A reinvestigation of the synthesis and revision of spectral data of 1,2-O-isopropylidene-α-l-sorbofuranose, 1,2:4,6-di-O-isopropylidene- α-l-sorbofuranose and derivatives

Article abstract of DOI:10.1016/j.carres.2013.05.019

Mono- and di-O-isopropylidene-l-sorbofuranose derivatives are important starting materials for the synthesis of modified sugars and useful chiral compounds. However, several inconsistencies in the spectral data of these compounds and erroneous structural assignments have been noted in the literature. The unambiguous synthesis of 1,2:4,6-di-O-isopropylidene-α-l- sorbofuranose and derivatives of 1,2- and 2,3-O-isopropylidene-α-l- sorbofuranoses has been achieved and definitive spectral data on these compounds are provided.

Full text of DOI:10.1016/j.carres.2013.05.019

Accepted Manuscript
A reinvestigation of the synthesis and revision of spectral data of 1,2-O-isopro‐
pylidene-α-l-sorbofuranose, 1,2:4,6-di-O-isopropylidene-α-l-sorbofuranose
and derivatives
Anna Biela-Banas, Estelle Gallienne, Olivier R. Martin
PII:
S0008-6215(13)00225-5
DOI:
http://dx.doi.org/10.1016/j.carres.2013.05.019
CAR 6495
Reference:
To appear in:
Carbohydrate Research
Received Date:
Accepted Date:
10 May 2013
30 May 2013
Please cite this article as: Biela-Banas, A., Gallienne, E., Martin, O.R., A reinvestigation of the synthesis and revision
of spectral data of 1,2-O-isopropylidene-α-l-sorbofuranose, 1,2:4,6-di-O-isopropylidene-α-l-sorbofuranose and
derivatives, Carbohydrate Research (2013), doi: http://dx.doi.org/10.1016/j.carres.2013.05.019
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CARBOHYDRATE RESEARCH Manuscript
NOTE
A reinvestigation of the synthesis and revision of spectral data of 1,2-O-
isopropylidene- -L-sorbofuranose, 1,2:4,6-di-O-isopropylidene- -L-
sorbofuranose and derivatives
Anna Biela-Banas, Estelle Gallienne, Olivier R. Martin
Institut de Chimie Organique et Analytique (ICOA), UMR 7311, Université d’Orléans and CNRS, Rue
de Chartres, BP 6759, 45067 Orléans cedex 2, France
Abstract
Mono- and di-O-isopropylidene-L-sorbofuranose derivatives are important starting materials
for the synthesis of modified sugars and useful chiral compounds. However, several
inconsistencies in the spectral data of these compounds and erroneous structural assignments
have been noted in the literature. The unambiguous synthesis of 1,2:4,6-di-O-isopropylidene-
-L-sorbofuranose and of derivatives of 1,2- and 2,3-O-isopropylidene- -L-sorbofuranoses has
been achieved and definitive spectral data on these compounds are provided.
1. Introduction
1,2:4,6-Di-O-isopropylidene- -L-sorbofuranose 1 (Figure 1) is a useful starting
material for the synthesis of various modified sugar derivatives including iminosugars,1,2,3 as
well as ligands and catalysts for asymmetric synthesis.4,5,6 As part of our on-going program on
the synthesis of iminosugar derivatives of biological interest,7,8 we required this L-
sorbofuranose derivative as starting material. This compound is now commercially available,
but our experience with a commercial sample, which was found to be heterogeneous and to
contain a significant amount of L-sorbose, led us to reinvestigate the synthesis of 1 and its
derivatives, and to examine literature data on these compounds. We have identified a number
of errors in literature reports, with instances of confusion between the 1,2:4,6-di-O-
isopropylidene derivative 1 and the more common 2,3:4,6-di-O-isopropylidene- -L-
sorbofuranose 2, as well as between the corresponding mono-O-isopropylidene derivatives.
We report in this note the results of our investigations and corrections of data from literature
reports with definitive spectral data on both families of compounds.
