Synthetic approach to tetrahydrofuran units and five-membered ring lactones fused to hexopyranosides

Article abstract of DOI:10.1081/CAR-120013489

A stereoselective synthesis of the miharamycin sugar moiety epimer at C-3′ was accomplished in high yield starting from an appropriate (Z)-Wittig product, synthesized by Wittig reaction of a 4,6-O-benzylidene protected hexopyranosid-3-ulose with [(ethoxycarbonyl)methylene]triphenylphosphorane followed by iodine promoted isomerisation of the (E)-Wittig product formed. Reduction of the (Z)-isomer obtained in quantitative yield, cyclisation and dihydroxylation with osmium tetroxide, gave the target molecule containing a cis-fused tetrahydrofuran ring in its structure. Synhesis of five-membered rings trans-fused to the hexopyranosidic units succeeded via two different synthetic pathways. Stereoselective Reformatsky reaction of a 2,6-di-O-pivaloyl protected hexopyranosid-3-ulose, followed by cyclisation with dimethylzinc gave a 3,4-trans-fused lactone. The approach using the reaction of 2,3-and 3,4-epoxides with the dianion of phenylselenoacetic acid led to low yield but novel phenylseleno derivatives of trans-fused five-membered rings, namely a phenylselenolactone 2,3-trans-fused to a 4,6-O-benzylidene-hexopyranoside and a phenylselenolactenol 3,4-trans-fused to a 6-O-pivaloyl-hexopyranoside.

Full text of DOI:10.1081/CAR-120013489

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SYNTHETIC APPROACH TO TETRAHYDROFURAN UNITS
AND FIVE-MEMBERED RING LACTONES FUSED TO
HEXOPYRANOSIDES *
Amélia P. Rauter a , Olga Oliveira a , Tana Canda a , Estelle Leroi b , Humberto Ferreira c ,
Maria J. Ferreira c & José A. Ascenso c
a Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade de
Lisboa, Edifício C8, 5° Piso, Campo Grande, Lisboa, 1749-016, Portugal
b Institut Universitaire de Technologie de Poitiers, France
c Centro de Química Estrutural do Instituto Superior Técnico, Av. Rovisco Pais, Lisboa,
Portugal
Version of record first published: 16 Aug 2006.
To cite this article: Amélia P. Rauter, Olga Oliveira, Tana Canda, Estelle Leroi, Humberto Ferreira, Maria J. Ferreira & José
A. Ascenso (2002): SYNTHETIC APPROACH TO TETRAHYDROFURAN UNITS AND FIVE-MEMBERED RING LACTONES FUSED TO
HEXOPYRANOSIDES * , Journal of Carbohydrate Chemistry, 21:4, 257-273
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JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 21, No. 4, pp. 257–273, 2002
SYNTHETIC APPROACH TO TETRAHYDROFURAN
UNITS AND FIVE-MEMBERED RING LACTONES
FUSED TO HEXOPYRANOSIDES*
Ame´lia P. Rauter,1,y Olga Oliveira,1 Tana Canda,1,2 Estelle Leroi,3
Humberto Ferreira,4 Maria J. Ferreira,4 and Jose´ A. Ascenso4
1Departamento de Qu´ımica e Bioqu´ımica da Faculdade de Cieˆncias da
Universidade de Lisboa, Edif´ıcio C8, 5° Piso, Campo Grande,
1749-016 Lisboa, Portugal
2Universidade Agostinho Neto, Luanda, Angola
3Institut Universitaire de Technologie de Poitiers, France
Centro de Quimica Estrutural do Instituto Superior Te´cnico,
Av. Rovisco Pais, Lisboa, Portugal
4
ABSTRACT
A stereoselective synthesis of the miharamycin sugar moiety epimer at C-3’
was accomplished in high yield starting from an appropriate (Z)-Wittig
product, synthesized by Wittig reaction of a 4,6-O-benzylidene protected
hexopyranosid-3-ulose with [(ethoxycarbonyl)methylene]triphenylphosphor-
ane followed by iodine promoted isomerisation of the (E)-Wittig product
formed. Reduction of the (Z)-isomer obtained in quantitative yield, cycli-
sation and dihydroxylation with osmium tetroxide, gave the target molecule
containing a cis-fused tetrahydrofuran ring in its structure. Synhesis of five-
membered rings trans-fused to the hexopyranosidic units succeeded via two
different synthetic pathways. Stereoselective Reformatsky reaction of a 2,6-
di-O-pivaloyl protected hexopyranosid-3-ulose, followed by cyclisation with
dimethylzinc gave a 3,4-trans-fused lactone. The approach using the reaction
*
Dedicated to the 60th birthday of Prof. Joachim Thiem.
y
Corresponding author. Fax: + 351-21-7500088; E-mail: aprauter@fc.ul.pt
257
DOI: 10.1081/CAR-120013489
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright D 2002 by Marcel Dekker, Inc.

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258
RAUTER ET AL.
of 2,3-and 3,4-epoxides with the dianion of phenylselenoacetic acid led to
low yield but novel phenylseleno derivatives of trans-fused five-membered
rings, namely a phenylselenolactone 2,3-trans-fused to a 4,6-O-benzylidene-
hexopyranoside and a phenylselenolactenol 3,4-trans-fused to a 6-O-pival-
oyl-hexopyranoside.
INTRODUCTION
Synthesis of the sugar moieties of the antibiotics amipurymicin (1)[1] and
miharamycin (2)[2,3] and the C-3’ epimer[3] have been previously reported. These two
antibiotics are natural nucleosides isolated from Streptomyces novoguineensis nov.
sp.[4] and are known to inhibit strongly Pyricularia oryzae, which produces the rice
blast disease. In this paper we describe an efficient and high yield stereoselective
synthesis of the miharamycin sugar moiety epimer 3 as well as the stereoselective
approach to five-membered ring lactones fused to appropriate hexopyranosidic units,
which can be regarded as precursors of novel miharamycin sugar analogues.
RESULTS AND DISCUSSION
The preparation of 3 was first reported by a non-stereoselective procedure based on
the Wittig reaction of methyl 2-O-benzoyl-4,6-O-benzylidene-a-D-ribo-hexopyranosid-
3-ulose (4) with [(ethoxycarbonyl)methylene]triphenylphosphorane, leading to the mix-
ture of the (Z/E)-isomers in 7:3 ratio, followed by osmylation of the Wittig products,
reduction, and cyclisation with an overall yield of 16%.[3] A stereoselective method
previously reported gave the target molecule 3 in 6% overall yield.[3]
Our stereoselective synthesis of 3 was initiated from the protected hexopy-
ranuloside 4. Wittig reaction of 4 with [(ethoxycarbonyl)methylene]triphenylphos-
phorane giving the expected mixture of the (Z/E)-isomers 5a/5b[3] in quantitative
yield, was followed by iodine promoted isomerisation of the (E)-isomer in dichlo-
romethane[5] at rt for 24 h (Scheme 1) to give 5a. Reduction of 5a with lithium
aluminum hydride in tetrahydrofuran at 0°C for 30 min and then at rt for 2.5 h gave
1
the diol 6, isolated in 90% yield. The olefinic proton in the H NMR spectrum of 5a
appeared at d 6.03 as a triplet, coupled with the hydroxymethyl group protons with
J=6.0 Hz. The resonances of these protons appeared as a multiplet at d 3.94 À 3.66.
The H-2 signal was displaced to a higher field (d 4.40) compared with the cor-
responding signal of the Wittig product 5a (d 5.92), suggesting deprotection at position
2 under these reaction conditions. The 13C NMR spectrum was also in agreement with
the proposed structure with the signals of the olefinic carbons at d 135.7 (C-3) and d

