Synthesis of l -Pyranosides by Hydroboration of Hex-5-enopyranosides Revisited

Article abstract of DOI:10.1021/acs.joc.6b01243

Extensive study of the diastereoselective synthesis of l-pyranosides utilizing hydroboration of substituted exo-glucals (5-enopyranosides) obtained from d-sugars is presented. On the basis of this study we present the empirical rules describing the reacti

Full text of DOI:10.1021/acs.joc.6b01243

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Article
Synthesis of L-Pyranosides by Hydroboration
of Hex-5-enopyranosides Revisited
Grzegorz #opatkiewicz, and Jacek Mlynarski
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01243 • Publication Date (Web): 09 Aug 2016
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Synthesis of L-Pyranosides by Hydroboration of Hex-5-enopyranosides Revisited
Grzegorz Łopatkiewicz, and Jacek Mlynarski*
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Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
jacek.mlynarski@gmail.com, www.jacekmlynarski.pl
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Table of Contents/Abstract Graphic
Abstract: Extensive study of the diastereoselective synthesis of L-pyranosides utilizing
hydroboration of substituted exo-glucals (5-enopyranosides) obtained from D-sugars is
presented. Based on this study we present the empirical rules describing the reaction
stereoselectivity and the correlation between the yield of the L-ido product and the size of
protecting groups used. Application of these guidelines revealed that the hydroboration of
methyl 2,3-O-methyl-6-deoxy--D-xylo-hex-5-enopyranoside resulted in exclusive formation
of L-ido product with high yield. This method can be successfully applied to the synthesis of
L-iduronic acid being essential component of anticoagulant drugs with the diastereoselectivity
superior to previously published protocols.
Introduction
Carbohydrates are one of the three most important components of living cells.1
Although the D-sugars are most commonly distributed in the world, their L-isomers are also
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players in numerous biological processes.2 The rare but biologically widespread L-sugars
(mostly L-hexoses) have been found in numerous important natural products to only mention
examples as alginates containing L-guluronic acid3 or the well-known potent antitumor
antibiotic Bleomycin comprising L-gulose (Fig. 1).4 Among L-form sugar units, only a few
such as L-arabinose, L-fucose, and L-rhamnose can be obtained from natural sources, thus
chemical synthesis remains the most common source of pure L-sugars.5 For instance, L-
iduronic acid is a typical component of several mammalian glycosaminoglycans i.e. heparin,
heparan sulfate6 widely used as injectable blood thinner. L-Iduronic acid having several
conformations in solution provides flexibility to the therapeutic polymer7 and this sugar part is
an essential component of polysaccharide-type synthetic anticoagulants as idraparinux (Fig.
1).8
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Fig 1. L-Hexoses as components of bioactive molecules and general retrosynthetic
approach for synthesis of L-idose from D-glucose
These interesting functions and increased medicinal interest in rare and unnatural
carbohydrates along with the poor commercial availability of L-hexoses attracted chemists to
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develop reliable methods for the acquisition of L-hexoses and their derivatives.5 Particularly,
stereoselective hydroboration9 of exocyclic alkenes constitutes valuable method for the
epimerization at the C5 of D-sugars into corresponding L-antipodes.10 Several reports have
focused on the study of hydroboration/oxidation of 5-enopyranosides,10-19 conveniently
obtained by the elimination of 6-iodo-6-deoxy-D-glucose (Fig. 1). Initial study revealed that
the addition of diborane to exocyclic alkene prepared from methyl glucoside, gave a mixture
of the methyl D-glucoside and methyl L-idoside only slightly favoring the L-isomer
(1:2.5).10,11 Further, stereoselectivities ranging from 10:1 to 1:8 (L-ido/D-gluco) have been
reported for the reactions of individual examples of protected exo-glucals under the treatment
of borane/THF complex12-17 and 9-BBN.18-19 Interestingly, while the investigation on
stereoselective transformation of various pyranosides appeared in the literature,16 there is no
systematic investigation on the kind of protecting groups and their influence on the reaction
stereoselectivity.19 Such investigation could be important for the planning strategy for the
efficient total synthesis of natural products and drugs containing L-sugars, and particularly
important L-iduronic acid being repeating unit of several mammalian glycosaminoglycans
(GAG, heparin) and a crucial component of various synthetic anticoagulant drugs. Indeed,
stereoselective C5 epimerisation in the glucose ring seems to be the most promising approach
for preparation of the L-iduronic acid building block. Therefore, we present here our
exhaustive studies on the hydroboration/oxidation of suitably protected methyl 6-deoxy--
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and -D-xylo-hex-5-enopyranosides and the significant influence of the size of substituents on
the reaction stereoselectivity.
Results and Discussion
Most of the previous studies described the hydroboration of exo-glucals with the -
anomeric configuration. This is rational approach, as the formation of required L-ido product
occurs via the attack of electrophile at C5 from the opposite site to the anomeric substituent at
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C1. On the other hand, heparin and heparin sulfate contain L-iduronic acid motifs
incorporated with -glycoside linkage and thus synthesis of L-iduronic acid with -configured
anomeric center seems to be crucial for the synthesis of anticoagulant drugs. Nevertheless, we
started our systematic investigation from the synthesis of various methyl 6-deoxy--D-xylo-
hex-5-enopyranosides (2a-k) from methyl -D-glucoside (1, Scheme 1). Stereocontrolling
auxiliaries of various size (H, Me, Bn, TBS, MOM) were located at C2, C3 and C4 with
natural configuration of glucopyranoside. Sugars 2a and 2b possess the same benzyl or
methyl ether at all three positions, while series 2c-e, 2f-h and 2i-j differs by substituents at
C4, C-3 and C2. Synthesis of 2k required inversion at the C3 of pyranose ring, which was
achieved by oxidation and stereoselective reduction of ketone by using NaBH4.
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Scheme 1. General Scheme of methyl α-5-enopyranosides synthesis
In all cases, treatment of suitably protected methyl -D-glucopyranoside (methyl -D-
allopyranoside 2k) with triphenylophosphine, iodine and imidazole afforded the 6-iodo
derivatives isolated in high yield.20 The dehydrohalogenation occurred easily by treatment of
6-iodo derivatives with potassium tert-butoxide. In some cases, however we used combined
elimination with etherification at C4 (O-4) promoted by sodium hydride in the presence of
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MeI or BnBr. Detailed information on the reaction protocols are presented in the
Experimental Section.
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Having in hand all desired compounds we attempted their hydroboration. At the initial
stage various boranes and conditions were tested by using methyl 2,3,4-tri-O-benzyl-6-deoxy-
-D-xylo-hex-5-enopyranoside (2a) and methyl 2,3,4-tri-O-methyl-6-deoxy--D-xylo-hex-5-
enopyranoside (2b) as the model substrates. The results are summarized in Table 1. In
contrast to previous study,19 the 9-borabicyclo[3.3.1]nonane (9-BBN) was not promising
electrophile neither at low nor at elevated temperature (Table 1, entries 1,2). However, a low-
temperature hydroboration of 2a and 2b with excess borane followed by oxidation yielded a
mixture of D-gluco and L-ido isomers favoring formation of L-sugar, albeit in low
stereoselectivity (entries 4 and 6). Interestingly, stereoselective formation of L-ido product
was preferred in the case of methyl residues (2b, D-gluco/L-ido 1:8.5) while hydroboration of
methyl 2,3,4-tri-O-benzyl-6-deoxy--D-xylo-hex-5-enopyranoside (2a) was less selective
(entry 4). Following the observation of Ikegami,16 we used ten-fold excess of borane complex
as essential amount for obtaining better stereoselectivity of L-ido product.
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Table 1. Hydroboration/oxidation of methyl α-5-enoglucopyranosides 2a-b
Entry Substrate
Borane
T [°C]
t [h]a Yield [%]b
D-Glc : L-Idoc
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0
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rt
0
1.5
2.5
1.5
1.5
1.5
1.5
1.5
traces
traces
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-
2a
2a
2a
2a
2a
2b
2b
9-BBN
9-BBNd
-
1 : 5.5
1 : 5.5
1 : 3.4
1 : 8.5
1 : 6.0
BH3·THF
BH3·THF
BH3·Me2S
BH3·THF
BH3·Me2S
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0
78
0
84
0
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aTime of hydroboration reaction. bYields for isolated diastereomers after column
chromatography. cDiastereomers were separated by column chromatography. d2 Equiv. of borane
was used.
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With these optimized conditions we attempted systematic study protected methyl 6-
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deoxy--D-xylo-hex-5-enopyranosides. First essential results are summarized in Scheme 2.
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Thus, in a series of -configured hex-5-enopyranosides with various substituents at C4
hydroboration stereoselectivity highly depends on the size of protective group attached to O-
4, next to the reaction center. Smaller methyl substituent supported the formation of desired L-
ido product (with up to 1:10 dr), while larger groups resulted in lower stereoselectivity. The
same tendency was observed for 2,3-di-O-benzyl (2a, 2f-2h) and 2,3-di-O-methyl (2b, 2c-2e)
derivatives.
Scheme 2. Hydroboration/oxidation of methyl α-5-enoglucopyranosides 2a-h
The best results in terms of stereoselectivity was documented for methyl 2,3-di-O-
methyl-6-deoxy--D-xylo-hex-5-enopyranoside (2d). In this case, “inversed” L-ido product
was formed exclusively, in high yield. However, synthetic application of 2f seems also
promising in the light of high stereoselectivity favoring L-ido isomer (1:10) and better
applicability of benzyl groups for the synthetic purposes. Since satisfactory results were
obtained by hydroboration of 2f possessing free OH at C4 and because complete and easy
separation of the isomers could be achieved by chromatography, this reaction can be
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recommended for the stereoselective inversion at C5 in the synthesis of L-iduronic acid from
glucose.
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Scheme 3 contains results with smallest substituent - methyl group - placed at the C2
(2j), C3 (2i) and finally C4 (2h) position. It confirms only the essential C4 position for
obtaining the best stereoselectivity in the 6-deoxy--D-xylo-hex-5-enopyranoside series.
However, epimerization at the C3 further enhanced the reaction selectivity. Hydroboration of
methyl 2,3-di-O-benzyl-4-O-methyl-6-deoxy--D-ribo-hex-5-enopyranoside (2k) carried out
under the same conditions resulted in a formation of L-talo isomer exclusively.
