Synthesis of a 'direct-linked' C-disaccharide from a pyranulose glycoside

Article abstract of DOI:10.1016/S0008-6215(98)00307-3

Syntheses of five 'direct linked' C-disaccharides 8a-e were reported. The (Et₃SiH/BF₃.Et₂O) reduction of pyranulose glycoside 1 yielded (6S)- and (6R)-6-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyran-3(2H,6H)-one (2a and 2b)

Full text of DOI:10.1016/S0008-6215(98)00307-3

Carbohydrate Research 315 (1999) 98–105
Synthesis of a ‘direct-linked’ C-disaccharide from a
pyranulose glycoside
Misa Yuasa, Shigeyuki Kanazawa, Natsu Nishimura, Taeko Higuchi, Isamu Maeba *
Faculty of Pharmacy, Meijo Uni6ersity, Tempaku, Nagoya 468, Japan
Received 20 October 1998; accepted 19 November 1998
Abstract
Syntheses of five ‘direct linked’ C-disaccharides 8a–e were reported. The (Et3SiH/BF3·Et2O) reduction of
pyranulose glycoside 1 yielded (6S)- and (6R)-6-(2,3,5-tri-O-benzoyl-b- -ribofuranosyl)pyran-3(2H,6H)-one (2a and
D
2b) in a ratio of ca. 2:1 and in 88% combined yield. The absolute stereochemistry of each was determined from its
CD spectrum. The reduction of 2a with NaBH4 in methanol afforded two allylic alcohols 6a and 6b in 14 and 73%
yield, respectively. The reduction of 2b with NaBH4 afforded 6c and 6d in 30 and 56% yield, respectively. Cis
hydroxylation of the double bond in compounds 6a–d with osmium tetroxide gave 7a–e. The stereoisomers 7a–e
1
were separated and their configuration was established by H NMR spectroscopy. Debenzoylation of compounds
7a–e with aqueous sodium carbonate produced deprotected C-disaccharides 8a–e. © 1999 Elsevier Science Ltd. All
rights reserved.
Keywords: Synthesis; Pyranulose glycoside; C-Disaccharide; Direct-linked C-disaccharide
C-Disaccharides in which two sugar moi-
eties are linked to a methylene group rather
than to an interglycosidic oxygen atom have
gained considerable attention due to their po-
tential role in the inhibition of glycosidases [1]
and as part of a treatment for metabolic dis-
eases such as diabetes [2]. To the best of our
knowledge, attention has been drawn in five
instances [3] to the synthesis of disaccharides
containing no spacer, i.e., compounds wherein
the two sugar moieties are joined directly by a
carbon–carbon bond. This paper describes
the preparation of ‘direct linked’ C-disaccha-
rides (8a–e) from pyranulose glycoside 1, 6-
tained readily from glycosylfuran by our pre-
viously published procedure [4].
Reduction of 1 with Et3SiH in the presence
of BF3·Et2O afforded a mixture of diasteroiso-
meric
6-(2,3,5-tri-O-benzoyl-b- -ribofuran-
D
osyl)pyran-3(2H,6H)-one 2a and 2b in a ratio
of ca. 2:1 and in 88% combined yield. These
compounds were separated by preparative
thin-layer chromatography (PTLC). Com-
pounds 2a and 2b showed strong nuclear
Overhauser enhancements (NOEs) between H-
6 and H-2a (Scheme 1). To determine the
absolute configuration of the chiral center cre-
ated at C-6 in compounds 2a and 2b, we
compared the CD spectra of the correspond-
ing hydrazone compounds 4a and 4b with the
spiro compounds 5a and 5b, whose absolute
configurations are reported in our previous
paper [5]. We prepared the hydrazone com-
pounds 3a and 3b from 2a and 2b using
hydroxy-6-(2,3,5-tri-O-benzoyl-b- -ribofuran-
D
osyl)pyran-3(2H,6H)-one, which can be ob-
* Corresponding author. Tel.: +81-52-8321781; fax: +81-
52-8348090.
E-mail address: maeba@meijo-u.ac.jp (I. Maeba)
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(98)00307-3

M. Yuasa et al. / Carbohydrate Research 315 (1999) 98–105
99
semicarbazide, followed by removal of the
sugar protecting groups to give compounds 4a
and 4b (Scheme 1). The CD spectrum of the
(6S)-compound 5a shows a positive Cotton
effect at 277 nm, whereas a negative Cotton
effect at 278 nm is observed for the (6R)-com-
pound 5b (Fig. 1). Since the longer wavelength
Cotton effect of less polar compounds is nega-
tive, we have assigned this compound the 6R
configuration (4b), while the more polar iso-
mer is considered to be the 6S-isomer (4a).
