (s, C3-
a
benzyl-CH, 1H, J = 12.5 Hz), 4.55 (d, benzyl-CH, 1H, J = 12.0
Hz), 4.53 (d, benzyl-CH, 1H, J = 11.0 Hz), 4.48 (dt, C4-H, 1H, J
methylene H ,1H), 5.25 (s, C2-H (anomeric), 1H), 5.12 (d, C4'-
b
H , 1H, J = 17.0 Hz), 5.07 (d, C4'-H , 1H, J = 10.0 Hz), 4.95 (d,
a
b
=
2.0 Hz, J = 9.0 Hz), 4.00 (ddd, 1H, C6-H, J = 2.0 Hz, J = 3.5
benzyl-CH, 1H, J = 12.0 Hz), 4.76 (d, benzyl-CH, 1H, J = 12.0
Hz), 4.69 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.66 (d, benzyl-CH,
1H, J = 12.0 Hz), 4.52 (d, benzyl-CH, 1H, J = 11.5 Hz), 4.44-
4.46 (m, benzyl-CH, C4-H, 2H), 4.16 (t, C6-H, 1H, 6.0 Hz), 4.02
Hz, J = 9.5 Hz), 3.81 (dd, C6-methylene H , 1H, J = 4.0 Hz, J =
a
1
0.5 Hz), 3.76 (dt, C1'-H , 1H, J = 7.5 Hz, J = 9.5 Hz), 3.73 (dd,
a
C6-methylene H , 1H, J = 2.0 Hz, J = 12.0 Hz), 3.66 (t, C5-H,
b
1
2
1
1
7
H, J = 9.5 Hz), 3.56 (dt, C1'-H , 1H, J = 7.0 Hz, J = 9.5 Hz),
(bs, C5-H, 1H), 3.73-3.78 (m, C1'-H , 1H), 3.54-3.61 (m, C6-
b
a
13
13
.39-2.43 (m, C2'-Ha,b, 2H). C NMR (CDCl , 125 MHz): δ
methylene H , C1'-H , 3H), 2.40 (m, C2'-H ,2H). C NMR
3
a,b
b
a,b
42.0, 138.2, 138.2, 138.0, 134.8, 128.3, 128.3, 128.3, 128.2,
27.9, 127.9, 127.8, 127.6, 116.6, 110.4, 101.2, 81.1, 79.9, 74.9,
3.3, 73.3, 71.5, 68.7, 66.5, 33.9. HRMS (ESI): calcd for
(CDCl , 125 MHz): δ 140.9, 138.6, 138.4, 138.1, 135.0, 128.3,
3
128.3, 128.0, 127.6, 127.6, 127.5, 127.4, 127.1, 116.5, 111.2,
101.4, 78.1, 75.5, 74.0, 73.4, 71.6, 70.7, 69.3, 66.5, 33.9. HRMS
(ESI): calcd for C H O +Na 523.2460 found 523.2461.
C H O +Na 523.2460 found 523.2464.
32
36
5
32 36
5
4
.14. (2S,4R,5S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-2-
4.17. (2S,4R,5R,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-2-
(pent-4-en-1-yloxy)-3-methylenetetrahydro-2H-pyran (28)
(pent-4-en-1-yloxy)-3-methylenetetrahydro-2H-pyran (25)
Compound 25 was synthesized from glycal 21 by following the
Compound 28 was synthesized from glycal 22 by following the
general experimental procedure A. Yield 69% as a colourless
general experimental procedure A. Yield 72% as a colourless
gum R = 0.52 (10% EtOAc/hexanes).
+24.4 (c 1.0,
gum. R = 0.52 (10% EtOAc/hexanes).
+0.8 (c 1.0, CHCl3);
f
f

7
-
1
IR (neat): 3057, 3024, 2904, 2356, 1726, 1452
A
, 1
C
35
C
3,
E
13
P
1
T
5
E
cm
D
.
MAC3
N
-H
U
,
S
2H
C
),
R
3.
I
78-3.87 (m, C7-H , C2-H, C2-methylene H , 3H),
a a
P
T
1
H NMR (CDCl , 400 MHz): δ 7.27-7.40 (m, Ar-H, 15H), 5.79-
3.62-3.72 (m, C7-H , C2-methylene H , 2H), 2.23-2.32 (m, C6-
3
b
b
13
5
.90 (m, C4'-H,1H), 5.45 (s, C3-methylene H , 1H), 5.29 (s, C2-
H , 1H), 2.13-2.21 (m, C6-H , 1H).