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Scheme 3. Hydroboration/oxidation of methyl α-hex-5-enoglucopyranosides 2h-j and α-
5-enoallopyranoside 2k
Previously presented results confirmed unambiguously the essential role of the C4
small substituent influencing the reaction stereoselectivity of the 6-deoxy--D-xylo-hex-5-
enopyranoside series. However, changing the configuration at the anomeric carbon atom
should have negative impact for the stereoselective formation of the L-ido product because of
the anomeric substituent shielding the attack of the electrophilic reagent at the double bond.
Indeed, comparison of the methyl -hex-5-enopyranoside (2h) and methyl -hex-5-
enopyranoside (2m) clearly confirmed the role of the configuration at the anomeric center.
Scheme 4. Hydroboration/oxidation of hex-5-enopyranosides 2h, 2l-r
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Stereoselectivity of the hydroboration was far less promising in the case of -anomer
2m barely reaching (1:2) ratio of D-/ L-forms. According to this rule, -configured
disaccharides should be less promising substrates for stereoselective hydroboration,
unfortunately. Indeed, hydroboration-oxidation sequence of disaccharides (2n-p) having
large -oriented substituent at C1 confirmed lower stereoselectivy observed for such
compounds. For these examples, similar results, ranging from predominance of D-gluco with
2o to almost equal formation of D-gluco/L-ido for compounds 2n/2p with smaller substituents
at C4 documented again observed rules (Scheme 4). To ultimately confirm crucial influence
on the stereoselectivity by C1 and C4 substituent configurations, we prepared and submitted
for hydroboration -configured disaccharide 2r being analogue of 2n with reversed
configuration at C1. To our delight, only L-ido-configured sugar was formed with 88% yield
in the reaction. This was ultimate confirmation of our expectation and shows that the efficient
synthesis of -configured disaccharides with L-iduronic acid requires inversion of the
configuration in the -configured monosaccharide prior to the subsequent glycosylation to
appropriate -disaccharides.
Scheme 5. Empirical rules for hydroboration of hex-5-enopyranosides
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Conclusions
In conclusion, we examined diastereoselective hydroboration/oxidation of 5-
enoglycopyranosides as a crucial step of the synthesis of L-iduronic acid from D-glucose.
Based on these research we demonstrated that the reactions of various suitably protected 5-
enopyranosides with borane afforded mixtures of D-gluco and L-ido pyranosides in the ratio
highly dependent on the used protecting groups at C4 of glucose substrate. It was revealed
that the reaction of -configured monosaccharides and disaccharides possessing small
substituents at C4 (OH, OMe) delivers L-ido pyranosides with high yield and
stereoselectivities (Scheme 5). Particularly, application of these guidelines for the
hydroboration of methyl 2,3-O-methyl-6-deoxy--D-xylo-hex-5-enopyranoside resulted in
exclusive formation of L-ido product. It is rational as the formation of required L-ido product
occurs via the attack of electrophile at C5 from the opposite site to the C4 substituent as well
as the anomeric substituent at C1. However, the size of the substituent attached to anomeric
center is not critical while the small substituent at C4 seems to be condition sine qua non for
the high stereoselectivity en route the L-ido product. In contrast, any larger substituent
attached at C1 with the -configuration affects the reaction stereoselectivity and promotes the
formation of the D-gluco derivative.
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Experimental Section
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General Information. All starting materials and reagents were purchased from commercial
sources and used without purification. Dry THF was distilled from potassium to prior to use.
Reactions were controlled using TLC on silica [alu-plates (0.2 mm)]. Plates were visualized
with UV light (254 nm) and by treatment with: aqueous cerium(IV) sulfate solution with
molybdic and sulfuric acid followed by heating. All organic solutions were dried over
anhydrous sodium sulfate. Reaction products were purified by flash chromatography using
silica gel 60 (240-400 mesh). Optical rotations were measured at room temperature with a
digital polarimeter. IR spectra were recorded on an FT-IR spectrometer. CDCl3, (CD3)2CO
and D2O were used as NMR solvents. 1H spectra were recorded with 600 MHz and referenced
relative to: CDCl3 - tetramethylsilane (δ = 0 ppm), (CD3)2CO - residual solvent peak (δ = 2.05
ppm) and D2O - acetonitrile (δ = 2.06 ppm). Data are reported as follows: chemical shift in
parts per million (ppm) , multiplicity (bs = broad singlet, s = singlet, d = doublet, t = triplet,
dd = doublet of doublets, ddd = doublet of doublet of doublets, dddd = doublet of doublet of
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doublet of doublets, m = multiplet), coupling constants (in hertz) and integration. C NMR
spectra were measured at 150 MHz with complete proton decoupling. Chemical shifts were
reported in ppm from the residual solvent as an internal standard: CDCl3 (δ = 77.16 ppm),
(CD3)2CO (δ = 29.84 ppm) and D2O (acetonitrile, δ = 1.47). High-resolution mass spectra
were acquired using ESI-TOF method.
General Procedure A
Benzylation of hydroxyl groups: To a stirred solution of the starting material (1 mmol) in
anhydrous DMF (10 mL) was added NaH - 60% dispersion in mineral oil - (2.0 equiv per OH
group) at 0 °C. After 30 min, BnBr (2.0 equiv per OH group) was added at 0 °C, and the
mixture was warmed to room temperature and stirred for 16 h. Subsequently, the reaction
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mixture was poured into ice-cold water and extracted with Et2O. The extracts were dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by
column chromatography.
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General Procedure B
Benzylidene cleavage: The water (0.5 mL) and 1 M HCl (1 mL) were added to a stirred
solution of 4,6-O-benzylidene protected derivative (1 mmol) in methanol (10 mL). The
reaction mixture was then stirred for 1-3 h at 55 °C and neutralized with aq sat. NaHCO3 (0.9
mL). Subsequently, solvents were concentrated under reduced pressure and residue was
dissolved in ethyl acetate/water 1:1 solution. Organic layer was separated and water phase
was extracted three times with ethyl acetate. The combined organic phases were dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by
column chromatography.
General Procedure C
Iodination: To a stirred solution of the starting material (1 mmol) in anhydrous toluene (25
mL) was added triphenylphosphine (1.2 equiv) and imidazole (2.6 equiv). The reaction
mixture was then warmed to 70-75 °C and after 30 min iodine (1.2 equiv) was added. The
temperature of reaction was held for 1-12 h and then cooled to room temperature.
Subsequently, the reaction mixture was diluted with ethyl acetate and extracted with 10 % aq
Na2S2O3, water and brine. Organic layer was separated, dried over anhydrous Na2SO4 and
concentrated under reduced pressure. The residue was purified by column chromatography.
General Procedure D
Silylation: To a stirred solution of the iodide (1 mmol) in anhydrous DCM (3 mL) was added
2,6-lutidine (1.5-2.0 equiv) at 0 °C. After 30 min, TBSOTf (1.2-1.5 equiv) was added in one
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portion at 0 °C, and the mixture was warmed to room temperature and stirred for 2-3 h.
Subsequently, the reaction was quenched with Et3N (1.5 equiv). After 5 min of stirring the
mixture was diluted with DCM and extracted with water and brine. The organic layer was
separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography.
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General Procedure E
Desilylation: To a stirred solution of the starting material (1 mmol) in anhydrous THF (20
mL) was added TBAF 1M solution in THF (2.0 equiv) at 0 °C. The mixture was then stirred
at room temperature for 1-2 h. Subsequently, the reaction mixture was diluted with ethyl
acetate and extracted with water and brine. The organic layer was separated, dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by
column chromatography.
General Procedure F1
Elimination of iodide: To a stirred solution of the iodide (1 mmol) in anhydrous THF (10
mL) was added t-BuOK (3.0 equiv) in one portion at 0 °C. After 30 min, the reaction mixture
was allowed to warm to room temperature and stirred for 24 h. Subsequently, the reaction
mixture was diluted with ethyl acetate and extracted twice with water and once with brine.
The organic layer was separated, dried over anhydrous Na2SO4 and concentrated under
reduced pressure. The residue was purified by column chromatography.
General Procedure F2
Elimination of iodide with etherification of O-4 position: To a stirred solution of the iodide
material (1 mmol) in anhydrous DMF (10 mL) was added MeI/BnBr/MOMCl (2.0 equiv) at 0
°C. After 30 min, NaH - 60% dispersion in mineral oil (10.0 equiv) was added at 0 °C, and
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the mixture was warmed to room temperature and stirred for 24-48 h. Subsequently, the
reaction mixture was poured into ice-cold water and extracted with Et2O. The extracts were
dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was
purified by column chromatography.
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General Procedure G
Hydroboration/Oxidation: To a stirred solution of the starting material (0.3 mmol) in
anhydrous THF (1 mL) was added a 1 M solution of borane THF complex in THF (10.0
equiv) at 0 °C. The temperature was held for 1.5 h. Then 30% H2O2 (1 mL) and 2 M NaOH
aq sol. (1.5 mL) were added at 0 °C and the reaction mixture was stirred at room temperature
for 50 min. Subsequently, the reaction mixture was diluted with ethyl acetate and extracted
twice with aq sat. NH4Cl, once with water and brine. The organic layer was separated, dried
over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by
column chromatography.
Following this procedure known compounds were synthesized: 3a,17 4a,17 3b,11 4b,11 3c,21
3e,22 3f,16 4f,16 3h,23 3i,24 3j,24 3m.25
Methyl 2,3,4-tri-O-benzyl-6-deoxy-α-D-xylo-hex-5-enopyranoside (2a);26 1H NMR (600 MHz,
Acetone) δ 7.42 – 7.24 (m, 15H), 4.91 (d, J = 3.4 Hz, 1H), 4.89 (d, J = 11.3 Hz, 1H), 4.84 (d,
J = 11.3 Hz, 1H), 4.82 (d, J = 2.0 Hz, 1H), 4.81 (d, J = 11.7 Hz, 1H), 4.78 (d, J = 11.7 Hz,
1H), 4.76 (d, J = 11.9 Hz, 1H), 4.73 (d, J = 11.9 Hz, 1H), 4.66 (d, J = 2.1 Hz, 1H), 3.93 (ddd,
J = 9.0, 2.0, 2.0 Hz, 1H), 3.85 (dd, J = 9.3, 9.2 Hz, 1H), 3.67 (dd, J = 9.4, 3.4 Hz, 1H), 3.39
(s, 3H); 13C NMR (151 MHz, Acetone) δ 155.4, 140.1, 139.8, 139.5, 129.1, 129.0, 128.6,
128.6, 128.6, 128.4, 128.1, 99.7, 96.6, 81.7, 80.7, 80.4, 75.7, 74.9, 73.3, 55.5.
Methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside (3a)17 and Methyl 2,3,4-tri-O-benzyl-β-L-
idopyranoside (4a);17 Prepared according to general procedure G. Compound 2a (151 mg,
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0.338 mmol), BH3·THF (1M, 3.38 mL, 3.38 mmol), THF (1 mL). Then 30% H2O2 (1 mL), 2
M NaOH (2 mL). Purified by column chromatography Hx-EA (2:1) to give first 3a (13%, 20
mg, 0.043 mmol); Next eluted was 4a (70%, 110 mg, 0.237 mmol).
Methyl 6-deoxy-2,3,4-tri-O-methyl-α-D-xylo-hex-5-enopyranoside (2b);27 1H NMR (600 MHz,
Acetone) δ 4.89 (d, J = 3.4 Hz, 1H), 4.66 (d, J = 2.0 Hz, 1H), 4.59 (d, J = 2.2 Hz, 1H), 3.52 (s,
3H), 3.52 (s, 3H), 3.51 – 3.49 (m, 1H), 3.43 (s, 3H), 3.37 (s, 3H), 3.34 (dd, J = 9.3, 9.1 Hz,
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1H), 3.26 (dd, J = 9.4, 3.4 Hz, 1H); C NMR (151 MHz, Acetone) δ 155.3, 99.3, 95.9, 83.2,
82.3, 82.1, 60.7, 60.1, 58.5, 55.4.
Methyl 2,3,4-tri-O-methyl-α-D-glucopyranoside (3b)11 and Methyl 2,3,4-tri-O-methyl-β-L-
idopyranoside (4b);11 Prepared according to general procedure G. Compound 2b (84 mg,
0.385 mmol), BH3·THF (1M, 3.85 mL, 3.85 mmol), THF (1 mL). Then 30% H2O2 (1 mL), 2
M NaOH (2 mL). Purified by column chromatography MeOH-EA (1:25) to give first 3b (9%,
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8 mg, 0.034 mmol); H NMR (600 MHz, CDCl3) δ 4.80 (d, J = 3.6 Hz, 1H), 3.82 (dd, J =
11.7, 2.9 Hz, 1H), 3.73 (dd, J = 11.7, 4.2 Hz, 1H), 3.63 (s, 3H), 3.57 (s, 3H), 3.56 – 3.50 (m,
2H), 3.52 (s, 3H), 3.41 (s, 3H), 3.17 (dd, J = 9.6, 3.6 Hz, 1H), 3.16 (dd, J = 9.9, 9.0 Hz, 1H),
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1.81 (bs, 1H); C NMR (151 MHz, CDCl3) δ 97.7, 83.5, 82.0, 79.8, 70.7, 62.1, 61.0, 60.7,
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59.2, 55.3. Next eluted was 4b (75%, 68 mg, 0.287 mmol); H NMR (600 MHz, CDCl3) δ
4.72 (d, J = 3.4 Hz, 1H), 4.07 (td, J = 5.4, 5.4, 5.4 Hz, 1H), 3.90 (dd, J = 12.0, 5.4 Hz, 1H),
3.82 (dd, J = 12.0, 5.4 Hz, 1H), 3.70 (dd, J = 7.7, 7.7 Hz, 1H), 3.58 (s, 3H), 3.53 (s, 3H), 3.52
(s, 3H), 3.52 (s, 3H), 3.38 (dd, J = 7.5, 5.5 Hz, 1H), 3.22 (dd, J = 7.8, 3.4 Hz, 1H), 2.51 (bs,
1H); 13C NMR (151 MHz, CDCl3) δ 99.5, 80.4, 80.3, 78.4, 74.8, 63.1, 60.2, 59.7, 59.5, 57.0.
Synthesis of methyl 4-O-tert-butyldimethylsilyl-6-deoxy-2,3-di-O-methyl-α-D-xylo-hex-5-
enopyranoside (2c) and methyl 6-deoxy-2,3-di-O-methyl-α-D-xylo-hex-5-enopyranoside
(2d):
Methyl
4-O-tert-butyldimethylsilyl-6-deoxy-6-iodo-2,3-di-O-methyl-α-D-
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glucopyranoside (6); Prepared according to general procedure D. Compound 528 (602 mg,
1.813 mmol), 2,6-lutidine (291 mg, 2.719 mmol), TBSOTf (575 mg, 2.175 mmol), DCM (6
mL), Et3N (0.3 mL), 2 h. Purified by column chromatography Hx-EA (4:1). Yield: 97% (784
mg, 1.756 mmol) as colorless oil; [훼]2D6 +77.4 (c 1.00, CHCl3); IR (neat) 1463, 1376, 1249,
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1162, 1091, 1051; H NMR (600 MHz, CDCl3) δ 4.84 (d, J = 3.6 Hz, 1H), 3.56 – 3.53 (m,
1H), 3.54 (s, 3H), 3.50 (s, 3H), 3.48 (s, 3H), 3.39 – 3.33 (m, 2H), 3.28 (dd, J = 8.6, 8.5 Hz,
1H), 3.25 (dd, J = 10.4, 6.4 Hz, 1H), 3.22 (dd, J = 9.5, 3.6 Hz, 1H), 0.90 (s, 9H), 0.14 (s, 3H),
0.13 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 97.4, 83.0, 82.7, 74.9, 70.7, 61.3, 58.7, 55.7,
26.2, 18.3, 8.5, –3.7, –4.3; HRMS: calcd. for C15H31IO5Si [M+Na]+: 469.0883, found
469.0859.
Methyl
4-O-tert-butyldimethylsilyl-6-deoxy-2,3-di-O-methyl-α-D-xylo-hex-5-enopyranoside
(2c); Prepared according to general procedure F1. Compound 6 (739 mg, 1.656 mmol), t-
BuOK (1M, 5 mL, 5 mmol), THF (20 mL). Purified by column chromatography Hx-EA (4:1).
Yield: 84% (442 mg, 1.388 mmol) as colorless oil; [훼]2D1 +60.7 (c 1.20, CHCl3); IR (neat)
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1664, 1473, 1252, 1162, 1112, 1087; H NMR (600 MHz, Acetone) δ 4.92 (d, J = 3.3 Hz,
1H), 4.77 (d, J = 2.0 Hz, 1H), 4.62 (d, J = 2.2 Hz, 1H), 3.91 (ddd, J = 8.7, 2.1, 2.1 Hz, 1H),
3.51 (s, 3H), 3.43 (s, 3H), 3.39 (s, 3H), 3.29 (dd, J = 9.4, 3.3 Hz, 1H), 3.25 (dd, J = 9.4, 8.7
Hz, 1H), 0.96 (s, 6H), 0.15 (s, 3H), 0.10 (s, 3H); 13C NMR (151 MHz, Acetone) δ 157.7, 99.2,
96.6, 84.0, 82.7, 73.1, 61.3, 58.3, 55.4, 26.3, 18.7, –4.4, –4.9; HRMS: calcd. for C15H30O5Si
[M+Na]+: 341.1760, found 341.1760.
Methyl 4-tert-butyldimethylsilyl-2,3-di-O-methyl-α-D-glucopyranoside (3c)21 and Methyl 4-
tert-butyldimethylsilyl-2,3-di-O-methyl-β-L-idopyranoside (4c); Prepared according to general
procedure G. Compound 2c (98 mg, 0.308 mmol), BH3·THF (1M, 3.08 mL, 3.08 mmol), THF
(1 mL). Then 30% H2O2 (1 mL), 2 M NaOH (1.6 mL). Purified by column chromatography
Hx-EA (2:1) to give mixture of 3c and 4c (90%, 93 mg, 0.276 mmol, 3c:4c = 1:2.6). Another
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column chromatography was made to isolate part of pure 3c; H NMR (600 MHz, CDCl3) δ
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– 3.56 (m, 1H), 3.55 (s, 3H), 3.51 (s, 3H), 3.47 (dd, J = 9.5, 8.7 Hz, 1H), 3.43 (s, 3H), 3.36
(dd, J = 9.5, 8.7 Hz, 1H), 3.18 (dd, J = 9.5, 3.6 Hz, 1H), 0.90 (s, 9H), 0.12 (s, 3H), 0.09 (s,
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3H); C NMR (151 MHz, CDCl3) δ 97.5, 83.4, 82.9, 72.1, 70.7, 62.1, 61.4, 58.8, 55.3, 26.1,
18.2, –3.8, –4.90. Next eluted was 4c as colorless oil; [훼]2D2 +47.1 (c 1.00, CHCl3); IR (neat)
3479, 1464, 1252, 1096, 1057; 1H NMR (600 MHz, CDCl3) δ 4.76 (d, J = 3.7 Hz, 1H), 3.97 –
3.92 (m, 2H), 3.83 (dd, J = 13.6, 7.5 Hz, 1H), 3.79 (dd, J = 8.4, 5.6 Hz, 1H), 3.56 (s, 3H),
3.55 (dd, J = 8.7, 8.4 Hz, 1H), 3.53 (s, 3H), 3.50 (s, 3H), 3.19 (dd, J = 8.7, 3.7 Hz, 1H), 0.91
(s, 9H), 0.13 (s, 3H), 0.11 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 99.4, 81.5, 79.7, 77.0, 72.3,
63.2, 61.0, 59.1, 57.2, 26.0, 18.2, –4.5, –4.8; HRMS: calcd. for C15H32O6Si [M+Na]+:
359.1866, found 359.1858.
Methyl 6-deoxy-2,3-di-O-methyl-α-D-xylo-hex-5-enopyranoside (2d); Prepared according to
general procedure E. Compound 2c (268 mg, 0.841 mmol), TBAF (1M, 1.68 mL, 1.68
mmol), THF (20 mL). Purified by gradient column chromatography Hx-EA (2:1) to (1:1).