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TETRAHYDROFURAN UNITS AND FIVE-MEMBERED RINGS
259
a) b)
O
O
O
O
O
O
Ph
Ph
C
O
BzO OMe
BzO OMe
H
CO2Et
4
5a
c)
O
O
O
O
O
d)
O
Ph
Ph
O
C
C
OMe
HO
OMe
H
H
CH2OH
6
7
e)
O
O
Ph
O
HO
HO
O
OMe
3
Scheme 1. a) Ph3P = CHCO2Et, CHCl3, D, 5.5 h, Z/E (7/3), Z = 100%; b) I2, CH2Cl2, rt, 24 h,
Z = 100%; c) LiAlH4, THF, 0°C, 0.5 h, rt, 2.5 h, Z = 90%; d) DEAD, Ph3P, CHCl3, molecular sieves
˚
4 A, 5°C, 6.5 h, Z = 88%; e) OsO4, Py, rt, 3 h, Z = 80%.
115.3 (C-3’), and the signal of C-3@ at d 30.2, respectively, (confirmed by DEPT).
Cyclisation with diethyl azodicarboxylate/triphenylphosphine in chloroform in the
˚
presence of 4 A molecular sieves at 5°C for 6.5 h under argon gave 7 in 88% yield.
The target molecule 3 was synthesized in 80% yield by dihydroxylation of 7 with
osmium tetroxide in pyridine at rt during 3 h. This stereoselective pathway is the most
efficient procedure described to date to prepare 3, with an overall yield of 63% starting
from the ketosugar 4.
In order to obtain novel miharamycin sugar analogues, we investigated the
formation of other five-membered rings fused to positions 2,3 or 3,4 of the hexopyra-
nosidic moiety. Application of the Reformatsky reaction to ketosugar 4 with ethyl bro-
moacetate in tetrahydrofuran in the presence of activated zinc gave 8 as a single isomer
(Scheme 2). The expected configuration of 8 at C-3 was confirmed by NOESY, with
correlations of the CH2-3’ protons with H-2, H-4, H-6a and H-6e. Treatment of 8 with
potassium carbonate in methanol at rt afforded the partially protected derivative 9 in
93% yield. Deprotection at position 2 was confirmed by the chemical shift of H-2 (d

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260
RAUTER ET AL.
O
O
O
a)
O
Ph
O
Ph
EtCO2CH2
O
O
BzO OM e
BzO OM e
HO
8
4
b)
O
O
c)
O
O
Ph
O
HOOM e
Ph
MeCO2CH2
O
OH
O
OM e
HO
O
9
10
Scheme 2. a) BrCH2CO2Et, Zn, THF, D, Z = 71%; b) K2CO3, MeOH, rt, Z = 93%; c) Me2Zn,
THF, rt.
3.62), which appeared at higher field in comparison to the H-2 signal of 8 (d 5.60).
Attempts to cyclise 9 with dimethylzinc in tetrahydrofuran at rt[6] failed and the lactone
10 was not detected by TLC.
The ketosugar 12 (Scheme 3), whose conformation is less rigid than that of 4,
was synthesized in 93% yield by acetylation of 11[1] with acetic anhydride in pyridine
at rt for 16 h. It was then used as the starting material for the Reformatsky reaction
with ethyl bromoacetate to give product 13 isolated only in 29% yield. The de-
acetylated compound 14 was also obtained (23%), probably formed during the work up
of the reaction mixture. NOESY spectra of 13 and of 14 showed in both cases
correlation between CH2-3’ and H-2, H-4 and the pivaloyl protons at position 6, thus
confirming the expected configuration at C-3. Cyclisation of 14 with dimethylzinc in
tetrahydrofuran at rt for 48 h gave the lactone 15 in 83% yield. The carbonyl group of
the five-membered ring lactone was confirmed by the band at 1780 cm À 1 in its IR
spectrum and by the signal at d 173.4 in its 13C NMR spectrum. The CH2-3’ 13C signal
appeared at d 37.3, while the two protons were observed as a singlet at d 2.75. The
13C and 1H NMR signals due to the ethoxy group were absent, implying also the
proposed lactonisation.
In an attempt to make the five-membered lactone 17, the a-acetoxyketosugar 12
(Scheme 4) was treated with the bulky base lithium bis(trimethylsilyl)amide.[7] Lactone
17 was not formed but rather deacetylation occurred giving 11[1] in 67% yield. A
second product 16 (33% yield) was also formed via tautomerisation, pivaloyl migration
and dehydration.
The reaction of the lithium salt of phenylselenoacetic acid with an epoxide to
build a five-membered ring lactone was previously used to prepare butenolides linked to
furanosidic systems by a C C bond.[8,9] This method, reported by J. Font and co-
workers,[10] was now used in order to synthesize five-membered ring lactones fused to
the hexopyranosidic unit in positions 3,4 or 2,3. The oxirane ring was built at positions

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TETRAHYDROFURAN UNITS AND FIVE-MEMBERED RINGS
261
OPiv
O
OPiv
O
a)
HO
AcO
O
O
PivOOM e
PivO OM e
12
11
b)
OPiv
O
OPiv
O
HO
Et CO CH2
AcO
Et CO CH2
+
2
2
HO
OM e
HO
PivOOM e
PivO
(23 %)
(29 %)
13
14
c)
OPiv
O
O
HO
OM e
O
PivO
15
Scheme 3. a) Ac2O, Py, rt, 16 h, Z = 93%; b) BrCH2CO2Et, Zn, THF, D; c) Me2Zn, THF, rt, 48 h,
Z = 83%.
3,4 by three different approaches (Scheme 5). The synthesis of 19 was first accom-
plished by treatment of methyl 2,6-di-O-pivaloyl-a-D-glucopyranoside[11] (18) with
diethyl azodicarboxylate and triphenylphosphine in benzene at 80°C for 48 h to give
the epoxide 19 in 26% yield. Reaction of 18 with triiodoimidazole/triphenylphos-
phine[12] in toluene at 90°C for 7 h afforded the olefin 20 in 62% yield, which was then
treated with 3-chloroperbenzoic acid/sodium acetate in dichloromethane[13] at rt for 40
h to also give the epoxide 19 (29% yield, based on the reacted alkene, recovered in
46% yield). Another procedure was also investigated in which the diol 18 was treated
with benzyltriethylammonium bromide (TEBA) in 50% aqueous sodium hydroxide and
dichloromethane, followed by addition of tosyl chloride[14] to give epoxide 21 in 88%
yield. When 21 was treated with the dianion of phenylselenoacetic acid, the enol 22 was
isolated in 8% yield and the deprotected epoxide 23 was obtained in 33% yield. The
13C NMR spectrum of the lactenol 22 showed the olefinic quaternary carbons at d 145.5
and d 144.9, and also the signals corresponding to the presence of the phenyl group,
thus confirming the structure of the phenylselenoenol. Additional spectral assignments
for 22 and 23 (see Experimental) are in agreement with the proposed structures.
The synthesis of the phenylselenolactone 28 (Scheme 6), which possesses the
expected trans-fused lactone ring, was initiated from the diol 24. Mesylation of 24[15]

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262
RAUTER ET AL.
OPiv
O
OPiv
O
OPiv
O
a)
AcO
HO
+
OM e
O
PivO
O
O
PivOOMe
PivOOM e
16 (33% )
12
11 (67% )
OPiv
O
O
HO
O
PivO OM e
17
Scheme 4. a) (Me3Si)2NLi, THF, À 78°C, 1.5 h; HCl 2N, rt.
OPiv
O
OPiv
O
a) or b)
HO
HO
O
RO OMe
PivO OMe
19 R = Piv
21 R = H
18
c)
d)
OPiv
O
e)
PivO OMe
20
OPiv
O
OH
O
O
HO
+
O
PhSe
HO OMe
OMe
HO
23 (33 %)
22 (8 %)
Scheme 5. a) DEAD, Ph3P, PhH, 80°C, 48 h, Z = 26%; b) TEBA, NaOH 50%, r 15 min, CH2Cl2,
TsCl, rt, 20 min, Z = 88%; c) Triiodoimidazole, Ph3P, toluene, 90°C, 7 h, Z = 62%; d) m-CPBA,
NaOAc, CH2Cl2, rt, 40 h, Z = 29%; e) PhSeCH2CO2H/LDA, THF, 0°C, 1 h, rt, 16 h; CH3CO2H
50%, 80°C, 20 h.

