One-pot inversion of D-mannono-1,4-lactone for the practical synthesis of L-ribose

Article abstract of DOI:10.1016/S0040-4039(03)00552-5

L-Ribose was synthesized in a concise manner from D-mannono-1,4-lactone using one-pot inversion conditions. Treatment of D-mannono-1,4-lactone with piperidine, followed by mesylation-induced S_N2-type O-alkylation, afforded the desired one-pot inversion in an optimum yield, and the following straightforward transformations provided L-ribose in good yields.

Full text of DOI:10.1016/S0040-4039(03)00552-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3051–3052
One-pot inversion of
D
-mannono-1,4-lactone for the practical
synthesis of
L-ribose
Myung Joon Seo,a Joungho An,a Jae Hak Shimb and Guncheol Kimb,*
aHanChem Co., Ltd, Jeonmin Dong, Yusung Gu, Daejeon 305-390, Republic of Korea
bDepartment of Chemistry, College of Natural Sciences, Chungnam National University, Daejon 305-764, Republic of Korea
Received 25 January 2003; revised 22 February 2003; accepted 26 February 2003
Abstract—
L
-Ribose was synthesized in a concise manner from
D-mannono-1,4-lactone using one-pot inversion conditions.
Treatment of
D
-mannono-1,4-lactone with piperidine, followed by mesylation-induced SN2-type O-alkylation, afforded the desired
one-pot inversion in an optimum yield, and the following straightforward transformations provided
© 2003 Elsevier Science Ltd. All rights reserved.
L-ribose in good yields.
Recently,
in medicinal and cosmetic applications.1 In particular, a
number of nucleosides derived from -sugars have
shown very potent antiviral activity and several
oligonucleotides using -nucleosides have shown poten-
tial antisense activity.2 Therefore, it has become neces-
sary to find a practical way to synthesize -sugars. For
L
-carbohydrates have been increasingly used
mannono-1,4-lactone for the preparation of L
-ribose.3a
Although the cyclization reaction on the basis of Mit-
sunobu condition was efficient, the use of expensive
reagents such as DEAD and the removal of by-prod-
ucts such as phosphine oxide would be a nuisance.
Therefore, we hoped to suggest a more practical route,
an inversion condition via stepwise opening lactone and
mesylation followed by in situ SN2-type O-alkylation in
one pot. After the reaction sequence, aqueous work-up
was expected to be enough for the hydrolysis. This
O-alkylation mechanism involving the amide must be
similar to that described for the displacement of triflate
by dimethylforamide4 (Scheme 1).
L
L
L
example, the synthesis of L-ribose has been an attrac-
tive target.3 As a part of our interest in finding an
economical method for the molecule, we tried to
develop a practical cyclization way using SN2-type reac-
tion from natural
way of synthesizing
lactone.
D
-sugars. Herein, we report a concise
-ribose from -mannono-1,4-
L
D
First, we tried to find the optimum conditions for
converting 2,3,5,6-di-O-isopropylidene-D-mannono-1,4-
In a recent paper, the Ikegami group reported the
application of intramolecular O-alkylation of a g-
lactone 1 into intermediate 5. For the first ring-opening
aminolysis step, 2 equiv. of piperidine were found to
open the g-lactone smoothly under mild conditions to
liberate the hydroxyl group, and intermediate 2 was
reacted with methanesulfonyl chloride under triethyl-
amine to afford mesylate 3, and in situ attack of the
carbonyl group furnished the desired inverted stereo-
hydoxamate intermediate derived from the same
D-
chemistry, yielding
L-gluno-1,4-lactone in 85% yield
after aqueous work-up and silica-gel column chro-
matography.5 We found that elimination by-products
were quite minor and an SN1-type pathway could be
ignored because a negligible amount of starting mate-
rial was recovered after the quantitative opening of 1.
Intramolecular attack of the piperidine amide seemed
to be quite fast and mild. Use of primary amine, such
as benzylamine, under various conditions, did not fur-
nish compound 5 at all, though the first aminolysis
proceeded.6
Scheme 1.
Keywords: L-ribose; inversion; D-mannono-1,4-lactone.
* Corresponding author. Tel.: 082-42-821-5475; fax: 082-42-823-1360;
e-mail: guncheol@cnu.ac.kr
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00552-5