Reduction of 2a with NaBH4 in methanol
afforded two allylic alcohols 6a and 6b in 14
D
-ribofuranosyl)-2,3-dihydro-6H-pyran was
ascribed to 6b. The reduction of 2b with
NaBH4 in methanol afforded two allylic alco-
hols 6c and 6d in 30 and 56% yield, respec-
tively. The H NMR spectrum of 6c showed
coupling constants of J2a,3 2.2 Hz and J2b,3
1
0
Hz, indicating a pseudoequatorial position for
H-3. In turn, compound 6d, with a lower Rf,
was predominant; its 1H NMR spectrum
showed coupling constants of J2a,3 6.6 Hz and
J2b,3 4.4 Hz, which indicated a pseudoaxial
position for H-3. The configuration at C-3
was established by an NOE experiment for 6d.
Irradiation of H-2a (l 3.40) enhanced the
signal at l 4.14 by 9.2%. Irradiation of H-2b
(l 4.08) in 6d enhanced the signal at l 4.39 by
1.7%. These data indicate that the configura-
tion of compounds 6c and 6d are 3S and 3R,
respectively.
Cis hydroxylation of the double bond in
compounds 6a and 6c with osmium tetroxide
in dry pyridine gave 7a and 7d in 78 and 85%
yield, respectively. These results show the pre-
dictable sensitivity of cis hydroxylation with
osmium tetroxide in relation to steric hin-
drance. With compounds 6a and 6c, which
have both substituents (C-6-ribose and C-3-
OH) on the same side of the ring, the reaction
is fully stereoselective. By assuming that the
hydroxylating agent attacked from the side
with less steric hindrance, we assigned to the
products the configurations of 3R,4S,5S,6S
1
and 73% yield, respectively. The H NMR
spectrum of 6a showed coupling constants of
J2a,3 2.2 Hz and J2b,3 0 Hz, which indicated a
pseudoequatorial position for H-3. The
configuration at C-3 was established by an
NOE experiment on 6a (Scheme 2). Irradia-
tion of H-6 (l 4.47) enhanced the signal at l
3.69 by 3.7%. Irradiation of the H-3 resonance
(l 3.83) in 6a enhanced the signal at l 3.69 by
3.8% and the signal at l 3.98 by 1.8%. Conse-
quently, it was concluded that 6a has the
structure of (3S,6S)-3-hydroxy-6-(2,3,5-tri-O-
benzoyl-b- -ribofuranosyl)-2,3-dihydro-6H-
D
pyran. In turn, compound 6b, with a lower Rf,
was predominant; its 1H NMR spectrum
showed coupling constants of J2a,3 8.4 Hz and
J2b,3 5.5 Hz, which pointed to a pseudoaxial
position for H-3. Therefore, the structure of
(3R)-3-hydroxy-(6S)-6-(2,3,5-tri-O-benzoyl-b-
Scheme 1. Reagents and conditions: (a) Et3SiH, BF3·Et2O, 0 °C, 20 s; (b) semicarbazide, dioxane, rt, 1.5 h; (c) concd aq Na2CO3,
MeOH, 5 h.

100
M. Yuasa et al. / Carbohydrate Research 315 (1999) 98–105
Fig. 1. CD spectra of the semicarbazones of the C-glycosides in MeOH.
(7a) and 3S,4R,5R,6R (7d). Cis hydroxylation
of compound 6b with osmium tetroxide gave
mixtures of two compounds 7b and 7c in a
ratio of ca. 1:5 and in 61% combined yield.
Both compounds were isolated by PTLC. Hy-
droxylation of 6b, in which the steric hin-
drance due to substituents at the C-6-ribose
and C-3-OH acts in opposite directions, re-
sults in a mixture of two products. The
configuration at C-4 and C-5 was established
by an NOE experiment with 7b. Irradiation of
H-6 (l 3.46) enhanced the signal at l 4.09 by
4.0% and the signal at l 3.36 by 1.9%.
(8a–e). Studies to evaluate the biological ac-
tivity of the disaccharides will be reported
elsewhere.
1. Experimental
Fast-atom-bombardment
mass
spectra
(FABMS) were run on a JMS-HX 110 spec-
1
13
trometer. The H and C NMR spectra were
measured with a JNM-A-400 or an A-600
(JEOL) spectrometer, with tetramethylsilane
as an internal standard. Optical rotations were
measured with a Jasco DIP-370 polarimeter
(10-cm cell) at 25 °C. Analytical TLC was
performed on glass plates coated with a 0.5-
mm layer of Silica Gel GF254 (E. Merck). The
compounds were detected by UV light (254
nm).