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TETRAHYDROFURAN UNITS AND FIVE-MEMBERED RINGS
263
with mesyl chloride in pyridine and dichloromethane at rt for 32 h gave 25 (77%
yield), which in turn was treated with sodium methoxide[16] to give 26 in 61% yield
and its diastereoisomer 27 in 31% yield, easily separated by column chromatography.
The confirmation of the orientation of the epoxide in 26 and 27 was possible from
NOESY experiments. While the NOESY spectrum from 26 gave correlations of H-2
with H-1 and H-3, and H-3 with H-4, with J3,4 =1.1 Hz (determined only at 400 MHz),
the experiment with 27 led to the correlations of H-2 with H-3 and OCH3, thus
confirming the proposed configurations for C-2 and C-3 in these diastereoisomers. The
synthesis of 27 starting from 24 in 68% yield was also accomplished using N-p-
tosylimidazole in DMF, a procedure already described in the literature.[17] Reaction of
26 with the dianion of phenylselenoacetic acid, followed by treatment with acetic acid
(50%) under reflux for 12 h gave the lactone 28 and the acid 29, isolated by column
chromatography in yields of 14% and 32%, respectively. The IR spectrum of 28
contained a carbonyl band at 1774 cm À 1 characteristic of a five-membered ring
1
lactone. In the H NMR spectrum of 28, H-2’ resonated at d 3.58 as a doublet, with a
coupling constant of J2,2’ = 12.3 Hz, while the signal of H-2 appeared at d 2.56, also as
a doublet. The carbonyl carbons, C-2 and C-2’ were detected at d 175.8, 48.3 and
48.9, respectively. The proposed structure for 28 was confirmed by NOESY
O
O
a)
O
O
Ph
Ph
O
O
MsO
HO
MsO OMe
HO OMe
24
25
b)
O
O
O
O
O
O
Ph
Ph
O
+
O
OMe
OMe
27 (31%)
26 (61 %)
c)
PhSe
H
C
SePh
H
O
O
O
O
Ph
Ph
O
O
H
H
+
HO
OMe
OH
OMe
C
O
O
O
29 (32 %)
28 (14 %)
Scheme 6. a) MsCl, Py, CH2Cl2, rt, 32 h, Z = 77%; b) NaOMe, 2.7 N, CH2Cl2, 2°C, 4 days, rt, 16
h; c) PhSeCH2CO2H/LDA, THF, 0°C, 1 h, rt, 20 h; CH3CO2H 50%, 80°C, 12 h.

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264
RAUTER ET AL.
experiments which indicated correlations between H-2’ and H-1, H-2, H-4 and Ph
protons, as well as those between H-2 and H-2’, H-1, and between H-4 and H-2’, C
HPh. The structure of 29 was found to contain a carboxylic acid unit, with an IR
1
carbonyl band at 1728 cm À 1. The H NMR spectrum of 29 showed H-2 as a doublet,
with J2,2’ = 1.5 Hz. A NOESY experiment showed correlations of H-2 with Ph protons
and H-1. The H-1 signal was seen as a broad singlet, and that of H-4 as a double
doublet with J3,4 =2.7 Hz and J4,5 = 9.6 Hz. HMQC and DEPT experiments allowed
assignment of the 13C NMR spectrum, with C-2 at d 47.0, C-2’ at d 58.1, C-3 at d
69.7, the carbonyl group at d 168.0 and the resonances confirming the presence of two
phenyl groups in the molecule.
In summary, a new synthetic pathway for the stereoselective synthesis of the
miharamycin sugar moiety C-3 epimer was described, which consists of an easy and
efficient method improving considerably the yield of the target molecule 3 (63%
overall yield starting from 4, in comparison with the yields 6% and 16% previously
reported[3]). Construction of a branch at positions 2 and 3 of pyranosidic units was also
investigated, leading to new five-membered ring compounds, some of which can be
regarded as interesting precursors of miharamycin sugar moiety analogues.
EXPERIMENTAL
General methods. Melting points were determined with a melting point appa-
ratus (Tottoli) and are uncorrected. Optical rotations were measured with a Perkin-Elmer
343 polarimeter, and IR spectra were recorded with a Biorad FTS 25 PC spec-
1
trophotometer. H NMR spectra were run with a Varian Unity-300 MHz spectrometer
and NOE and HMQC experiments with a Bruker AM-400 WB. Chemical shifts are
1
expressed in parts per million downfield from TMS. Homonuclear H{1H} experiments
were performed at 400 MHz in C3D6O or CDCl3, using a low decoupler setting (typically
40 L, 5 mW approximately) with a total presaturation time of 6 s. The FIDs were
acquired using 16 K points and a sweep width of 5000 Hz in alternate groups of eight,
irradiation on/off resonance. A 90° pulse was used during acquisition. The 13C NMR
spectra were recorded with a Varian Unity spectrometer at 75.4 MHz. The progress of all
reactions was monitored by thin-layer chromatography (TLC) using aluminum sheets
precoated with silica gel 60F254 with a thickness of 0.2 mm (Merck). Preparative TLC
was performed with aluminum plates coated with silica gel 60F254 with a thickness of 0.5
mm (Merck). Detection was effected by observation under UV light (254 nm) and/or by
spraying the sheets with a 3% vanillin–sulfuric acid solution. Column chromatography
was conducted with silica gel (0.040–0.063 mm, Merck) under low pressure.
Methyl 2,300-Anhydro-4,6-O-benzylidene-3-C-[(R)-1,2-dihydroxyethyl]-a-D-glu-
copyranoside (3). Osmium tetroxide (130 mg, 0.51 mmol) was added to a soln of 7
(110 mg, 0.38 mmol) in pyridine (3 mL), and the mixture was stirred at rt for 3 h.
Saturated NaHSO3 soln (11.5 mL) and pyridine (4 mL) were added to the reaction
mixture and within 5 min the complex was cleaved to give an orange soln, which was
extracted with chloroform (3 ꢀ 25 mL). The organic phase was dried over sodium
sulfate and concentrated to give crystalline 3 (100 mg, 80%): mp 125–126°C (lit. 124–

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TETRAHYDROFURAN UNITS AND FIVE-MEMBERED RINGS
265
126°C).[3] Physical and spectroscopic data were in full agreement with those reported
previously in the literature.[3]
Methyl 2-O-Benzoyl-4,6-O-benzylidene-3-C-[(Z)-(ethoxycarbonyl)methylene]-
a-D-ribo-hexopyranoside (5a). A soln of [(ethoxycarbonyl)methylene]triphenylphos-
phorane (1.7 g, 4.9 mmol) in dry chloroform (8 mL) was added at rt to a soln of 4[3]
(465 mg, 1.21 mmol) in dry chloroform (2 mL). The mixture was stirred under reflux
for 5.5 h. Evaporation of the solvent and purification by column chromatography eluted
with ethyl acetate–petroleum ether (2:7 v/v) afforded a mixture of the (Z/E)-isomers in
a 7:3 ratio as a syrup (559 mg, 100%). Its spectroscopic data were in accordance with
those reported in the literature.[3] The soln of the (Z/E)-mixture (285 mg, 0.63 mmol) in
dichloromethane (45 mL) was added to a soln of iodine (38 mg, 0.15 mmol) in
dichloromethane (3 mL), and the mixture was stirred at rt in the dark for 24 h. A
saturated soln of Na2S2O3 was added until the reaction mixture changed from violet to
colorless. The organic phase was extracted with dichloromethane (3 ꢀ 20 mL) and dried
over sodium sulfate. Evaporation of the solvent gave a residue which was purified by
column chromatography eluted with ethyl acetate–hexane (1:3 v/v) to give 5a (285 mg,
100%) as a syrup. Its physical and spectroscopic data were in agreement with those
reported in the literature.[3]
Methyl 4,6-O-Benzylidene-3-C-[(Z)-(hydroxymethyl)methylene]-a-D-ribo-he-
xopyranoside (6). A soln of 5a[3] (132 mg, 0.29 mmol) in dry THF (6 mL) was ad-
ded to a suspension of LiAlH4 (135 mg, 3.4 mmol) in dry THF (5 mL) at 0°C, and the
mixture was stirred for 30 min at 0°C and then for 2.5 h at rt. A mixture of dry THF/
chloroform (20 mL, 1:1 v/v) was added, followed by a saturated soln of ammonium
chloride (7 mL). After stirring for 2 h, the mixture was extracted with THF/chloroform
(3:1 v/v). The organic phase was dried over sodium sulfate and concentrated to dryness.
The residue was purified by column chromatography eluted with ethyl acetate–toluene
(2:1 v/v) to give crystalline 6 (89.6 mg, 90%); mp 158–160°C; [a]D20 + 12.7 (c 0.5,
EtOH); Rf 0.37 (ethyl acetate–toluene 2:1); 1H NMR (CDCl3) d 7.51 À 7.46 (m, 5H, Ph),
6.03 (t, 1H, H-3’, J3’,3@a = J3’,3@b =6 Hz), 5.60 (s, 1H, CHPh), 4.75 (d, 1H, H-1, J1,2 =3 Hz),
4.40 (d, 1H, H-2), 4.37 À 4.27 (m, 2H, H-4, H-6e), 3.94 À 3.66 (m, 4H, H-6a, H-5, H-3@a,
H-3@b), 3.47 (s, 1H, OCH3); 13C NMR (CDCl3) d 137.1 (Cq, Ph), 135.7 (C-3), 129.0,
128.7, 128.3, 128.1, 126.1 (Ph), 115.3 (C-3’), 101.4 (CHPh), 97.2 (C-1), 87.4 (C-4), 73.3
(C-2), 69.1 (C-6), 58.7 (C-5), 51.2 (OCH3), 30.2 (C-3@).
Anal. Calcd for C16H20O6 (308.33): C, 62.33; H, 6.54. Found: C, 62.61; H, 6.48.
Methyl 2,300-Anhydro-4,6-O-benzylidene-3-C-[(Z)-(hydroxymethyl) methyl-
˚
ene]-a-D-ribo-hexopyranoside (7). Triphenylphosphine (292 mg, 1.11 mmol) and 4 A
powdered molecular sieves (42 mg) were added to a soln of 6 (139 mg, 0.45 mmol) in
dry chloroform (11.5 mL) at rt under argon. After cooling to 5°C, diethyl azo-
dicarboxylate (0.2 mL, 1.33 mmol) was added and the reaction was stirred at 5°C for
6.5 h. Filtration and solvent evaporation gave a residue which was purified by column
chromatography eluted with ethyl acetate–hexane (2:3 v/v) giving 7 (115 mg, 88%) as