3052
M. J. Seo et al. / Tetrahedron Letters 44 (2003) 3051–3052
9883–9887; (e) Ohno, M.; Ostuka, M. In Recent Progress
in the Chemical Synthesis of Antibiotics; Lukacs, G.; Ohno,
M., Eds.; Springer: New York, 1990; pp. 397–414.
2. Mikhailopulo, I. A.; Sivets, G. G. In Synthesis of Perac-
ylated Derivatives of
L
-Ribofuranose from
D-Ribose and
Their Use for the Preparation of i-
L
-Ribonucleosides. Col-
Scheme 2.
lection Symposium Series; Holy, A.; Hocek, M., Eds.;
Institute of Organic Chemistry and Biochemistry,
Academy of Sciences of the Czech Republic: Prague, 1999;
Vol. 2, pp. 53–56.
3. (a) Takahashi, H.; Iwai, Y.; Hitomi, Y.; Ikegami, S. Org.
Lett. 2002, 4, 2401–2403; (b) Sivets, G. G.; Klennitskaya,
T. V.; Zhernosek, D. V.; Mikhailopulo, I. A. Synthesis
2002, 253–259; (c) Shi, Z.-D.; Yang, B.-H.; Wu, Y.-L.
Tetrahedron Lett. 2001, 42, 7651–7653; (d) Jung, M. E.;
Xu, Y. Tetraheron Lett. 1997, 38, 4199–4202.
4. Feenstra, R. W.; Stokkingreef, E. H. M.; Nivard, R. J. F.;
Ottenheijim, H. C. J. Tetrahedron 1998, 44, 5583–5595.
5. Experimental procedure: 2,3:5,6-Di-O-isopropylidene-D-
Scheme 3.
mannono-1,4-lactone 1 (160 g, 0.62 mol) was dissolved in
anhydrous EtOAc (or CH2Cl2, 320 mL) and then pipe-
ridine (123 mL, 1.24 mol) was added dropwise at 0°C. The
mixture was stirred at room temperature for 4 h. After
TLC revealed the completion of reaction, excess piperidine
and solvent were removed by distillation under reduced
pressure to obtain crude 2. The reactants were dissolved
again by adding EtOAc (or CH2Cl2, 1 L). Subsequently,
triethylamine (Et3N, 138 mL) and dimethylaminopyridine
(1 g) were added under a nitrogen gas stream, and
methanesulfonyl chloride (72 mL) was added dropwise at
0°C. After the addition, the temperature in the reaction
vessel was raised to room temperature and the reaction
was carried out at room temperature for about 5 h. After
TLC revealed the completion of reaction, water was added
to quench the reaction. The reaction mixture was extracted
with EtOAc (or CH2Cl2, 1 L×3) from the aqueous layer.
The organic layer was washed with 1% HCl solution,
water, and brine. After filtration, the organic layer was
dried over anhydrous magnesium sulfate to remove the
moisture in the organic layer, and concentrated under
reduced pressure. The residue was purified by silica gel
column chromatography (hexane/EtOAc=3/1) to give
compound 5 (136 g, yield 85%) as a white solid. Com-
pound 2: mp 110–111°C; [h]2D0=−21.5 (CHCl3, c=1.00);
Having obtained compound 5, we attempted to convert
5 to -ribose in a new concise manner. Treatment of 5
L
with H5IO6 afforded partial hydrolysis to a diol inter-
mediate and cleavage to aldehyde.3c Both functional
groups, aldehyde and lactone in the crude product,
were readily reduced to alcohol and hemiacetal with 2
equiv. of DIBAL-H to provide 6 in 80% yield. Finally,
acidic hydrolysis deprotected the isopropylidene group
to afford
L-ribose in 70% yield (Scheme 2).
Although the route described above yielded
L
-ribose in
good yields, total 48% from 1, we wanted to suggest an
alternative way. Reduction of 5 with DIBAL-H yielded
a mixture which was converted to compound 7 with
benzoyl chloride in pyridine in 93% yield, and partial
hydrolysis of 7 with H5IO6, followed by reduction,
afforded compound 8 as a mixture in 91% yield.
Finally, hydrolysis with base followed by acid provided
L
-ribose in 80% yield (Scheme 3).
In conclusion, we have suggested an efficient and prac-
tical route to
conditions of
L
-ribose by developing one-pot inversion
-mannono-1,4-lactone. This is the first
D
application of the in situ SN2-type cyclization for the
synthesis of an -furanose. The process for large-scale
production of -ribose is being developed, and further
application of this type of reaction towards the related
1
IR (KBr): wmax 3393, 1630; H NMR (500 MHz, CDCl3):
L
l 4.99 (1H, d, J=6.7 Hz), 4.47 (1H, d, J=6.7 Hz), 4.08
(2H, m), 3.98 (2H, m), 3.67 (1H, m), 3.55 (1H, m), 3.42
(2H, m), 3.27 (1H, d, J=8.25 Hz), 3.08 (bt, 1H). Com-
pound 5: mp 129–130°C; [h]2D0=42.0 (CHCl3, c=1.00); IR
(KBr): wmax 1770; 1H NMR (500 MHz, CDCl3): l 4.75
(1H, d, J=5.5 Hz), 4.73 (1H, d, J=5.5 Hz), 4.52 (1H, s),
4.24 (1H, dd, J=7.0, 7.5 Hz), 4.09 (1H, dd, J=8.0, 7.0
Hz), 3.95 (1H, dd,=8.0, 7.5 Hz), 1.44 (3H, s), 1.35 (3H, s),
1.31 (3H, s), 1.29 (3H, s), 1.31 (3H, s), 1.29 (3H, s); 13C
NMR (125 MHz, CDCl3): l 174.08, 113.22, 110.50, 79.56,
78.42, 75.05, 74.97, 64.97, 26.67, 25.49, 25.41, 25.37. Anal.
calcd for C12H18O6: C, 55.81 H, 7.07. Found: C, 55.75 H,
7.12.
L
L
-sugars is currently under study.
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