An expedient synthesis of L-ribulose and derivatives

Article abstract of DOI:10.1016/j.carres.2011.01.013

A significant improvement in the production of l-ribulose from inexpensive and commercially available starting materials, l-arabinose and sodium aluminate, is demonstrated. This has facilitated expeditious access to gram-scale quantities of l-ribulofurano

Full text of DOI:10.1016/j.carres.2011.01.013

Carbohydrate Research 346 (2011) 703–707
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
An expedient synthesis of L-ribulose and derivatives
⇑
Geeta Meher, Ramanarayanan Krishnamurthy
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A significant improvement in the production of L-ribulose from inexpensive and commercially available
Received 17 November 2010
Received in revised form 24 December 2010
Accepted 13 January 2011
starting materials,
L
-arabinose and sodium aluminate, is demonstrated. This has facilitated expeditious
-ribulofuranoside derivatives.
Ó 2011 Elsevier Ltd. All rights reserved.
access to gram-scale quantities of
L
Available online 31 January 2011
Keywords:
L
L
L
L
-Ribulose
-Nucleosides
-Sugars
-Arabinose
1. Introduction
practical method for a large-scale chemical synthesis of L-ribulose,
while satisfying the needs in our etiological pursuit, would be
beneficial.
In the ongoing work on the search for potentially natural struc-
tural alternatives to RNA and DNA in the context of a ‘Chemical
Etiology of Nucleic Acid Structure’, an approach pioneered and sys-
tematically implemented by Eschenmoser,1 we needed a quick and
L
-Ribulose is produced from
zation using -arabinose isomerase (
ribitol has also been used as a precursor.11
chemically synthesized by the base-catalyzed isomerization of
D
-arabinose using pyridine (in ca. 20% yield).12 For our needs,
L
-arabinose by enzymatic isomeri-
-AI).9 Apart from
-arabinose,
-Ribulose has been
L
L
L
D
efficient access to large quantities of L L-erythropentulose,
-ribulose2 (
1, Fig. 1). We also realized that this investigation, though initiated
in an etiological context, has an augmented significance because
this method was not suitable because of low conversion (recov-
ery of 65% of starting material) and a lengthy purification pro-
of the demonstrated and potential applications of
-nucleosides4 in the area of chemotherapeutics. From that point of
view, we detail here a noteworthy enhancement to the production
of -ribulose from -arabinose, and describe the preparation of its
derivatives.
-Sugars are used as low-calorie sweeteners,3 and interest in
-nucleosides have greatly increased in recent years. -Nucleosides
L
-sugars3 and
L
cedure.
starting from
monohydrate.2
More recently,
the base-catalyzed isomerization of
D
-Ribulose has also been synthesized in ca. 20% yield
D
-arabinose via pentose-2-ulose using cupric acetate
L
L
L
-ribulose has been synthesized in 64% yield by
-arabinose using freshly pre-
L
L
L
L
pared aluminate solution, followed by bromination to remove
unreacted aldose from the reaction mixture (Scheme 1).13 It was
also reported by the same group that the addition of aluminum
oxide to boiling pyridine solution of aldoses increases the rate of
aldose–ketose transformation.14
have significant applications in antiviral, antimalarial, and antitu-
mour chemotherapy.5 For example, some important FDA-approved
L
-nucleosides are lamivudine (
as an anti-hepatitis B and an anti-HIV agent,5 telbivudine (
and clevudine5c,7 -FMAU) as anti-HBV, emtricitabine5c,6c (FTC)
as anti-HIV and troxacitabine (TRO) as anti-cancer drugs.8
Despite the enormities of potential applications9 in this context
(e.g., as source of -ribose and -ribonucleosides), the chemistry of
-ribulose has been minimally explored,10 perhaps because of its
L
-b-1,3-oxathiolanylcytosine, 3TC)
L
-dT)6
(
L
CH2OH
O
H
H
OH
L
L
OH
HO
OH
L
HO
HO
O
OH
HO
high cost and limited availability. Therefore, a convenient and
O
OH
20%
OH
CH2OH
17% α-furanose
63% β-furanose
⇑
1
Corresponding author. Tel.: +1 858 784 8520; fax: +1 858 784 9573.