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266
RAUTER ET AL.
a syrup; [a]D20 +34 (c 0.9, chloroform); Rf 0.57 (ethyl acetate–hexane 2:3); IR (cm À 1
,
1
KBr) 3500 (OH); H NMR (CDCl3) d 7.41 À 7.36 (m, 5H, Ph), 5.77 (s, 1H, H-3’), 5.65
(s, 1H, CHPh), 4.89 À 4.79 (m, 4H, H-1, H-2, H-3@a, H-3@b), 4.29 (dd, 1H, H-6e,
4
J
6e,6a =10 Hz, J5,6e =4.2 Hz), 4.23 (dd, 1H, H-4, J4,5 = 9 Hz, J3’,4 =2.4 Hz), 3.85 (t, 1H,
H-6a, J5,6a =10 Hz), 3.76 (ddd, H-5), 3.45 (s, 1H, OCH3); 13C NMR (CDCl3) d137.5
(Cq, Ph), 133.2 (C-3), 129.2, 128.3, 128.2, 126.3 (Ph), 116.6 (C-3’), 100.4 (CHPh), 97.2
(C-1), 84.0 (C-4), 69.5 (C-6), 64.8 (C-2), 55.3 (C-5), 51.2 (OCH3), 29.7 (C-3@).
Anal. Calcd for C16H18O5 (290.31): C, 66.19; H, 6.25. Found: C, 65.85; H, 6.33.
Methyl 2-O-Benzoyl-4,6-O-benzylidene-3-C-(ethoxycarbonyl)methylene-a-D-
allopyranoside (8). Ethyl bromoacetate (1.67 mL, 15.6 mM), diluted with THF
(4.5 mL), was added dropwise to the suspension of activated zinc (1.09 g, 16.7 mM)
in a soln of 4[3] (2 g, 5.2 mM) in anhydrous THF (8 mL), under argon. After
stirring at 60°C for 3 days, the mixture was cooled to rt. Addition of conc.
ammonium hydroxide (4 mL) in water (16 mL) under stirring was followed by
extraction with dichloromethane (3 ꢀ 25 mL). The organic phase was dried over
sodium sulfate and concentrated under reduced pressure. The residue was purified by
column chromatography with ethyl acetate/toluene (1:5 v/v) to give 8 (1.75 g, 71%); mp
125–126°C; [a]D20 + 71° (c 1.0, dichloromethane); Rf 0.5 (ethyl acetate–toluene 1:5);
1
IR (KBr) 3372 cm À 1 (OH), 1736 cm À 1 (C O); H NMR (C6D6) d 8.27 À 8.24 (m,
4H, Ph), 7.69 À 7.68 (m, 6H, Ph), 5.60 (d, 1H, H-2), 5.51 (s, 1H, CHPh), 5.10 (d, 1H,
J
1,2 =3.9 Hz, H-1), 4.35 À 4.19 (m, 2H, H-5, H-6e), 4.01 À 3.69 (m, 3H, H-4, CH2, Et),
d 3.59 (t, 1H, J6e,6a = J5,6a =10.3 Hz, H-6a), 3.16, 3.11, 2.97, 2.92 (H-3’a, H-3’b, AB
system, JA,B = 15.3 Hz), 2.80 (s, 3H, OCH3), 0.80 (t, 3H, JCH2,CH3 = 6.8 Hz, CH3, Et);
13C NMR (C6D6) d 170.6 (C O, CO2Et), 165.8 (C O, Bz), 138.4 (Cq, Ph), 136.5
(Cq, Ph), 133.5 (C-3), 130.3, 129.9, 129.1, 128.8, 127.7, 126.9 (Ph), 102.3 (CHPh),
98.8 (C-1), 79.6 (C-4), 71.5 (C-2), 69.2 (C-6), 60.5 (CH2, Et), 59.7 (C-5), 55.5 (OCH3),
37.5 (CH2-3’), 13.9 (CH3, Et).
Anal. Calcd for C25H28O9 (472.46): C, 63.55; H, 5.97. Found: C, 63.26; H, 5.95.
Methyl 4,6-O-Benzylidene-3-C-(methoxycarbonyl)methylene-a-D-allopyrano-
side (9). Dry potassium carbonate (29 mg, 0.21 mmol) was added to a soln of 8
(100 mg, 0.21 mmol) in anhyd methanol (5 mL). The suspension was stirred for 60 h at
rt under argon. Neutralisation with Amberlite IR 120 (H + ), filtration, solvent evapo-
ration and purification by column chromatography eluted with ethyl acetate–hexane
(1:1) gave 9 (63 mg, 93%); mp 185.5–186.5°C; [a]D20 +19° (c 1.0, dichloromethane);
Rf 0.22 (ethyl acetate–hexane 1:1); IR (KBr) 3556 cm À 1 (OH), 1710 cm À 1 (C O);
1H NMR (CDCl3): d 7.45 À 7.34 (m, 5H, Ph), 5.53 (s, 1H, CHPh), 4.76 (d, 1H, H-1,
J
1,2 =4.2 Hz), 4.35 (dd, 1H, H-6e, J6e,5 =5.4 Hz, J6e,6a =10.5 Hz), 4.14 (ddd, 1H, H-5),
3.73 (t, 1H, H-6a, J5,6a =10.2 Hz), 3.62 (d, 1H, H-2), 3.58 (d, 1H, H-4, J4,5 =9.3 Hz),
3.50 (s, 3H, OCH3), 3.48 (s, 3H, OCH3), 2.95, 2.90, 2.62, 2.57 (H-3’a, H-3’b, AB
system, J3’a,3’b =15.3 Hz); 13C NMR (CDCl3): d 172.6 (C O), 137.0 (Cq, Ph), 129.0,
128.1, 126.2 (Ph), 101.7 (CHPh), 100.2 (C-1), 80.5 (C-4), 73.0 (C-3), 70.3 (C-2), 69.0
(C-6), 58.5 (C-5), 56.4 (OCH3), 51.8 (COO CH3), 37.7 (C-3’).
Anal. Calcd for C17H22O8 (354.3): C, 57.62; H, 6.25. Found: C, 57.13; H, 6.14.