a
C NMR (CDCl , 100
a
b
3
H (anomeric), 1H), 5.23 (s, C3-methylene H ,1H), 4.94-5.08 (m,
MHz): δ 138.3, 137.9, 137.6, 131.9, 130.1, 128.4, 128.3, 128.2,
127.9, 127.9, 127.8, 127.7, 127.7, 127.4, 92.4, 80.7, 79.5, 74.0,
73.3, 71.4, 69.6, 69.0, 60.6, 25.0. HRMS (ESI): calcd for
C H O +Na 495.2147 found 495.2148. Compounds (30) and
b
C5'-H , 2H), 4.75 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.69 (d,
a,b
benzyl-CH, 1H, J = 12.0 Hz), 4.66 (d, benzyl-CH, 1H, J = 11.2
Hz), 4.60 (d, benzyl-CH, 1H, J = 11.6 Hz), 4.52 (d, benzyl-CH,
30
32
5
1
=
3
H, J = 12.0 Hz), 4.46 (s, C4-H, 1H), 4.44 (d, benzyl-CH, 1H, J
12.0 Hz), 4.14 (t, C6-H, 1H, J = 8.0 Hz), 4.03 (s, C5-H, 1H),
.44-3.75 (m, C6-methylene H , C1'-H , 4H), 2.12-2.17 (m,
(32): Obtained as an inseparable mixture. R = 0.62 (20%
f
EtOAc/hexanes). IR (neat): 3066, 3028, 2917, 2866, 1721, 1496,
-
1
1453, 1361, 1263 cm . Compound 32: HRMS (ESI): calcd for
a,b
a,b
1
3
C3'-H , 2H), 1.68-1.77 (m, C2'-H , 2H). C NMR (CDCl , 100
C H O +Na 523.2460 found 523.2460.
a,b
a,b
3
32 36
5
MHz): δ 141.1, 138.7, 138.4, 138.1, 138.1, 128.5, 128.4, 128.3,
4
.20. (E,Z)-1,8-bis(((2S,4R,5S,6R)-4,5-bis(benzyloxy)-6-
1
7
28.1, 127.8, 127.6, 127.5, 127.2, 114.8, 111.3, 101.6, 78.1, 75.5,
4.0, 73.4, 71.6, 70.7, 69.4, 66.7, 30.4, 28.7. HRMS (ESI): calcd
(
(benzyloxy)methyl)-3-methylenetetrahydro-2H-pyran-2-
yl)oxy)oct-4-ene (33).
for C H O +Na 537.2617 found 537.2618.
33
38
5
Compound 33 (as a cis, trans mixture) was synthesized from 25
by following the general experimental procedure B. Yield 62% as
4
4
.18. (4R,5S,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-
,5,6,7a-tetrahydro-2H-furo[2,3-b]pyran (29) and
a colourless gum. R = 0.54 (20% EtOAc/hexanes). IR (neat):
f
(3aR,4R,5S,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-
-
1 1
3
063, 3030, 2926, 2854, 1956, 1720, 1490, 1452, 1358 cm . H
4
,5,6,7a-tetrahydro-3aH-furo[2,3-b]pyran (30)
NMR (CDCl , 500 MHz): δ 7.15-7.39 (m, Ar-H, 30H), 5.42 (t,
3
Compound 29 and 30 were synthesized from 23 by following the
C4'-H, 1H, J = 3.5 Hz), 5.38 (t, C4'-H, 1H, J = 4.5 Hz), 5.29 (s,
general experimental procedure B. Yield 61% with 50:50 ratio,
C3-methylene H , 2H), 5.13 (bs, C3-methylene H , C2-H
a
b
respectively as a colourless gum. Compound (29): R = 0.4 (20%
(anomeric), 4H), 4.87 (d, benzyl-CH, 2H, J = 10.5 Hz), 4.78 (d,
benzyl-CH, 2H, J = 11.5 Hz), 4.71 (d, benzyl-CH, 2H, J = 11.0
Hz), 4.63 (d, benzyl-CH, 2H, J = 12.0 Hz), 4.51 (d, benzyl-CH,
2H, J = 12.5 Hz), 4.50 (d, benzyl-CH, 2H, J = 12.0 Hz), 4.44 (d,
C4-H, 2H, J = 9.0 Hz), 3.92-3.95 (m, C6-H, 2H), 3.74-3.77 (m,
C6-methylene H , 2H), 3.63-3.69 (m, C6-methylene H , C1'-H ,
f
EtOAc/hexanes).