E-mail address: rkrishna@scripps.edu (R. Krishnamurthy).
L-Ribulose is commercially available from ZuCarbTM (500 mg, $495; 2 g, $995) and
Carbosynth Ltd (500 mg, $425).
Figure 1. L-Ribulose (L-erythropentulose); percent composition from Ref. 2a;
c = 0.3 M, 15% v/v D2O. 50 mM acetate buffer, pH 4.0.
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.01.013

704
G. Meher, R. Krishnamurthy / Carbohydrate Research 346 (2011) 703–707
(i) NaAlOa2,
H
O
H2O, 35 oC, 48 h
OH
HO
OH
(ii) Amberlite IR-120 (H+)
H
OH
HO OH
OH
O
HO
HO
H
(iii) Br2, CaCO3
(iv) Dowex-1 (HCO3 )
(v) Amberlite IR-120 (H )
(vi) Dowex-1 (HCO3 )
H
CH2OH
2
-
O
OH
1
64%
HO
+
-
L-Arabinose (0.1 M)
a Freshly prepared NaAlO2 was used. 69% conversionat 35 oC after 40 h (by GC MS analysis).
Scheme 1. Literature procedure for preparation of
L
-ribulose.13
Table 1
the filtrate led to the formation of a solid material instead of the
expected syrupy liquid.
Optimization of reaction conditions for the preparation of L-ribulosea
The 1H NMR data of the crude
L
-ribulose, obtained after Amber-
lite IR-120 (H+) ion-exchange, was identical with that of
-ribulose
reported in the literature.2b The conversion of
-arabinose to
-ribulose was optimized with respect to amount of NaAlO2, con-
Entry NaAlO2
(g)
Deionized water
(mL)
Temp
(°C)
Time
(h)
Conversionb
(%)
D
L
1
2
3
4
5
6
7
1.64
1.64
1.64
1.64
1
60
30
30
30
30
30
30
40
40
55
55
45
45
50
64
64
24
48
24
48
24
77.8
77.8
84.2
86.5
86.0
89.7
91.3
L
centration of L-arabinose, temperature, and time (Table 1). Reduc-
ing the concentration of the reaction volume to half did not affect
the conversion efficiency (entry 2), and translated advantageously
to less water removal during workup. Subsequently for all these
exploratory reactions, 30 mL of deioinzed water was used. When
the temperature was raised to 55 °C (entry 3), after 24 h, the 1H
1
1
a
All reactions were performed on 1 g scale of
% conversion was calculated by the ratio of integration of
L-arabinose.
b
L-arabinose and L-
ribulose (1H NMR in D2O).à
NMR spectrum showed an 84% conversion to
the time (48 h, entry 4) led to only a marginal increase in conver-
sion. A 1:1 wt/wt ratio of -arabinose to NaAlO2 was found to work
L-ribulose; extending
L
2. Results and discussion
equally well (entry 5, Fig. 2). However, lesser amounts of NaAlO2
and lower temperatures led to inefficient conversions. The reaction
carried out at 50 °C for 24 h with 1:1 wt/wt ratio of L-arabinose to
NaAlO2 (entry 7) resulted in about 91% conversion as indicated by
1H NMR spectroscopy (Scheme 2, Fig. 2). The conditions described
in entries 6 and 7 were found to be optimal (circumventing
multiple resin exchanges, water washings, and minimizing the
amount of water), and were used for preparations on larger scales
Due to the relative simplicity, we chose to focus on the prepara-
tion of
tion of
L
-ribulose by the NaAlO2-mediated keto–aldol tautomeriza-
-arabinose (Scheme 1).13 However, after many trials, a
-ribulose was obtained in our hands.