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TETRAHYDROFURAN UNITS AND FIVE-MEMBERED RINGS
267
Methyl 4-O-Acetyl-2,6-di-O-pivaloyl-a-D-ribo-hexopyranosid-3-ulose (12).
Acetic anhydride (0.147 mL, 1.55 mmol) was added to a soln of 11[1] (80 mg, 0.77
mmol) in dry pyridine (1 mL). The mixture was stirred for 16 h at rt. After solvent
evaporation, the residue was purified by column chromatography eluted with ethyl
acetate–toluene (1:5, v/v) to give 12 (290 mg, 93%) as a syrup. [a]D20 + 100° (c 1.0,
1
chloroform); Rf 0.65 (ethyl acetate–toluene 1:5); IR (neat): 1746 cm À 1 (C O); H
NMR (CDCl3) d 5.36 (d, 1H, H-2, J1,2 =3 Hz), 5.30 (d, 1H, H-4, J4,5 =9 Hz), 5.18 (d,
1H, H-1), 4.37 À 4.20 (m, 3H, H-5, H-6a, H-6b), 3.45 (s, 3H, OCH3), 2.16 (s, 3H, CH3,
Ac), 1.26 (s, 9H, CH3, Piv), 1.23 (s, 1H, 9H, CH3, Piv); 13C NMR (CDCl3) d 193.0
(C-3, C O), 177.8 (C O, Piv), 176.8 (C O, Piv), 168.6 (C O, Ac), 99.8 (C-1),
74.2, 72.0, (C-2, C-4), 69.5 (C-5), 62.1 (C-6), 55.6 (OCH3), 38.9 (Cq, Piv), 27.0
(CH3, Piv), 26.9 (CH3, Piv), 20.1 (CH3, OAc).
Anal. Calcd for C19H30O9 (402.4): C, 56.71; H, 7.50. Found: C, 57.11; H, 8.00.
Methyl 4-O-Acetyl-2,6-di-O-pivaloyl-3-C-(ethoxycarbonyl)methylene-a-D-glu-
copyranoside (13) and Methyl 2,6-Di-O-pivaloyl-3-C-(ethoxycarbonyl)methylene-
a- D-glucopyranoside (14). A soln of ethyl bromoacetate (0.234 mL, 2.12 mmol) in
anhyd THF (0.6 mL) was added dropwise to a suspension of activated zinc (10.15 mg,
2.28 mmol) in the soln of 12 (315 mg, 0.783 mmol) in THF (0.6 mL) under argon. The
mixture was stirred at 50°C for two days and cooled to rt. Ammonium hydroxide (0.3
mL) was then added and the mixture was extracted with diethyl ether (3 ꢀ 5 mL) and
with dichloromethane (3 ꢀ 5 mL). The organic phase was dried with sodium sulfate,
concentrated in vacuo and the residue purified by column chromatography eluted with
ethyl acetate–toluene (1:5 v/v) to give 13 (95 mg, 29%) and 14 (73 mg, 23%), on the
basis of the reacted starting material, recovered in 16% yield.
Physical and spectroscopic data of 13: [a]D20 + 54° (c 1, dichloromethane); Rf 0.50
1
(ethyl acetate–toluene 1:5); IR (neat) 3492 cm À 1 (OH),1744 cm À 1 (C O); H NMR
(CDCl3) d 5.18 À 5.13 (m, 2H, H-2, H-4), 5.04 (d, 1H, H-1, J1,2 =3.9 Hz), 4.23 À 4.18
(m, 3H, H-5, H-6a, H-6b), 4.22 (q, 2H, CH2, Et), JCH2,CH3 = 7.2 Hz), 3.44 (s, 3H, OCH3),
2.67, 2.62, 2.53, 2.48 (H3’a, H3’b, AB system, J3’a,3’b = 16.2 Hz), 2.14 (s, 3H, CH3, Ac),
1.26 À 1.21 (m, 21H, CH3, Piv, CH3, Et); 13C NMR (CDCl3) d 177.2 (C O, Piv), 169.4
(C O, CO2Et), 167.9 (C O, Ac), 97.4 (C-1), 73.6 (C-3), 69.2 (C-2), 68.8 (C-4), 65.5
(C-5), 62.5 (C-6), 60.8 (OCH2, Et), 56.0 (OCH3), 37.3 (CH2CO2Et), 27.1 (CH3, Piv),
26.9 (CH3, Piv), 20.6 (CH3, Ac), 13.9 (CH3, Et).
Anal. Calcd for C23H38O11 (490.5): C, 56.32; H, 7.80. Found: C, 56.54; H, 7.79.
Physical and spectroscopic data of 14: [a]D20 +11° (c 1.0, dichloromethane); Rf
1
0.12 (ethyl acetate–toluene 1:5); IR(neat) 3488 cm À 1 (OH), 1738 cm À 1 (C O); H
NMR (CDCl3) d 4.98 (d, 1H, H-2, J1,2 =3.6 Hz), 4.93 (d, 1H, H-1), 4.48 (dd, 1H, H-6a,
J
6a,5 = 2.1 Hz), 4.31 (dd, 1H, H-6b, J5,6b =5.7 Hz, J6a,6b = 11.7 Hz), 4.08 (q, 2H, CH2,
Et), 3.85 (ddd, 1H, H-5), 3.75 (t, 1H, H-4, J4,5 =9.9 Hz), 3.40 (s, 3H, OCH3), 2.73 (d,
1H, OH, J4,OH =10,2 Hz), 2.84, 2.79, 2.61, 2.55 (H-3’a, H-3’b, AB system, J3’a,3’b =15
Hz), 1.24 (s, 9H, CH3, Piv), 1.22 (s, 9H, CH3, Piv), 1.19 (t; 3H, CH3, Et); 13C
NMR(CDCl3) d 177.3 (C O, Piv), 176.4 (C O, Piv), 170.1 (C O, CO2Et), 97.5
(C-1), 73.9 (C-3), 69.3 (C-2 ), 68.0 (C-4), 67.8 (C-5), 63.6 (C-6), 60.7 (OCH2, Et),
55.9 (OCH3), 37.3 (CH2-3’), 27.2 (CH3, Piv), 27.0 (CH3, Piv), 14.0 (CH3, Et).
Anal. Calcd for C21H36O10 (448.47): C, 56.24; H, 8.08. Found: C, 56.05; H, 8.00.