Corresponding author. Tel.: +33 238 494 581; fax: +33 238 417 281.
E-mail address: olivier.martin@univ-orleans.fr (O. R. Martin).

3
2
1
Figure 1. Mono- and di-O-isopropylidene derivatives of L-sorbofuranose
2. Results and Discussion
It is well known since Reichstein’s work in the 30’s that the reaction of L-sorbose with
acetone under acidic conditions provides 2,3:4,6-di-O-isopropylidene- -L-sorbofuranose 2 in
high yield.9 The 1,2:4,6-isomer 1 has been observed for the first time as a minor product in
the reaction mixture from the acetonation of L-sorbose using acetone diethyl acetal in the
presence of pTsOH, and was characterized (mp and optical activity) by Tokuyama and Honda
in 1964.10 Further investigations on the reaction of L-sorbose with acetone acetals were
performed by Maeda and co-workers who isolated also one mono-O-isopropylidene-L-
sorbofuranose derivative11 and reported the first NMR data on this family of compounds.12 It
should be noted that in Maeda’s paper,12 the spectrum shown in Fig. 6 corresponds to that of
the -anomer VIIa and not to that of the -anomer IXa (incorrect structure number). The first
convenient method for the selective preparation of 1,2:4,6-di-O-isopropylidene- -L-sorbose 1
was reported in 1988 by Chen and Whistler,13 as a prelude to their synthesis of L-fructose.
The method consists in refluxing L-sorbose in 2,2-dimethoxypropane containing 1,2-
dimethoxyethane (DME) in the presence of a catalytic amount of SnCl2 as a Lewis acidic
catalyst, which is the key feature of this protocol. This procedure has been used subsequently
by other groups (Tyler,2 Overkleeft,3, Wang4, Zhao14) with yields in the order of 40% when
the acetonation was coupled with subsequent reactions (mesylation for example). Behling and
co-workers have modified the protocol in order to obtain 1,2-O-isopropylidene- -L-
sorbofuranose 3 (Figure 1) as the major product, and as the starting material for a short
synthesis of 1-deoxynojirimycin.1
Initially we have experienced difficulties with the protocols of Wang4 or Chen13 which
consisted in refluxing the reaction mixture until complete disappearance of starting material
(the solution becomes clear after 3-4h on a 5g-scale). In our hands, these conditions led to a
In this article, the catalyst is indicated as SnCl4; this is a mistake (H. Overkleeft, personal communication)

mixture of 1 and 2 that could not be separated by crystallisation. As suggested by Zhao,14 we
decreased the reaction temperature to 70°C and stopped it before the solution became clear
(1h, 10g-scale). Although the reaction was not complete (66% of L-sorbose was recovered),
we were able to obtain mainly the desired isomer 1 that could be purified by recrystallisation
from hexane. The purity of 1,2:4,6-di-O-isopropylidene- -L-sorbose 1 obtained by this
procedure was sufficient to continue the synthesis (yield of 16%, 46% based on consumed L-
sorbose).
More recently, Mukhopadhyay and co-workers15 reported a method of synthesis of O-
isopropylidene and di-O-isopropylidene sugar derivatives using sulfuric acid immobilized on
silica as the catalyst in refluxing acetone. Among the reported applications of this convenient
procedure, the authors indicated that L-sorbose was converted into 1,2:4,6-di-O-isopropyli-
dene- -L-sorbofuranose 1 in 86% yield. However, the 1H and 13C-NMR spectra of the isolated
compound shown in supplementary materials clearly do not match those of 1, but matched the
spectra of the isomeric 2,3:4,6-di-O-isopropylidene- -L-sorbofuranose 2.