Yield: 95% (164 mg, 0.799 mmol) as pale yellow oil; [훼]2D6 +103.4 (c 1.30, CHCl3); IR (neat)
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3453, 1663, 1369, 1156, 1084, 1019; H NMR (600 MHz, Acetone) δ 4.89 (d, J = 3.2 Hz,
1H), 4.76 (d, J = 2.1 Hz, 1H), 4.57 (d, J = 5.7 Hz, 1H), 4.55 (d, J = 2.3 Hz, 1H), 3.86 (dddd, J
= 8.7, 5.7, 2.3, 2.1 Hz, 1H), 3.51 (s, 3H), 3.41 (s, 3H), 3.36 (s, 3H), 3.29 (dd, J = 9.5, 8.7 Hz,
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1H), 3.24 (dd, J = 9.5, 3.2 Hz, 1H); C NMR (151 MHz, Acetone) δ 157.9, 99.2, 95.4, 83.9,
82.1, 72.1, 60.9, 58.3, 55.3; HRMS: calcd. for C9H16O5 [M+Na]+: 227.0895, found 227.0899.
Methyl 2,3-di-O-methyl-β-L-idopyranoside (4d); Prepared according to general procedure G.
Compound 2d (71 mg, 0.348 mmol), BH3·THF (1M, 3.48 mL, 3.48 mmol), THF (1 mL).
Then 30% H2O2 (1 mL), 2 M NaOH (1.8 mL). Purified by column chromatography EA.
Yield: 79% (61 mg, 0.275 mmol) as colorless oil; [훼]2D2 +25.1 (c 1.14, CHCl3); IR (neat)
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3485, 1447, 1374, 1154, 1099, 1043; 1H NMR (600 MHz, CDCl3) δ 4.63 (d, J = 1.2 Hz, 1H),
3.98 (dd, J = 11.5, 7.0 Hz, 1H), 3.85 (ddd, J = 7.0, 4.5, 1.1 Hz, 1H), 3.81 (dd, J = 11.5, 4.5
Hz, 1H), 3.67 – 3.64 (m, 2H), 3.58 (s, 3H), 3.57 (s, 3H), 3.44 (s, 3H), 3.44 – 3.42 (m, 1H),
2.24 (bs, 1H), 1.69 (bs, 1H); 13C NMR (151 MHz, CDCl3) δ 100.7, 77.6, 77.3, 75.1, 66.6,
62.8, 60.3, 58.0, 57.1; HRMS: calcd. for C9H18O6 [M+Na]+: 245.1001, found 245.0999.
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Methyl 4-O-benzyl-6-deoxy-2,3-di-O-methyl-α-D-xylo-hex-5-enopyranoside (2e);29 1H NMR
(600 MHz, Acetone) δ 7.45 – 7.26 (m, 5H), 4.92 (d, J = 3.4 Hz, 1H), 4.79 (d, J = 2.0 Hz, 1H),
4.78 (d, J = 11.6 Hz, 1H), 4.76 (d, J = 11.6 Hz, 1H), 4.63 (d, J = 2.1 Hz, 1H), 3.80 (ddd, J =
9.0, 2.1, 2.1 Hz, 1H), 3.55 (s, 3H), 3.46 – 3.43 (m, 1H), 3.44 (s, 3H), 3.38 (s, 3H), 3.30 (dd, J
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= 9.4, 3.4 Hz, 1H); C NMR (151 MHz, Acetone) δ 155.4, 139.7, 129.1, 128.5, 128.3, 99.3,
96.4, 83.6, 82.2, 80.1, 74.7, 60.9, 58.5, 55.4.
Methyl 4-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoside (3e)22 and Methyl 4-O-benzyl-2,3-
di-O-methyl-β-L-idopyranoside (4e); Prepared according to general procedure G. Compound
2e (89 mg, 0.302 mmol), BH3·THF (1M, 3.02 mL, 3.02 mmol), THF (1 mL). Then 30% H2O2
(1 mL), 2 M NaOH (1.6 mL). Purified by column chromatography Hx-EA (1:2) to give first
3e (12%, 11 mg, 0.035 mmol). Next eluted was 4e (64%, 67 mg, 0.192 mmol) as colorless oil;
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[훼]2D2 +57.6 (c 1.02, CHCl3); IR (neat) 3481, 1497, 1453, 1373, 1096, 1053; H NMR (600
MHz, CDCl3) δ 7.39 – 7.28 (m, 5H), 4.80 (d, J = 11.7 Hz, 1H), 4.71 (d, J = 3.4 Hz, 1H), 4.62
(d, J = 11.7 Hz, 1H), 3.97 (ddd, J = 5.5, 5.5, 5.5 Hz, 1H), 3.90 (dd, J = 11.9, 5.7 Hz, 1H), 3.81
(dd, J = 11.9, 5.2 Hz, 1H), 3.74 (dd, J = 7.9, 7.9 Hz, 1H), 3.60 (dd, J = 7.7, 5.5 Hz, 1H), 3.59
(s, 3H), 3.52 (s, 3H), 3.51 (s, 3H), 3.22 (dd, J = 8.0, 3.4 Hz, 1H); 13C NMR (151 MHz,
CDCl3) δ 138.0, 128.7, 128.1, 128.1, 99.5, 80.6, 78.8, 77.8, 75.2, 73.9, 63.3, 60.4, 59.4, 57.0;
HRMS: calcd. for C16H24O6 [M+Na]+: 335.1471, found 335.1472.
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Synthesis of methyl 2,3-di-O-benzyl-6-deoxy-4-O-(methoxymethyl)-α-D-xylo-hex-5-
enopyranoside (2g): Methyl 2,3-di-O-benzyl-6-deoxy-4-O-(methoxymethyl)-α-D-xylo-hex-5-
enopyranoside (2g); Prepared according to general procedure F2. Compound 730 (303 mg,
0.626 mmol), NaH (250 mg, 6.256 mmol), MOMCl (178 mg, 1.251 mmol), DMF (10 mL), 24
h. Purified by column chromatography Hx-EA (6:1). Yield: 78% (196 mg, 0.489 mmol) as
colorless oil; [훼]2D2 –7.3 (c 1.03, CHCl3); IR (neat) 1663, 1497, 1454, 1150, 1090, 1044, 1027;
1H NMR (600 MHz, Acetone) δ 7.41 – 7.24 (m, 10H), 4.91 (d, J = 3.4 Hz, 1H), 4.90 (d, J =
11.2 Hz, 1H), 4.87 (d, J = 6.5 Hz, 1H), 4.81 (d, J = 2.0 Hz, 1H), 4.79 (d, J = 11.2 Hz, 1H),
4.75 (d, J = 11.9 Hz, 1H), 4.72 (d, J = 11.9 Hz, 1H), 4.72 (d, J = 6.5 Hz, 1H), 4.66 (d, J = 2.0
Hz, 1H), 4.01 (ddd, J = 9.2, 2.0, 2.0 Hz, 1H), 3.80 (dd, J = 9.4, 9.3 Hz, 1H), 3.68 (dd, J = 9.5,
3.4 Hz, 1H), 3.40 (s, 3H), 3.35 (s, 3H); 13C NMR (151 MHz, Acetone) δ 155.4, 140.0, 139.7,
129.1, 129.0, 128.6, 128.6, 128.4, 128.2, 99.6, 98.0, 96.7, 81.6, 80.8, 76.9, 75.7, 73.2, 56.4,
55.5; HRMS: calcd. for C23H28O6 [M+Na]+: 423.1784, found 423.1766.
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Methyl 2,3-di-O-benzyl-4-O-(methoxymethyl)-α-D-glucopyranoside (3g) and Methyl 2,3-di-O-
benzyl-4-O-(methoxymethyl)-β-L-idopyranoside (4g); Prepared according to general procedure
G. Compound 2g (115 mg, 0.287 mmol), BH3·THF (1M, 2.87 mL, 2.87 mmol), THF (1 mL).
Then 30% H2O2 (1 mL), 2 M NaOH (1.5 mL). Purified by column chromatography Hx-EA
(1:1) to (1:2) to give first 3g (33%, 40 mg, 0.096 mmol) as pale yellow oil; [훼]2D1 +76.6 (c
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1.06, CHCl3); IR (neat) 3318, 1496, 1455, 1356, 1161, 1103, 1059, 1026; H NMR (600
MHz, CDCl3) δ 7.37 – 7.27 (m, 10H), 4.96 (d, J = 11.0 Hz, 1H), 4.91 (d, J = 6.3 Hz, 1H),
4.77 (d, J = 12.1 Hz, 1H), 4.73 (d, J = 11.0 Hz, 1H), 4.64 (d, J = 12.1 Hz, 1H), 4.61 (d, J = 6.3
Hz, 1H), 4.58 (d, J = 3.6 Hz, 1H), 3.91 (dd, J = 9.2, 9.2 Hz, 1H), 3.86 (d, J = 12.3 Hz, 1H),
3.75 (d, J = 10.9 Hz, 1H), 3.62 (ddd, J = 10.0, 3.4, 2.3 Hz, 1H), 3.57 (dd, J = 10.0, 9.0 Hz,
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MHz, CDCl3) δ 138.8, 138.2, 128.6, 128.5, 128.3, 128.1, 128.0, 127.8, 99.0, 98.4, 81.7, 80.1,
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76.4, 75.8, 73.5, 70.6, 61.9, 56.4, 55.4; HRMS: calcd. for C23H30O7 [M+Na]+: 441.1889,
found 441.1878. Next eluted was 4g (60%, 72 mg, 0.172 mmol) as colorless oil; [훼]2D2 +65.1
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(c 1.05, CHCl3); IR (neat) 3481, 1496, 1454, 1363, 1149, 1099, 1036; H NMR (600 MHz,
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CDCl3) δ 7.35 – 7.27 (m, 10H), 4.76 (d, J = 6.6 Hz, 1H), 4.75 (d, J = 11.2 Hz, 1H), 4.72 (d, J
= 12.3 Hz, 1H), 4.69 (d, J = 12.3 Hz, 1H), 4.65 (d, J = 11.2 Hz, 1H), 4.64 (d, J = 6.6 Hz, 1H),
4.58 (d, J = 3.2 Hz, 1H), 4.05 (ddd, J = 5.3, 5.2, 5.2 Hz, 1H), 3.98 (dd, J = 7.3, 7.3 Hz, 1H),
3.92 (dd, J = 12.1, 5.1 Hz, 1H), 3.88 (dd, J = 12.1, 4.9 Hz, 1H), 3.77 (dd, J = 7.2, 5.3 Hz, 1H),
3.51 (s, 3H), 3.49 (dd, J = 7.4, 3.2 Hz, 1H), 3.36 (s, 3H), 2.87 (bs, 1H); 13C NMR (151 MHz,
CDCl3) δ 138.4, 128.5, 128.5, 128.2, 128.0, 127.9, 127.9, 100.2, 97.5, 77.8, 77.0, 75.7, 75.4,
74.6, 73.9, 62.9, 57.1, 56.1; HRMS: calcd. for C23H30O7 [M+Na]+: 441.1889, found 441.1886.
