Synthesis of new 2- or 3-deoxy carbapyranoses from furan

Article abstract of DOI:10.1016/S0040-4039(01)01353-3

The synthesis of new 2- or 3-deoxy carbapyranoses of the allo-, galacto-, gluco- and manno-series starting from furan are described.

Full text of DOI:10.1016/S0040-4039(01)01353-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7041–7043
Synthesis of new 2- or 3-deoxy carbapyranoses from furan
Odo´n Arjona,* Gema Lorenzo, Roc´ıo Medel and Joaqu´ın Plumet*
Departamento de Qu´ımica Orga´nica I, Facultad de Qu´ımica, Universidad Complutense, 28040 Madrid, Spain
Received 6 July 2001; accepted 20 July 2001
Abstract—The synthesis of new 2- or 3-deoxy carbapyranoses of the allo-, galacto-, gluco- and manno-series starting from furan
are described. © 2001 Published by Elsevier Science Ltd.
Carbasugars are carbocyclic analogues of carbohy-
drates having a methylene group instead of the ring
oxygen atom.1 This family of carbohydrate mimics,
currently attracts interest among chemists as well as
biochemists due to the interesting biological activities
which they exhibit.2 Consequently several methodolo-
gies have been developed for the synthesis of both
carbafuranoses and carbapyranoses3 and today all 16
racemic carbapyranoses and most of the 32 enan-
tiomeric carbapyranoses have already been prepared.
This active research includes the deoxycarbafuranoses
as component of carbocyclic nucleosides2a but the
corresponding deoxy carbapyranoses have received less
attention and, to the best of our knowledge, only three
6-deoxy carbapyranoses have been described.4
Following our interest in the development of synthetic
methods to carbapyranoses and derivatives,5 in this
paper we report the synthesis of new 2- or 3-deoxy
carbapyranoses, carbohydrate mimics of the corre-
sponding deoxypyranoses which are components of
many natural products.6
Scheme 1. Reagents and conditions: (a) NaBH4, MeOH, 0°C, 78%; (b) n-BuLi, THF, −78°C, 93%; (c) Na-Hg, Na2HPO4, MeOH,
−20°C to rt, 60%; (d) OsO4, 4-methylmorpholine N-oxide, NaHCO3, THF:t-BuOH:H2O, rt, 92%; (e) Ac2O, pyr, DMAP, 80%;
(f) BF3·OEt2, EtSH; (g) Ac2O, pyr, DMAP, 60% (two steps); (h) Ac2O, pyr, DMAP, 82%; (i) BF3·OEt2, EtSH; (j) Ac2O, pyr,
DMAP, 65% (two steps).
* Corresponding authors.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)01353-3