+77.2 (c 0.45, CHCl ); IR (neat): 3062,
3
-1 1
3
029, 2862, 1790, 1733, 1670, 1496, 1453, 1362, 1327 cm . H
NMR (CDCl , 400 MHz): δ 7.16-7.41 (m, Ar-H, 15H), 6.23 (d,
3
C7a-H, 1H, J = 1.2 Hz), 6.20-6.22 (m, C3-H, 1H, J = 2.4 Hz),
4
.71-4.80 (m, C4-H, 2H), 4.63 (m, benzyl-CH, C4-H, 2H), 4.56
d, benzyl-CH, 1H, J = 11.6 Hz), 4.54 (d, benzyl-CH, 1H, J =
2.4 Hz), 4.43 (d, benzyl-CH, 1H, J = 11.6 Hz), 4.39-4.42 (m,
benzyl-CH , 2H), 3.88 (dd, C8-H , 1H, J = 1.6 Hz, J = 8.8 Hz),
a
b
a
(
1
4H), 3.61 (t, C5-H, 2H, J = 9.5 Hz), 3.40-3.45 (m, C1'-H , 2H),
a
2.01-2.12 (m, C3'-H , 4H), 1.65 (quin, C2'-H , 4H, J = 7.0 Hz).
a,b
a,b
13
2
a
C NMR (CDCl , 125 MHz): δ 142.6, 138.4, 138.4, 138.2,
3
3
9
1
1
.70 (m, C8-H , C5-H, 2H), 3.62 (dt, C6-H, 1H, J = 3.6Hz, J =
130.0, 129.5, 128.4, 128.3, 128.3, 127.9, 127.8, 127.7, 127.6,
127.6, 127.5, 110.2, 101.4, 81.3, 80.1, 74.9, 73.4, 71.6, 68.9,
b
13
.2 Hz). C NMR (CDCl , 100 MHz): δ 138.2, 137.5, 137.5,
3
+
34.4, 130.7, 128.4, 128.3, 128.2, 127.9, 127.8, 127.8, 127.4,
04.4, 79.6, 76.0, 74.9, 73.3, 72.2, 71.7, 70.4, 68.3. HRMS
66.7, 29.4, 29.1. HRMS (ESI): calcd for C H O +NH
64
72 10
4
1018.5469 found 1018.5461.
(
ESI): calcd for C H O +Na 481.1991 found 481.1991.
29 30 5
4
.21. (E)-1,4-bis(((2S,4R,5R,6R)-4,5-bis(benzyloxy)-6-
Compound (30): R = 0.6 (20% EtOAc/hexanes).
1
1
+35.0 (c
f
((benzyloxy)methyl)-3-methylenetetrahydro-2H-pyran-2-
.0, CHCl ); IR (neat): 2917, 2850, 1619, 1596, 1492, 1448,
3
-
1 1
yl)oxy)but-2-ene (34)
362, 1258 cm . H NMR (CDCl , 400 MHz): δ 7.20-7.39 (m,
3
Ar-H, 15H), 6.53 (t, C2-H, 1H, J = 2.8 Hz), 6.02 (d, C7a-H, 1H,
J = 8.4 Hz), 5.00 (t, C3-H, 1H, J = 2.8 Hz), 4.65 (s, benzyl-CH2,
Compound 34 was synthesized from 26 by following the general
experimental procedure B. Yield 49%, as a colourless gum. R =
f
2
1
H), 4.63 (d, benzyl-CH, 1H, J = 12.4 Hz), 4.62 (d, benzyl-CH,
H, J = 12.0 Hz), 4.59 (d, benzyl-CH, 1H, 12.0 Hz), 4.46 (d,
0
2
.4 (20% EtOAc/hexanes).
923, 2857, 1720, 1498, 1451, 1368 cm . H NMR (CDCl , 500
+9.5 (c 1.0, CHCl ); IR (neat):
3
-1 1
3
benzyl-CH, 1H, J = 11.6 Hz), 3.88-3.91 (m, C6-H, 1H), 3.73-
.77 (m, C4-H, C5-H, 2H), 3.69-3.70 (m, C8-H , 2H), 3.25
MHz): δ 7.27-7.39 (m, Ar-H, 30H), 5.82 (t, C2'-H, 2H, J = 2.5
3
a,b
Hz), 5.43 (t, C3-methylen H , 2H, J = 1.5 Hz), 5.27 (s, C3-
a
13
(ddd, C3a-H, 1H, J = 2.4 Hz, J = 4.8 Hz, J = 10.4 Hz). C NMR
CDCl , 100 MHz): δ 146.1, 138.1, 138.0, 137.9, 128.4, 128.3,
methylen H , 2H), 5.24 (s, C2-H (anomeric), 2H), 4.92 (d,
b
(
3
benzyl-CH, 2H, J = 12.0 Hz), 4.72 (d, benzyl-CH, 2H, J = 12.0
Hz), 4.65 (d, benzyl-CH, 2H, J = 10.5 Hz), 4.63 (d, benzyl-CH,
1
7
28.2, 127.8, 127.7, 127.7, 127.7, 127.5, 102.3, 102.1, 79.1, 75.5,
3.3, 72.5, 71.7, 71.0, 69.5, 43.7. HRMS (ESI): calcd for
2
H, J = 12.0 Hz), 4.48 (d, benzyl-CH, 2H, J = 11.5 Hz), 4.44 (d,
C4-H, 2H, J = 2.5 Hz), 4.41 (d, benzyl-CH, 2H, J = 12.0 Hz),
.18 (dd, C1'-H , 2H, J = 2.5 Hz, J = 13.0 Hz), 4.10-4.13 (m, C6-
C H O +Na 481.1991 found 481.1991.