These data indicate that the configurations
of compounds 7b and 7c are 3S,4R,5R,6S and
3S,4S,5S,6S, respectively. On the other hand,
treatment of 6d under the same reaction con-
ditions also afforded an 83% yield of 7e with
1
no trace of the other isomer. The H NMR
spectrum of 7e shows a large H-5 and H-6
coupling constant (9.5 Hz), confirming the
trans diaxial relationship for this set of hydro-
gens. Consequently, it was concluded that 7e
has the structure (3R,4R,5R)-3,4,5-trihydroxy-
(6S)- and (6R)-6-(2,3,5-Tri-O-benzoyl-i- -
D
ribofuranosyl)pyran-3(2H,6H)-one (2a) and
(2b).—To a solution of 1 (1.28 g, 2.30 mmol)
and Et3SiH (0.5 mL) in acetonitrile (20 mL)
was added BF3·Et2O (0.56 g, 3.95 mmol), and
the mixture was stirred at 0 °C for 20 s. The
reaction mixture was neutralized with satu-
rated NaHCO3 and then extracted with
CHCl3 (3×10 mL). The extracts were com-
(6R)-6-(2,3,5-tri-O-benzoy-b- -ribofuranosyl)-
D
tetrahydropyran. Debenzoylation of com-
pounds (7a–e) with aqueous sodium carbon-
ate produced deprotected disaccharides

M. Yuasa et al. / Carbohydrate Research 315 (1999) 98–105
101
bined, washed with water, dried over MgSO4,
and evaporated to dryness. The residual syrup
was separated by PTLC with CHCl3 as eluent
after three elutions.
H, J5%a,5%b 12.1, J4%a,5%b 3.7 Hz, H-5%a), 4.54 (dd,
1 H, J6,1%=J1%,2% 3.7 Hz, H-1%), 4.62 (m, 1 H,
H-4%), 4.69 (dd, 1 H, J6,1% 3.7, J5,6 1.8 Hz, H-6),
4.78 (dd, 1 H, J5%a,5%b 12.1, J4%,5%b 3.3 Hz, H-5%b),
5.67 (dd, 1 H, J2%,3%=J3%,4% 6.4 Hz, H-3%), 5.84
(dd, 1 H, J2%,3% 6.4, J1%,2% 3.7 Hz, H-2%), 6.21 (dd,
1 H, J4,5 10.3, J2a,4 2.4 Hz, H-4), 7.07 (dd, 1 H,
J4,5 10.3, J5,6 1.8 Hz, H-5), 7.35–8.06 (m, 15
Compound 2a. Yield: 695.9 mg (56%); Rf
1
0.38; H NMR (CDCl3): d 4.04 (dd, 1 H, J2a,2b
16.5, J2a,4 2.0 Hz, H-2a), 4.21 (d, 1 H, J2a,2b
16.5 Hz, H-2b), 4.49 (dd, 1 H, J5%a,5%b 12.1,
J4%,5%a 4.1 Hz, H-5%a), 4.53 (m, 2 H, H-6,1%),
4.67 (m, 1 H, H-4%), 4.83 (dd, 1 H, J5%a,5%b 11.7,
J4%,5%b 3.3 Hz, H-5%b), 5.70 (dd, 1 H, J2%,3% 5.5,
J3%,4% 7.1 Hz, H-3%), 5.75 (dd, 1 H, J1%,2% 2.8, J2%,3%
5.5 Hz, H-2%), 6.24 (dd, 1 H, J4,5 10.6, J2a,4 2.0
Hz, H-4), 7.16 (dd, 1 H, J4,5 10.6, J5,6 1.8 Hz,
H-5), 7.34–8.09 (m, 15 H, Ph); 13C NMR
(CDCl3): l 63.5 (C-5%), 71.5 (C-2), 72.2, 72.6,
74.1, 79.3, 83.6 (C-6,1%,2%,3%,4%), 128.3–133.5
(Ph, C-4), 146.7 (C-5), 165.3, 165.3, 166.1
(CꢀO), 193.9 (C-3). FABMS (nitrobenzyl al-
cohol as matrix): Calcd for C31H27O9; [MH]
543.1655. Found: [MH]+ m/z 543.1680.
13
H, Ph); C NMR (CDCl3): l 63.0 (C-5%), 71.6
(C-2), 72.1, 72.7, 73.0, 79.4, 83.4 (C-
6,1%,2%,3%,4%), 128.4–133.5 (Ph, C-4), 147.2 (C-
5), 165.3, 165.5, 166.1 (CꢀO), 193.7 (C-3).
FABMS (nitrobenzyl alcohol as matrix):
Calcd for C31H27O9 [MH] 543.1655. Found:
[MH]+ m/z 543.1631.
(6S)-6-(2,3,5-Tri-O-benzoyl-i- -ribofuran-
D
osyl)pyran-3(2H,6H)-one semicarbazone (3a).
—To a solution of 2a (74.0 mg, 0.137 mmol)
in dioxane (2 mL) was added semicarbazide
hydrochloride (24 mg, 1 mmol), and the mix-
ture was stirred at room temperature (rt) for
1.5 h. Water was added and the mixture was
extracted with CHCl3 (3×10 mL). The ex-
tracts were combined, washed with water,
dried over MgSO4, and evaporated to
Compound 2b. Yield: 397.7 mg (32%); Rf
1
0.32; mp 129–130 °C; H NMR (CDCl3): l
4.12 (dd, 1 H, J2a,2b 16.3, J2a,4 2.0 Hz, H-2a),
4.22 (d, 1 H, J2a,2b 16.3 Hz, H-2b), 4.49 (dd, 1
Scheme 2. Reagents and conditions: (a) NaBH4, 20 °C, 20 min; (b) OsO4, dry pyridine, rt, 2 h; (c) concd aq Na2CO3, MeOH, rt,
5 h.