Furthermore, the same authors reported the same year16 the use of the same supported
acidic catalyst for the selective hydrolysis of the less stable O-isopropylidene group in
common di-O-isopropylidene derivatives of hexoses and hexuloses. The reported applications
included the selective cleavage of the 4,6-O-isopropylidene group in 1, as well as in the 3-O-
acetyl, 3-O-benzoyl, 3-O-benzyl, and 3-O-p-methoxybenzyl derivatives of 1, to form the
corresponding 1,2-O-isopropylidene derivatives of L-sorbose. Considering the error in the
first paper, we decided to repeat the synthesis of two of these derivatives, and of the
corresponding derivatives in the 2,3:4,6-di-O-isopropylidene- -L-sorbofuranose series in order
to verify this report.

MeOH
H2SO4-silica
R = Ac
R = PMB
R = Ac
R = PMB
1a
1b
3a
3b
MeOH
H2SO4-silica
R = Ac
R = PMB
R = H
R = Ac
R = PMB
2a
2b
4
4a
4b
Scheme 1. Selective hydrolysis of di-O-isopropylidene- -L-sorbofuranose derivatives
Thus the O-acetyl and O-p-methoxybenzyl derivatives of 1 and 2, compounds 1a,11,12 1b,
2a,12,17 and 2b (Scheme 1), were prepared by standard procedures and then submitted to the
selective hydrolysis procedure of Mukhopadhyay et al.16 Compounds 3a, 3b, 4a,17,20 and 4b
were isolated generally in good yields (21-80%), and their NMR spectra recorded. For
reference, the 1H and 13C-NMR of the important compounds 3b and 4b are shown in Figures
2 and 3 (others are provided in supplementary materials). Comparison of these data with the
spectra provided in supplementary materials by Mukhopadhyay show clearly that the
compounds that they have made are not the 1,2-O-isopropylidene derivatives, but the 2,3-O-
isopropylidene derivatives. That compound 3b is the correct isomer is further supported by
the large chemical shift of the H-3 proton in the 3-O-acetyl derivative 3a ( =4.403 ppm).
3b

4b
Figure 2. Partial 1H-NMR spectra of 3b and 4b (CDCl3, 250 MHz)
3b
4b
Figure 3. 13C-NMR spectra of 3b and 4b (CDCl3, 100 MHz)
Thus it appears clearly that the entire series of compounds made by these authors in the L-
sorbose series arises from 2,3:4,6-di-O-isopropylidene 2, which they had incorrectly assigned
in the preceding paper. Such compounds are important starting materials and therefore it is
significant to note this correction. The same error appears in the 2010 review by Rauter and
co-workers on zeolites and other silicon-based promoters in carbohydrate chemistry.18

A further correction is required in a study by Rauter and co-workers.19 This group
reported in 1995 the use of zeolite HY as a catalyst for the acetonation of various free sugars.
L-Sorbose was submitted to these conditions, and reported to give 2,3:4,6-di-O-isopropylidene
derivative 2 in 37% yield; however, spectral data provided for this compound indicate that
they have obtained the 1,2:4,6-di-O-isopropylidene derivative 1. Thus the procedure reported
by this group provides an alternative synthesis of 1, although the reported yield is not
significantly better than that of the SnCl2-catalyzed method.
3. Conclusion
We have achieved in this study the unambiguous synthesis of mono- and di-O-
isopropylidene- -L-sorbofuranose derivatives in order to verify a number of literature reports.
Definitive spectral and characterization data are provided herein for the 3-O-acetyl and 3-O-p-
methoxybenzyl derivatives of 1,2-O-isopropylidene- -L-sorbofuranose and for the isomeric 1-
O-substituted 2,3-O-isopropylidene- -L-sorbofuranose. These compounds are readily available
and therefore constitute useful starting materials for the synthesis of other sugar derivatives or
sugar-derived biologically important compounds.
4. Experimental section
4.1. General methods
All reactions requiring anhydrous conditions were carried out using oven-dried
glassware under an atmosphere of dry Ar. All reagent-grade chemicals were obtained from
commercial suppliers and were used as received. Analytical thin layer chromatography was
performed using Silica Gel 60F254 precoated plates (Merck) with visualization by ultraviolet
light and phosphomolybdic acid or ceric sulfate/ammonium molybdate solutions. Flash
chromatography was performed on Silica Gel 60 (230-400 mesh).