L
maximum yield of only 38% of
L
The procedure was found to be very time consuming due to the re-
moval of the gelatinous precipitate that was formed during acidifi-
cation with Amberlite IR-120 (H+) ion-exchange resin. The yield of
isolated material varied from one run to another probably because
of (a) the varying quality of the NaAlO2 that was prepared from Al
metal and aq sodium hydroxide, and (b) the loss of material in suc-
cessive resin exchanges and washings. Moreover, attempts to scale
up the reaction were rendered impractical due to the need to evap-
orate huge amounts of water accumulated during the workup.
To eliminate the uncertainty posed by the quality of NaAlO2, we
decided to utilize the commercially available material.à A solution
of L-arabinose and commercial NaAlO2 in deionized water was
heated at 40 °C for 64 h. The resulting reaction mixture was treated
with Amberlite IR-120 (H+) to remove the metal ions by ion-
exchange; the pH of the solution was ꢀ2.80. The resin was filtered,
and the filtrate was evaporated to dryness to obtain a syrupy liquid.
Gratifyingly, 1H NMR (in D2O) of this residue showed ca. 78% conver-
sion of L-arabinose to L-ribulose (entry 1 of Table 1).
The use of commercially available NaAlO2 was found to be very
effective for the aldose–ketose isomerization reaction. Equally
important was the role, and control, of pH during the ion-exchange
treatment. It was observed that a pH of ꢀ2.80 resulted in a clear
solution with none of the vexing gelatinous precipitation present.
This enabled the easy filtration of the solution within a matter of
minutes (instead of hours). When the pH of the solution was
around neutral (apart from the filtration problem), evaporation of
(5–20 g). The quality of crude
to be satisfactory for further use.
Treatment of the crude -ribulose (containing traces of L-arabi-
L-ribulose thus obtained was found
L
nose) with 1% HCl in anhyd MeOH (w/w) following Tipson’s proce-
dure12 led to a residue containing an anomeric mixture of methyl
L
-erythro-pentulofuranosides15 (3) that was used in subsequent
steps without purification. Benzoylationof this residue with benzoyl
chloride in pyridine gave, after column chromatography, a mixture
of
enzoylated methyl
spectral data for 4a and 4b was found to be identical that of the
known b and -anomer of 4b was
anomers in the D-series.12 The
a
and b anomers (ratio 35:65 by 1H NMR spectroscopy) of perb-
L
-pentulofuranosides (4)12 (Scheme 3). 1H NMR
a
a
recrystallized from AcOEt–hexanes, and its configuration at the ano-
meric carbon was unambiguously proven by single-crystal X-ray
structure analysis (Fig. 3), which confirmed the structural assign-
ments based on 1H and 13C NMR spectral data. This three-step proto-
col proved amenable to scale-up; for example, starting from 5 to 15 g
of
mixture of
70–73% yield per step starting from
The crude methyl -erythro-pentulofuranoside (3) could be
perbenzylated under standard conditions to produce 1,3,5-tri-O-
benzyl derivative 5 as a mixture of and b anomers (Scheme 3),
which was also amenable to scale-up. For example, starting from
5 g of
-arabinose (2), we obtained about 6 g of 5 in ꢀ44% overall
yield, which corresponds to an average of 76% yield per step.
In conclusion, an expedient and convenient access to -ribulose
(ca. 90% conversion starting from -arabinose) using commercially
L
-arabinose (2), we could prepare about 5–18 g of compound 4 as a
and b anomers (4a and 4b) in overall yield of 34–40% (av
-arabinose).
a
L
L
a
L
à
L
See Supplementary data. All new compounds were fully characterized by
spectroscopic methods.
L

G. Meher, R. Krishnamurthy / Carbohydrate Research 346 (2011) 703–707
705
Figure 2. Comparison of 1H NMR spectra of authentic
L-ribulose and crude L-ribulose from entries 5 and 7 of Table 1 (peaks from L-arabinose are indicated by arrows).
H
O
(i) 1:1 (wt./wt.) NaAlOa2,
H2O, 50 oC, 24 h
OH
HO
OH OH OH
OH
O
H
HO
HO
OH
H
H
(ii) Amberlite
O
OH
IR-120 (H+) ion exchange
α/β
CH2OH
HO
1
2
b
≈
91% conversion
L-Arabinose (0.22 M)
a
NaAlO
2 wasused (contained8% water)
Commercial
b % Conversioncalculation based on 1H NMR spectroscopy(in D2O).