29
30
5
4
a
4
2
.19. (2R,3S,4R,8aS)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-
,3,4,6,7,8a-hexahydropyrano[2,3-b]pyran (31), (30) and 2-
H, 2H), 3.99-4.03 (m, C1'-H , C5-H, 4H), 3.53-3.59 (m, C6-
b
13
methylene H , 4H). C NMR (CDCl , 125 MHz): δ 140.7,
(
((2R,3S,4R)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-3,4-
a,b
3
1
1
38.7, 138.4, 138.1, 128.9, 128.4, 128.3, 128.1, 127.7, 127.6,
27.5, 127.4, 127.1, 111.6, 100.8, 78.2, 75.5, 74.0, 73.4, 71.7,
dihydro-2H-pyran-5-yl)methyl)butanal (32)
Compound 31 and (30+32) were synthesized from 24 by
following the general experimental procedure B. Yield 68% with
70.8, 69.4, 66.7. HRMS (ESI): calcd for C H O +Na 967.4397
60 64 10
found 967.4399.
.22. (E)-1,8-bis(((2S,4R,5R,6R)-4,5-bis(benzyloxy)-6-
5
=
(
0:50 ratio, respectively as a colourless gum. Compound (31): Rf
0.42 (20% EtOAc/hexanes). +48.3 (c 0.8, CHCl ); IR
neat): 3024, 2891, 2860, 1723, 1663, 1501, 1453, 1363, 1328
4
3
((benzyloxy)methyl)-3-methylenetetrahydro-2H-pyran-2-
-
1
1
yl)oxy)oct-4-ene (35)
cm . H NMR (CDCl , 400 MHz): δ 7.15-7.38 (m, Ar-H, 15H),
3
6
4
=
.06 (t, C5-H, 1H, J = 3.2 Hz), 5.44 (d, C8a-H, 1H, J = 1.2 Hz),
.64 (d, benzyl-CH, 1H, J = 12.4 Hz), 4.62 (d, benzyl-CH, 1H, J
12.0 Hz), 4.57 (d, benzyl-CH, 1H, J = 12.4 Hz), 4.50 (d,
Compound 35 was synthesized from 28 by following the general
experimental procedure B. Yield 56%, as a colourless gum. R =
f
0
3
.4 (20% EtOAc/hexanes).
035, 2865, 1726, 1621, 1457 cm . H NMR (CDCl , 500 MHz):
+4.1 (c 1.0, CHCl ); IR (neat):
3
-1 1
benzyl-CH, 1H, J = 11.6 Hz), 4.39 (d, benzyl-CH, 1H, J = 11.6
Hz), 4.36 (d, benzyl-CH, 1H, J = 12.0 Hz), 3.93-3.97 (m, C4-H,
3

8
Tetrahedron
δ 7.24-7.38 (m, Ar-H, 30H), 5.36-5.45
A
(m
C
,
C
C
E
4'
P
-H
T
,
E
C
D
3- MA4.
NU
25
. (2
S
S
C
,4R
R
,5
I
S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-2-
P
T
methylene H , 4H), 5.25 (s, C3-methylene H , 2H), 5.18 (s, C2-H
(((R)-1-phenylallyl)oxy)-3-methylenetetrahydro-2H-pyran (40)
a
b
(
(
4
3
anomeric), 2H), 4.91 (d, benzyl-CH, 2H, J = 12.0 Hz), 4.62-4.73
m, benzyl-CH, 6H), 4.48 (d, benzyl-CH, 2H, J = 11.5 Hz), 4.39-
.42 (m, benzyl-CH, C4-H, 4H), 4.11 (t, C6-H, 2H, J = 6.0 Hz),
Compound 40 (major isomer) was synthesized from glycal 38 by
following the general experimental procedure A. Yield 25% as a
colourless gum. R = 0. 6 (10% EtOAc/hexanes).