Melting points were determined in capillary tubes with a Büchi apparatus and are
uncorrected. Optical rotations were measured in appropriate solvent at the indicated
temperature in a 1-dm cell with a Perkin-Elmer 341 polarimeter. 1H and 13C NMR spectra
were recorded on Bruker Avance DPX 250 or Bruker Avance 400 spectrometers. Chemical
shifts are given in ppm and are referenced to the residual solvent signal or to TMS as internal
standard. Carbon multiplicities were assigned by distortionless enhancement by polarization
transfer (DEPT) experiments. 1H and 13C signals were attributed on the basis of H-H and H-C
correlations. High resolution mass spectra were recorded on a Bruker Q-TOF MaXis
spectrometer .

4.2. 1,2:4,6-Di-O-isopropylidene- -L-sorbofuranose (1)10,11,12
The reaction was conducted under argon. To a suspension of L-sorbose (10 g, 0.056
mol) in 2,2-dimethoxypropane (30 mL) was added SnCl2 (50 mg, 0.005 eq) in DME (1 mL).
The reaction was left stirring 1h at 70°C and then quenched with Et3N (0.26 mL, 0.06 eq).
The remaining sorbose was removed by filtration and the filtrate was concentrated under
vacuum. The residue was dissolved in EtOAc (100 mL) and washed with H2O (2x50 mL).
The organic phase was dried over MgSO4 and concentrated under vacuum. The crude product
was obtained as a yellow oil which crystallized overnight. Recrystallization from n-hexane
gave pure 1 as a white solid (2.275 g, 16%; 46% based on consumed L-sorbose): 1H NMR
(250 MHz, CDCl3) 4.26 (dd, 1H, H-4, J4-3=1.3 Hz, J4-5=2.8 Hz), 4.17-4.14 (m, 3H, 2H-1, H-
5), 4.00-3.95 (m, 3H, 2H-6, H-3), 2.85 (d, 1H, OH, J=2.3 Hz), 1.54 (s, 3H, CH3), 1.46 (s, 3H,
CH3), 1.42 (s, 3H, CH3), 1.36 (s, 3H, CH3); 13C NMR (62.5 MHz, CDCl3) 111.23, 110.51
(CIViPr), 97.42 (C-2), 79.31 (C-3), 74.34 (C-4), 72.90 (C-1), 72.43 (C-5), 60.43 (C-6), 28.49,
26.33, 25.42, 19.23 (CH3).
4.3. General procedure for acetylation
To a solution of 1 or 2 (1 eq) in pyridine (0.5 M) was added Ac2O (5 eq). The reaction
was left stirring overnight at room temperature. CH2Cl2 (13 mL/mL of pyridine) was then
added. The organic phase was separated, washed with 1N aqueous HCl, then with water and
dried over MgSO4. After concentration under vacuum, 1a or 2a were obtained as clean
products.
4.3.1. 3-O-Acetyl 1,2:4,6-di-O-isopropylidene- -L-sorbofuranose (1a)11,12
From 1 (150 mg, 0.58 mmol), 1a was obtained as a colorless oil (173 mg, 99 %): [ ]D -
1
64.7 (c 1.12, CHCl3); H NMR (400 MHz, CDCl3) 5.15 (br s, 1H, H-3), 4.31 (dd, 1H, H-4,
J4-3=1.4 Hz, J4-5=2.8 Hz), 4.29 (d, 1H, H-1b, J1b-1a=9.2 Hz), 4.18 (d, 1H, H-1a, J1a-1b=9.2 Hz),
4.14 (q, 1H, H-5, J~2.8 Hz), 4.03 (dd, 1H, H-6b, J6b-5=2.8 Hz, J6b-6a=13.2 Hz), 3.95 (dd, 1H,
H-6a, J6a-5=2.8 Hz, J6a-6b=13.2 Hz), 2.12 (s, 3H, OAc), 1.50 (s, 3H, CH3), 1.42 (s, 3H, CH3),
1.37 (s, 3H, CH3), 1.34 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) 169.44 (C=O), 111.03,
110.25 (CIViPr), 97.90 (C-2), 79.31 (C-3), 73.59 (C-1), 73.31 (C-4), 72.06 (C-5), 60.36 (C-6),
28.47, 25.94, 25.79, 19.52 (CH3), 20.73 (CH3CO); HRMS Calcd for C14H26NO7 [M+NH4]+

m/z = 320.170379. Found: 320.169904. Calcd for C14H22NaO7 [M+Na]+ m/z = 325.125774.