102
M. Yuasa et al. / Carbohydrate Research 315 (1999) 98–105
dryness. The residual syrup was purified by
PTLC with 49:1 CHCl3 –MeOH as eluent.
Compound 3a. Yield: 65.2 mg (80%); Rf
Compound 6a. Yield: 15.8 mg (14%); Rf
1
0.18; H NMR (CDCl3): l 2.85 (br d, 1 H,
OH, exchanged with D2O), 3.69 (dd, 1 H,
J2a,2b 12.1. J2a,3 2.2 Hz, H-2a), 3.83 (br, 1 H,
H-3), 3.98 (d, 1 H, J2a,2b 12.1 Hz, H-2b), 4.39
(dd, 1 H, J1%,2% 6.1, J6,1% 2.7 Hz, H-1%), 4.47
(apparent s, 1 H, H-6), 4.58 (dd, 1 H, J5a%,5b%
11.7, J4%,5a% 3.5 Hz, H-5%a), 4.66 (m, 1 H, H-4%),
4.71 (dd, 1 H, J5a%,5b% 11.7, J4%,5b% 3.3 Hz, H-5%b),
5.70 (dd, 1 H, J2%,3% 6.1, J3%,4% 3.8 Hz, H-3%), 5.77
(dd, 1 H, J4,5 10.2, J5,6 1.5 Hz, H-5), 5.95
1
0.33; colorless prisms; mp 137–138 °C; H
NMR (CDCl3): l 4.19 (d, 1/2 H, J2a,2b 13.7
Hz, H-2a), 4.21 (d, 1/2 H, J2a,2b 15.9 Hz,
H-2a), 4.31 (d, 1/2 H, J2a,2b 13.7 Hz, H-2b)
4.43 (m, 3/2 H, H-6,1%), 4.53 (m, 3/2 H, H-
6,5%a), 4.64 (m, 1 H, H-4%), 4.76 (m, 1 H,
H-5%b), 4.84 (d, 1/2 H, J2a,2b 15.9 Hz, H-2b),
5.72 (m, 2 H, H-2%,3%), 6.27 (dd, 1/2 H, J4,5
10.5, J5,6 1.2 Hz, H-5), 6.31 (dd, 1/2 H, J4,5
10.5, J4,6 1.6 Hz, H-4), 6.44 (dd, 1/2 H, J4,5
10.7, J5,6 2.0 Hz, H-5), 6.85 (dd, 1/2 H, J4,5
10.7, J4,6 2.4 Hz, H-4), 7.30–8.09 (m, 15 H,
Ph), 9.35, 9.60 (each s, each 1/2 H, NH,
exchanged with D2O). Anal. Calcd for
C32H29N3O9·0.5 H2O C, 63.15; H, 4.97; N,
6.90. Found: C, 63.09; H, 5.00; N, 6.78.
(apparent t, 1 H, H-4), 6.21 (dd, 1 H, J1%,2%
=
J2%,3% 6.1 Hz, H-2%), 7.29–8.20 (m, 15 H, Ph);
13C NMR (CDCl3): l 62.1 (C-3), 64.1 (C-5%),
70.8 (C-2), 73.0 (C-6), 69.9, 73.6, 80.0, 83.1
(C-1%,2%,3%,4%), 128.3–133.5 (Ph, C-4,5), 165.5,
165.6, 166.3 (CꢀO). FABMS (nitrobenzyl al-
cohol as matrix): Calcd for C31H29O9; [MH]
545.1812. Found: [MH]+ m/z 545.1797.
(6R)-6-(2,3,5-Tri-O-benzoyl-i- -ribofuran-
D
Compound 6b. Yield: 81.6 mg (73%); Rf
osyl)pyran-3(2H,6H)-one semicarbazone (3b).
—This compound was prepared from 2b as
described above for 3a.