Methyl 2,3-di-O-benzyl-6-deoxy-4-O-methyl-α-D-xylo-hex-5-enopyranoside (2h);31 1H NMR
(600 MHz, Acetone) δ 7.43 – 7.24 (m, 10H), 4.88 (d, J = 3.3 Hz, 1H), 4.85 (d, J = 11.4 Hz,
1H), 4.82 (d, J = 11.4 Hz, 1H), 4.75 (d, J = 11.9 Hz, 1H), 4.72 (d, J = 11.9 Hz, 1H), 4.71 –
4.70 (m, J = 1.9 Hz, 1H), 4.63 (d, J = 2.1 Hz, 1H), 3.75 (dd, J = 9.2, 9.2 Hz, 1H), 3.65 – 3.61
(m, 2H), 3.55 (s, 3H), 3.38 (s, 3H); 13C NMR (151 MHz, Acetone) δ 155.3, 140.3, 139.8,
129.1, 129.0, 128.6, 128.3, 128.1, 99.7, 96.0, 82.6, 81.6, 80.5, 75.6, 73.3, 60.3, 55.5.
Methyl 2,3-di-O-benzyl-4-O-methyl-α-D-glucopyranoside (3h)23 and Methyl 2,3-di-O-benzyl-
4-O-methyl-β-L-idopyranoside (4h); Prepared according to general procedure G. Compound
2h (140 mg, 0.378 mmol), BH3·THF (1M, 3.78 mL, 3.78 mmol), THF (1 mL). Then 30%
H2O2 (1 mL), 2 M NaOH (1.9 mL). Purified by column chromatography Hx-EA (3:2) to (2:3)
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to give first 3h (9%, 13 mg, 0.033 mmol) H NMR (600 MHz, CDCl3) δ 7.40 – 7.27 (m,
10H), 4.94 (d, J = 10.9 Hz, 1H), 4.82 (d, J = 10.9 Hz, 1H), 4.79 (d, J = 12.1 Hz, 1H), 4.65 (d,
J = 12.1 Hz, 1H), 4.56 (d, J = 3.6 Hz, 1H), 3.88 (dd, J = 9.3, 9.3 Hz, 1H), 3.81 (dd, J = 11.8,
2.9 Hz, 1H), 3.72 (dd, J = 11.8, 4.2 Hz, 1H), 3.57 (ddd, J = 10.0, 4.0, 3.1 Hz, 1H), 3.56 (s,
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3H), 3.45 (dd, J = 9.6, 3.6 Hz, 1H), 3.37 (s, 1H), 3.23 (dd, J = 9.9, 9.1 Hz, 1H); C NMR
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(151 MHz, CDCl3) δ 139.0, 138.3, 128.6, 128.5, 128.2, 128.1, 128.1, 127.7, 98.4, 81.9, 79.9,
79.9, 75.8, 73.6, 70.8, 62.1, 61.0, 55.4. Next eluted was 4h (87%, 128 mg, 0.330 mmol) as
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colorless oil; [훼]2D2 +25.1 (c 1.14, CHCl3); IR (neat) 3485, 1496, 1454, 1362, 1091, 1052; H
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NMR (600 MHz, CDCl3) δ 7.37 – 7.27 (m, 10H), 4.78 (d, J = 11.1 Hz, 1H), 4.75 (d, J = 12.2
Hz, 1H), 4.71 (d, J = 11.1 Hz, 1H), 4.68 (d, J = 12.2 Hz, 1H), 4.56 (d, J = 3.4 Hz, 1H), 4.08
(ddd, J = 5.4, 5.4, 5.4 Hz, 1H), 3.99 (dd, J = 7.9, 7.9 Hz, 1H), 3.91 (dd, J = 12.1, 5.3 Hz, 1H),
3.83 (dd, J = 12.1, 5.2 Hz, 1H), 3.49 (s, 3H), 3.48 (s, 3H), 3.47 (dd, J = 8.1, 3.4 Hz, 1H), 3.43
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(dd, J = 7.8, 5.6 Hz, 1H), 2.36 (bs, 1H); C NMR (151 MHz, CDCl3) δ 138.6, 138.4, 128.6,
128.5, 128.2, 128.0, 128.0, 127.8, 100.0, 80.8, 78.1, 76.9, 74.9, 74.8, 73.9, 63.2, 59.7, 57.0;
HRMS: calcd. for C22H28O6 [M+Na]+: 411.1784, found 411.1763.
Synthesis of methyl 2,4-di-O-benzyl-6-deoxy-3-O-methyl-α-D-xylo-hex-5-enopyranoside
(2i): Methyl 2-O-benzyl-6-deoxy-6-iodo-3-O-methyl-α-D-glucopyranoside (9); Prepared
according to general procedure C. Compound 824 (616 mg, 2.065 mmol), PPh3 (650 mg, 2.478
mmol), imidazole (366 mg, 5.369 mmol) I2 (629 mg, 2.478 mmol), toluene (50 mL), 75 °C, 1
h. Purified by column chromatography Hx-EA (3:1). Yield: 88% (739 mg, 1.810 mmol) as
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colorless oil; [훼]2D1 +42.5 (c 1.05, CHCl3); IR (neat) 3436, 1454, 1372, 1066; H NMR (600
MHz, CDCl3) δ 7.38 – 7.28 (m, 5H), 4.75 (d, J = 12.1 Hz, 1H), 4.62 (d, J = 12.1 Hz, 1H),
4.61 (d, J = 3.5 Hz, 1H), 3.67 (s, 3H), 3.56 (dd, J = 10.7, 2.5 Hz, 1H), 3.54 (dd, J = 9.3, 9.0
Hz, 1H), 3.46 – 3.42 (m, 2H), 3.42 (s, 3H), 3.30 – 3.24 (m, 2H), 2.63 (bs, 1H); 13C NMR (151
MHz, CDCl3) δ 138.0, 128.6, 128.1(2C), 98.3, 82.5, 79.9, 73.9, 73.1, 69.9, 61.6, 55.7, 7.2;
HRMS: calcd. for C15H21IO5 [M+Na]+: 431.0331, found 431.0333.
Methyl 2,4-di-O-benzyl-6-deoxy-3-O-methyl-α-D-xylo-hex-5-enopyranoside (2i); Prepared
according to general procedure F2. Compound 9 (353 mg, 0.865 mmol), NaH (346 mg, 8.647
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mmol), BnBr (296 mg, 1.729 mmol), DMF (10 mL), 48 h. Purified by column
chromatography Hx-EA (9:1). Yield: 80% (256 mg, 0.691 mmol) as white solid; mp 38-39
°C; [훼]2D1 +1.3 (c 1.00, CHCl3); IR (neat) 3662, 1497, 1454, 1365, 1089; 1H NMR (600 MHz,
Acetone) δ 7.44 – 7.39 (m, 4H), 7.38 – 7.33 (m, 4H), 7.31 – 7.27 (m, 2H), 4.85 (d, J = 2.8 Hz,
1H), 4.79 (d, J = 2.0 Hz, 1H), 4.79 (d, J = 11.6 Hz, 1H), 4.76 (d, J = 11.6 Hz, 1H), 4.74 (d, J
= 11.9 Hz, 1H), 4.70 (d, J = 11.9 Hz, 1H), 4.62 (d, J = 2.1 Hz, 1H), 3.83 – 3.80 (m, 1H), 3.60
(s, 3H), 3.56 – 3.52 (m, 2H), 3.36 (s, 3H); 13C NMR (151 MHz, Acetone) δ 155.3, 139.8,
139.6, 129.1(2C), 128.5, 128.4, 128.3, 128.3, 99.7, 96.5, 83.6, 80.4, 80.1, 74.7, 73.2, 61.1,
55.4; HRMS: calcd. for C22H26O5 [M+Na]+: 393.1678, found 393.1683.
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Methyl 2,4-di-O-benzyl-3-O-methyl-α-D-glucopyranoside (3i)24 and Methyl 2,4-di-O-benzyl-3-
O-methyl-β-L-idopyranoside (4i); Prepared according to general procedure G. Compound 2i
(84 mg, 0.227 mmol), BH3·THF (1M, 2.27 mL, 2.27 mmol), THF (1 mL). Then 30% H2O2 (1
mL), 2 M NaOH (1.2 mL). Purified by column chromatography Hx-EA (3:2) to give first 3i
(15%, 13 mg, 0.033 mmol). Next eluted was 4i (76%, 67 mg, 0.172 mmol) as white solid; mp
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63-65 °C; [훼]2D6 +40.5 (c 1.10, CHCl3); IR (neat) 3460, 1497, 1454, 1095, 1055; H NMR
(600 MHz, CDCl3) δ 7.38 – 7.27 (m, 10H), 4.81 (d, J = 11.7 Hz, 1H), 4.76 (d, J = 12.2 Hz,
1H), 4.68 (d, J = 12.2 Hz, 1H), 4.61 (d, J = 11.7 Hz, 1H), 4.49 (d, J = 3.5 Hz, 1H), 3.94 (ddd,
J = 5.7, 5.7, 4.9 Hz, 1H), 3.90 (dd, J = 11.8, 5.7 Hz, 1H), 3.80 (dd, J = 11.8, 4.9 Hz, 1H), 3.76
(dd, J = 8.1, 8.1 Hz, 1H), 3.60 (s, 3H), 3.58 (dd, J = 8.0, 5.7 Hz, 1H), 3.45 (s, 3H), 3.39 (dd, J
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= 8.2, 3.5 Hz, 1H), 2.76 (bs, 1H); C NMR (151 MHz, CDCl3) δ 138.4, 138.0, 128.6, 128.5,
128.1, 128.1(2C), 127.9, 99.9, 79.2, 78.3, 78.1, 75.1, 73.9, 73.8, 63.3, 60.6, 57.0; HRMS:
calcd. for C22H28O6 [M+Na]+: 411.1784, found 411.1788.