Scheme 2. Improved procedure for the conversion of L-arabinose to L-ribulose.
available NaAlO2 has been demonstrated. This has enabled the syn-
thesis of derivatives of -ribulose in large quantities. The chemistry
of -ribulose and its derivatives is under investigation.
77.23 ppm, respectively. 1H NMR chemical shifts in D2O were ref-
erenced to HOD at 4.80 ppm. Mass analysis was performed on an
Agilent ESI-TOF mass spectrometer at an ESI voltage of 4000 V
L
L
and a flow rate of 200
3.2. Conversion of -arabinose to
-Arabinose (2, 5.000 g, 33.33 mmol) was added to a solution of
lL/min.
3. Experimental
L
L-ribulose
3.1. Methods and materials
L
commercial available NaAlO2 (5.000 g) dissolved in 300 mL of
deionized H2O. The resulting solution was heated at 45 °C for
48 h. The reaction mixture was cooled to room temperature and
treated with excess of Amberlite IR-120 (H+) resin to exchange
the metal ions (until there was no further change in the pH); the
pH of the solution after ion-exchange was ꢀ2.80. The solution
was filtered and the filtrate was concentrated under vacuum to ob-
tain a syrupy colorless liquid. This syrupy liquid was kept under
vacuum (over P2O5) to obtain 4.295 g of a residue containing crude
All reagents and solvents were obtained from commercial
sources and used without purification. L(+)-Arabinose was pur-
chased from Sigma–Aldrich Chemical Co.; NaAlO2 (contained 8%
H2O) was obtained from Fisher Scientific Co. Pre-coated flexible sil-
ica gel TLC F254 plates were obtained from Whatman Ltd. Flash
chromatography was performed using Silica Gel 60 (40–60 lm)
from Fisher Scientific Co. 1H and 13C NMR spectra were recorded
on a Bruker DRX-600 instrument at 600 MHz for proton and
150 MHz for carbon, respectively. 1H and 13C NMR chemical shifts
in CDCl3 were referenced to chloroform at 7.26 ppm and
L-ribulose (1) (with ꢁ10% of
L-arabinose), which was used in the
next step without further purification.

706
G. Meher, R. Krishnamurthy / Carbohydrate Research 346 (2011) 703–707
reaction mixture was evaporated to dryness in vacuo, and the res-
5a β (71%)
5b α (29%)
idue was partitioned between CH2Cl2 (300 mL) and H2O (300 mL).
The organic layer was separated, washed successively with satd aq
KHSO4 (3 ꢂ 100 mL), H2O (2 ꢂ 100 mL), satd aq NaHCO3
(2 ꢂ 100 mL), H2O (100 mL), and finally with brine solution
(100 mL). The organic layer was dried over anhyd MgSO4 and con-
centrated in vacuo to obtain 11.0 g of a crude mixture of anomers
OBn
OMe
O
41-44%
(over 3 steps from 2)
BnO
NaH, BnBr
anhyd DMF, rt, 5 h
OBn
of methyl 1,3,4-tri-O-benzoyl-L-erythro-pentulofuranosides (4).
