Convenient preparation of L-arabino-hexos-5-ulose derivatives from lactose

Article abstract of DOI:10.1016/j.carres.2003.08.001

2,6-Di-O-benzyl- (9), 2-O-benzyl-3,4-O-isopropylidene- (19), and 2-O-benzyl-6-O-m-chlorobenzoyl-L-arabino-hexos-5-ulose (20) have been prepared using 4′-deoxy-4′-eno- and 6′-deoxy-5′-eno lactose dimethyl acetal derivatives 7 and 14 as key intermediates. The synthesis of enol ethers 7 and 14 has been performed with good yields by base-promoted elimination of acetone or p-toluenesulfonic acid from 2′,6′-di-O- benzyl-, and 6′-O-p-toluenesulfonyl-2,3:5,6:3′,4′-tri-O- isopropylidenelactose dimethyl acetal, respectively. The epoxidation with MCPBA of 7 and 14 in methanol or dichloromethane furnishes C-5′-methoxy and C-5′-m-chlorobenzoyloxy derivatives, easily transformed with good yields into L-arabino 5-ketoaldohexoses 9, 19 and 20.

Full text of DOI:10.1016/j.carres.2003.08.001

Carbohydrate Research 338 (2003) 2349ꢀ2358
/
www.elsevier.com/locate/carres
Convenient preparation of
L
-arabino-hexos-5-ulose derivatives from
lactoseꢀ
Giorgio Catelani,a,* Antonino Corsaro,b Felicia D’Andrea,a Manuela Mariani,a
Venerando Pistara`,b Elisa Vittorinob
a Dipartimento di Chimica Bioorganica e Biofarmacia, Universita` di Pisa, Via Bonanno 33, I-56126, Pisa, Italy
b Dipartimento di Scienze Chimiche, Universita` di Catania, viale A. Doria 6, I-95125 Catania, Italy
Received 19 June 2003; accepted 13 August 2003
Abstract
2,6-Di-O-benzyl- (9), 2-O-benzyl-3,4-O-isopropylidene- (19), and 2-O-benzyl-6-O-m-chlorobenzoyl-
L-arabino-hexos-5-ulose (20)
have been prepared using 4?-deoxy-4?-eno- and 6?-deoxy-5?-eno lactose dimethyl acetal derivatives 7 and 14 as key intermediates.
The synthesis of enol ethers 7 and 14 has been performed with good yields by base-promoted elimination of acetone or p-
toluenesulfonic acid from 2?,6?-di-O-benzyl-, and 6?-O-p-toluenesulfonyl-2,3:5,6:3?,4?-tri-O-isopropylidenelactose dimethyl acetal,
respectively. The epoxidation with MCPBA of 7 and 14 in methanol or dichloromethane furnishes C-5?-methoxy and C-5?-m-
chlorobenzoyloxy derivatives, easily transformed with good yields into
# 2003 Elsevier Ltd. All rights reserved.
L-arabino 5-ketoaldohexoses 9, 19 and 20.
Keywords:
L-arabino-Hexos-5-uloses; Lactose; Ketopyranose glycals; Epoxidation
1. Introduction
sugars, that can be considered as endo- or exo-ketopyr-
anose glycals, respectively.
Monosaccharides having two unprotected carbonyl
functions (dialdoses, diuloses and aldosuloses) have
long been known as intermediates in several degradation
reactions as well as constituents of few naturally
occurring compounds.2 Little attention has, however,
been devoted to the class of hexos-5-uloses (3), the sole
As a part of an ongoing project on the chemical
valorisation of milk-derived sugars,1 we present here a
convenient preparation from lactose of some differently
protected
which have been previously used for the stereoselective
synthesis of 1-deoxy-
-galactostatin8 and epi-inositol.9
L
-arabino-hexos-5-ulose derivatives,14 some of
D
known member of which was, until 20 years ago, the D-
xylo stereoform.3ꢀ6 More recently, these compounds
have attracted attention as synthetic precursors both of
1,5-dideoxy-1,5-iminoalditols7,8
(1-deoxynojirimycin
2. Results and discussion
and its stereo analogues, 4) and cyclitols9,10 (5) (Scheme
1). Two conceptually similar general approaches to
hexos-5-uloses (Scheme 1) are based on the epoxydation
of 4-deoxy-hex-4-enopyranosides11,12 (1) or 6-deoxy-
hex-5-enopyranosides13 (2), two classes of unsaturated
A first approach to 2,6-di-O-benzyl-
ulose (9) was based on the preparation of the enol ether
(Scheme 2) by treatment of 2?,6?-di-O-benzyl-
2,3:5,6:3?,4?-tri-O-isopropylidenelactose dimethyl acetal
(6)15 with t-BuOK in DMF following the method
previously applied11 to the methyl b-galactopyranoside
analogue.
L-arabino-hexos-5-
7
ꢀ See Ref. 1.
The yield of the expected 4?-hexeno derivative 7 was,
however, depressed by the formation of two by-pro-
* Corresponding author. Tel.: ꢁ
050-43-321.
E-mail address: giocate@farm.unipi.it (G. Catelani).
/
39-050-44-074; fax: ꢁ39-
/
ducts, the disaccharide diene 10 and the known16
glucose derivative 11.
D-
0008-6215/03/$ - see front matter # 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2003.08.001

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G. Catelani et al. / Carbohydrate Research 338 (2003) 2349ꢀ2358
/
Scheme 1.
Table 1
Products distributiona in the base-promoted acetone elimina-
tion from 6.
Run
Reaction conditionsb
7
10 11
1
2
3
4
80 8C, 2 h
15 35
50 8C, 1 h
rt, 24 h
rt, 24 h, then Et3NHCl
21 18 55
48 15 12
65 10 15
Under selected reaction conditions (rt, 24 h, Table 1,
run 4) and quenching the reaction with a large excess of
triethylammonium chloride before concentration of the
solvent, 7 was obtained in good yield (65%), after
chromatographic separation from the two side-products
10 (10%) and 11 (15%).
a
Isolated yields after flash chromatography.
In all cases, the same excess of t-BuOK (10 equiv) and the
same concentration of 6 (0.1 M) were used (see Section 3).
b
of the other double bond of the diene 10 was deduced
from the deshielding of the C-6 carbon atom (Dd 8.2
ppm) with respect to that of 7, indicating that the second
elimination of acetone involves the 5,6-O-isopropyli-
dene group rather than the more hindered 3,4 one. It
should also be noted that the formation of 11, caused by
an interglycoside bond cleavage, rather unexpected in
The structure of 7 was firmly confirmed through
NMR analysis; in particular, the hex-4-enopyranoside
ring shows diagnostic 1H parameters very close to those
reported for the corresponding methyl glycoside,11
suggesting also a similar conformational situation, i.e.,
a large preference (ꢀ
/
80%) of the conformer having
three axially oriented substituents.17 The location in 4,5
Scheme 2. (a) t-BuOK, DMF; (b) MCPBA, MeOH; (c) CF3COOH, 4:1 CH3CNÃ
/
water.