Found: 325.125450.
4.3.2. 1-O-Acetyl 2,3:4,6-di-O-isopropylidene- -L-sorbofuranose (2a)12,17
From 2 (200 mg, 0.77 mmol), 2a was obtained as a colorless oil (233 mg, quant): [ ]D
-13.9 (c 1.01, CHCl3); 1H NMR (400 MHz, CDCl3) 4.56 (d, 1H, H-1b, J1b-1a=12.0 Hz), 4.43
(s, 1H, H-3), 4.33 (d, 1H, H-4, J4-5=2.0 Hz), 4.17 (d, 1H, H-1a, J1a-1b=12.0 Hz), 4.12 (q, 1H,
H-5, J~2.0 Hz), 4.10-4.00 (m, 2H, 2H-6), 2.11 (s, 3H, OAc), 1.51 (s, 3H, CH3), 1.44 (s, 3H,
CH3), 1.39 (s, 3H, CH3) , 1.37 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) 169.97 (C=O
from OAc), 112.56, 112.16 (CIViPr), 97.28 (C-2), 84.55 (C-3), 73.11 (C-4), 72.34 (C-5), 63.42
(C-1), 60.04 (C-6), 28.82, 27.34, 26.26, 18.57 (CH3), 20.76 (CH3OAc); HRMS Calcd for
C14H23O7 [M+H]+ m/z = 303.143829. Found: 303.140610. Calcd for C14H26NO7 [M+NH4]+
m/z = 320.170379. Found: 320.170543. Calcd for C14H22NaO7 [M+Na]+ m/z = 325.125774.
Found: 325.125708.
4.4. General procedure for protection with a p-methoxybenzyl group
To a solution of 1 or 2 (1 eq) in anhydrous DMF (0.5 M) at 0°C was added sodium
hydride (60% dispersion in oil, 2 eq). When H2 evolution ceased (5 min), p-methoxybenzyl
chloride (1.5 eq) was added dropwise. The reaction mixture was left stirring overnight at
room temperature. The reaction was quenched with ice-water. EtOAc (4 mL/mL of DMF)
was added. The organic phase was washed with water, saturated NaHCO3 and then dried over
MgSO4. After concentration under vacuum, the crude product was purified by flash column
chromatography on silica gel (Pet. Ether/EtOAc 8:2) to afford pure 1b or 2b.
4.4.1. 3-O-p-Methoxybenzyl-1,2:4,6-di-O-isopropylidene- -L-sorbofuranose (1b)
From 1 (100 mg, 0.38 mmol), 1b was obtained as a slightly yellow solid (136 mg,
93%): mp 98-99 °C; [ ]D -18.7 (c 1.86, CHCl3); 1H NMR (250 MHz, CDCl3) 7.29 (d, 2H,
Har, J=8.5 Hz), 6.87 (d, 2H, Har, J=8.75 Hz), 4.71 (d, 1H, CH2OPMB, J=11.8 Hz), 4.61 (d,
1H, CH2OPMB, J=11.8 Hz), 4.26 (dd, 1H, H-4, J4-3=1.8 Hz, J4-5=3.5 Hz), 4.19 (br q, 1H, H-5,
J=3.5 Hz), 4.14 (d, 1H, H-1b, J=9.5 Hz), 4.02 (d, 1H, H-1a, J=9.5 Hz), 3.96 (dd, 1H, H-6b, J6b-
5=3.5 Hz, J6b-6a=12.8 Hz), 3.84 (dd, 1H, H-6a, J6a-5=3.5 Hz, J6a-6b=12.8 Hz), 3.80 (s, 4H,
CH3O, H-3), 1.54 (s, 3H, CH3), 1.48 (s, 3H, CH3), 1.38 (s, 3H, CH3), 1.34 (s, 3H, CH3); 13C
NMR (100 MHz, CDCl3) 159.42 (CIVar), 129.84 (CIVar), 129.61 (Car), 113.85 (Car), 110.94,
110.80 (CIViPr), 97.96 (C-2), 84.55 (C-3), 74.01 (C-4), 73.27 (CH2OPMB), 72.67 (C-1),72.14

(C-5), 60.59 (C-6), 55.31 (CH3O), 28.02, 26.30, 26.12, 20.28 (4CH3); HRMS Calcd for
C20H29O7 [M+H]+ m/z = 381.190780. Found: 381.190771. Found: 398.217264. Calcd for
C20H28NaO7 [M+Na]+ m/z = 403.172724. Found: 403.172306.