The residue was subjected to column chromatography (silica gel,
3–8% AcOEt–hexanes) to obtain 3.73 g of the b anomer 4a as syrup,
CH2OH
OH
HO
OH
OH
OMe
O
O
H
H
1% HCl
O
(anhyd MeOH)
HO
HO
0.876 g of the
a anomer 4b as white solid and 0.733 g of a mixture
HO
3(α/β)
rt, 1 h
(4a + 4b). The overall yield of 4 from
L
-arabinose over the three
CH2OH
1
HO
steps was 5.341 g (33.6%). The 1H NMR spectra of both the anomers
were found to be identical to the ones reported in the literature for
the D-series.12
OH
crude residue
crude L-ribulose
OBz
OMe
O
BzCl, Py
-15 oC, 1 h
3.3.1. Methyl 1,3,4-tri-O-benzoyl-b-L-erythro-pentulofuranoside
BzO
(4a)
4a β (65%)
34-39%
Syrupy liquid; Rf 0.47 (20:80 AcOEt–hexanes); ½a D24
ꢃ
+96.5 (c 1.0,
OBz
4b α (35%)
(over 3 steps from 2)
CHCl3). 1H NMR (600 MHz, CDCl3): d 3.40 (s, 3H, OMe), 4.16 (dd,
J = 10.2, 4.8 Hz, 1H, H-5), 4.46 (d, J = 12.0 Hz, 1H, H-1), 4.48 (dd,
J = 10.2, 6.6 Hz, 1H, H-50), 4.92 (d, J = 12.6 Hz, 1H, H-10), 5.85 (d,
J = 5.4 Hz, 1H, H-3), 5.84–5.89 (m, 1H, H-4), 7.27–7.30 (m, 2H,
arom.), 7.34–7.40 (m, 4H, arom.), 7.46–7.50 (m, 1H, arom.), 7.50–
7.54 (m, 2H, arom.), 7.80–7.84 (m, 2H, arom.), 7.94–8.00 (m, 4H,
arom.); 13C NMR (150 MHz, CDCl3): d 49.3 (OMe), 59.3 (C-1), 70.7
(C-5), 72.9 (C-4), 75.6 (C-3), 107.2 (C-2), 128.6, 128.6, 128.7,
129.3, 129.4, 129.6, 129.8, 129.9, 130.0, 133.4, 133.5, 133.6,
165.2, 165.9, 166.1 (arom. C); HRMS (ESI-TOF high-acc); calcd for
Scheme 3. Preparation of derivatives of L-ribulose.
C
27H24O8 (M+Na+), m/z 499.1363; found, m/z 499.1361.
3.3.2. Methyl 1,3,4-tri-O-benzoyl-a-L-erythro-pentulofuranoside
(4b)
Colorless blades; TLC: Rf 0.40 (20:80 AcOEt–hexanes); mp 94–
95 °C; ½a 2D4
ꢃ
+121.5 (c 1.0, CHCl3); 1H NMR (600 MHz, CDCl3): d
3.52 (s, 3H, OMe), 4.18 (dd, J = 10.8, 3.6 Hz, 1H, H-5), 4.52 (dd,
J = 10.8, 6.0 Hz, 1H, H-50), 4.57 (d, J = 12.0 Hz, 1H, H-1), 4.64 (d,
J = 11.4 Hz, 1H, H-10), 5.68 (d, J = 6.6 Hz, 1H, H-3), 5.77–5.81 (m,
1H, H-4), 7.27–7.33 (m, 4H, arom.), 7.36–7.41 (m, 2H, arom.),
7.46–7.57 (m, 2H, arom.), 7.52–7.57 (m, 1H, arom.), 7.92–7.98
(m, 4H, arom.), 7.98–8.03 (m, 2H, arom.); 13C NMR (150 MHz,
CDCl3): d 49.8 (OMe), 63.0 (C-1), 70.3 (C-4), 71.2 (C-5), 73.6
(C-3), 103.1 (C-2), 128.5, 128.5, 128.6, 129.3, 129.7, 129.8, 129.9,
130.0, 130.1, 133.3, 133.4, 133.4 (arom. C), 165.6, 166.0 (CO);
Figure 3. Ball-and-stick representation of the X-ray structure of the a-anomer 4b.
3.3. Preparation of methyl 1,3,4-tri-O-benzoyl-L-erythro-
pentulofuranoside (4)
HRMS (ESI-TOF high-acc): calcd for C
27H24O8 (M+Na+), m/z
499.1363; found, m/z 499.1371.
Crude L-ribulose (1, 4.295 g) obtained from the previous step
was dissolved in 260 mL of 1% HCl in anhyd MeOH (w/w), and
the solution was kept at room temperature for 1 h. The excess
HCl was bubbled off with nitrogen sparging. Ag2CO3 (20.62 g,
74.77 mmol) was added to the solution, and the suspension was
stirred at room temperature for 1 h and filtered over a bed of Celite.