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O. Arjona et al. / Tetrahedron Letters 42 (2001) 7041–7043
Scheme 2. Reagents and conditions: (a) NaBH4, MeOH, 0°C, 71%; (b) n-BuLi, THF, −78°C, 72%; (c) Na-Hg, Na2HPO4, MeOH,
−20°C to rt, 65%; (d) OsO4, 4-methylmorpholine N-oxide, NaHCO3, THF:t-BuOH:H2O, rt, 70%; (e) Ac2O, pyr, DMAP, 84%; (f)
BF3·OEt2, EtSH; (g) Ac2O, pyr, DMAP, 55% (two steps); (h) BF3·OEt2, EtSH; (i) Ac2O, pyr, DMAP, 64% (two steps).
Our starting material was the oxabicyclic vinyl sulfones
1 and 2, easily obtained from furan and acrylic acid7 in
8 steps (40% overall yield) and 6 steps (45% overall
yield), respectively.
In summary, the synthesis of new 2-deoxy carbapyran-
oses of the allo- and galacto-series and new 3-deoxy
carbapyranoses of the gluco- and manno-series has been
achieved in a divergent fashion from furan via the
readily available oxanorbornenic sulfones 1 and 2. It
should be pointed out that both compounds 1 and 2 are
easily available in optically pure form since the starting
Diels–Alder adduct of furan and acrylic acid has been
obtained in both enantiomeric forms via optical resolu-
tion.11 Studies are now underway to extend this strategy
to the preparation of other carbasugars derivatives as
well as carba-C-glycosides and carba-C-disaccharides
and will be reported in due course.
Thus, reduction of the double bond in 1 (NaBH4,
MeOH, 0°C) led to exo sulfone 3, which was trans-
formed into the key intermediate 4 by a deprotonation
of the sulfonyl group followed by b elimination of the
bridged oxygen atom.5d Desulfonylation of the resulting
cyclohexenol 4 with Na-Hg and further bishydroxyla-
tion with OsO4 afforded the benzyl derivatives of 2-
deoxy carbasugars
5 and 6 (ratio 1.2:1). After
separation by column chromatography, treatment of 5
with Ac2O in pyridine yielded 7. Finally, deprotection
of the benzylated hydroxy group with BF3·OEt2 fol-
lowed by acetylation gave 1,3,4,6-tetra-O-acetyl-2-
deoxy-5a-carba-a-DL-allopyranose 88 (Scheme 1).
Acknowledgements
Financial support was obtained from DGI-MCYT no.
BQU2000-0653. R.M. thanks Ministerio de Educacio´n
y Cultura for a predoctoral fellowship.
On the other hand, the same three-step sequence for
triol 6, allowed us to obtain 1,3,4,6-tetra-O-acetyl-2-
deoxy-5a-carba-a-DL-galactopyranose 10.9
The synthesis of the 3-deoxy carbapyranoses was
achieved following a similar procedure (Scheme 2).
Reduction of 2 with NaBH4 followed by ring opening
reaction in 11 gave the cyclohexenyl sulfone 12. Desul-
fonylation and bishydroxylation produced an insepar-
able 1.5:1 mixture of both isomers. We achieved the
chromatographic separation of the two deoxy carbasug-
ars derivatives after acetylation of the mixture of triols.
At this stage, treatment of 14 and 15 with BF3·OEt2
and further acetylation allowed us to obtain 1,2,4,6-
tetra-O-acetyl-3-deoxy-5a-carba-a-DL-glucopyranose 16
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mannopyranose 17.10