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RAUTER ET AL.
Methyl 2,6-Di-O-pivaloyl-3-C-(carboxymethyl)-a-D-allopyranoside-30,3-lactone
(15). A soln of 14 (77 mg, 0.17 mmol) in anhyd THF (2.6 mL) was added to a soln
of 2 M dimethylzinc in toluene (0.75 mL, 1.5 mmol) under argon and stirred at rt for
29 h. A saturated soln of ammonium chloride (5 mL) was added, and the mixture was
stirred at rt for 24 h. The organic phase was extracted with diethyl ether (3 ꢀ 5 mL),
dried with sodium sulfate and concentrated in vacuo. The residue was purified by
column chromatography eluted with ethyl acetate–toluene (1:2 v/v) to give 15 (57 mg,
83%) as a syrup. [a]D20 + 38° (c 1.0, dichloromethane); Rf 0.20 (ethyl acetate–
toluene1:2); IR (neat) 1780 cm À 1 (C O), 1736 cmÀ 1 (C O, Piv); 1H NMR (CDCl3) d
4.97 (d, 1H, H-1, J1,2 =3.6 Hz), 4.88 (d, 1H, H-2), 4.68 (d, 1H, H-4, J4,5 =9.9 Hz), 4.48
(dd, 1H, H-6a, J6a,6b =12 Hz, J6a,5 =2.1 Hz), 4.34 (dd, 1H, H-6b, J6b,5 =5.4 Hz),
3.91 À 3.86 (m, 1H, H-5), 3.43 (s, 3H, OCH3), 2.75 (s, 2H, H-3’a, H-3’b), 1.25 (s, 9H,
CH3, Piv), 1.23 (s, 9H, CH3, Piv); 13C NMR (CDCl3) d 177.5 (C O, Piv), 179.0
(C O, Piv), 173.4 (C-3@), 97.4 (C-1), 74.2 (C-3) 69.9, 68.4, 67.7 (C-2, C-4, C-5),
63.6 (C-6), 56.0 (OCH3), 39.1 (Cq, Piv), 37.3 (C-3’), 27.2 (CH3, Piv), 26.9 (CH3, Piv).
Anal. Calcd for C19H30O9 (402.40): C, 56.71; H, 7.50. Found: C, 56.51; H, 7.25.
Methyl 4-Deoxy-3,6-di-O-pivaloyl-a-D-glycero-hex-3-enopyranosid-2-ulose
(16). A soln of 12 (240 mg, 0.6 mmol) in anhyd THF (3.8 mL) was added dropwise
to a 2 M soln of lithium bis(trimethylsilyl)amide (1.4 mL, 2.8 mmol) in THF (2.5 mL),
previously cooled to À 78°C, under argon. The mixture was stirred at À 78°C for 1.5 h
and then poured into an HCl 2N soln (2 mL). The mixture was stirred until rt was
reached. The organic layer was separated, and the aqueous phase was extracted with
ethyl acetate (3 ꢀ 5 mL). The organic phases were stirred over sodium chloride and
concentrated. The residue was extracted with dichloromethane, dried with sodium
sulfate, concentrated and purified by column chromatography eluted with ethyl
acetate–toluene (1:8 v/v) to give methyl 2,6-di-O-pivaloyl-a-D-ribo-hexopyranosid-2-
ulose 11[1] (74 mg, 67%) and 16 (36 mg, 33%) as a syrup, on the basis of the reacted
starting material, recovered in 43% yield. Physical and spectroscopic data of 16:
[a]D20 + 38° (c 1, dichloromethane); Rf 0.60 (ethyl acetate–toluene 1:8); IR (neat):
1
1766 cm À 1 (C O), 1726 cm À 1 (C O), 1663 cm À 1 (C C); H NMR (CDCl3) d
6.55 (d, 1H, H-4, J4,5 =1.5 Hz), 4.94 (td, 1H, H-5), 4.89 (s, 1H, H-1), 4.41 (dd, 1H, H-
6a, J5,6a = 5.7 Hz, J6a,6b =11.7 Hz), 4.23 (dd, 1H, H-6b, J5,6b =5.1 Hz), 3.55 (s, 3H,
OCH3), 1.25 (s, 9H, CH3, Piv), 1.24 (s, 9H, CH3, Piv) 13C NMR (CDCl3) d 182.4
(C-2), 178.1 (C O, Piv), 175.7 (C O, Piv), 142.2 (C-3), 132.1 (C-4), 99.1 (C-1), 67.6
(C-5), 64.3 (C-6), 56.9 (OCH3), 39.0 (Cq, Piv), 27.1 (CH3, Piv).
Anal. Calcd for C17H26O7 (342.40): C, 59.63; H, 7.65. Found: C, 59.55; H, 7.87.
Methyl 2,6-Di-O-pivaloyl-3,4-anhydro-a-D-allopyranoside (19). Method 1.
Triphenylphosphine (946 mg, 3.61 mmol) was added to a soln of 18 (500 mg, 1.38
mmol) in anhyd benzene (24 mL). The soln was stirred for 15 min at rt, then activated
˚
molecular sieves powder 3 A (1.1 g) was added and DEAD (0.58 mL, 3.61 mmol) was
added dropwise. The reaction mixture was stirred for 48 h at 80°C. Filtration and
evaporation of the solvent gave a residue which was purified by column chromatography
eluted with ethyl acetate–toluene (1:5 v/v) to give 19 (122.2 mg, 26% yield).

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TETRAHYDROFURAN UNITS AND FIVE-MEMBERED RINGS
269
Method 2. m-CPBA (264 mg, 1.53 mmol) and sodium acetate (126 mg, 1.53
mmol) were added to a soln of 20 (130 mg, 0.33 mmol) in dichloromethane (7 mL), and
the reaction mixture was stirred at rt for 40 h. A saturated sodium hydrogen carbonate
soln was added, and the organic phase was extracted with dichloromethane, washed
with a saturated sodium thiosulfate soln, with a saturated soln of sodium chloride, with
water, dried over sodium sulfate and concentrated. The residue was purified by column
chromatography as described for Method 1 to give 19 (20 mg, 29%) on the basis of the
reacted starting material, recovered in 46% yield. Physical and spectroscopic data of 19:
[a]D20 +47° (c 1, dichloromethane); Rf 0.57 (ethyl acetate–hexane 1:3); mp 51–52.5°C;
1
IR (KBr): 1738 cm À 1 (C O), 1852 cm À 1 (C O); H NMR (CDCl3) d 4.86 (d, 1H,
H-1, J1,2 =6 Hz), 4.71 (d, 1H, H-2), 4.30 À 4.15 (m, 3H, H-5, H-6a, H-6b), 3.37 (s, 3H,
OCH3), 3.26 À 3.24 (m, 2H, H-3, H-4), 1.22 (s, 9H, CH3, Piv), 1.21 (s, 9H,CH3, Piv),
13C NMR (CDCl3): d 178.0 (C O, Piv), 94.1 (C-1), 65.4 (C-2), 63.5 (C-5), 63.3 (C-6),
55.8 (OCH3), 51.0 (C-3), 49.7 (C-4), 27.1 (CH3, Piv), 27.0 (CH3, Piv).
Anal. Calcd for C17H28O7 (344.36): C, 59.30; H, 8.20. Found: C, 58.63; H, 7.96.
Methyl 3,4-Dideoxy-2,6-di-O-pivaloyl-a-D-erythro-hex-3-enopyranoside (20).
Triphenylphosphine (472 mg, 2.63 mmol), 18 (280 mg, 0.657 mmol), triiodoimidazole
(472 mg, 1.045 mmol) recently prepared[12] and imidazole (90 mg, 1.3 mmol) were
added to toluene (15 mL), and the reaction mixture was stirred at 90°C for 7 h. The
mixture was cooled to rt, toluene (15 mL) was added and then a saturated hydrogen
carbonate soln (90 mL). After stirring for 10 min at rt, the organic phase was washed
with aqueous sodium thiosulfate, then with a saturated sodium hydrogen carbonate soln
and finally with water. The organic phase was dried over sodium sulfate and
concentrated. The residue was purified by column chromatography eluted with ethyl
acetate–hexane (1:4 v/v) to give 20 as a syrup (130 mg, 62%); [a]D20 +16° (c 1,
dichloromethane); Rf 0.36 (ethyl acetate–hexane 1:4); IR (neat) 1740 cm À 1 (C O);
1H NMR (CDCl3): d 5.85 (dt, 1H, H-3, J3,4 =19.5 Hz, J2,3 =J3,5 = 1.5 Hz), 5.73 (dt, 1H,
H-4, J4,5 = J2,4 =2.7 Hz), 5.24 (ddd, 1H, H-2, J1,2 =4.2 Hz), 5.11 (d, 1H, H-1), 4.39 (m,
1H, H-5), 4.27 (dd, 1H, H-6a, J5,6a =5.4 Hz, J6a,6b =11.4 Hz), 4.16 (dd, 1H, H-6b,
J
5,6b = 4.2 Hz), 3.47 (s, 3H, OCH3), 1.23 (s, 9H, CH3, Piv), 1.21 (s, 9H, CH3, Piv); 13C
NMR (CDCl3): d 178.0 (C O, Piv), 128.0 (C-3), 124 (C-4), 95.8 (C-1), 66.7 (C-5),
66.1 (C-2), 64.8 (C-6), 56.0 (OCH3), 27.1 (CH3, Piv), 27.0 (CH3, Piv).
Anal. Calcd for C17H28O6 (328.38): C, 62.17; H, 8.58. Found: C, 62.47, H, 8.45.
Methyl 6-O-Pivaloyl-3,4-anhydro-a-D-allopyranoside (21). À 50% aqueous
sodium hydroxide (2.8 mL) was added to the mixture of 18 (2 g, 5.5 mmol) and
benzyltriethylammonium bromide (55 mg) in dichloromethane (10 mL). The mixture
was stirred at rt for 15 min and then cooled to 0°C. A soln of tosyl chloride (1.048 g,
5.5 mmol) in dichloromethane (5.5 mL) was added dropwise under cooling, and the
reaction mixture was then stirred at 25°C for 20 min. Water was added (10 mL), and
the organic phase was separated, dried with sodium sulfate and concentrated. The
residue was purified by column chromatography eluted with ethyl acetate-hexane 1:2 to
give 21 (1.26 g, 88%); mp 75–76°C; [a]D20 +17° (c 1, chloroform); IR (KBr) 1736
1
cm À 1 (C O), 3544 cm À 1 (OH), 1299 cm À 1 (C O, epoxide); H NMR (CDCl3) d