+63.2 (c
f
.99 (s, C5-H, 2H), 3.62-3.67 (m, C1'-H , 2H), 3.56 (d, C6-
a
1
.0, CHCl ); IR (neat): 3090, 2915, 2858, 1603, 1489, 1453,
3
metylene H , 4H, J = 6.5 Hz), 3.41-3.49 (m, C1'-H , 2H), 2.04-
2
a,b
b
-1 1
13
1360, 1303 cm . H NMR (CDCl , 400 MHz): δ 7.18-7.43 (m,
3
.06 (m, C3'-H , 4H), 1.63-1.66 (m, C2'-H , 4H). C NMR
a,b a,b
Ar-H, 20H), 5.96-6.04 (m, C2'-H, 1H), 5.21-5.27 (m, C3-
(CDCl , 125 MHz): δ 141.1, 138.7, 138.4, 138.1, 130.0, 129.7,
3
methylene CH , C3'-H , 2H), 5.19 (d, C2'-H, 1H, J = 6.0 Hz),
a
a
1
1
2
1
29.0, 128.3, 128.3, 128.1, 127.7, 127.6, 127.5, 127.4, 127.1,
11.1, 101.5, 78.2, 75.5, 74.0, 73.4, 71.6, 70.7, 69.4, 66.8, 29.6,
5
.14 (dt, C3'-H , 1H, J = 1.2 Hz, J = 10.4 Hz), 5.11 (s, C3-
b
+
methylene CH , 1H), 4.98 (s, C2-H (anomeric), 1H), 4.90 (d,
b
9.1. HRMS (ESI): calcd for C H O +NH 1018.5469 found
64
72 10
4
benzyl-CH, 1H, J = 10.8 Hz), 4.81 (d, benzyl-CH, 1H, J = 11.6
Hz), 4.76 (d, benzyl-CH, 1H, J = 11.2 Hz), 4.68 (d, benzyl-CH,
018.5483.
4
.23. (3aR,4S,5R,7aS)-4,5-bis(benzyloxy)hexahydro-2H-
1H, J = 12.0 Hz), 4.51-4.56 (m, benzyl-CH , C4-H, 3H), 4.10-
2
furo[2,3-b]pyran (36)
4
.14 (m, C6-H, 1H), 3.82 (dd, C6-methylene H , 1H, J = 4.0 Hz,
b
J = 11.6 Hz), 3.74 (dd, C6-methylene H , 1H, J = 2.0 Hz, J =
a
To a stirred solution of 14 (20 mg, 0.059 mmol) in ethanol (3
13
1
0.8 Hz), 3.65 (t, C5-H, 1H, J = 9.6 Hz). C NMR (CDCl , 100
3
mL) was added Et N (16 µL, 0.12 mmol), 10% Pd/C (4 mg). The
3
MHz): δ 142.3, 139.8, 138.6, 138.3, 138.3, 138.2, 128.5, 128.4,
mixture was stirred for 4h under H2 atmosphere. After
completion of the reaction (by TLC) the suspension was filtered
through a pad of Celite and concentrated in vacuo, the obtained
residue was further purified by silica gel column chromatography
provided the compound 36 as the single diastereomer in 88%
1
1
6
5
28.3, 128.3, 128.0, 127.8, 127.8, 127.7, 127.7, 127.6, 127.5,
27.3, 115.5, 110.3, 98.5, 81.3, 80.1, 77.9, 75.0, 73.5, 73.4, 71.9,
+
8.8. HRMS (ESI): calcd for C H O +NH 580.3063 found
37
38
5
4
80.3066.
yield. R = 0.48 (30% EtOAc/hexanes).
-5.2 (c 1.0, CHCl );
4.26. (2R,4R,5S,6R,7aS)-4,5-bis(benzyloxy)-6-
((benzyloxy)methyl)-2-phenyl-4,5,6,7a-tetrahydro-2H-furo[2,3-
b]pyran (41)
f
3
-
1
1
IR (neat): 2915, 2854, 1731, 1594, 1452, 1364 cm . H NMR
CDCl , 500 MHz): δ 7.28-7.35 (m, Ar-H, 10H), 5.30 (d, C7a-H,
(
3
1
H, J = 3.0 Hz), 4.72 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.67 (d,
Compound 41 was synthesized from 40 by following the general
benzyl-CH, 1H, J = 12.0 Hz), 4.61 (d, benzyl-CH, 1H, J = 12.0
Hz), 4.54 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.00 (dt, C2-H , 1H, J
=
3
H, C6-H , 2H), 3.69 (dd, C4-H, 1H, J = 2.0 Hz, J = 5.5 Hz),
2
experimental procedure B. Yield 50%, as a colourless gum. R =
f
a
0
. 42 (10% EtOAc/hexanes).