The filtrate was evaporated in vacuo to obtain 4.382 g of a residue
3.4. Preparation of anomers of methyl 1,3,4-tri-O-benzyl-
erythro-pentulofuranoside (5)
L-
L-Arabinose 2 (5.000 g, 33.33 mmol) was added to a solution of
commercially available NaAlO2 (5.000 g) dissolved in 150 mL of
deionized H2O. The resulting solution was heated at 50 °C for
24 h. The reaction mixture was cooled to room temperature and
treated with an excess of Amberlite IR-120 (H+) resin to exchange
the metal ions (until there was no further change in the pH); the
pH of the solution after ion-exchange was ꢀ2.80. The solution
was filtered and concentrated under vacuum to obtain a syrupy li-
quid. This syrupy liquid was kept under vacuum over a P2O5 in a
containing an anomeric mixture of methyl L-erythro-pentulofur-
anosides (3) (checked by 1H NMR spectroscopy15). This crude ano-
meric mixture was used in the next step without further
purification.
Crude 3 (4.278 g) was dissolved in anhyd pyridine (30 mL). The
solution was cooled with an ice–salt bath, and benzoyl chloride
(10.3 mL, 89.3 mmol) was added with vigorous stirring. The reac-
tion mixture was stirred in an ice salt bath for 15 min, then further
stirred for 1 h at room temperature and cooled again with the ice–
salt bath. Moist pyridine (40 mL containing few drops of water)
was added, and the solution was stirred for 40 min with ice–salt
bath cooling. Satd aq NaHCO3 (20 mL) was added, and the reaction
mixture was stirred for 30 min with ice–salt bath cooling. The
desiccator to obtain 4.675 g of crude
ꢀ10% of -arabinose), and was used in the next step without any
further purification.
Crude -ribulose (1, 4.675 g) obtained from the previous step
L-ribulose (1) (containing
L
L
was dissolved in 260 mL of 1% HCl in anhyd MeOH (w/w). The solu-
tion was kept at room temperature for 1 h. The excess HCl was
bubbled off with nitrogen sparging. Ag2CO3 (12.00 g, 43.52 mmol)

G. Meher, R. Krishnamurthy / Carbohydrate Research 346 (2011) 703–707
707
was added to the solution, and the suspension was stirred at room
temperature for 1 h and filtered over a bed of Celite. The filtrate
was evaporated under vacuum to obtain 4.700 g of a residue con-
Astrobiology: Exobiology and Evolutionary Biology Program (Grant
NNX07AK18G).
taining a mixture of anomers of methyl L-erythro-pentulofurano-
Supplementary data
sides (3, checked by 1H NMR spectroscopy15), and was used in
the next step without any further purification.
1H NMR spectra for the
L-arabinose to L-ribulose conversion
reactions, 1H and 13C NMR spectra of compounds and X-ray data
for 4b. Complete crystallographic data for the structural analysis
for 4b have been deposited with the Cambridge Crystallographic
Data Centre, CCDC No. 800959. Copies of this information may be
obtained free of charge from the Director, Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
(fax: +44 1223 336033, e-mail: deposit@ccdc.cam.ac.uk or via:
www.ccdc.cam.ac.uk). Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
j.carres.2011.01.013.