Synthesis of methyl 3,4-di-O-benzyl-6-deoxy-2-O-methyl-α-D-xylo-hex-5-enopyranoside
(2j): Methyl 3-O-benzyl-2-O-methyl-α-D-glucopyranoside (11); Prepared according to general
procedure B. Compound 1024 (972 mg, 2.515 mmol), H2O (1.25 mL), 1 M HCl (2.5 mL)
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MeOH (25 mL), 55 °C, 1 h. Purified by column chromatography EA. Yield: 97% (728 mg,
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2.440 mmol) as colorless oil; [훼]2D6 +63.5 (c 1.20, CHCl3); IR (neat) 3440, 1454, 1052; H
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NMR (600 MHz, CDCl3) δ 7.39 – 7.26 (m, 5H), 4.96 (d, J = 11.5 Hz, 1H), 4.86 (d, J = 3.5
Hz, 1H), 4.68 (d, J = 11.5 Hz, 1H), 3.81 (dd, J = 11.8, 3.4 Hz, 1H), 3.76 (dd, J = 11.8, 4.4 Hz,
1H), 3.72 (dd, J = 9.2, 9.1 Hz, 1H), 3.61 (ddd, J = 7.7, 3.8, 3.8 Hz, 1H), 3.54 (dd, J = 9.7, 9.0
Hz, 1H), 3.51 (s, 3H), 3.43 (s, 3H), 3.30 (dd, J = 9.6, 3.5 Hz, 1H), 2.55 (bs, 1H), 2.14 (bs,
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1H); C NMR (151 MHz, CDCl3) δ 138.9, 128.7, 128.0, 128.0, 97.6, 82.2, 81.4, 75.3, 70.9,
70.4, 62.5, 58.9, 55.4; HRMS: calcd. for C15H22O6 [M+Na]+: 321.1314, found 321.1313.
Methyl 3-O-benzyl-6-deoxy-6-iodo-2-O-methyl-α-D-glucopyranoside (12); Prepared according
to general procedure C. Compound 11 (681 mg, 2.283 mmol), PPh3 (718 mg, 2.739 mmol),
imidazole (404 mg, 5.935 mmol) I2 (695 mg, 2.739 mmol), toluene (50 mL), 75 °C, 1 h.
Purified by column chromatography Hx-EA (4:1). Yield: 83% (775 mg, 1.898 mmol) as
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colorless oil; [훼]2D1 +52.5 (c 0.90, CHCl3); IR (neat) 3476, 1454, 1362, 1067; H NMR (600
MHz, CDCl3) δ 7.39 – 7.29 (m, 5H), 4.98 (d, J = 11.6 Hz, 1H), 4.89 (d, J = 3.6 Hz, 1H), 4.64
(d, J = 11.6 Hz, 1H), 3.70 (dd, J = 9.2, 8.8 Hz, 1H), 3.54 (dd, J = 10.7, 2.5 Hz, 1H), 3.53 (s,
3H), 3.49 (s, 3H), 3.40 (ddd, J = 9.2, 6.8, 2.5 Hz, 1H), 3.35 – 3.31 (m, 2H), 3.30 (dd, J = 10.7,
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6.8 Hz, 1H); C NMR (151 MHz, CDCl3) δ 138.7, 128.8, 128.1(2C), 97.6, 82.2, 80.8, 75.3,
73.6, 69.8, 58.8, 55.7, 7.3; HRMS: calcd. for C15H21IO5 [M+Na]+: 431.0331, found 431.0336.
Methyl 3,4-di-O-benzyl-6-deoxy-2-O-methyl-α-D-xylo-hex-5-enopyranoside (2j); Prepared
according to general procedure F2. Compound 12 (327 mg, 0.801 mmol), NaH (320 mg,
8.010 mmol), BnBr (274 mg, 1.602 mmol), DMF (10 mL), 48 h. Purified by column
chromatography Hx-EA (6:1). Yield: 85% (252 mg, 0.680 mmol) as colorless oil; [훼]2D6 +6.6
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(c 1.00, CHCl3); IR (neat) 1662, 1497, 1454, 1356, 1091; H NMR (600 MHz, Acetone) δ
7.40 – 7.24 (m, 10H), 4.97 (d, J = 3.4 Hz, 1H), 4.83 (d, J = 11.4 Hz, 1H), 4.81 (d, J = 2.0 Hz,
1H), 4.80 (d, J = 11.4 Hz, 1H), 4.79 (d, J = 11.9 Hz, 1H), 4.77 (d, J = 11.9 Hz, 1H), 4.66 (d, J
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= 2.1 Hz, 1H), 3.91 (ddd, J = 9.1, 2.0, 2.0 Hz, 1H), 3.75 (dd, J = 9.3, 9.3 Hz, 1H), 3.47 (s,
3H), 3.42 (dd, J = 9.4, 3.4 Hz, 1H), 3.40 (s, 3H); 13C NMR (151 MHz, Acetone) δ 155.3,
140.1, 139.4, 129.1, 128.9, 128.6, 128.5, 128.3, 128.1, 99.2, 96.5, 82.4, 81.6, 80.1, 75.5, 74.8,
58.7, 55.4, HRMS: calcd. for C22H26O5 [M+Na]+: 393.1678, found 393.1682.
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Methyl 3,4-di-O-benzyl-2-O-methyl-α-D-glucopyranoside (3j)24 and Methyl 3,4-di-O-benzyl-
2-O-methyl-β-L-idopyranoside (4j); Prepared according to general procedure G. Compound 2j
(95 mg, 0.256 mmol), BH3·THF (1M, 2.56 mL, 2.56 mmol), THF (1 mL). Then 30% H2O2 (1
mL), 2 M NaOH (1.3 mL). Purified by column chromatography Hx-EA (1:2) to give first 3j
(15%, 15 mg, 0.039 mmol). Next eluted was 4j (67%, 67 mg, 0.172 mmol) as colorless oil;
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[훼]2D5 +53.7 (c 1.02, CHCl3); IR (neat) 3482, 1497, 1454, 1092, 1055; H NMR (600 MHz,
CDCl3) δ 7.37 – 7.27 (m, 10H), 4.79 (d, J = 11.1 Hz, 1H), 4.76 (d, J = 11.7 Hz, 1H), 4.75 (d, J
= 3.4 Hz, 1H), 4.75 (d, J = 11.1 Hz, 1H), 4.57 (d, J = 11.7 Hz, 1H), 4.02 (dd, J = 7.7, 7.6 Hz,
1H), 4.00 (ddd, J = 5.5, 5.4, 5.4 Hz, 1H), 3.90 (dd, J = 11.9, 5.5 Hz, 1H), 3.85 (dd, J = 11.9,
5.4 Hz, 1H), 3.64 (dd, J = 7.6, 5.4 Hz, 1H), 3.52 (s, 3H), 3.52 (s, 3H), 3.30 (dd, J = 7.7, 3.4
Hz, 1H), 2.67 (bs, 1H); 13C NMR (151 MHz, CDCl3) δ 138.4, 137.9, 128.6, 128.5, 128.2,
128.1, 128.0, 127.9, 99.6, 80.6, 77.4, 76.5, 75.2, 74.8, 73.8, 63.2, 59.5, 57.0; HRMS: calcd.
for C22H28O6 [M+Na]+: 411.1784, found 411.1780.
Synthesis of methyl 2,3-di-O-benzyl-6-deoxy-4-O-methyl-α-D-ribo-hex-5-enopyranoside
(2k): Methyl 2-O-benzyl-4,6-O-benzylidene-α-D-allopyranoside (14); Compound 1332 (749
mg, 2.022 mmol) was suspended in 69% aq EtOH (43 mL). Next solution of NaBH4 (97 mg,
2.564 mmol) in H2O (5 mL) was added. Subsequently, mixture was diluted with MeOH (10
mL). After 5.5 h of stirring the mixture was washed three times with DCM. Combined
organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure.
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The residue was purified by column chromatography Hx-EA (2:1). Yield: 97% (731 mg,
1.963 mmol) as white solid; mp 75-77 °C; [훼]2D2 +4.7 (c 1.00, CHCl3); IR (neat) 3493, 1497,
1452, 1103; 1H NMR (600 MHz, CDCl3) δ 7.54 – 7.47 (m, 2H), 7.40 – 7.29 (m, 8H), 5.52 (s,
1H), 4.78 (d, J = 12.4 Hz, 1H), 4.75 (d, J = 3.6 Hz, 1H), 4.60 (d, J = 12.4 Hz, 1H), 4.46 – 4.41
(m, 1H), 4.34 (dd, J = 10.3, 5.2 Hz, 1H), 4.15 (ddd, J = 10.0, 10.0, 5.2 Hz, 1H), 3.70 (dd, J =
10.3, 10.3 Hz, 1H), 3.50 (dd, J = 3.4, 3.4 Hz, 1H), 3.44 (s, 3H), 3.41 (dd, J = 9.7, 2.6 Hz, 1H),
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3.20 (d, J = 6.3 Hz, 1H); C NMR (151 MHz, CDCl3) δ 137.3, 137.2, 129.2, 128.7, 128.3,
128.2, 128.1, 126.4, 102.1, 99.7, 78.9, 73.9, 70.5, 69.2, 67.0, 57.9, 56.0; HRMS: calcd. for
C21H24O6 [M+Na]+: 395.1471, found 395.1476.