4.4.2. 1-O-p-Methoxybenzyl-2,3:4,6-di-O-isopropylidene- -L-sorbofuranose (2b)
From 1 (100 mg, 0.38 mmol), 2b was obtained as a colorless oil (127 mg, 87%):[ ]D
-4.80 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) 7.27 (d, 2H, Har, J=8.4 Hz), 6.86 (d, 2H,
Har, J=8.4 Hz), 4.65 (d, 1H, CH2OPMB, J=11.6 Hz), 4.52 (d, 1H, CH2OPMB, J=11.6 Hz),
4.48 (s, 1H, H-3), 4.29 (d, 1H, H-4, J4-5=2.4 Hz), 4.10-4.07 (m, 1H, H-5), 4.04 (dd, 1H, H-6b,
J6b-5=2.2 Hz, J6b-6a=13.6 Hz), 3.98 (d, 1H, H-6a, J6a-6b=13.6 Hz), 3.79 (s, 3H, CH3), 3.77 (d,
1H, H-1b, J1b-1a=10.8 Hz), 3.69 (d, 1H, H-1a, J1a-1b=10.8 Hz), 1.51 (s, 3H, CH3), 1.41 (s, 3H,
CH3), 1.40 (s, 3H, CH3), 1.29 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) 159.17 (CIVar),
130.37 (CIVar), 129.30 (Car), 114.24 (CIViPr), 113.76 (Car), 112.27 (CIViPr), 97.30 (C-2), 84.37
(C-3), 73.32 (C-4), 73.30 (CH2OPMB), 72.16 (C-5), 69.63 (C-1), 60.40 (C-6), 55.31
(CH3OBn), 28.97, 27.66, 26.60, 18.69 (CH3); HRMS Calcd for C20H32NO7 [M+NH4]+ m/z =
398.217329. Found: 398.217460. Calcd for C20H28NaO7 [M+Na]+ m/z = 403.172724. Found:
403.172497.
4.5. General procedure for selective cleavage of the 4,6-O-isopropylidene group16
H2SO4 on silica was prepared according to the protocol of Mukhopadhyay.15 To a
solution of 1a, 2a, 1b or 2b (1 mmol) in MeOH (5 mL), silica-H2SO4 (100 mg) was added.
The mixture was left stirring at room temperature until completion of the reaction (TLC, 1h-
4h). The suspension was filtered on a membrane and the filtrate was concentrated under
vacuum to give respectively crude 3a, 4a, 3b or 4b. Flash column chromatography on silica
gel (CH2Cl2/MeOH 95:5) afforded the pure products.