G. Catelani et al. / Carbohydrate Research 338 (2003) 2349ꢀ
/2358
2351
the strong basic reaction conditions, was also previously
observed during the LiAlH4 reduction of 2?-oximino
disaccharide derivatives of 6,18 suggesting the presence,
in both cases, of a base-promoted degradative pathway
of the non-reducing ring.
The epoxidation of 7 with MCPBA in methanol led in
67% yield to the diol 8 (Scheme 2), as a result of a C-5?
regioselective and anti-stereoselective ‘‘in situ’’ opening
of an intermediate epoxide formed, in turn, with a
complete stereospecific manner owing to the syn-direct-
ing effect of the free allyl OH group of 7.11 The C-5?
configuration of 8 was not directly attributed, but is
reasonably assigned as (R) by analogy with the product
selective tosylation (TsCl, CH2Cl2Ã
/
Py, rt, 48 h) of the
crude diol 12, available by a two-step, ‘‘one-pot’’
demethoxyisopropylation of
procedure of acetonationꢀ
/
lactose.15 The treatment of 13 with NaH in DMF
followed, after 3 h, by addition of BnBr led directly to
the fully protected hex-5?-enopyranoside 14, as a crystal-
line solid in 78% yield.
The epoxidation of 14 with MCPBA in CH2Cl2 led
with almost quantitative yield to a crude product, the 1H
NMR analysis of which (CD3CN) showed four sepa-
rated doublets characteristic for H-1? at d 5.35, 5.27,
5.19, and 5.14 with relative intensities 60:19:7:14. NMR
parameters of the more abundant component suggested
a structure corresponding to a 5?-C-m-chlorobenzoate
17. We suppose that one of the other three components
of the crude mixture could correspond to the other C-5?
anomer 17, even if any structural determination of the
three minor components was not possible on the basis of
the NMR analysis. An attempt at separation of this
crude mixture through silica gel chromatography led to
recovery of a different product identified as a 4:1
mixture of 6?-O-m-chlorobenzoates 18 (81% yield from
14), evidently arising by a silica gel promoted intramo-
lecular shift of the benzoate group from the anomeric
OH-5? to the primary OH-6? function. The structure of
18 was confirmed by NMR analysis, in particular the
migration of the benzoate group was deduced from the
contemporary 13C NMR deshielding of the C-6? meth-
obtained in the epoxidationꢀ
monosaccharide analogous.11
2,6-Di-O-benzyl- -arabino-hexos-5-ulose (9) was, fi-
nally, obtained by treatment of 8 with CF3COOH in
CH3CNÃwater (50 8C, 14 h) and isolated in high yield
(83%) after separation from -glucose by extraction
with EtOAc. As previously reported,11 9 was present in
/methanolysis of the methyl
L
/
D
CD3CN soln as an anomeric mixture (9a:9b:
/4:1) of
1,4-furanose tautomers.
The second way to
L-arabino-hexos-5-ulose deriva-
tives (Scheme 3) follows the Murphy’s approach13 based
on the epoxidation of a 6-deoxy-hex-5-enopyranoside.
An efficient preparation of the enol ether disaccharide
14 was made starting by the previously unreported 6?-O-
tosylate 13, easily obtained with an overall 73% yield by
Scheme 3. (a) TsCl-Py; (b) BnBr, NaH, DMF; (c) MCPBA, MeOH; (d) BnBr, 18-crown-6, KOH, THF; (e) MCPBA, CH2Cl2; (f)
SiO2 chromatography; (g) CF3COOH; (h) NEt3, 5:1 MeOHÃwater.
/

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G. Catelani et al. / Carbohydrate Research 338 (2003) 2349ꢀ2358
/
ylene (Dd 5.0 ppm) and shielding of the C-5? methine
(Dd 8.7 ppm), with respect to 17.
The 4:1 mixture of 6?-O-m-benzoates 18 was, finally,
hydrolysed with CF3COOH (Scheme 3) in CH3CNÃ
H2O (rt, 1 h) to give, after separation from -glucose
by extraction with EtOAc and chromatography purifi-
cation, 2-O-benzyl-6-O-m-chlorobenzoyl- -arabino-
hexos-5-ulose 20 (80% yield), the NMR spectra of which
revealed that it exists in CD3CNÃD2O exclusively as a
/
It is worthy of note that the expected spontaneous
scission of 18 into the alcohol 11 and the pertinent
dicarbonyl hexose (19) was not observed either during
the chromatographic process or the storage. The for-
mation of a stable glycopyranoside having a C-5
hemiacetal group has been observed in a specific case
by Murphy,13 as an apparent consequence of the pattern
of protecting groups.
D
L
/
mixture of the a- and b-1,4-furanose forms (a/b ratio:
/
7:3) (Scheme 4) analogously to the above described 2,6-
di-O-benzyl derivative 9.
The epoxidationꢀmethanolysis of 14 (Scheme 3), as
/
described above for 7, took place in a manner which was
not completely selective leading, after flash chromato-
graphy, to an approximately 4:1 C-5? anomeric mixture
of 1?,5?-bis-glycosides 15, obtained as the main reaction
products with 70% yield, and to minor amounts (20%)
of the 6?-O-m-chlorobenzoate 18, evidently derived by
the above described transformation over silica of the
benzoates 17, in turn arising from the opening of the
intermediate epoxides by the m-chlorobenzoate present
in the reaction medium.
3. Experimental
3.1. General methods
Melting points were determined with a Kofler hot-stage
apparatus and are uncorrected. Optical rotations were
measured on a Perkinꢀ
/
Elmer 241 polarimeter at 209
/
2 8C. 1H NMR spectra were recorded with a Bruker AC
200 instrument at 200 MHz and with a Varian Unity
Inova instrument at 500 MHz in the stated solvent
(Me4Si was used as the internal standard). 13C NMR
spectra were recorded with a Bruker AC 200 instrument
at 50 MHz. Assignments were made, when possible,
with the aid of DEPT experiments, for comparison with
values for known compounds and applying the known20
additivity rules, and, in the case of anomeric mixtures,
referring to the differences in the peak intensities. All
reactions were followed by TLC on Kieselgel 60 F254
with detection by UV light and/or with ethanolic 10%
phosphomolybdic or sulphuric acid, and heating. Kie-
The stereochemistry at position C-5? of 15, 17 or 18
could not be inferred by routine NMR analysis, owing
to the absence of diagnostic vicinal proton couplings.
The absolute configuration of the two bis-glycosides 15
formed during the epoxidationꢀmethanolysis of 14
/
(Scheme 3) was, however, assigned transforming 8 into
the C-5? anomerically pure (5R)-16 by acetonation
(DMP, TsOH) and verifying (NMR) that it corresponds
to the major constituent of the anomeric mixture of 16
obtained by benzylation of 15.
The mixture of bis-glycosides 16 was, finally, hydro-
lysed as described above for 8, to give with high yield 9
(Scheme 3).
selgel 60 (E. Merck, 70ꢀ
/
230 and 230ꢀ400 mesh,
/
respectively) was used for column and flash chromato-
graphy. Solvents were dried by distillation according to
standard procedure,21 and storage over 4 A molecular
sieves activated at least 24 h at 400 8C. MgSO4 was used
as the drying agent for solns.