1
0.13; H NMR (CDCl3): l 1.67 (br d, 1 H,
OH, exchanged with D2O), 3.33 (dd, 1 H,
J2a,2b 10.8, J2a,3 8.4 Hz, H-2a), 4.09 (dd, 1 H,
J2a,2b 10.8, J2a,3 5.5 Hz, H-2b), 4.37 (m, 3 H,
H-3,6,1%), 4.51 (dd, 1 H, J5a%,5b% 11.9, J4%,5%a 4.6
Hz, H-5%a), 4.62 (m, 1 H, H-4%), 4.75 (dd, 1 H,
J5a%,5b% 11.9, J4%,5b% 3.7 Hz, H-5b), 5.70 (dd, 1 H,
J2%,3% 5.6, J3%,4% 6.8 Hz, H-3%), 5.75 (dd, 1 H, J1%,2%
3.2, J2%,3% 5.6 Hz, H-2%), 5.85 (dd, 1 H, J5,6 1.6,
J4,5 10.6 Hz, H-5), 5.97 (dd, 1 H, J3,4 1.0, J4,5
10.6 Hz, H-4), 7.03–8.09 (m, 15 H, Ph); 13C
NMR (CDCl3): l 62.8 (C-3), 63.9 (C-5%), 69.2
(C-2), 72.6 (C-6), 72.4, 73.9, 79.0, 84.3 (C-
1%,2%,3%,4%), 127.0 (C-5), 128.3–133.3 (Ph, C-4),
155.2, 165.4, 166.2 (CꢀO). FABMS (nitroben-
zyl alcohol as matrix): Calcd for C31H29O9;
[MH] 545.1812. Found: [MH]+ m/z 545.1808.
(3R)- and (3S)-3-Hydroxy-(6R)-6-(2,3,5-
Compound 3b. Yield: 82%; Rf 0.30; colorless
1
prisms; mp 137–138 °C; H NMR (CDCl3): l
4.24 (d, 1/2 H, J2a,2b 13.5 Hz, H-2a), 4.26 (d,
1/2 H, J2a,2b 15.9 Hz, H-2a), 4.36 (d, 1/2 H,
J2a,2b 13.5 Hz, H-2b), 4.48 (m, 3 H, H-6,1%,5%a),
4.59 (m, 3/2 H, H-4%,5%b), 4.73 (d, 1/2 H, J2a,2b
15.9 Hz, H-2b), 4.81 (dd, 1/2 H, J5%a,5%b 12.1,
J4%,5%b 3.5 Hz, H-5%b), 5.70 (m, 1 H, H-3%), 5.83
(m, 1 H, H-2%), 6.23 (dd, 1/2 H, J4,5 10.4, J5,6
1.8 Hz, H-5), 6.29 (dd, 1/2 H, J4,5 10.4, J4,6 2.1
Hz, H-4), 6.38 (dd, 1/2 H, J4,5 10.7, J5,6 2.1
Hz, H-5), 6.85 (dd, 1/2 H, J4,5 10.7, J4,6 2.4
Hz, H-4), 7.32–3.06 (m, 15 H, Ph), 9.36, 9.55
(each s, each 1/2 H, NH, exchanged with
D2O). Anal. Calcd for C32H29N3O9·0.5 H2O:
C, 63.15; H, 4.97; N, 6.90. Found: C, 63.35;
H, 4.86; N, 6.74.
tri-O-benzoyl-i- -ribofuranosyl)-2,3-dihydro-
D
6H-pyran (6c) and (6d).—The same procedure
was used as for the reduction of 2a with
NaBH4.
(3S)- and (3R)-3-Hydroxy-(6S)-6-(2,3,5-
tri-O-benzoyl-i- -ribofuranosyl)-2,3-dihydro-
D
6H-pyran (6a) and (6b).—To a solution of 2a
(111.3 mg, 0.21 mmol) in MeOH (4 mL) was
slowly added NaBH4 (10.4 mg, 0.27 mmol) at
0 °C for 20 min. Water was added and the
mixture was extracted with CHCl3 (3×10
mL). The extracts were combined, washed
with water, dried over MgSO4, and evapo-
rated to dryness. The residual syrup was sepa-
rated by PTLC with 8:1 CHCl3–EtOAc as
eluent.
Compound 6c. Yield: 30%; Rf 0.23; 1H
NMR (CDCl3): l 3.16 (br d, 1 H, OH, ex-
changed with D2O), 3.63 (dd, 1 H, J2a,2b 12.1,
J2a,3 2.2 Hz, H-2a), 3.81 (m, 2 H, H-2b,3), 4.36
(apparent s, 1 H, H-6), 4.41 (dd, 1 H, J1%,2% 6.2,
J6%,1% 3.1 Hz, H-1%), 4.62 (m, 2 H, H-4%,5%a), 4.78
(dd, 1 H, J5%a,5%b 12.0, J4%,5%b 3.1 Hz, H-5%b), 5.72
(dd, 1 H, J2%,3% 6.2, J3%,4% 4.2 Hz, H-3%), 5.86 (dd,
1 H, J1%,2%=J2%,3% 6.2 Hz, H-2%), 5.90 (dd, 1 H,

M. Yuasa et al. / Carbohydrate Research 315 (1999) 98–105
103
J5%a,5%b 12.2, J4%,5%a 4.9 Hz, H-5%a), 4.58 (dd, 1 H,
J6,1% 4.3, J1%,2% 2.6 Hz, H-1%), 4.64 (m, 1 H,
H-4%), 4.78 (dd, 1 H, J5%a,5%b 12.2, J4%,5%b 3.2 Hz,
H-5%b), 5.64 (dd, 1 H, J3%,4% 7.9, J2%,3% 5.4 Hz,
H-3%), 5.88 (dd, 1 H, J2%,3% 5.4, J1%,2% 2.6 Hz,
H-2%), 7.26–8.09 (m, 15 H, Ph); 13C NMR
(CDCl3): l 63.6, 67.4 (C-5%, 2), 66.4, 69.6,
70.0, 72.3, 73.2, 75.4, 78.3, 83.9 (C-
3,4,5,6,1%,2%,3%,4%), 128.4–133.5 (Ph), 165.6,
166.0, 166.4 (CꢀO). FABMS (nitrobenzyl al-
cohol as matrix): Calcd for C31H31O11; [MH]