+3.0 (c 0.6, CHCl ); IR
3
-1 1
7.0 Hz, 5.0 Hz), 3.91 (dd, C6-H , 1H, J = 4.5 Hz, J = 8.5 Hz),
a
(neat): 3023, 2920, 2858, 1722, 1593, 1448, 1360, 1288 cm . H
.88 (dt, C2-H , 1H, J = 7.0 Hz, J = 5.0 Hz), 3.74-3.79 (m, C5-
b
NMR (CDCl , 400 MHz): δ 7.16-7.39 (m, Ar-H, 20H), 6.31 (t,
3
b
C7a-H, 1H, J = 1.6 Hz), 6.18 (t, C3-H, 1H, J = 1.6 Hz), 5.89 (s,
C2-H, 1H), 4.68 (d, benzyl-CH, 1H, J = 12.0 Hz), 4.67 (d,
benzyl-CH, 1H, J = 12.4 Hz), 4.57 (d, benzyl-CH, 1H, J = 12.0
Hz), 4.53 (d, benzyl-CH, 1H, J = 11.6 Hz), 4.45 (d, benzyl-CH,
.46-2.51 (m, C3a-H, 1H), 1.95-2.02 (m, C3-H , 1H), 1.82-1.89
a
13
(m, C3-H , 1H). C NMR (CDCl , 125 MHz): δ 138.4, 138.3,
b
3
1
7
3
28.4, 128.4, 127.9, 127.8, 127.7, 127.6, 100.9, 75.2, 71.7, 71.2,
1.0, 66.4, 62.0, 42.4, 26.3. HRMS (ESI): calcd for C H O +Na
21
24
4
1
H, J = 11.2 Hz), 4.44 (d, benzyl-CH, 1H, J = 11.6 Hz), 4.38 (d,
63.1572 found 363.1574.
C4-H, 1H, J = 2.0 Hz), 3.92 (dd, C5-H, 1H, J = 1.6 Hz, J = 7.6
13
4
.24. (2R,3S,4R,4aR,8aS)-3,4-bis(benzyloxy)-2-
Hz), 3.73-3.82 (m, C6-H, C8-H , 3H). C NMR (CDCl , 100
a,b 3
((benzyloxy)methyl)octahydropyrano[2,3-b]pyran (37)
MHz): δ 148.1, 138.4, 137.5, 137.5, 134.6, 134.2, 128.6, 128.5,
1
8
28.3, 128.3, 128.0, 127.9, 127.8, 127.7, 127.4, 125.9, 104.3,
6.7, 79.7, 76.0, 73.3, 72.4, 71.7, 70.5, 68.8. HRMS (ESI): calcd
To a stirred solution of 31 (25 mg, 0.052 mmol) in ethanol (4
mL) was added Et N (16 µL, 0.105 mmol), 10% Pd/C (5 mg).
3
for C H O +Na 557.2304 found 557.2300.
35
34
5
The mixture was stirred for 6h under H2 atmosphere. After
completion of the reaction (by TLC) the suspension was filtered
through a pad of Celite and concentrated in vacuo, the obtained
residue was further purified by silica-gel column chromatography
provided the compound 37 as the single diastereomer in 90%
Acknowledgments
The authors thank Board of Research in Nuclear Sciences
(BRNS), Sanction No. 37(2)/14/32/2014-BRNS for financial
yield. R = 0.5 (30% EtOAc/hexanes).
+38.8 (c 0.6,
f
support. B.C.V thank UGC for D. S. Kothari Fellowship.
-
CHCl ); IR (neat): 2927, 2866, 1727, 1589, 1494, 1446, 1356 cm
3
1
1
.
H NMR (CDCl , 400 MHz): δ 7.17-7.36 (m, Ar-H, 15H), 4.93
3
References and notes
(d, benzyl-CH, 1H, J = 11.2 Hz), 4.83 (d, benzyl-CH, 1H, J =
1
2
0.4 Hz), 4.80 (d, C8a-H, 1H, J = 3.6 Hz), 4.66 (d, benzyl-CH2,
H, J = 11.6 Hz), 4.58 (d, benzyl-CH, 1H, J = 11.2 Hz), 4.52 (d,
1
.
Rateb, M. E.; Houssen, W. E.; Schumacher, M.; Harrison, W. T.
A.; Diederich, M.; Ebel, R.; Jaspars, M. J. Nat. Prod. 2009, 72,
1471-1476.
benzyl-CH, 1H, J = 12.0 Hz), 3.97-4.04 (m, C2-H, C7-H , 2H),
a
3
.91 (dd, C4-H, 1H, J = 8.8 Hz, J = 10.4 Hz), 3.78 (dd, C2-
2. Thines, E.; Arendholz, W.-R.; Anke, H.; Sterner, O. J. Antibiot.
997, 50, 13-17.
1
methylene H , 1H, J = 3.2 Hz, J = 10.8 Hz), 3.72 (t, C3-H, 1H, J
=
Hz), 3.53 (td, C7-H , 1H, J = 2.0 Hz, J = 12.4 Hz), 2.08 (d, C5-
H , 1H, J = 12.8 Hz), 1.92 (dd, C4a-H, 1H, J = 2.0 Hz, J = 10.8
a
3
.