In order to obtain differently protected
L-arabino-
˚
hexos-5-ulose derivatives, compound 17 was treated
with Et3N in aq MeOH (Scheme 3), as reported19 for
the hydrolysis of benzoate groups. In these conditions,
the deprotection of the C-5?-hemiacetal OH was fol-
lowed by the loss of the protected
D
-glucose moiety (11)
3.2. Base-promoted acetone elimination from 4-O-(2,6-
di-O-benzyl-3,4-O-isopropylidene-b-D-galactopyranosyl)-
with contemporary formation of the dicarbonyl sugar
19. An identical result was obtained submitting the 6?-
O-benzoate 18 to the same treatment. Evidently, the
presence of NEt3 considerably accelerates the chain-ring
tautomerism of the reducing unit, leading to the
unmasking of the ketone function. The chromato-
graphic separation of the reaction products gave with
acceptable yield (65%) 2-O-benzyl-3,4-O-isopropyli-
2,3:5,6-di-O-isopropylidene-aldehydo-
acetal (6)
D-glucose dimethyl
A soln of 615 (3.84 g, 5.58 mmol) in 55 mL of anhyd
DMF was treated under stirring at rt with solid
commercial t-BuOK (Fluka) (6.26 g, 55.9 mmol). After
24 h stirring, the starting material was consumed (TLC,
dene-
L
-arabino-hexos-5-ulose (19) as an approximately
1:1 hexaneꢀEtOAc, Rf 0.60) and the mixture was
/
11:9 mixture of the two tautomers 19a and 19b (Scheme
4). These bicyclic tautomers, derived from a first
hemiacetalisation of the aldehyde group with OH-6
followed by a second one between the 5-keto group and
the hemiacetalic OH-1, were recently identified by
Murphy13 as the sole components of the tautomeric
equilibrium of 19.
treated with solid triethylammonium chloride (10.4 g,
75.4 mmol), stirred for 20 min and concentrated under
diminished pressure. The residue was partitioned be-
tween brine (120 mL) and CH2Cl2 (120 mL), the water
phase extracted further with CH2Cl2 (4ꢂ20 mL) and
/
the combined organic phases were dried and concen-
trated to dryness to give a crude residue (4.78 g),

G. Catelani et al. / Carbohydrate Research 338 (2003) 2349ꢀ
/2358
2353
Scheme 4.
containing three components with Rf 0.51, 0.41, and
0.12 (TLC, 1:1 hexaneꢀEtOAc). The flash chromato-
graphy of the crude product eluting in the order with 7:3
hexaneꢀEtOAc, 1:1 hexaneꢀEtOAc and 1:4 hexaneꢀ
EtOAc, led to the three following compounds.
hex-4-enose dimethyl acetal (10). Syrup (0.32 g, 10%
yield), [a]D 59.68 (c 0.5, CHCl3); Rf 0.12 (1:1 hexaneꢀ
EtOAc); 1H NMR (200 MHz, CD3CN): d 7.39ꢀ
7.25 (m,
10 H, aromatic H), 5.70 (dd, 1 H, J1?,2? 3.4 Hz, J1?,3? 1.0
Hz, H-1?), 5.41 (t, 1 H, J5,6a J5,6b 7.6 Hz, H-5), 5.16
(dd, 1 H, J3?,4? 4.4 Hz, J4?,6?a J4?,6?b 0.7 Hz, H-4?), 4.82
/
ꢃ
/
/
/
/
/
/
ꢄ
/
ꢄ
/
(d, 1 H, J1,2 7.5 Hz, H-1), 4.76, and 4.68 (AB system, 2
H, JA,B 11.7 Hz, CH2Ph), 4.49 (s, 2 H, CH2Ph), 4.39 (d,
1 H, J2,3 6.3 Hz, H-3), 4.08 (m, 2 H, H-2, H-3?), 4.06 (m,
2 H, H-6a, H-6b), 3.91 (bs, 2 H, H-6?a, H-6?b), 3.80
(ddd, 1 H, J2?,3? 1.2 Hz, H-2?), 2.91 (d, 1 H, J3?,OH 4.5 Hz,
OH-3?), 2.73 (bs, 1 H, OH-6), 3.31, 3.28 (2 s, each 3 H, 2
OMe), 1.36, 1.35 (2 s, each 3 H, CMe2). 13C NMR (50
MHz, CD3CN): d 150.8 (C-4), 148.8 (C-5?), 139.4, 139.3
3.2.1. 4-O-(2,6-Di-O-benzyl-4-deoxy-a-
enopyranosyl)-2,3:5,6-di-O-isopropylidene-aldehydo-
glucose dimethyl acetal (7). Clear syrup, (2.29 g, 65%
yield), [a]D 38.38 (c 1.5, CHCl3); Rf 0.51 (1:1 hexaneꢀ
EtOAc); 1H NMR (200 MHz, CD3CN): d 7.37ꢀ
7.31 (m,
10 H, aromatic H), 5.60 (dd, 1 H, J1?,2? 3.3 Hz, J1?,3? 1.2
Hz, H-1?), 5.18 (m, 1 H, H-4?), 4.67 (s, 2 H, CH2Ph),
4.54, and 4.50 (AB system, 2 H, JA,B 11.8 Hz, CH2Ph),
4.33 (d, 1 H, J1,2 6.3 Hz, H-1), 4.26 (dddd, 1 H, J4,5 3.2
Hz, J5,6a 6.3 Hz, J5,6b 7.4 Hz, H-5), 4.14 (dd, 1 H, H-4),
4.07 (dd, 1 H, J3,4 1.5 Hz, H-3), 3.99 (dd, 1 H, J2,3 5.2
Hz, H-2), 3.95 (ddd, 1 H, J3?,4? 4.9 Hz, J2?,3? 2.7 Hz, H-
L
-threo-hex-4-
D-
ꢃ
/
/
/
(2 aromatic C), 129.3ꢀ127.3 (aromatic CH), 111.0
/
(CMe2), 110.6 (C-5), 105.5 (C-1), 103.3 (C-1?), 96.0 (C-
4?), 78.1, 77.1 (C-2, C-2?), 74.4 (C-3), 72.9, 71.6 (2
CH2Ph), 69.9 (C-6?), 64.3 (C-3?), 57.4 (C-6), 55.3, 54.7 (2
OMe), 27.2, 26.6 (CMe2). Anal. Calcd for C31H40O10:
C, 65.02; H, 7.04. Found: C, 65.16; H, 7.11.