Methyl 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-allopyranoside (15);33 Prepared according to
general procedure A. Compound 14 (680 mg, 1.826 mmol), NaH (146 mg, 3.652 mmol),
BnBr (625 mg, 3.654 mmol), DMF (15 mL). Purified by column chromatography Hx-EA
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(4:1) to (7:3). Yield: 86% (727 mg, 1.572 mmol); H NMR (600 MHz, CDCl3) δ 7.49 – 7.22
(m, 15H), 5.45 (s, 1H), 4.94 (d, J = 12.6 Hz, 1H), 4.88 (d, J = 12.6 Hz, 1H), 4.70 (d, J = 4.1
Hz, 1H), 4.58 (d, J = 12.7 Hz, 1H), 4.44 (d, J = 12.7 Hz, 1H), 4.39 – 4.35 (m, 1H), 4.33 (dd, J
= 10.0, 5.3 Hz, 1H), 4.19 (dd, J = 2.8, 2.8 Hz, 1H), 3.65 (t, J = 10.1, 10.1 Hz, 1H), 3.50 – 3.47
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(m, 1H), 3.47 (s, 3H), 3.44 (dd, J = 3.8, 3.8 Hz, 1H); C NMR (151 MHz, CDCl3) δ 139.0,
137.7, 137.7, 129.2, 128.6, 128.4, 128.4, 128.1, 128.1, 128.0, 127.3, 126.4, 102.1, 99.1, 79.9,
74.8, 73.7, 72.3, 70.9, 69.5, 58.1, 56.3.
Methyl 2,3-di-O-benzyl-α-D-allopyranoside (16);34 Prepared according to general procedure
B. Compound 15 (700 mg, 1.513 mmol), H2O (1 mL), 1 M HCl (2 mL) MeOH (20 mL), 55
°C, 3 h. Purified by column chromatography Hx-EA (1:4) Yield: 97% (550 mg, 1.469 mmol).
Methyl 2,3-di-O-benzyl-6-deoxy-6-iodo-α-D-allopyranoside (17); Prepared according to
general procedure C. Compound 16 (495 mg, 1.322 mmol), PPh3 (416 mg, 1.586 mmol),
imidazole (234 mg, 3.437 mmol) I2 (403 mg, 1.588 mmol), toluene (30 mL), 75 °C, 2 h.
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as pale yellow oil; [훼]1D5 +44.9 (c 1.07, CHCl3); IR (neat) 3526, 1454, 1063; H NMR (600
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4.71 (d, J = 12.3 Hz, 1H), 4.67 (d, J = 12.3 Hz, 1H), 4.60 (d, J = 11.6 Hz, 1H), 4.04 (dd, J =
3.1, 3.1 Hz, 1H), 3.65 – 3.60 (m, 1H), 3.55 (dd, J = 10.7, 2.5 Hz, 1H), 3.52 – 3.51 (m, 1H),
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3.51 (s, 3H), 3.28 – 3.23 (m, 1H), 3.24 (dd, J = 10.7, 7.5 Hz, 1H), 2.43 (bs, 1H); C NMR
(151 MHz, CDCl3) δ 138.5, 137.7, 128.7, 128.7, 128.3, 128.2, 128.0, 127.9, 98.2, 77.1, 75.5,
74.6, 71.9, 70.6, 67.8, 56.4, 7.9; HRMS: calcd. for C21H25IO5 [M+Na]+: 507.0644, found
507.0645.
Methyl 2,3-di-O-benzyl-6-deoxy-4-O-methyl-α-D-ribo-hex-5-enopyranoside (2k); Prepared
according to general procedure F2. Compound 17 (338 mg, 0.698 mmol), NaH (279 mg,
6.975 mmol), MeI (198 mg, 1.395 mmol), DMF (10 mL), 24 h. Purified by column
chromatography Hx-EA (3:1). Yield: 80% (206 mg, 0.556 mmol) as white solid; mp 78-80
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°C; [훼]2D7 +21.8 (c 1.06, CHCl3); IR (neat) 2921, 2893, 1667, 1450, 1114, 1103; H NMR
(600 MHz, Acetone) δ 7.45 – 7.39 (m, 4H), 7.36 – 7.32 (m, 2H), 7.30 – 7.26 (m, 3H), 7.23 –
7.19 (m, 1H), 4.92 (d, J = 3.8 Hz, 1H), 4.88 (d, J = 12.3 Hz, 1H), 4.77 (d, J = 12.3 Hz, 1H),
4.70 (d, J = 12.0 Hz, 1H), 4.68 (d, J = 12.0 Hz, 1H), 4.64 (d, J = 1.6 Hz, 1H), 4.63 (d, J = 1.2
Hz, 1H), 4.33 (dd, J = 2.9, 2.9 Hz, 1H), 3.81 (dd, J = 3.8, 2.8 Hz, 1H), 3.78 – 3.76 (m, 1H),
3.41 (s, 3H), 3.40 (s, 3H); 13C NMR (151 MHz, Acetone) δ 154.1, 141.0, 139.7, 129.1, 128.7,
128.4, 128.3, 128.2, 127.6, 101.3, 96.2, 79.0, 77.4, 75.6, 73.8, 71.9, 57.5, 56.1; HRMS: calcd.
for C22H26O5 [M+Na]+: 393.1678, found 393.1676.
Methyl 2,3-di-O-benzyl-4-O-methyl-β-L-talopyranoside (4k); Prepared according to general
procedure G. Compound 2k (136 mg, 0.367 mmol), BH3·THF (1M, 3.67 mL, 3.67 mmol),
THF (1 mL). Then 30% H2O2 (1 mL), 2 M NaOH (1.9 mL). Purified by column
chromatography EA. Yield: 87% (124 mg, 0.319 mmol) as colorless oil; [훼]2D6 +69.6 (c 1.07,
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CHCl3); IR (neat) 3463, 1496, 1453, 1113, 1065; H NMR (600 MHz, CDCl3) δ 7.46 – 7.42
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(m, 2H), 7.34 – 7.18 (m, 8H), 4.97 (d, J = 12.9 Hz, 1H), 4.74 (d, J = 12.9 Hz, 1H), 4.48 (d, J =
12.2 Hz, 1H), 4.43 (d, J = 12.2 Hz, 1H), 4.29 (d, J = 1.2 Hz, 1H), 4.05 (dd, J = 11.5, 7.3 Hz,
1H), 3.82 (dd, J = 11.5, 4.8 Hz, 1H), 3.81 (s, 1H), 3.59 (s, 3H), 3.57 – 3.55 (m, 1H), 3.52 (s,
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3H), 3.49 – 3.45 (m, 1H), 3.43 – 3.40 (m, 1H), 2.53 (bs, 1H); C NMR (151 MHz, CDCl3) δ
139.0, 137.9, 128.2, 127.9, 127.8, 127.4, 127.0, 127.0, 102.7, 78.4, 75.8, 75.5, 74.1, 73.9,
70.6, 62.2, 60.1, 56.6; HRMS: calcd. for C22H28O6 [M+Na]+: 411.1784, found 411.1781.
Synthesis of phenyl 2,3-di-O-benzyl-6-deoxy-4-O-methyl-α-D-xylo-hex-5-enopyranoside
(2l): Phenyl 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside (18);35 1H NMR (600
MHz, CDCl3) δ 7.51 – 7.03 (m, 20H), 5.57 (s, 1H), 5.44 (d, J = 3.7 Hz, 1H), 4.98 (d, J = 11.2
Hz, 1H), 4.90 (d, J = 11.2 Hz, 1H), 4.86 (d, J = 12.0 Hz, 1H), 4.72 (d, J = 12.0 Hz, 1H), 4.26
(dd, J = 9.3, 9.3 Hz, 1H), 4.19 (dd, J = 10.3, 4.9 Hz, 1H), 4.00 (ddd, J = 10.0, 10.0, 4.9 Hz,
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1H), 3.74 – 3.67 (m, 3H); C NMR (151 MHz, CDCl3) δ 156.7, 138.9, 138.1, 137.5, 129.7,
129.1, 128.6, 128.5, 128.4, 128.1, 128.1, 127.8, 126.2, 122.8, 117.1, 101.5, 96.5, 82.2, 79.2,
78.6, 75.5, 73.8, 69.0, 63.3.
Phenyl 2,3-di-O-benzyl-α-D-glucopyranoside (19); Prepared according to general procedure
B. Compound 18 (658 mg, 1.254 mmol), H2O (1 mL), 1 M HCl (2 mL) MeOH (20 mL), 55
°C, 3 h. Purified by column chromatography Hx-EA (2:1) to (1:1). Yield: 92% (504 mg,
1.155 mmol) as white solid; mp 121-123 °C; [훼]2D6 +77.0 (c 1.00, CHCl3); IR (neat) 3269,
1599, 1491, 1231, 1058; 1H NMR (600 MHz, CDCl3) δ 7.43 – 7.25 (m, 12H), 7.10 – 7.00 (m,
3H), 5.43 (d, J = 3.5 Hz, 1H), 5.07 (d, J = 11.4 Hz, 1H), 4.79 (d, J = 11.4 Hz, 1H), 4.75 (d, J
= 11.9 Hz, 1H), 4.66 (d, J = 11.9 Hz, 1H), 4.01 (dd, J = 9.2, 9.2 Hz, 1H), 3.77 – 3.66 (m, 4H),
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3.64 (dd, J = 9.5, 3.5 Hz, 1H), 2.70 (bs, 1H), 2.06 (bs, 1H); C NMR (151 MHz, CDCl3) δ
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156.8, 138.8, 137.9, 129.6, 128.7, 128.6, 128.1, 128.1, 128.0, 122.7, 117.1, 95.7, 81.3, 79.7,
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Phenyl 2,3-di-O-benzyl-6-deoxy-6-iodo-α-D-glucopyranoside (20); Prepared according to
general procedure C. Compound 19 (464 mg, 1.063 mmol), PPh3 (335 mg, 1.277 mmol),
imidazole (188 mg, 2.762 mmol) I2 (324 mg, 1.277 mmol), toluene (40 mL), 70 °C, 3 h.
Purified by column chromatography Hx-EA (4:1). Yield: 94% (545 mg, 0.997 mmol) as
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colorless oil; [훼]2D2 +53.2 (c 0.80, CHCl3); IR (neat) 3442, 1597, 1494, 1219, 1060; H NMR
(600 MHz, CDCl3) δ 7.40 – 7.23 (m, 12H), 7.15 – 7.03 (m, 3H), 5.47 (d, J = 3.5 Hz, 1H), 5.09
(d, J = 11.4 Hz, 1H), 4.75 (d, J = 11.4 Hz, 1H), 4.75 (d, J = 11.9 Hz, 1H), 4.67 (d, J = 11.9
Hz, 1H), 4.05 – 4.01 (m, 1H), 3.68 (dd, J = 9.5, 3.5 Hz, 1H), 3.49 – 3.40 (m, 3H), 3.34 – 3.31
(m, 1H), 2.31 (bs, 1H); 13C NMR (151 MHz, CDCl3) δ 156.8, 138.7, 137.9, 129.6, 128.8,
128.7, 128.2, 128.1, 128.0, 122.8, 117.2, 95.8, 80.7, 79.9, 75.6, 73.8, 73.1, 70.0, 7.6; HRMS:
calcd. for C26H27IO5 [M+Na]+: 569.0801, found 569.0806.