Graziano, G.; Danielle, S.; Graziano, D. G.; Fernando, D. Mar.
Drugs 2010, 8, 2080-2116.
9.6 Hz), 3.67 (dd, C2-methylene H , 1H, J = 2.0 Hz, J = 10.4
b
b
4
.
Bishara, A.; Rudi, A.; Goldberg, I.; Benayahu, Y.; Kashman, Y.
Tetrahedron 2006, 62, 12092-12097.
a
Hz), 1.51-1.55 (m, C5-H , 1H), 1.41-1.48 (m, C6-H , 1H), 1.18
5. (a) Shim, S. H.; Swenson, D. C.; Gloer, J. B.; Dowd, P. F.;
Wicklow, D. T. Org. Lett. 2006, 8, 1225-1228. (b) Shim, S. H.;
Gloer, J. B.; Wicklow, D. T. J. Nat. Prod. 2006, 69, 1601-1605.
b
a
13
(
d, C6-H ,1H, J = 13.6 Hz). C NMR (CDCl , 100 MHz): δ
b
3
1
1
38.4, 138.3, 138.0, 128.4, 128.3, 128.3, 128.1, 127.9, 127.7,
27.6, 127.5, 98.5, 79.5, 77.1, 75.0, 74.6, 73.5, 73.1, 68.5, 67.6,
(c) Gaich, T.; Mulzer, J. Org. Lett. 2010, 12, 272-275.
6
.
Rateb, M. E.; Houssen, W. E.; Schumacher, M.; Harrison, W. T.
A.; Diederich, M.; Ebel, R.; Jaspars, M. J. Nat. Prod. 2009, 72,
1471-1476.
4
0.9, 22.7, 20.2. HRMS (ESI): calcd for C H O +Na 497.2304
30 34 5
found 497.2309.

9
7
8
.
.
Tischler, M.; Anderson, R. J.; Choudhary, M. I.; Clardy, J. J. Org.
Chem. 1991, 56, 42-47.
Zhou, H.; Yang, Y.-B.; Duan, R.-T.; Yang, X.-Q.; Zhang, J.-C.;
Xie, X.-G.; Zhao, L.-X.; Ding, Z.-T. Chin. Chem. Lett.
ACCEPTED MANU(a)SCSu
R
p
I
plementary Material
P
T
1
13
H and C NMR spectra of all new compounds and the 2D
NMR of 8, 12, 13, 17, 30, 36, 37 and 41 are provided.
2
016, 27, 1044-1047.
Mootoo, D. R.; Fraser-Reid, B. J. Org. Chem. 1989, 54, 5548-
550.
9
1
1
.
5
0. Wang, X.-J, Zhang, J.; Wang, J.-D.; Qian, P.-T, Liu, C.-X.; Xiang,
W.-S. Nat. Prod. Res. 2013, 27, 1863-1869.
1. Airoldi, C.; Cardona, F.; Sironi, E.; Colombo, L.; Salmona, M.;
Silva, A.; Nicotra, F.; La Ferla, B. Chem. Commun. 2011, 47,
1
0266-10268.
2. (a) Harrison, T.; Pattenden, G.; Myers, P. L. Tetrahedron Lett.
988, 29, 3869-3872. (b) Mayer, S.; Prandi, J.; Bamhaoud, T.;
1
1
Bakkas, S.; Guillou, O. Tetrahedron 1998, 54, 8753-8770. (c)
Inoue, A.; Shinokubo, H.; Oshima, K. Org. Lett. 2000, 2, 651-653.
(d) Wakabayashi, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem.
Soc. 2001, 123, 5374-5375. (e) Mikami, S.; Fujita, K.; Nakamura,
T.; Yorimitsu, H.; Shinokubo, H.; Matsubara, S.; Oshima, K. Org.
Lett. 2001, 3, 1853-1855. (f) Ami, E.; Rajesh, S.; Wang, J.;
Kimura, T.; Hayashi, Y.; Kiso, Y.; Ishida, T. Tetrahedron Lett.
2
002, 43, 2931-2934. (g) Yanada, R.; Koh, Y.; Nishimori, N.;
Matsumura, A.; Obika, S.; Mitsuya, H.; Fujii, N.; Takemoto, Y. J.
Org. Chem. 2004, 69, 2417-2422.
1
3. (a) Scheffold, R.; Albrecht, S.; Orlinski, R.; Ruf, H.-R.; Stamouli,
P.; Tinembart, O.; Walder, L.; Weymuth, C. Pure Appl. Chem.
1
987, 59, 363-372. (b) Pattenden, G. Chem. Soc. Rev. 1988, 17,
3
61-382. (c) Coveney, D. J.; Patel, V. F.; Pattenden, G.;
Thompson, D. M. J. Chem. Soc, Perkin Trans 1, 1990, 2721-2728.