3?), 3.93 (m, 2 H, H-6a, H-6b), 3.92 (m, 2 H, J4?,6?a
ꢄ
/
J4?,6?b 0.3 Hz, H-6?a, H6?b), 3.75 (ddd, 1 H, J2?,4? 1.27 Hz,
H-2?), 3.38, 3.34 (2 s, each 3 H, 2 OMe); 1.36, 1.35, 1.31,
1.30 (4 s, each 3 H, 2 CMe2). 13C NMR (50 MHz,
CD3CN): d 148.8 (C-5?), 139.4, 139.2 (2 aromatic C),
3.3. 4-O-[(5R)-2,6-Di-O-benzyl-5-C-methoxy-a-
arabino-hexopyranosyl]-2,3:5,6-di-O-isopropylidene-
aldehydo- -glucose dimethyl acetal (8)
L-
129.3ꢀ128.4 (aromatic CH), 110.9, 108.8 (2 CMe2),
/
D
106.4 (C-1), 102.5 (C-4?), 99.0 (C-1?), 78.6 (C-5), 78.4 (C-
3), 77.5 (C-2), 77.2 (C-2?), 75.1 (C-4), 73.0, 72.8 (2
CH2Ph), 69.9 (C-6?), 65.6 (C-6), 63.8 (C-3?), 56.7, 54.7 (2
OMe), 27.3, 27.3, 26.8, 25.3 (2 CMe2). Anal. Calcd for
C34H46O11: C, 64.75; H, 7.35. Found: C, 65.11; H, 7.29.
A solution of 7 (3.00 g, 4.76 mmol) in MeOH (30 mL)
was cooled at 0 8C and treated, under stirring, with
commercial (Fluka) 70% MCPBA (1.76 g, 7.16 mmol).
The mixture was slowly warmed at rt, with continuous
stirring until 7 was consumed (3 h, TLC, 1:1 hexaneꢀ
/
3.2.2. 2,3:5,6-Di-O-isopropylidene-aldehydo-
dimethyl acetal (11). Syrup, identical to an authentic
sample,18 (0.26 g, 15% yield), Rf 0.41 (1:1 hexaneꢀ
EtOAc). NMR data were in good agreement with the
reported ones.16
D-glucose
EtOAc); the reaction mixture was made alkaline by
adding satd aq NaHCO3 (10 mL), stirred for 30 min,
concentrated to dryness. The semisolid residue was
partitioned between water (30 mL) and CH2Cl2 (50
/
mL) and the aqueous phase extracted with CH2Cl2 (5ꢂ
/
50 mL); the combined organic extracts were dried
(MgSO4) and concentrated to give a crude residue
(2.87 g). A flash chromatographic purification (1:1
3.2.3. 4-O-(2,6-Di-O-benzyl-4-deoxy-a-
enopyranosyl)-2,3-O-isopropylidene-aldehydo-
L
-threo-hex-4-
-threo-
L

2354
G. Catelani et al. / Carbohydrate Research 338 (2003) 2349ꢀ2358
/
hexaneꢀ
white solid, mp 100ꢀ
(c 0.9, CHCl3); Rf 0.38 (1:1 hexaneꢀ
(200 MHz, CDCl3): d 7.37ꢀ7.26 (m, 10 H, aromatic H),
4.90 (d, 1 H, J1?,2? 7.8 Hz, H-1?), 4.95, and 4.57 (AB
system, 2 H, JA,B 12.2 Hz, CH2Ph), 4.65, and 4.50 (AB
system, 2 H, JA,B 11.4 Hz, CH2Ph), 4.49 (dd, 1 H, J2,3
5.8 Hz, H-2), 4.32 (d, 1 H, J1,2 6.4 Hz, H-1), 4.23 (m, 1
H, H-5), 4.18 (dd, 1 H, J6a,6b 8.5 Hz, J5,6b 5.8 Hz, H-6b),
/
EtOAc) give pure 8 (2.16 g, 67% yield) as a
103 8C (from EtOAc), [a]D 2.18
EtOAc); H NMR
(50 MHz, CD3CN): d 145.6, 133.3 (2 aromatic C),
131.1, 128.8 (aromatic CH), 110.6, 110.5, 109.7 (3
CMe2), 106.1 (C-1), 104.0 (C-1?), 80.0, 78.4, 77.6, 77.9,
77.6 (C-2, C-3, C-5, C-3?), 76.3 (C-4), 74.4, 73.8 (C-2?, C-
4?), 71.3 (C-5?), 69.5 (C-6?), 66.0 (C-6), 56.4, 54.3 (2
OMe), 28.2, 27.5, 27.0, 26.5, 26.4, 25.2 (3 CMe2), 21.7
(MePh). Anal. Calcd for C30H46O14S: C, 54.37; H, 7.00.
Found: C, 54.11; H, 7.10.
/
ꢁ
/
1
/
/
4.06ꢀ
/
3.88 (m, 5 H, H-3?, H-4?, H-3, H-4, H-6a), 3.57,
3.5. 4-O-(2-O-Benzyl-6-deoxy-3,4-O-isopropylidene-a-
L
and 3.50 (AB system, 2 H, JA,B 10.4 Hz, H-6?a, H-6?b),
3.48 (dd, 1 H, J2?,3? 9.5 Hz, H-2?), 2.51 (d, 1 H, J 2.6 Hz,
OH), 2.44 (d, 1 H, J 3.8 Hz, OH), 3.30, 3.28, 3.25 (3 s,
each 3 H, 3 OMe), 1.43, 1.42, 1.41, 1.32 (4 s, each 3 H, 2
CMe2). 13C NMR (50 MHz, CDCl3): d 138.4, 137.7 (2
-arabino-hex-5-enopyranosyl)-2,3:5,6-di-O-
isopropylidene-aldehydo-D-glucose dimethyl acetal (14)
A suspension of pre-washed (hexane) 60% NaH in
mineral oil (637 mg, 16.3 mmol) in dry DMF (20 mL)
was cooled at 0 8C and treated under argon with a soln
of 13 (2.17 g, 3.27 mmol) in dry DMF (15 mL). The
mixture was gently warmed at rt, left under stirring until
aromatic C), 128.5ꢀ127.7 (aromatic CH), 110.0, 108.5 (2
/
CMe2), 105.5 (C-1), 100.5 (C-5?), 98.9 (C-1?), 79.0, 77.7,
77.5 (C-2?, C-3, C-5), 74.6, 74.4 (C-2, C-4), 74.5, 73.4 (2
CH2Ph), 70.1 (C-3?), 69.4 (C-4?), 65.2, 64.9 (C-6, C-6?),
55.7, 52.7 (2 OMe-1), 48.0 (OMe-5), 27.3, 26.6, 26.3,
25.1 (2 CMe2). Anal. Calcd for C35H50O13: C, 61.93; H,
7.42. Found: C, 62.13; H, 7.49.
13 was consumed (3 h, TLC, 3:7 hexaneꢀEtOAc),
/
treated with neat BnBr (0.8 mL, 6.54 mmol) and further
stirred for 45 min. The reaction mixture was cooled at
0 8C, treated with crushed ice (30 mL) and extracted
with Et2O (5ꢂ20 mL); the collected organic extracts
/
3.4. 4-O-(3,4-O-Isopropylidene-6-O-p-toluenesulfonyl-
were dried (MgSO4) and concentrated to give a crude
residue (2.03 g), that was directly subjected to a flash
b-
aldehydo-
D
-galactopyranosyl)-2,3:5,6-di-O-isopropylidene-
D-glucose dimethyl acetal (13)
chromatographic purification, eluting with 7:3 hexaneꢀ
EtOAcꢁ1˜ Et3N, to give pure 14 (1.48 g, 78% yield) as
a white crystalline solid, mp 93ꢀ95 8C (from hexane);
[a]D
EtOAc); H NMR (200 MHz, CD3CN): d 7.37ꢀ
/
/
A crude sample of 12 obtained, as previously de-
scribed,15 by acetonationꢀ
demethoxyisopropylation of
/
/
ꢁ
/
21.98 (c 1.2, CHCl3); Rf 0.28 (7:3 hexaneꢀ
/
1
lactose (6.91 g, 20.2 mmol) was dissolved in a 1:1
mixture of pyridine and CH2Cl2 (66 mL) and treated at
rt under stirring with solid TsCl (4.82 g, 28.0 mmol).