579.1866. Found: [MH]+ m/z 579.1851.
J4,5 10.0, J5,6 1.1 Hz, H-5), 6.15 (apparent t, 1
H, H-4), 7.29–8.14 (m, 15 H, Ph); 13C NMR
(CDCl3): l 62.2 (C-3), 64.1 (C-5%), 71.0 (C-2),
71.5, 73.0, 73.2, 80.6, 82.4 (C-6,1%,2%,3%,4%),
128.4–133.4 (Ph, C-4,5), 165.5, 165.7 (CꢀO).
FABMS (nitrobenzyl alcohol as matrix):
Calcd for C31H29O9; [MH] 545.1812. Found:
[MH]+ m/z 545.1813.
Compound 6d. Yield: 56%; Rf 0.15; 1H
NMR (CDCl3): l 1.82 (br d, 1 H, OH, ex-
changed with D2O), 3.40 (dd, 1 H, J2a,2b 11.0,
J2a,3 6.6 Hz, H-2a), 4.08 (dd, 1 H, J2a,2b 11.0,
J2b,3 4.4 Hz, H-2b), 4.14 (apparent s, 1 H,
H-6), 4.39 (m, 2 H, H-3,1%), 4.51 (dd, 1 H,
J5%a,5%b 11.7, J4%,5%a 4.4 Hz, H-5%a), 4.56 (m, 1 H,
H-4%), 4.75 (dd, 1 H, J5%a,5%b 11.7, J4%,5%b 3.7 Hz
H-5%b), 5.71 (dd, 1 H, J2%,3%=J3%,4% 5.5 Hz,
H-3%), 5.80 (dd, 1 H, J1%,2%=J2%,3% 5.5 Hz, H-2%),
5.85 (dd, 1 H, J4,5 10.3, J5,6 1.6 Hz, H-5), 6.05
(apparent d, 1 H, H-4), 7.31–8.10 (m, 15 H,
Ph); 13C NMR (CDCl3): l 62.4 (C-3), 63.9
(C-5%), 69.2 (C-2), 72.3, 72.6, 72.6, 79.5, 83.5
(C-6,1%,2%,3%,4%), 127.4 (C-5), 128.4–133.4 (Ph,
C-4), 165.4, 165.4, 166.2 (CꢀO). FABMS (ni-
trobenzyl alcohol as matrix): Calcd for
C31H29O9; [MH] 545.1812. Found: [MH]+ m/z
545.1801.
(3S,4R,5R)- and (3S,4S,5S)-3,4,5-Trihy-
droxy-(6S)-6-(2,3,5-tri-O-benzoyl-i- -ribo-
D
furanosyl)tetrahydropyran (7b) and (7c).—The
same procedure was used as for the oxidation
of 6a with osmium tetroxide.
Compound 7b. Yield: 10%; Rf 0.38; 1H
NMR (CDCl3): l 1.68 (br, 3 H, OH, ex-
changed with D2O), 3.05 (dd, 1 H, J2a,2b =J2a,3
10.6 Hz, H-2a), 3.36 (dd, 1 H, J3,4 9.0, J4,5 3.4
Hz, H-4), 3.46 (d, 1 H, J5,6 3.4 Hz, H-6), 3.92
(m, 1 H, H-3), 3.99 (dd, 1 H, J2a,2b 10.6, J2b,3
5.4 Hz, H-2b), 4.09 (dd, 1 H, J4,5=J5,6 3.4 Hz,
H-5), 4.47 (m, 2 H, H-1%,5%a), 4.61 (m, 1 H,
H-4%), 4.81 (dd, 1 H, J5%a,5%b 12.1, J4%,5%b 3.3 Hz,
H-5%b), 5.67 (dd, 1 H, J3%,4% 8.2, J2%,3% 5.1 Hz,
H-3%), 5.93 (dd J2%,3% 5.1 J1%,2% 1.7 Hz, H-2%),
7.35–8.08 (m, 15 H, Ph); 13C NMR (CDCl3):
l 63.4, 69.8 (C-2,5%), 67.7, 69.0, 72.3, 74.3,
75.2, 77.8, 79.5, 83.1 (C-3,4,5,6,1%,2%,3%,4%),
128.4–133.6 (Ph), 165.4, 166.2, 166.5 (CꢀO).