4. De Mesmaeker, A.; Hoffmann, P. Ernst, B. Tetrahedron Lett.
1
1
1
989, 30, 57-60.
5. Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc.
987, 109, 2547-2549.
1
1
1
6. Bamhaoud T.; Prandi, J. Chem. Commun. 1996, 1229-1230.
7. (a) Audin, C.; Lancelin, J.-M.; Beau, J.-M. Tetrahedron Lett,
1
988, 29, 3691-3694. (b) Yamazaki, O.; Yamaguchi, K.;
Yokoyama, M.; Togo, H. J. Org. Chem. 2000, 65, 5440-5442.
1
1
2
8. Ma, X.; Tian,Q.; Tang, Q.; Zhao, J.; Shao, H. Org. Lett. 2011, 13,
4
276-4279.
9. Sridhar, P. R.; Reddy, G.M.; Seshadri, K. Eur. J. Org. Chem.
012, 6228-6235.
2
0. (a) Haveli, S. D.; Sridhar, P. R.; Suguna, P.; Chandrasekaran, S.
Org. Lett. 2007, 9, 1331-1334; (b) Ma, X.; Tang, Q.; ke, J.; Zhang,
J.; Yang, X.; Shen, X.; Shao, H. Org. Biomol. Chem. 2014, 12,
7
381-7388. (c) Ma, X.; Tang, Q.; ke, J.; Zhang, J.; Wang, C.;
Wang, H.; Li, Y.; Shao, H. Chem. Commun. 2013, 49, 7085-7087.
1. (a) Ansari, A. A.; Rajasekaran, P.; Khan, M. M.; Vankar, Y. D. J.
Org. Chem. 2014, 79, 1690-1699. (b) Borowski, D.; Zweibohmer,
T.; Ziegler, T. Eur. J. Org. Chem. 2016, 5248–5256.
2. (a) Suzuki, Y.; Nishimaki, R.; Ishikawa, M.; Murata, T.; Takao,
K.-I.; Tadano, K.-I. J. Org. Chem. 2000, 65, 8595-8607. (b)
Quaedflieg, P. J. L. M.; Kesteleyn, B. R. R.; Wigerinck, P. B. T.
P.; Goyvaerts, N. M. F.; Vijn, R. J.; Liebregts, C. S. M.; Kooistra,
J. H. M. H.; Cusan, C. Org. Lett. 2005, 7, 5917-5920.
2
2
2
3. (a) Evans, D. A.; Olhava, E. J.; Johnson, J. S.; Janey, J. M. Angew.
Chem., Int. Ed. 1998, 37, 3372-3375. (b) Zhuang, W.; Thorhauge,
J.; Jørgensen, K. A. Chem. Commun. 2000, 459-460. (c) Sugita,
Y.; Kawai, K.; Yokoe, I. Heterocycles 2001, 55, 135-144.
2
2
2
4. Duhamel, P.; Deyine, A.; Dujardin, G.; Ple´, G.; Poirier, J. M. J.
Chem. Soc., Perkin Trans 1. 1995, 2103-2114.
5. Alonso, F.; Lorenzo, E.; Mele´ndez, J.; Yus, M. Tetrahedron
2
003, 59, 5199-5208.
6. (a) Reddy, G. M.; Sridhar, P. R. Eur. J. Org. Chem. 2014, 1496-
1
1
504. (b) Reddy, G. M.; Sridhar, P. R. Org. Biomol. Chem. 2014,
2, 8408 – 8414.
2
2
2
7. Sridhar, P. R.; Sudharani, C. RSC Adv. 2012, 2, 8596-8598.
8. Nagaraj, P.; Ramesh, N. G. Tetrahedron 2010, 66, 599-604.
9. The stereochemistry at the anomeric position was assigned based
on the chemical shift value of anomeric carbon in 13C NMR.
Dorman, D. E.; Roberts, J. D. J. Am. Chem. Soc. 1970, 92, 1355-
1
361.
0. Ramesh, N.G.; Balasubramanian, K. K. Tetrahedron Lett. 1991,
2, 3875-3878.
1. (a) Kashyap, S.; Vidadala, S. R.; Hotha, S. Tetrahedron
Lett. 2007, 48, 8960-8962. (b) Roy, R.; Rajasekaran, P.; Mallick,
A.; Vankar, Y. D. Eur. J. Org. Chem. 2014, 5564-5573.
3
3
3
3
2. (a) Schmidt, B. Eur. J. Org. Chem. 2004, 1865-1880. (b) Nelson,
S. G.; Bungard, C. J.; Wang, K. J. Am. Chem. Soc. 2003, 125,
1
3000-13001.