After 24 h the diol 12 was completely consumed (TLC,
/7.30
(m, 5 H, aromatic H), 4.94 (d, 1 H, J1?,2? 7.6 Hz, H-1?),
4.75 (s, 1 H, H-6?a), 4.81, and 4.71 (AB system, 2 H, JA,B
11.9 Hz, CH2Ph), 4.66 (s, 1 H, H-6?b), 4.63 (d, 1 H, J3?,4?
7.0 Hz, H-4?), 4.40 (dd, 1 H, J2,3 7.1 Hz, H-2), 4.38 (d, 1
H, J1,2 6.2 Hz, H-1), 4.22 (m, 1 H, H-5), 4.21 (dd, 1 H,
J2?,3? 7.6 Hz, H-3?), 4.10 (dd, 1 H, J3,4 1.3 Hz, H-3), 4.05
(dd, 1 H, J6a,6b 8.5 Hz, J5,6a 6.1 Hz, H-6a), 3.96 (dd, 1 H,
J4,5 5.3 Hz, H-4), 3.93 (dd, 1 H, J5,6b 6.4 Hz, H-6b), 3.43
3:7 hexaneꢀ
aq NaHCO3 (40 mL), stirred for 15 min and extracted
with CH2Cl2 (4ꢂ50 mL). The organic extracts were
collected, dried (MgSO4) and concentrated by repeated
co-evaporation with toluene (3ꢂ50 mL), the residue
partitioned between CH2Cl2 (40 mL) and water (40 mL),
and the aqueous phase extracted with CH2Cl2 (3ꢂ40
/
EtOAc); the mixture was treated with satd
/
/
(t, 1 H, J1?,2?ꢄJ2?,3? 7.6 Hz, H-2?); 3.41, 3.39 (2 s, each 3
/
/
H, 2 OMe), 1.37, 1.36, 1.35, 1.34, 1.33, 1.28, (6 s, each 3
H, 3 CMe2). 13C NMR (50 MHz, CD3CN): d 154.3 (C-
mL). The organic phases were collected, dried (MgSO4)
and concentrated under diminished pressure. The crude
residue was directly applied to a flash chromatography
5?), 139.4 (aromatic C), 129.1ꢀ127.5 (aromatic CH),
/
111.0, 110.6, 109.2 (3 CMe2), 98.9 (C-6?), 106.7 (C-1),
103.0 (C-1?), 80.1 (C-2?), 78.5, 78.1, 77.9 (C-3?, C-3, C-4),
76.9, 76.3 (C-2, C-5), 74.17 (2 CH2Ph), 73.9 (C-4?), 66.3
(C-6), 56.5, 54.3 (2 OMe), 27.7, 27.5, 27.2, 26.9, 26.0,
25.5 (3 CMe2). Anal. Calcd for C30H44O11: C, 62.05; H,
7.64. Found: C, 61.85; H, 7.52.
column eluting with 3:7 hexaneꢀ
give pure 13 as a foam solid (9.77 g, 73% yield from
lactose), mp 57ꢀ59 8C, [a]D 15.88 (c 1.1, CHCl3); Rf
0.47 (3:7 hexaneꢀ
EtOAc); 1H NMR (200 MHz,
/
EtOAcꢁ1˜ Et3N to
/
/
ꢁ
/
/
CD3CN): d 7.81, 7.45 (2 d, each 2 H, J 8.1 Hz, aromatic
H), 4.40 (d, 1 H, J1?,2? 8.1 Hz, H-1?), 4.38 (dd, 1 H, J6?a,6?b
12.1 Hz, J5?,6?b 6.2 Hz, H-6?b), 4.32 (dd, 1 H, J5?,6?a 6.4
3.6. 4-O-[(5R)- and/or (5S)-2-O-Benzyl-3,4-O-
isopropylidene-5-C-m-chlorobenzoyloxy-a-L-arabino-
Hz, H-6?a), 4.23 (m, 1 H, H-5), 4.15ꢀ
/
3.91 (m, 8 H, H-3?,
H-4?, H-5?, H-1, H-2, H-3, H-6a, H-6b), 3.84 (dd, 1 H,
J3,4 1.6 Hz, J4,5 4.7 Hz, H-4), 3.30 (ddd, 1 H, J2?,3? 6.9
Hz, J2?,OH 3.1 Hz, H-2?), 3.60 (d, 1 H, OH-2?), 3.38, 3.35
(2 s, each 3 H, 2 OMe), 2.44 (s, 3 H, MePh), 1.39, 1.36,
1.32, 1.31, 1.29, 1.22 (6 s, each 3 H, 3 CMe2). 13C NMR
hexopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-
glucose dimethyl acetal [(5R)- and/or (5S)-17]
D-
A soln of 14 (1.50 g, 2.58 mmol) in dry CH2Cl2 (28 mL)
was treated at 0 8C with a pre-dried (MgSO4) soln of

G. Catelani et al. / Carbohydrate Research 338 (2003) 2349ꢀ
/2358
2355
70% MCPBA (751 mg, 3.05 mmol) in CH2Cl2 (37 mL)
and stirred until the starting material was consumed (2.5
80.3, 78.1, 77.2, 77.0 (C-2?, C-3?, C-3, C-5), 76.8, 75.9,
74.2 (C-4?, C-2, C-4), 73.1 (CH2Ph), 67.9 (C-6?), 65.0 (C-
6), 56.1, 53.7 (2 OMe), 27.3, 27.1, 26.7, 26.5, 24.8, 24.7 (3
CMe2). Anal. Calcd for C37H49ClO14: C, 59.0; H, 6.56.