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270
RAUTER ET AL.
4.61 (d, 1H, H-1, J1,2 = 4.2 Hz), 4.44 (d, 1H, H-2, J2,3 = 4.2 Hz, 4.26 À 4.23 (m, 3H, H-
5, H-6a, H-6b), 3.35 (s, 3H, OCH3), 3.22 À 3.21 (m, 2H, H-3, H-4), 1.21 (s, 9H, CH3,
Piv); 13C NMR (CDCl3) d 178.0 (C O, Piv), 94.4 (C-1), 71.0 (C-2), 64.1 (C-5), 63.0
(C-6), 55.9 (OCH3), 50.9 (C-3), 49.8 (C-4), 38.8 (Cq, Piv), 27.1 (CH3, Piv).
Anal. Calcd for C12H20O6 (260.3): C, 55.38; H, 7.74. Found: C, 55.70; H, 7.66.
Methyl 300,4-Anhydro-3-deoxy-6-O-pivaloyl-3(S)-C-(300,300-dihydroxy-30-phenyl-
selenylethenyl)-a-D-ribo-hexopyranoside (22) and Methyl 3,4-Anhydro-a-D-allopy-
ranoside (23). 1.6 M n-BuLi in hexane (3.83 mL, 6.13 mmol) was added dropwise to a
soln of diispropylamine (0.9 mL, 6.13 mmol) in THF (12 mL), previously cooled to 0°C,
under argon. After stirring for 25 min at 0°C, a soln of phenylselenoacetic acid (622 mg,
2.88 mmol) in anhyd THF (3 mL) was added dropwise for 1 h at 0°C under stirring, and
a white precipitate was formed after a few minutes indicating the formation of the
dianion. A soln of 21 (497 mg, 1.44 mmol) in anhyd THF (1.5 mL) was then added
dropwise for 1 h at 0°C. The reaction mixture was stirred for 23 h at rt, and the
precipitate dissolved, giving a clear soln. A 50% soln of acetic acid (2.5 mL) was added
and the reaction mixture was heated at 80°C for 20 h. After cooling, neutralisation was
effected with a saturated NaHCO3 soln, and the organic phase was extracted with diethyl
ether (3 ꢀ 10 mL), dried with sodium sulfate and concentrated. The syrup was purified
by column chromatography eluted with ethyl acetate–toluene 1:8 to give 22 (68 mg,
20
8%) and 23 (107 mg, 33%). Physical and spectroscopic data of 22: [a]D + 18° (c 1,
dichloromethane); Rf 0.45 (ethyl acetate–hexane 1:3); IR (neat): 3450 cm À 1 (OH),
1
1732 cm À 1 (C O); H NMR (CDCl3): d 7.91 (d, 1H, H-6@, J5@,6@ =9 Hz), 7.79 (d, 1H,
H-2@, J2@,3@ =9 Hz), 7.53 (d, 1H, H-4@, J3@,4@ =9 Hz), 7.34 À 7.26 (m, 2H, Ph, H-3@, H-5@),
5.10 (t, 1H, H-3, J3,4 =9.6 Hz), 4.78 À 4.73 (m, 2H, H-1, H-4), 4.36 (dd, 1H, H-6a,
J5,6a =1.8 Hz), 4.24 (dd, 1H, H-2, J1,2 = 3.3 Hz, J2,3 =9.6 Hz), 4.10 (dd, 1H, H-6b,
J
6a,6b =12 Hz, J5,6b =5.1 Hz), 3.95 (ddd, 1H, H-5), 3.24 (s, 3H, OCH3), 1.23 (s, 9H, CH3,
Piv); 13C NMR (CDCl3): 177.8 (C O, Piv), 145.4, 144.9 (C-3’,C-4’), 132.6 (Cq, Ph),
129.8, 129.6, 128.4, 128.0 (CH, Ph), 96.4 (C-1), 75.6 (C-3), 75.5 (C-2 ), 73.1 (C-4), 67.6
(C-5), 61.7 (C-6), 55.6 (OCH3), 38.8 (Cq, Piv), 27.1 (CH3, Piv).
Anal. Calcd for C20H26O8Se (437.35): C, 54.92; H, 5.98; Se, 17.26. Found: C,
54.25; H, 6.12.
Physical and spectroscopic data of 23: mp 128–129°C; [a]D20 +38° (c 1, di-
1
chloromethane); Rf 0.20 (ethyl acetate–hexane 1:3); IR (neat): 3500 cm À 1 (OH); H
NMR (CDCl3): d 4.59 (d, 1H, H-1, J1,2 = 6 Hz), 4.40 (d, 1H, H-2), 4.02 (brt, 1H,H-5),
3.82 À 3.70 (m, 2H, H-6a, H-6b), 3.33 (s, 3H, OCH3), 3.21 À 3.16 (m, 2H, H-3, H-4);
13C NMR (CDCl3): d 94.4 (C-1), 71.1 (C-2), 66.0 (C-5), 62.5 (C-6), 55.9 (OCH3), 50.4,
50.0 (C-3, C-4).
Anal. Calcd for C7H12O5 (176.14): C, 47.73; H, 6.86. Found: C, 48.08; H, 6.74.
Methyl 4,6-O-Benzylidene-2,3-di-O-mesyl-a-D-glucopyranoside (25). Mesyl
chloride (2.5 mL, 32.4 mmol) was added dropwise to a stirred soln of 24[15] (3 g,
10.63 mmol) in anhyd dichloromethane (48 mL) and anhyd pyridine (18 mL), previously
cooled to À 20°C. The reaction mixture was stirred for 32 h at rt and then cooled to 0°C.
Addition of solid sodium hydrogen carbonate was followed by extraction of the organic