4.5.1. 3-O-Acetyl-1,2-O-isopropylidene- -L-sorbofuranose (3a)
From 1a (67 mg, 0.22 mmol), 3a was obtained as a white solid (44 mg, 76%): mp 133-
135 °C; [ ]D -111.4 (c 1.23, MeOH); 1H NMR (400 MHz, CD3OD)
(d, 1H, H-3, J3-4=5.2
Hz), 4.40 (t, 1H, H-4, J4-3=5.2 Hz, J4-5=5.6 Hz), 4.20 (d, 1H, H-1b, J=9.2 Hz), 4.16 ( q, 1H,
H-5, J~5 Hz), 4.05 (d, 1H, H-1a, J=9.2 Hz), 3.75 (dd, 1H, H6b, J5-6b=4.4 Hz, J6a-6b=12.0 Hz),
3.71 (dd, 1H, H6a, J5-6a=5.2 Hz, J6a-6b=12.0 Hz), 2.10 (s, 3H, OAc), 1.44 (s, 3H, CH3), 1.30 (s,
3H, CH3); 13C NMR (100 MHz, CD3OD) 171.90 (C=O), 112.11, 109.58 (CIViPr, C-2), 80.48

(C-5), 80.44 (C-3), 74.77 (C-4), 73.13 (C-1), 61.79 (C-6), 26.49, 26.31 (2xCH3), 20.67
(CH3CO); HRMS Calcd for C11H18NaO7 [M+Na]+ m/z = 285.094474. Found: 285.094838.
4.5.2. 1-O-Acetyl 2,3-O-isopropylidene- -L-sorbofuranose (4a)17,20
From 2a (100 mg, 0.33 mmol), 4a was obtained (30 mg, 34%) along with deacetylated
4 (39 mg, 53%) as yellow oils. 4a: 1H NMR (250 MHz, CD3OD) 4.46 (d, 1H, H-1b, J1b-
1a=11.8 Hz), 4.40 (s, 1H, H-3), 4.28 (ddd, 1H, H-5, J5-4=2.8 Hz, J5-6b=5.0 Hz, J5-6a=6.25 Hz),
4.17 (d, 1H, H-4, J4-5=2.8 Hz), 4.09 (d, 1H, H-1a, J1a-1b=11.8 Hz), 3.80 (dd, 1H, H-6b, J5-
6b=5.0 Hz, J6a-6b=11.8 Hz), 3.74 (dd, 1H, H-6a, J5-6a=6.25 Hz, J6a-6b=11.75 Hz), 2.07 (s, 3H,
OAc), 1.47 (s, 3H, CH3), 1.36 (s, 3H, CH3); 13C NMR (100 MHz, CD3OD) 171.98 (C=O),
113.67, (CIViPr), (C-2), 87.00 (C-3), 83.41 (C-5), 75.76 (C-4), 64.49 (C-1), 61.13 (C-6),
27.72, 26.77 (CH3), 20.75 (CH3OAc).
4.5.3. 2,3-O-Isopropylidene- -L-sorbofuranose (4)11,21
1H NMR (250 MHz, CD3OD) 4.39 (s, 1H, H-3), 4.29 (ddd, 1H, H-5, J5-4=2.8 Hz, J5-
6b=5.3 Hz, J5-6a=6.3 Hz), 4.13 (d, 1H, H-4, J4-5=2.8 Hz), 3.81 (dd, 1H, H-6b, J6b-5=5.3 Hz, Jba-
6b=11.5 Hz), 3.73 (dd, 1H, H-6a, J6a-5=6.3 Hz, J6a-6b=11.5 Hz), 3.68 (s, 2H, 2H-1), 1.48 (s, 3H,
CH3), 1.36 (s, 3H, CH3); 13C NMR (62.5 MHz, CD3OD) 115.54, 113.12 (CIViPr, C-2), 86.79
(C-3), 83.33 (C-5), 75.65 (C-4), 63.78 (C-1), 61.13 (C-6), 27.77, 26.86 (2xCH3).