Found: C, 59.21; H, 6.62.
h, TLC, 3:2 hexaneꢀ/EtOAc). The reaction mixture was
washed with 10% aq Na2S2O3 (3ꢂ/40 mL), dried
(MgSO4) and concentrated to give a mixture (clear
syrup, 189 g, 97% yield) of four products, as judged
through 1H NMR analysis (200 MHz, CD3CN) showing
four separated doublets attributed to H-1? at d 5.35
(J1?,2? 8.5 Hz), 5.27 (J1?,2? 8.3 Hz), 5.19 (J1?,2? 8.4 Hz), and
5.14 (J1?,2? 7.8 Hz) in a 60:19:7:14 ratio. Selected NMR
signals of the more abundant component: 1H NMR (200
MHz, CDCl3): d 5.42 (d, 1 H, J1?,2? 8.5 Hz, H-1?). 13C
3.8. 4-O-[(5R)- and (5S)-2-O-Benzyl-3,4-O-
isopropylidene-5-C-methoxy-a-L-arabino-
hexopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-
glucose dimethyl acetal [(5R)- and (5S)-15]
D-
NMR (50 MHz, CDCl3): d 162.7 (CÄ
/
O), 137.8, 134.4,
A soln of 14 (899 mg, 1.55 mmol) in MeOH (9 mL) was
treated at 0 8C under stirring with a soln of 70%
commercial MCPBA (470 mg, 1.90 mmol) in MeOH
(4 mL), warmed at rt and stirred until the starting
131.8 (3 aromatic C), 133.3ꢀ127.4 (aromatic CH), 110.3,
/
109.6, 108.3 (3 CMe2), 106.9 (C-1), 104.6 (C-5?), 98.7 (C-
1?), 78.2, 78.2, 78.1, 77.8 (C-3, C-5, C-3?, C-2?), 75.4,
73.8, 73.5 (C-2, C-4, C-4?), 73.3 (CH2Ph), 62.1 (C-6?),
65.0 (C-6), 57.3, 54.4 (2 OMe), 27.5, 27.1, 26.5, 26.3,
26.2, 25.2 (3 CMe2).
material was consumed (6 h, TLC, 1:1 hexaneꢀEtOAc).
/
The reaction mixture was neutralised by addition of satd
aq NaHCO3, stirred for 15 min, concentrated and
partitioned between CH2Cl2 (30 mL) and satd aq
NaHCO3 (20 mL). The aqueous phase was extracted
3.7. 4-O-[(5R and (5S)-2-O-Benzyl-6-O-m-
chlorobenzoyl-3,4-O-isopropylidene-5-hydroxy-a-
arabino-hexopyranosyl]-2,3:5,6-di-O-isopropylidene-
aldehydo- -glucose dimethyl acetal (18)
L
-
with CH2Cl2 (3ꢂ35 mL), the combined extracts were
collected, dried (MgSO4) and concentrated to give a
crude reaction product (1.02 g) that was subjected to
/
D
flash chromatography (1:1 hexaneꢀ/EtOAc) to give,
A sample (820 mg) of the above crude product derived
by epoxidation with MCPBA in CH2Cl2 of 14 was
subjected to flash chromatography over silica gel eluting
after a first fraction with Rf 0.30 (1:1 hexaneꢀ
/
EtOAc),
corresponding to the 4:1 mixture of 6-O-m-chloro-
benzoates 18 (239 mg, 20% yield), a 4:1 mixture of the
title compounds (686 mg, 70% yield) as a colourless
with 1:1 hexaneꢀ
4:1 mixture of (5?R and 5?S)-18 (580 mg, 81% yield
from 14) as a colourless syrup, [a]D 33.38 (c 1.5,
CHCl3); Rf 0.49 (1:1 hexaneꢀEtOAc); NMR data of the
major component: H (500 MHz, CDCl3): d 8.03, 7.94,
7.55 (3 m, each 1 H, aromatic H), 7.41ꢀ7.25 (m, 6 H,
/EtOAc recovering an approximately
syrup, [a]D
ꢁ
/
2.28 (c 1.4, CHCl3); Rf 0.20 (1:1 hexaneꢀ
/
ꢃ
/
EtOAc); selected 1H NMR (200 MHz, CD3CN) signals:
(5R)-15: d 4.83 (d, 1 H, J1?,2? 8.3 Hz, H-1?), 4.81, and
4.68 (AB system, 2 H, JA,B 12.1 Hz, CH2Ph), 4.11 (dd, 1
H, J6a,6b 8.7 Hz, J5,6b 5.2 Hz, H-6b), 3.93 (dd, 1 H, J5,6a
6.3 Hz, H-6a), 3.90 (dd, 1 H, J3,4 1.3 Hz, J4,5 5.5 Hz, H-
4), 3.70, and 3.48 (AB system, 2 H, JA,B 12.2 Hz, H-6?a,
H-6?b), 3.27 (dd, 1 H, J2?,3? 7.0 Hz, H-2?), 3.39, 3.38, 3.33
(3 s, each 3 H, 3 OMe); (5S)-15: d 4.94 (d, 1 H, J1?,2? 8.4
Hz, H-1?), 4.74 (s, 2 H, CH2Ph), 4.54 (dd, 1 H, J1,2 6.5
Hz, J2,3 7.4 Hz, H-2), 3.85 (dd, 1 H, J6a,6b 8.5 Hz, J5,6a
5.9 Hz, H-6a), 3.82 (dd, 1 H, J3,4 1.4 Hz, J4,5 6.8 Hz, H-
4), 3.65, and 3.43 (AB system, 2 H, JA,B 12.7 Hz, H-6?a,
H-6?b), 3.35 (m, 1 H, H-2?), 3.40, 3.37, 3.32 (3 s, each 3
H, 3 OMe). 13C NMR (50 MHz, CD3CN): (5R)-15: d
139.6 (aromatic C), 110.2, 110.1, 109.2 (3 CMe2), 106.9
(C-1), 100.6 (C-5?), 98.7 (C-1?), 80.5 (C-2?), 79.0, 78.8,
78.5, (C-3?, C-3, C-5), 76.1, 76.4, 75.8 (C-4?, C-2, C-4),
74.3 (CH2Ph), 66.1 (C-6), 60.0 (C-6?), 56.8, 54.1 (2 OMe-
1), 48.7 (OMe-5); (5S)-15: d 137.4 (aromatic C), 111.7,
110.4, 110.1 (3 CMe2), 106.9 (C-1), 100.8 (C-1?), 100.7
(C-5?), 80.5 (C-2?), 78.5, 78.0, 77.4 (C-3?, C-3, C-5), 76.6,
76.2, 75.0 (C-4?, C-2, C-4), 73.6 (CH2Ph), 66.8 (C-6),
62.4 (C-6?), 56.9, 54.5 (2 OMe-1), 50.1 (OMe-5). Clusters
/
1
/
aromatic H), 5.21 (d, 1 H, J1?,2? 8.0 Hz, H-1?), 4.82, and
4.76 (AB system, 2 H, JA,B 12.0 Hz, CH2Ph), 4.57 (dd, 1
H, J1,2 6.5 Hz, J2,3 7.5 Hz, H-2), 4.65, and 4.37 (AB
system, 2 H, JA,B 11.5 Hz, H-6?a, H-6?b), 4.34 (d, 1 H,
H-1), 4.30 (m, 2 H, H-3?, H-5), 4.17 (dd, 1 H, J6a,6b 9.0
Hz, J5,6b 5.7 Hz, H-6b), 4.14 (d, 1 H, J3?,4? 5.5 Hz, H-4?),
4.07 (dd, 1 H, J3,4 1.5 Hz, H-3), 3.97 (dd, 1 H, J5,6a 6.5
Hz, H-6a), 3.93 (dd, 1 H, J4,5 5.5 Hz, H-4), 3.41 (dd, 1
H, J2?,3? 5.5 Hz, H-2?), 3.44, 3.43 (2 s, each 3 H, 2 OMe),
1.88 (bs, 1 H, OH), 1.42, 1.41, 1.40, 1.34, 1.32, 1.31 (6 s,
each 3 H, 3 CMe2). 13C (50 MHz, CDCl3): d 165.4 (CÄ
O), 138.1, 134.5, 131.4 (3 aromatic C), 133.2ꢀ126.9
/
/
(aromatic CH), 109.9, 109.7, 108.6 (3 CMe2), 106.3 (C-
1), 97.8 (C-1?), 95.9 (C-5?), 78.8, 78.1, 77.5, 77.0 (C-2?, C-
3?, C-3, C-5), 75.9, 75.4, 75.2 (C-4?, C-2, C-4), 73.4
(CH2Ph), 67.1 (C-6?), 65.6 (C-6), 56.2, 54.1 (2 OMe),
27.6, 27.2, 26.6, 26.5, 26.2, 25.2 (3 CMe2). Selected
NMR data of the minor component: 1H (500 MHz,
CDCl3): d 5.19 (d, 1 H, J1?,2? 6.7 Hz, H-1?). 13C (50
MHz, CDCl3): d 164.5 (CÄ
aromatic C), 133.2ꢀ126.9 (aromatic CH), 110.7, 110.0,
108.1 (3 CMe2), 105.2 (C-1), 99.6 (C-1?), 95.1 (C-5?),
/
O), 138.1, 134.3, 131.4 (3
of signals for both anomers: d 129.0ꢀ
CH), 28.3ꢀ25.5 (CMe2). Anal. Calcd for C31H48O13: C,
59.22; H, 7.70. Found: C, 59.01; H, 7.60.