O. Arjona et al. / Tetrahedron Letters 42 (2001) 7041–7043
7043
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2.11 (s, 3H, COCH3), 2.41–2.38 (m, 1H, H-5), 3.87 (dd,
1H, J=6.0, 10.8 Hz, CH2O), 3.96 (dd, 1H, J=9.0, 11.4
Hz, CH2O), 5.12 (td, 1H, J=3.0, 10.2 Hz, H-3), 5.28 (t,
1H, J=3.0 Hz, H-1), 5.00 (bs, 1H, H-4). 13C NMR
(CDCl3, 75 MHz): l 20.8, 20.9, 21.3, 26.7, 29.7, 33.6,
63.4, 67.5, 68.4, 68.5, 170.2, 170.2, 170.3, 170.9. IR
(CHCl3): w 2960, 2928, 1736, 1647 cm−1. Anal. calcd for
C15H22O8: C, 54.54; H, 6.67. Found: C, 54.68; H, 6.82.
10. Data for: 1,2,4,6-tetra-O-acetyl-3-deoxy-5a-carba-a-DL
-
1
glucopyranose, 16: H NMR (CDCl3, 300 MHz): l 1.59
(ddd, 1H, J=2.4, 13.2, 15.6 Hz, H-6), 2.01 (s, 3H,
COCH3), 2.06 (s, 3H, COCH3), 2.07 (s, 3H, COCH3),
2.08–1.84 (m, 3H, 2 H-3 and H-5), 2.13 (s, 3H, COCH3),
2.20–2.11 (m, 1H, H-6), 3.97 (dd, 1H, J=3.0, 11.1 Hz,
CH2O), 4.13 (dd, 1H, J=4.8, 11.1 Hz, CH2O), 4.79 (td,
1H, J=4.8, 11.1 Hz, H-1), 4.86 (ddd, 1H, J=3.0, 4.5,
12.3 Hz, H-2), 5.35 (bs, H-1). 13C NMR (CDCl3, 75
MHz): l 20.8, 21.0, 21.1, 29.2, 29.7, 30.9, 35.3, 63.5, 67.6,
69.3, 170.0, 170.1, 170.9. IR (CHCl3): w 2926, 2854, 1740
cm−1. Anal. calcd for C15H22O8: C, 54.54; H, 6.67.
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8. Data for: 1,3,4,6-tetra-O-acetyl-2-deoxy-5a-carba-a-DL
-
allopyranose, 8: 1H NMR (CDCl3, 300 MHz): l 1.70
(ddd, 1H, J=3.4, 11.2, 14.6 Hz, H-6), 1.85 (dt, 1H,
J=3.4, 15.6 Hz, H-2), 2.04–2.00 (m, 1H, H-6), 2.04 (s,
3H, COCH3), 2.07 (s, 6H, 2COCH3), 2.08 (s, 3H,
COCH3), 2.27 (dd, 1H, J=2.4, 15.6 Hz, H-2), 2.63–2.54
(m, 1H, H-5), 4.01 (dd, 1H, J=3.4, 11.2 Hz, CH2O), 4.20
(dd, 1H, J=4.9, 11.2 Hz, CH2O), 4.90 (dd, 1H, J=2.9,
10.3 Hz, H-4), 5.05 (t, 1H, J=3.4 Hz, H-1), 5.30 (d, 1H,
J=3.4 Hz, H-3). 13C NMR (CDCl3, 75 MHz): l 20.8,
21.1, 21.3, 29.7, 31.5, 31.7, 63.7, 67.1, 68.0, 70.7, 170.2,
170.9. IR (CHCl3): w 2962, 2928, 1736, 1711 cm−1. Anal.
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H, 6.80.
Data for: 1,2,4,6-tetra-O-acetyl-3-deoxy-5a-carba-b-DL
-
1
mannopyranose, 17: H NMR (CDCl3, 300 MHz): l 1.66
(ddd, 1H, J=2.7, 10.8, 13.7 Hz, H-6), 2.03 (s, 3H,
COCH3), 2.06 (s, 3H, COCH3), 2.08 (s, 3H, COCH3),
2.11–1.77 (m, 3H, 2H-3 and H-5), 2.14 (s, 3H, COCH3),
2.27 (dt, 1H, J=4.5, 13.9 Hz, H-6), 4.09 (m, 2H, CH2O),
4.93 (ddd, 1H, J=2.5, 4.5, 11.1 Hz, H-1), 5.02–4.97 (m,
1H, H-4), 5.37 (bs, 1H, H-4). 13C NMR (CDCl3, 75
MHz): l 21.2, 21.4, 21.5, 27.8, 30.1, 33.6, 39.7, 64.8, 68.7,
68.9, 70.7, 170.5, 170.7, 171.3. IR (CHCl3): w 2930, 2854,
1739 cm−1. Anal. calcd for C15H22O8: C, 54.54; H, 6.67.
Found: C, 54.42; H, 6.79.
9. Data for: 1,3,4,6-tetra-O-acetyl-2-deoxy-5a-carba-a-DL
-
galactopyranose, 10: 1H NMR (CDCl3, 300 MHz): l
1.63–1.58 (m, 1H, H-6), 1.73 (dt, 1H, J=2.9, 14.2 Hz,
H-6), 1.95 (dd, 2H, J=2.9, 9.3 Hz, 2H-2), 2.00 (s, 3H,
COCH3), 2.05 (s, 3H, COCH3), 2.08 (s, 3H, COCH3),
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