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TETRAHYDROFURAN UNITS AND FIVE-MEMBERED RINGS
271
phase with dichloromethane, which was dried over magnesium sulfate. The soln was
concentrated, dissolved in toluene (15 mL), and concentrated again. This procedure was
repeated 3 times. The residue was purified by column chromatography eluted with ethyl
acetate–toluene 1:4 to give 25 (3.6 g, 77%); mp 241–242°C; [a]D20 +9° (c 1, di-
1
chloromethane); Rf 0.27 (ethyl acetate–toluene 1:4); IR (KBr) 1372 cm À 1 (S O); H
NMR (CDCl3): d 7.47 À 7.37 (m, 5H, Ph), 5.56 (s, 1H, CHPh), 5.10 (t, 1H, H-3,
J
2,3 = J3,4 =9.6 Hz), 5.03 (d, 1H, H-1, J1,2 =3.6 Hz), 4.64 (dd, 1H, H-2), 4.35 (dd, 1H, H-
6e, J5,6e =4.8 Hz, J6e,6a =10.5 Hz), 3.95 (ddd, 1H, H-5, J4,5 =9.6 Hz), 3.83 À 3.71 (m, 2H,
H-4, H-6a), 3.50 (s, 3H, OMe), 3.18, 2.98 (each s, 3H, Me, Ms); 13C NMR (CDCl3): d
136.2 (Cq, Ph), 129.5, 128.5, 126.0 (Ph), 102.0 (CHPh), 98.8 (C-1), 79.0 (C-4), 77.1
(C-3), 75.8 (C-2), 68.7 (C-6), 62.2 (C-5), 56.1 (OMe), 38.9, 38.8 (Me, Ms).
Anal. Calcd for C16H22O10S2 (438.45): C, 43.83; H, 5.05; S, 14.62. Found: C,
44.29; H, 55.23; S, 14.33.
Methyl 2,3-Anhydro-4,6-O-benzylidene-a-D-allopyranoside (26)[18] and
Methyl 2,3-Anhydro-4,6-O-benzylidene-a-D-mannopyranoside (27)[17]
.
Sodium
methoxide 2.7 N (14 mL) was added to a soln of 25[15] (3.36 g, 7.62 mmol) in
anhyd dichloromethane (78.5 mL), previously cooled to 0°C, and the reaction mixture
was kept at 2°C for 4 days and then at rt for 16 h. After addition of dichloromethane
(70 mL) and water (25 mL) under stirring, the aqueous phase was extracted with
dichloromethane (3 ꢀ 20 mL), and the organic phase was washed with water until pH 7,
dried over sodium sulfate and concentrated. The residue was purified by column
chromatography eluted with ethyl acetate–hexane 1:2 to give 26 (1226 mg, 61%) and
27 (623 mg, 31%). Physical and spectroscopic data of 26: mp 198–200°C; Rf 0.32
(ethyl acetate–hexane 1:3); [a]D20 +90° (c 1, chloroform); IR (KBr) 1257 cm À 1
1
(C O, epoxide); H NMR (CDCl3) d 7.45 À 7.42 (m, 2H, Ph), 7.31 À 7.29 (m, 3H,
Ph), 5.51 (s, 1H, CHPh), 4.83 (dd, 1H, H-6a, J5,6a = 5.1 Hz, J6a,6b = 10.2 Hz), 4.00 (ddd,
1H, H-5, J5,6b =10.2 Hz, J4,5 =9.0 Hz), 3.90 (d, 1H, H-4), 3.62 (t, 1H, H-6b),
3.47 À 3.44 (m, 5H, OCH3, H-2, H-3); 13C NMR (CDCl3) d 137.2 (Cq, Ph), 129.2,
128.3, 126.3 (Ph), 102.8 (CHPh), 95.4 (C-1), 78.0 (C-4), 68.9 (C-6), 60.1 (C-5), 55.8
(OCH3), 53.1, 50.7 (C-2, C-3). Physical and spectroscopic data of 27: mp 144–145.5°C
(lit.[17] 145.5–146°C); [a]D20 + 100° (c 1,chloroform); Rf 0.50 (ethyl acetate–hexane
1
1:3); IR (KBr) 1257 cm À 1 (C O, epoxide); H NMR (CDCl3) d 7.45 À 7.42 (m, 2H,
Ph), 7.35 À 7.31 (m, 3H, Ph), 5.53 (s, 1H, CHPh), 4.84 (s, 1H, H-1), 4.20 (dd, 1H, H-
6a, J5,6a = 7.8 Hz, J6a,6b =14.1 Hz), 3.71 À 3.59 (m, 3H, H-4, H-5, H-6b), 3.45 À 3.37
(m, 4H, OMe, H-3), 3.10 (d, 1H, H-2, J2,3 = 3.6 Hz); 13C NMR (CDCl3): d 137.1 (Cq,
Ph), 129.3, 128.4, 126.2 (Ph), 102.4 (CHPh), 96.9 (C-1), 74.9 (C-4), 69.4 (C-6), 61.7
(C-5), 55.8 (OMe), 53.8 (C-3), 50.5 (C-2).
Anal. Calcd for C14H16O5 (264.3): C, 63.63; H, 6.10. Found: C, 63.59; H, 6.05.
Methyl 4,6-O-Benzylidene-2(S)-deoxy-2-C-[20(S)-(carboxy)phenylselenyl-
methyl]-a-D-ribo-hexopyranoside-3,20-lactone (28) and Methyl 4,6-O-Benzylidene-
3(S)-deoxy-3-C-[(carboxy)phenylselenylmethyl]-a-D-ribo-hexopyranoside (29). 1.6
M n-BuLi in hexane (1.33 mL, 2.04 mmol) was added dropwise to a soln of diispro-
pylamine (0.3 mL, 2.04 mmol) in THF (4 mL), previously cooled to 0°C, under argon.

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272
RAUTER ET AL.
After stirring for 25 min at 0°C, a soln of phenylselenoacetic acid (216 mg, 1 mmol) in
anhyd THF (1 mL) was added dropwise for 1 h at 0°C under stirring, and a white
precipitate was formed after a few minutes indicating the formation of the dianion. A
soln of 26 (130 mg, 0.5 mmol) in anhyd THF (0.5 mL) was then added dropwise for 1 h
at 0°C. The reaction mixture was stirred for 20 h at rt and the precipitate was dissolved,
giving a clear soln. A 50% soln of acetic acid (2.5 mL) was added, and the reaction
mixture was heated at 80°C for 12 h. After cooling and neutralisation with a saturated
hydrogen carbonate soln, the organic phase was extracted with diethyl ether (3 ꢀ 10
mL), dried with sodium sulfate and concentrated. The syrup was purified by column
chromatography eluted with ethyl acetate–toluene 1:5 to give 28 (30 mg, 14%) and 29
20
(70 mg, 32%). Physical and spectroscopic data of 28: mp 181–182°C; [a]D À 34° (c 1,
À 1
dichloromethane); Rf 0.35 (ethyl acetate–toluene 1:5); IR (KBr) 1774 cm
(C O);
1H NMR (CDCl3): d 7.62 À 7.44 (m, 4H, Ph), 7.34 À 7.23 (m, 6H, Ph), 5.60 (s, 1H,
CHPh), 5.24 (s,1 H, H-1), 4.31 À 4.20 (m, 3H, H-3, H-5, H-6a), 3.91 (d, 1H, H-4,
J
4,5 =9.9 Hz), 3.78 (t, 1H, H-6b, J6a,6b =J5,6b =10.2 Hz), 3.58 (d, 1H, H-2’, J2,2’ = 12.3
Hz), 3.41 (s, 3H, OMe), 2.56 (d, 1H, H-2); 13C NMR (CDCl3): d 175.8 (C O), 137.4
(Cq, Ph), 133.2, 129.0, 128.2, 127.2, 126.2 (Ph), 102.1 (CHPh), 101.5 (C-1), 77.4 (C-4),
69.3 (C-6), 68.0 (C-3), 58.7 (C-5), 55.6 (OMe), 48.9 (C-2’), 48.3 (C-2).
Anal. Calcd for C22H22O6Se (461.35): C, 57.27; H, 4.80. Found: C, 57.82; H, 4.74.
Physical and spectroscopic data of 29: [a]D20 +49° (c 1, dichloromethane); Rf
À 1
À 1
1
(C O); H
0.58 (ethyl acetate–toluene 1:5); IR (neat) 3802 cm
(OH), 1728 cm
NMR (CDCl3): d 7.52À 7.43 (m, 4H, Ph), 7.29 À 7.18 (m, 6H, Ph), 5.59 (s, 1H, CHPh),
4.94 (brs, 1H, H-1), 4.29 À 4.15 (m, 4H, H-2’, H-3, H-5, H-6a), 4.05 (dd, 1H, H-4,
J
J
4,5 =9.6 Hz, J3,4 = 2.7 Hz), 3.78 (t, 1H, H-6b, J5,6b =J6a,6b = 9.9 Hz), 3.55 (d, 1H, H-2,
2,2’ =1.5 Hz), 3.34 (s, 3H, OMe); 13C NMR (CDCl3): d 168.0 (C O), 137.4 (Cq, Ph),
134.2, 129.7, 129.3, 128.4, 126.3 (Ph), 102.4 (CHPh), 102.2 (C-1), 77.8 (C-4), 69.7
(C-3), 69.3 (C-6), 58.8 (C-5), 58.1 (C-2’), 55.8 (OMe), 47.0 (C-2).
Anal. Calcd for C22H24O7Se (479.39): C, 55.12; H, 5.05. Found: C, 55.52; H, 4.95.
ACKNOWLEDGMENTS
The authors are grateful to the Junta Nacional de Investigac¸a˜o Cient´ıfica e Tec-
nolo´gica for a research grant and Eng. Fernando Matos for running some NMR spectra.
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Received June 22, 2001
Accepted April 30, 2002