4.5.4. 3-O-p-Methoxybenzyl-1,2-O-isopropylidene- -L-sorbofuranose (3b)
From 1b (136 mg, 0.36 mmol), 3b was obtained as a white solid (25 mg, 21%): mp
119-120 °C; [ ]D -57.6 (c 0.86, MeOH); 1H NMR (250 MHz, CDCl3) 7.30 (d, 2H, Har, J=8.5
Hz), 6.89 (d, 2H, Har, J=8.7 Hz), 4.74 (d, 1H, CH2OPMB, J=11.8 Hz), 4.68 (d, 1H,
CH2OPMB, J=11.8 Hz), 4.54 (dt, 1H, H-4, J4-5=7.0 Hz, J4-3=6.0 Hz, J4-OH=7 Hz), 4.25 (dt,
1H, H-5, J5-6=3.25 Hz, J4-5=7.0 Hz), 4.05 (d, 1H, H-1, J=9.25 Hz), 3.97 (d, 1H, H-1, J=9.25
Hz), 3.87 (dd, 2H, 2H6, J6-5=3.25 Hz, J6-OH=6.25 Hz), 3.81 (s, 3H, CH3O), 3.77 (d, 1H, H-3,
J3-4 =6.0 Hz), 3.04 (d, 1H, 4-OH, J=7.25 Hz), 2.20 (t, 1H, CH2OH, J=6.5 Hz), 1.51 (s, 3H,
CH3), 1.46 (s, 3H, CH3); 13C NMR (62.5 MHz, CDCl3) 159.53, 129.99 (CIVar), 129.64,
114.04 (Car), 111.70, 108.33 (CIViPr, C-2), 84.37 (C-3), 77.13 (C-4), 76.89 (C-5), 72.12 (C-1),
71.29 (CH2OPMB), 62.07 (C-6), 55.43 (CH3O), 26.74, 26.31 (2xCH3); HRMS Calcd for
C17H28NO7 [M+NH4]+ m/z = 358.186029. Found: 358.185917. Calcd for C17H24NaO7
[M+Na]+ m/z = 363.141424. Found: 363.141514.

4.5.5. 1-O-p-Methoxybenzyl-2,3-O-isopropylidene- -L-sorbofuranose (4b)
From 2b (127 mg, 0.33 mmol), 4b was obtained as a white solid (90 mg, 80%): mp
60-61 °C; [ ]D +4.15 (c 1.42, MeOH); 1H NMR (400 MHz, CDCl3) 7.24 (d, 2H, Har, J=8.5
Hz), 6.86 (d, 2H, Har, J=8.6 Hz), 4.60 (d, 1H, CH2OPMB, J=11.3 Hz), 4.51 (d, 1H,
CH2OPMB, J=11.3 Hz), 4.40 (br s, 1H, H-3), 4.33 (td, 1H, H-5, J4-5=2.8 Hz, J5-6=5.2 Hz),
4.16 (dd, 1H, H-4, J4-5=2.7 Hz, J4-OH= 10.6 Hz), 3.89 (br t, 2H, 2H-6, J5-6=5.6 Hz), 3.84 (d,
1H, OH, J=10.6 Hz), 3.80 (d, 1H, H-1, J=10.0 Hz), 3.79 (s, 3H, CH3O), 3.61 (d, 1H, H-1,
J=10.0 Hz), 2.63 (t, 1H, CH2OH, J=6.1 Hz), 1.50 (s, 3H, CH3), 1.30 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3) 159.63 (CIVar), 129.66 (Car), 128.82 (CIVar), 114.05 (Car), 112.72, 112.41
(CIViPr, C-2), 86.82 (C-3), 81.87 (C-5), 75.31 (C-4), 73.67 (CH2OPMB), 71.13 (C-1), 61.09
(C-6), 55.29 (CH3O), 27.23, 26.18 (2xCH3); HRMS Calcd for C17H25NO7[M+H]+ m/z =
341.159480. Found: 341.159301. Calcd for C17H24NaO7 [M+Na]+ m/z = 363.141424. Found:
363.141371.
Acknowledgements
The authors want to thank Pr. Arnaud Tatibouët for the gift of compound 2, the “Ministère de
l’Enseignement Supérieur et de la Recherche” for a PhD fellowship (ABB) and the LABEX
SynOrg (ANR-11-LABX-0029) for financial support.
Supplementary data
Supplementary data associated with this article can be found, in the on-line version, at http://
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