Phenyl 2,3-di-O-benzyl-6-deoxy-4-O-methyl-α-D-xylo-hex-5-enopyranoside (2l); Prepared
according to general procedure F2. Compound 20 (160 mg, 0.293 mmol), NaH (117 mg,
2.928 mmol), MeI (83 mg, 0.586 mmol), DMF (7 mL), 24 h. Purified by column
chromatography Hx-EA (9:1). Yield: 93% (118 mg, 0.273 mmol) as colorless oil; [훼]2D6 +74.3
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(c 0.70, CHCl3); IR (neat) 1666, 1598, 1495, 1454, 1090; H NMR (600 MHz, Acetone) δ
7.47 – 7.02 (m, 15H), 5.75 (d, J = 3.4 Hz, 1H), 4.93 (d, J = 11.3 Hz, 1H), 4.90 (d, J = 11.3 Hz,
1H), 4.82 (d, J = 11.8 Hz, 1H), 4.78 (d, J = 11.8 Hz, 1H), 4.70 (d, J = 2.0 Hz, 1H), 4.48 (dd, J
= 2.1, 0.4 Hz, 1H), 3.98 (dd, J = 9.2, 9.2 Hz, 1H), 3.85 (dd, J = 9.5, 3.4 Hz, 1H), 3.76 (ddd, J
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= 4.1, 2.1, 2.1 Hz, 1H), 3.57 (s, 3H); C NMR (151 MHz, Acetone) δ 157.8, 154.6, 140.1,
139.4, 130.2, 129.2, 129.0, 128.6, 128.5, 128.4, 128.1, 123.2, 117.9, 96.9, 96.8, 82.3, 81.6,
80.0, 75.7, 73.5, 60.3; HRMS: calcd. for C27H28O5 [M+Na]+: 455.1834, found 455.1835.
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Phenyl 2,3-di-O-benzyl-4-O-methyl-α-D-glucopyranoside (3l) and Phenyl 2,3-di-O-benzyl-4-
O-methyl-β-L-idopyranoside (4l); Prepared according to general procedure G. Compound 2l
(98 mg, 0.227 mmol), BH3·THF (1M, 2.27 mL, 2.27 mmol), THF (1 mL). Then 30% H2O2 (1
mL), 2 M NaOH (1.2 mL). Purified by column chromatography Hx-EA (7:3) to (3:2) to give
first 3l (7%, 7 mg, 0.016 mmol) as colorless oil; [훼]2D6 +50.1 (c 0.54, CHCl3); IR (neat) 3462,
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1598, 1495, 1454, 1225, 1098; H NMR (600 MHz, CDCl3) δ 7.43 – 7.26 (m, 12H), 7.07 –
7.02 (m, 3H), 5.41 (d, J = 3.6 Hz, 1H), 5.02 (d, J = 10.8 Hz, 1H), 4.88 (d, J = 10.8 Hz, 1H),
4.80 (d, J = 12.0 Hz, 1H), 4.68 (d, J = 12.0 Hz, 1H), 4.11 (dd, J = 9.3, 9.3 Hz, 1H), 3.76 –
3.69 (m, 3H), 3.62 (dd, J = 9.6, 3.6 Hz, 1H), 3.60 (s, 3H), 3.38 (dd, J = 9.3, 9.3 Hz, 1H); 13C
NMR (151 MHz, CDCl3) δ 156.8, 138.9, 138.1, 129.7, 128.6, 128.6, 128.1, 128.1, 128.1,
127.8, 122.7, 117.0, 95.7, 81.8, 79.8, 79.4, 75.8, 73.5, 71.7, 61.8, 61.1; HRMS: calcd. for
C27H30O6 [M+Na]+: 473.1940, found 473.1943. Next eluted was 4l (81%, 83 mg, 0.184
mmol) as colorless oil; [훼]2D6 +89.4 (c 1.10, CHCl3); IR (neat) 3493, 1598, 1495, 1223, 1100;
1H NMR (600 MHz, CDCl3) δ 7.37 – 7.25 (m, 12H), 7.08 – 7.01 (m, 3H), 5.44 (d, J = 3.2 Hz,
1H), 4.81 (d, J = 11.1 Hz, 1H), 4.77 (d, J = 12.2 Hz, 1H), 4.73 (d, J = 12.2 Hz, 1H), 4.72 (d, J
= 11.1 Hz, 1H), 4.20 – 4.16 (m, 1H), 4.07 (dd, J = 7.6, 7.4 Hz, 1H), 3.86 (dd, J = 12.1, 5.6 Hz,
1H), 3.79 (dd, J = 12.1, 6.9 Hz, 1H), 3.64 (dd, J = 7.6, 3.2 Hz, 1H), 3.49 (s, 3H), 3.50 – 3.47
(m, 1H), 2.14 (bs, 1H); 13C NMR (151 MHz, CDCl3) δ 157.0, 138.4, 138.2, 129.8, 128.5,
128.5, 128.2, 128.0, 128.0, 127.9, 122.5, 116.2, 96.4, 80.2, 77.5, 76.4, 75.4, 74.8, 73.8, 63.1,
59.5; HRMS: calcd. for C27H30O6 [M+Na]+: 473.1940, found 473.1947.
Synthesis of methyl 2,3-di-O-benzyl-6-deoxy-4-O-methyl-β-D-xylo-hex-5-enopyranoside
(2m): Methyl 2,3-di-O-benzyl-6-O-deoxy-6-iodo-β-D-glucopyranoside (21);36 1H NMR (600
MHz, CDCl3) δ 7.43 – 7.25 (m, 10H), 4.95 (d, J = 11.6 Hz, 1H), 4.93 (d, J = 11.2 Hz, 1H),
4.69 (d, J = 11.2 Hz, 1H), 4.63 (d, J = 11.6 Hz, 1H), 4.37 – 4.33 (m, J = 7.5 Hz, 1H), 3.60 (s,
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3H), 3.55 (dd, J = 10.6, 2.3 Hz, 1H), 3.45 – 3.40 (m, 2H), 3.32 (ddd, J = 8.6, 5.9, 2.5 Hz, 1H),
3.24 (dd, J = 10.6, 7.8 Hz, 1H), 3.16 – 3.12 (m, 1H), 2.25 (d, J = 2.4 Hz, 1H); 13C NMR (151
MHz, CDCl3) δ 138.4, 138.4, 128.8, 128.5, 128.2, 128.2, 128.1, 127.9, 104.7, 83.4, 82.0, 75.3,
74.6, 74.2, 73.5, 57.3, 6.1.
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Methyl 2,3-di-O-benzyl-6-deoxy-4-O-methyl-β-D-xylo-hex-5-enopyranoside (2m); Prepared
according to general procedure F2. Compound 21 (539 mg, 1.113 mmol), NaH (445 mg,
11.129 mmol), MeI (316 mg, 2.226 mmol), DMF (10 mL), 24 h. Purified by column
chromatography Hx-EA (9:1) to (6:1). Yield: 93% (384 mg, 1.034 mmol) as white solid; mp
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62-64 °C; [훼]2D3 –38.4 (c 1.00, CHCl3); IR (neat) 1662, 1498, 1452, 1095, 1072; H NMR
(600 MHz, Acetone) δ 7.38 – 7.25 (m, 10H), 4.76 (d, J = 11.7 Hz, 1H), 4.75 (d, J = 11.6 Hz,
1H), 4.71 (d, J = 11.6 Hz, 1H), 4.70 (d, J = 5.8 Hz, 1H), 4.67 (d, J = 11.7 Hz, 1H), 4.57 (dd, J
= 1.2, 0.5 Hz, 1H), 4.50 (dd, J = 1.3, 0.5 Hz, 1H), 3.90 – 3.88 (m, 1H), 3.55 – 3.51 (m, 2H),
3.50 (s, 3H), 3.48 (s, 3H); 13C NMR (151 MHz, Acetone) δ 155.3, 139.7, 139.6, 129.0, 128.6,
128.6, 128.3, 128.2, 104.0, 93.0, 82.9, 82.3, 80.8, 73.9, 73.8, 58.8, 56.6; HRMS: calcd. for
C22H26O5 [M+Na]+: 393.1678, found 393.1686.
Methyl 2,3-di-O-benzyl-4-O-methyl-β-D-glucopyranoside (3m)25 and Methyl 2,3-di-O-benzyl-
4-O-methyl-α-L-idopyranoside (4m); Prepared according to general procedure G. Compound
2m (95 mg, 0.256 mmol), BH3·THF (1M, 2.56 mL, 2.56 mmol), THF (1 mL). Then 30%
H2O2 (1 mL), 2 M NaOH (1.3 mL). Purified by column chromatography Hx-EA (3:2) to give
first 3m (27%, 27 mg, 0.070 mmol). Next eluted was 4m (61%, 61 mg, 0.157 mmol) as white
solid; mp 92-94 °C; [훼]2D3 –23.4 (c 1.10, CHCl3); IR (neat) 3276, 1498, 1453, 1101, 1063; 1H
NMR (600 MHz, CDCl3) δ 7.36 – 7.27 (m, 10H), 4.76 (d, J = 11.6 Hz, 1H), 4.74 (d, J = 3.8
Hz, 1H), 4.70 (d, J = 11.9 Hz, 1H), 4.59 (d, J = 11.8 Hz, 1H), 4.57 (d, J = 11.5 Hz, 1H), 4.09
(ddd, J = 6.5, 4.2, 4.2 Hz, 1H), 3.93 (dd, J = 11.8, 6.5 Hz, 1H), 3.78 (dd, J = 11.0, 5.3 Hz,
1H), 3.73 (dd, J = 6.5, 5.3 Hz, 1H), 3.47 (dd, J = 6.5, 3.8 Hz, 1H), 3.43 (s, 3H), 3.43 – 3.42
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