FABMS (nitrobenzyl alcohol as matrix):
Calcd for C31H31O11; [MH] 579.1866. Found:
[MH]+m/z, 579.1864.
(3R,4S,5S)-3,4,5-Trihydroxy-(6S)-6-(2,3,5-
tri-O-benzoyl-i- -ribofuranosyl)tetrahydro-
D
pyran (7a).—Osmium tetroxide (18 mg, 0.01
mmol) in 0.2 mL of dry pyridine was added to
a solution of 34.0 mg (0.063 mmol) of 6a in
0.5 mL of pyridine at rt. The solution was
stirred for 2 h at rt and then treated with a
solution of 34 mg of sodium bisulfite in a
mixture of 0.2 mL of pyridine and 0.3 mL of
water and then stirred for an additional 1 h.
Compound 7c. Yield: 51%; Rf 0.32; 1H
NMR (CDCl3): 1.78, 2.63, 3.05 (each br, each
1 H, OH, exchanged with D2O), 3.41 (dd, 1 H,
The
solution
was
extracted
with
dichloromethane (3×10 mL). The extracts
were combined, washed with water, dried over
MgSO4, and evaporated to dryness. The resid-
ual syrup was separated by PTLC with 19:1
CHCl3–MeOH as eluent.
J2a,2b=J2a,3 10.5 Hz, H-2a), 3.70 (m, 2 H,
H-2b,6), 3.77 (m, 1 H, H-3), 3.84 (dd, 1 H, J5,6
10.0, J4,5 2.7 Hz, H-5), 4.20 (dd, 1 H, J3,4 =J4,5
2.7 Hz, H-4), 4.54 (dd, J5%a,5%b 12.2, J4%,5%a 3.2
Hz, H-5%a), 4.58 (dd, 1 H, J6,1% 2.9, J1%,2% 2.4 Hz,
H-1%), 4.64 (m, 1 H, H-4%), 4.77 (dd, 1 H, J5%a,5%b
12.2, J4%,5%b 3.2 Hz, H-5%b), 5.62 (dd, 1 H, J3%,4%
8.1, J2%,3% 5.4 Hz, H-3%), 5.80 (dd, 1 H, J2%,3% 5.4,
J1%,2% 2.4 Hz, H-2%), 7.33–8.09 (m, 15 H, Ph);
13C NMR (CDCl3): l 63.5, 65.7 (C-2,5%), 67.0,
68.8, 70.5, 72.2, 73.1, 74.5, 78.3, 83.9 (C-
3,4,5,6,1%,2%,3%,4%), 128.4–133.5 (Ph), 165.5,
166.1, 166.4 (CꢀO). FABMS (nitrobenzyl al-
1
Compound 7a. Yield: 28.1 mg (78%); H
NMR (CDCl3): l 1.71, 2.63, 3.35 (each br,
each 1 H, OH, exchanged with D2O), 3.67 (d,
1 H, J2a,2b 12.2 Hz, H-2a), 3.72 (dd, 1 H, J5,6
10.0, J6,1% 4.3 Hz, H-6), 3.83 (apparent s, 1 H,
H-3), 3.86 (d, 1 H, J2%a,2%b 12.2 Hz, H-2b), 4.06
(dd, 1 H, J3,4=J4,5 3.2 Hz, H-4), 4.12 (dd, 1
H, J5,6 10.0, J4,5 3.2 Hz, H-5), 4.53 (dd, 1 H,

104
M. Yuasa et al. / Carbohydrate Research 315 (1999) 98–105
purified by PTLC to afford the free C-
nucleoside.
cohol as matrix): Calcd for C31H31O11; [MH]
579.1866. Found: [MH]+ m/z 579.1857.
(3S,4R,5R)-3,4,5-Trihydroxy-(6R)-6-(2,3,
(6S) - 6 - (i - - Ribofuranosyl)pyran - 3 - (2H,
D
6H)-one semicarbazone (4a). Yield: 89%; CD
(MeOH)/nm 237.0 (Dm −3.33), 273.4 (Dm +
5-tri-O-benzoyl-i- -ribofuranosyl)tetrahydro-
D
pyran (7d).—The same procedure was used as
for the oxidation of 6a with osmium tetroxide.