A crude mixture of 3 (4.614 g) was dissolved in anhyd DMF
(230 mL). The solution was cooled to 0 °C, followed by addition
of NaH (60% dispersion in oil, 6.752 g, 168.80 mmol) with vigorous
stirring. The reaction mixture was stirred for 30 min at 0 °C, fol-
lowed by dropwise addition of benzyl bromide (30 mL,
253.20 mmol) at 0 °C. The reaction mixture was warmed to room
temperature and stirring was continued for 5 h. The reaction mix-
ture was quenched by addition of MeOH and evaporated to dryness
under reduced pressure. The residue obtained was dissolved in
AcOEt (250 mL) and washed with water (3 ꢂ 250 mL). The organic
layer was washed with brine solution (100 mL), dried over anhyd
MgSO4 and concentrated under vacuum to obtain 20.10 g of a
residue containing a crude mixture of anomers of methyl 1,3,4-
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L
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3.4.1. Methyl 1,3,4-tri-O-benzyl-b-L-erythro-pentulofuranoside
(5a)
Syrupy liquid; TLC: Rf 0.45 (20:80 AcOEt–hexanes); ½a D24
ꢄ10.96
ꢃ
(c 1, CHCl3); 1H NMR (600 MHz, CDCl3): d 3.21 (s, 3H, OMe), 3.63 (d,
J = 10.2 Hz, 1H, H-1), 3.74 (d, J = 10.8 Hz, 1H, H-10), 3.89–3.92 (m,
H-5), 3.95–4.01 (m, 2H, H-3 and H-50), 4.38–4.44 (m, 2H, H-4 and
CH2OBn), 4.51 (d, J = 12.0 Hz, 1H, CH2OBn), 4.53 (d, J = 12.0 Hz,
1H, CH2OBn), 4.62 (d, J = 12.0 Hz, 1H, CH2OBn), 4.73 (s, 2H,
CH2OBn), 7.24–7.39 (m, 15H, arom.); 13C NMR (150 MHz, CDCl3):
d 48.7 (OMe), 65.2 (C-1), 69.5 (C-5), 72.6 (CH2OBn), 73.7 (CH2OBn),
74.0 (CH2OBn), 78.7 (C-4), 80.2 (C-3), 108.9 (C-2), 127.8, 127.8,
127.9, 128.0, 128.3, 128.3, 128.5, 128.6, 128.6, 137.9, 138.2, 138.5
(arom. C); HRMS (ESI-TOF high-acc): calcd for C27H30O5 (M+H)+,
m/z 435.2166; found, m/z 435.2170; calcd for C27H30O5 (M+Na)+,
m/z 457.1985; found m/z 457.2006.
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3.4.2. Methyl 1,3,4-tri-O-benzyl-a-L-erythro-pentulofuranoside
(5b)
Syrupy liquid, TLC: Rf 0.35 (20:80 AcOEt–hexanes); ½a D24
ꢄ3.02
ꢃ
(c 1, CHCl3); 1H NMR (600 MHz, CDCl3): d 3.43 (s, 3H, OMe), 3.53
(d, J = 10.2 Hz, 1H, H-1), 3.56 (d, J = 10.2 Hz, 1H, H-10), 3.94–4.01
(m, 3H, H-4, H-5 and H-50), 4.06 (d, J = 6.0 Hz, 1H, H-3), 4.46 (d,
J = 12.0 Hz, 1H, CH2OBn), 4.52 (d, J = 12.0 Hz, 1H, CH2OBn), 4.55
(d, J = 12.0 Hz, 1H, CH2OBn), 4.62 (d, J = 12.0 Hz, 1H, CH2OBn),
4.65 (s, 2H, (CH2OBn)), 7.22–7.37 (m, 15H, arom.); 13C NMR
(150 MHz, CDCl3): d 50.2 (OMe), 70.3 (C-1), 71.0 (C-5), 72.4
(CH2OBn), 72.9 (CH2OBn), 73.7 (CH2OBn), 74.9 (C-4), 78.3 (C-3),
104.7 (C-2), 127.8, 127.9, 127.9, 127.9, 128.1, 128.4, 128.5, 128.5,
128.6, 138.1, 138.3, 138.4 (arom. C); HRMS (ESI-TOF high-acc):
calcd for C27H30O5 (M+Na)+, m/z 457.1985; found m/z 457.1997.
14. Ekeberg, D.; Morgenlie, S.; Stenstrøm, Y. Carbohydr. Res. 2005, 340, 373–377.
ˇ
ˇ
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Acknowledgments
We thank Professor A. Eschenmoser for the stimulating discus-
sions that led to this work. This work was supported by NASA