/
128.4 (aromatic
/
/

2356
G. Catelani et al. / Carbohydrate Research 338 (2003) 2349ꢀ2358
/
3.9. 4-O-[(5R)-2,6-Di-O-benzyl-3,4-O-isopropylidene-5-
C-methoxy-a- -arabino-hexopyranosyl]-2,3:5,6-di-O-
isopropylidene-aldehydo-D-glucose dimethyl acetal [(5R)-
mixture shown for the major constituent spectral para-
meters identical to those of (5R)-16 and the following
selected signals for (5S)-16: 1H NMR (200 MHz,
L
16]
CD3CN): d 7.57ꢀ7.23 (m, 10 H, aromatic H), 4.96 (d,
/
0
0
1 H, J1 ;2 8.3 Hz, H-1?), 4.77, and 4.71 (AB system, 2 H,
JA,B 11.3 Hz, CH2Ph), 4.60, and 4.50 (AB system, 2 H,
JA,B 11.8 Hz, CH2Ph), 3.79 (dd, 1 H, J3,4 1.4 Hz, J4,5 6.8
Hz, H-4), 3.63, and 3.53 (AB system, 2 H, JA,B 10.7 Hz,
H-6?a, H-6?b), 3.44, 3.33, 3.32 (3 s, each 3 H, 3 OMe).
13C NMR (50 MHz, CD3CN): d 139.7, 139.4 (2
A soln of 8 (182 mg, 0.27 mmol) in 2,2-dimethoxypro-
pane (3 mL) was treated with p-TsOH (5 mg), stirred at
rt until the starting material was consumed (1 h, TLC,
1:1 hexaneꢀEtOAc), treated with Et3N (0.2 mL) and
/
concentrated under diminished pressure. Flash chroma-
tographic purification of the crude residue (2.03 g),
aromatic C), 129.2ꢀ128.4 (aromatic CH), 111.4, 110.5,
/
eluting with 3:2 hexaneꢀ
/
EtOAcꢁ
/
1˜ Et3N, gave pure
109.2 (3 CMe2), 106.9 (C-1), 100.8 (C-5?), 100.7 (C-1?),
80.7 (C-2?), 78.8, 78.5, 78.4, 77.4 (C-3?, C-2, C-3, C-5),
74.9, 74.3 (C-4?, C-4), 74.3, 73.6 (2 CH2Ph), 70.6 (C-6?),
66.9 (C-6), 56.6, 54.4 (2 OMe-1), 50.1 (OMe-5). Anal.
Calcd for C38H54O13: C, 63.49; H, 7.57. Found: C,
63.47; H, 7.60.
(5R)-16 (172.5 mg, 92% yield) as a syrup, Rf 0.52 (1:1
1
hexaneꢀ
/
EtOAc); [a]D
ꢁ
/
22.18 (c 1.6, CHCl3); H NMR
(200 MHz, CD3CN): d 7.38ꢀ
/7.29 (m, 10 H, aromatic
H), 4.81 (d, 1 H, J1?,2? 8.4 Hz, H-1?), 4.82, and 4.67 (AB
system, 2 H, JA,B 12.1 Hz, CH2Ph), 4.56, and 4.49 (AB
system, 2 H, JA,B 12.0 Hz, CH2Ph), 4.30 (m, 2 H, H-1,
H-2), 4.21 (m, 1 H, H-5), 4.09 (dd, 1 H, J6a,6b 8.6 Hz,
J5,6b 5.7 Hz, H-6b), 4.12 (d, 1 H, H, J3?,4? 2.2 Hz, H-4?),
4.10 (dd, 1 H, J2?,3? 5.4 Hz, H-3?), 4.02 (dd, 1 H, J2,3 7.3
Hz, J3,4 1.3 Hz, H-3), 3.91 (dd, 1 H, J5,6a 6.3 Hz, H-6a),
3.83 (dd, 1 H, J4,5 5.6 Hz, H-4), 3.65, and 3.40 (AB
system, 2 H, JA,B 10.5 Hz, H-6?a, H-6?b), 3.30 (m, 1 H,
H-2?), 3.31, 3.27, 3.26 (2 s, each 3 H, 2 OMe), 1.34, 1.33,
1.31, 1.27, 1.26, 1.23 (6 s, each 3 H, 3 CMe2). 13C NMR
(50 MHz, CD3CN): d 139.6, 139.2 (2 aromatic C),
3.11. 2,6-Di-O-benzyl-L-arabino-hexos-5-ulose (9)
A 4:1 anomeric mixture of 16 (728 mg, 1.01 mmol) was
dissolved in 4:1 (v/v) CH3CNꢀwater (15 mL), treated
/
with 90% aq CF3COOH (1.5 mL) and warmed at 50 8C
for 16 h. The soln was concentrated under diminished
pressure and repeatedly co-evaporated with toluene
(3ꢂ20 mL). The crude residue was extracted three
/
times with EtOAc (50 mL) and the turbid solns were
filtered, collected, dried (MgSO4) and concentrated to
give pure 9 (299 mg, 83% yield), having NMR para-
meters identical to those of a sample previously pre-
pared by us,11 and constituted by an approximately 4:1
mixture of a- and b-1,4-furanose anomers.
129.6ꢀ128.4 (aromatic CH), 111.4, 110.0, 109.2 (3
/
CMe2), 106.7 (C-1), 100.2 (C-5?), 98.6 (C-1?), 80.5 (C-
2?), 78.8, 78.5, 77.9 (C-3?, C-3, C-5), 76.6, 76.1, 76.0 (C-
4?, C-2, C-4), 74.3, 74.9 (2 CH2Ph), 66.9, 66.1 (C-6?, C-
6), 48.6 (OMe-5), 56.6, 53.7 (2 OMe-1), 28.3, 27.6, 27.0,
26.9, 26.7, 25.6 (3 CMe2). Anal. Calcd for C38H54O13: C,
63.49; H, 7.57. Found: C, 63.58; H, 7.63.
The treatment with an identical procedure of pure 8
led to 9 in analogous yield.
3.10. 4-O-[(5R)- and (5S)-2,6-Di-O-benzyl-3,4-O-
isopropylidene-5-C-methoxy-a-
3.12. 2-O-Benzyl-5-C-hydroxy-3,4-O-isopropylidene-
1,6-anhydro-b-L-talopyranose (19a) and 2-O-benzyl-5-C-
hydroxy-3,4-O-isopropylidene-1,6-anhydro-b-D-
galactopyranose (19b)
L
-arabino-
hexopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-
glucose dimethyl acetal [(5R)- and (5S)-16]
D-
A 4:1 mixture of 15 (1.00 g, 1.59 mmol) was dissolved in
wet THF (10 mL) and the soln was treated with 18-
crown-6 (10 mg) and crushed KOH (712 mg, 12.7
mmol). The mixture was stirred at rt for 1 h, treated
with BnBr (0.38 mL, 3.20 mmol) and stirred until the
A 4:1 mixture of crude m-chlorobenzoates 17 (324 mg,
0.45 mmol) was dissolved in 5:1 MeOHꢀwater (5 mL),
treated at rt with Et3N (1.5 mL) and stirred until the
starting material was consumed (3 h, TLC, 1:1 hexaneꢀ
EtOAc). The reaction mixture was concentrated under
diminished pressure and the residue partitioned between
EtOAc (25 mL) and water (10 mL). The organic phase
was dried (MgSO4), concentrated and submitted to
/
/
starting material was consumed (2 h, TLC, 1:1 hexaneꢀ
/
EtOAc). MeOH (2 mL) was added, the soln stirred for
15 min, concentrated under diminished pressure and the
residue partitioned between CH2Cl2 (50 mL) and H2O
(25 mL). The aqueous phase was extracted with CH2Cl2
column chromatography (9:1 CH2Cl2ꢀEt2O) to give in
/
the order an approximately 9:11 mixture (NMR im-
mediately after dissolution) of the title compounds as a
clear syrup (86 mg, 65% yield) and 11 (170 mg,
quantitative yield). The treatment with an identical
procedure of pure 18 led to 19 in analogous yield.
Some of the following NMR signals closely corre-
sponded to those reported by Murphy.13
(3ꢂ
concentrated and the crude residue (1.24 g) subjected
to flash chromatography (7:3 hexaneꢀEtOAc) to give an
approximately 4:1 anomeric mixture of 16 (1.04 g, 91%
yield) as a syrup, [a]D 12.78 (c 1.1, CHCl3); Rf 0.54
(1:1 hexaneꢀEtOAc); NMR analysis of the crude
/50 mL), the organic extracts collected, dried,
/
ꢁ
/
/

G. Catelani et al. / Carbohydrate Research 338 (2003) 2349ꢀ
/2358
2357
3.12.1. NMR signals of 19a. 1H NMR (200 MHz,
CDCl3): d 7.38ꢀ7.24 (m, 5 H, aromatic H), 5.42 (d, 1
H, J1,2 2.7 Hz, H-1), 4.79, and 4.60 (AB system, 2 H,
JA,B 12.0 Hz, CH2Ph), 4.43 (dd, 1 H, H-3), 4.31 (d, 1 H,
J3,4 6.7 Hz, H-4), 3.86, and 3.62 (AB system, 2 H, JA,B
8.1 Hz, H-6a, H-6b), 3.48 (dd, 1 H, J2,3 4.6 Hz, H-2),
1.53, 1.34 (2 s, each 3 H, CMe2). 13C NMR (50 MHz,
aromatic H), 7.34ꢀ7.25 (m, 6 H, aromatic H), 5.48 (d, 2
/
/
H, J1,2 3.5 Hz, H-1), 5.36, and 5.21 (AB system, 2 H,
JA,B 18.0 Hz, H-6a, H-6b), 4.57 (s, 2 H, CH2Ph), 4.44
(dd, 1 H, J2,3 3.7 Hz, J3,4 4.0 Hz, H-3), 4.29 (d, 1 H, H-
4); 3.77 (dd, 1 H, H-2). 13C NMR (50 MHz, CD3CNꢀ
/
D2O): d 205.3 (C-5), 165.6 (CÄ
/
O), 138.5, 135.1, 132.4 (3
aromatic C), 134.2ꢀ128.8 (aromatic CH), 98.6 (C-1),
/
CDCl3): d 137.3 (aromatic C), 128.4ꢀ
/
126.9 (aromatic
87.0 (C-4), 82.9 (C-2), 76.7 (C-3), 72.9 (CH2Ph), 68.8 (C-
6).
Anal. Calcd for C20H19ClO7: C, 59.05; H, 4.71.
Found: C, 58.89; H, 4.68.
CH), 111.6 (CMe2), 100.9 (C-5), 99.9 (C-1), 78.7, 78.0,
76.8 (C-2, C-3, C-4), 71.4, 69.2 (C-6, CH2Ph), 27.4, 26.2
(CMe2).
3.12.2. NMR signals of 19b. 1H NMR (200 MHz,
CDCl3): d 7.38ꢀ
H, H-1), 4.71, and 4.60 (AB system, 2 H, JA,B 11.5 Hz,
CH2Ph), 4.40ꢀ4.33 (m, 2 H, H-3, H-4), 4.16 (d, 1 H,
J6a,6b 7.8 Hz, H-6b), 3.61 (d, 1 H, J2,3 0.9 Hz, H-2), 3.25
(dd, 1 H, J4,6a 1.5 Hz, H-6a), 1.45, 1.38 (2 s, each 3 H,
CMe2). 13C NMR (50 MHz, CDCl3): d 137.0 (aromatic
/
7.24 (m, 5 H, aromatic H), 5.48 (s, 1
Acknowledgements
/
This work was performed with funds provided by
Consorzio Interuniversitario Nazionale La Chimica
per l’Ambiente (INCA) within the project ‘‘Ambiente
Terrestre: Chimica per l’Ambiente’’ financed in accor-
dance with law n. 488/92. Partial support to G.C. from
University of Pisa is also acknowledged.
C), 128.4ꢀ126.9 (aromatic CH), 108.8 (CMe2), 101.9 (C-
/
5), 100.8 (C-1), 77.5, 76.4, 75.1 (C-2, C-3, C-4); 72.1
(CH2Ph), 65.8 (C-6), 25.9, 24.1 (CMe2).
3.13. 2-O-Benzyl-6-O-m-chlorobenzoyl-L-arabino-
hexos-5-ulose (20)
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