Compound 7d. Yield: 85%; 1H NMR
(CDCl3): l 1.80, 2.80, 3.05 (each br, each 1 H,
OH, exchanged with D2O), 3.48 (d, 1 H, J2a,2b
11.8 Hz, H-2a), 3.65 (dd, 1 H, J5,6 9.8, J6,1% 1.7
Hz, H-6), 3.71 (apparent s, 1 H, H-3), 3.83 (d,
1 H, J2a,2b 11.8 Hz, H-2b), 4.07 (apparent s, 1
H, H-4), 4.12 (d, 1 H, J5,6 9.8 Hz, H-5), 4.62
(m, 1 H, H-4%), 4.67 (dd, 1 H, J1%,2% 4.1, J6,1% 1.7
Hz, H-1%), 4.72 (m, 2 H, H-5%), 5.74 (dd, 1 H,
J2%,3%=J3%,4% 5.6 Hz, H-3%), 5.81 (dd, 1 H, J2%,3%
5.6, J1%,2% 4.1 Hz, H-2%), 7.33–8.09 (m, 15 H,
1
6.52); H NMR (CD3OD): l 3.57 (dd, 1 H,
J5%a,5%b 12.0, J4%,5%b 5.4 Hz, H-5%a), 3.73 (dd, 1 H,
J5%a,5%b 12.0, J4%,5%b 3.1 Hz, H-5%b), 3.83 (m, 1 H,
H-4%), 3.91 (m, 2 H, H-6,2%), 4.06 (dd, 1 H,
J2%,3% 5.4, J3%,4% 3.7 Hz, H-3%), 4.23 (m, 3/2 H,
H-2a,1%), 4.36 (d, 1/2 H, J2a,2b 13.9 Hz, H-2b),
4.82 (m, 1 H, H-2a,2b), 6.33 (dd, 1/2 H, J4,5
10.5, J4,6 1.8 Hz, H-4), 6.37 (dd, 1/2 H, J4,5
10.5, J5,6 1.5 Hz, H-5), 6.53 (dd, 1/2 H, J4,5
10.7, J5,6 2.0 Hz, H-5), 6.80 (dd, 1/2 H, J4,5
10.7, J4,6 2.4 Hz, H-4). FABMS (nitrobenzyl
alcohol as matrix): m/z 288 [MH]+.
13
Ph); C NMR (CDCl3): l 64.0, 67.2 (C-2,5%),
(6R)-6-(i- -Ribofuranosyl)-pyran-3(2H,
D
64.2, 69.9, 70.2, 73.1, 73.4, 74.4, 80.0, 80.9
(C-3,4,5,6,1%,2%,3%,4%), 128.4–133.4 (Ph), 165.5,
165.7, 166.7 (CꢀO). FABMS (nitrobenzyl al-
cohol as matrix): Calcd for C31H31O11: [MH]
579.1866. [MH]+ m/z 579.1843.
6H)-one semicarbazone (4b). Yield: 76%; CD
(MeOH)/nm 238.2 (Dm +5.66), 271.8 (Dm −
1
1.03); H NMR (CD3OD): l 3.59 (m, 1 H,
H-5%a), 3.69 (dd, 1 H, J5%a,5%b 12.0, J4%,5%b 3.4 Hz,
H-5%b), 3.81 (dd, 1 H, J2%,3% 8.5, J1%,2% 5.4 Hz,
H-2%), 3.92 (m, 2 H, H-3%,4%), 4.05 (t, 1 H,
J6,1%=J1%,2% 5.4 Hz, H-1%), 4.27 (d, 1/2 H, J2a,2b
13.8 Hz, H-2a), 4.28 (d, 1/2 H, J2a,2b 15.7 Hz,
H-2a), 4.33 (m, 1/2 H, H-6), 4.41 (d, 1/2 H,
J2a,2b 13.8 Hz, H-2b), 4.44 (m, 1/2 H, H-6),
4.82 (d, 1/2 H, J2a,2b 15.7 Hz, H-2b), 6.34 (dd,
1/2 H, J4,5 10.5, J5,6 1.7 Hz, H-5), 6.38 (dd, 1/2
H, J4,5 10.5, J4,6 1.7 Hz, H-4), 6.52 (dd, 1/2 H,
J4,5 10.7, J5,6 2.2 Hz, H-5), 6.82 (dd, 1/2 H, J4,5
10.7, J4,6 2.6 Hz, H-4). FABMS (nitrobenzyl
alcohol as matrix): m/z 288 [MH]+.
(3R,4R,5R)-3,4,5-Trihydroxy-(6R)-6-(2,3,
5-tri-O-benzoyl-i- -ribofuranosyl)tetrahydro-
D
pyran (7e).—The same procedure was used as
for the oxidation of 6a with osmium tetroxide.
Compound 7e. Yield: 83%; 1H NMR
(CDCl3): l 2.10, 2.52, 2.60 (each br, each 1 H,
OH, exchanged with D2O), 3.42 (m, 2 H,
H-2a,3), 3.54 (dd, 1 H, J2a,2b 9.9, J2b,3 4.8 Hz,
H-2b), 3.65 (dd, 1 H, J5,6 9.5, J6,1% 1.5 Hz,
H-6), 3.76 (dd, 1 H, J5,6 9.5, J4,5 2.6 Hz, H-5),
4.14 (d, 1 H, J4,5 2.6 Hz, H-4), 4.42 (dd, 1 H,
J5%a,5%b 12.5, J4%,5%a 3.7 Hz, H-5%a), 4.60 (m, 2 H,
H-4%,1%), 4.84 (dd, 1 H, J5%a,5%b 12.5, J4%,5%b 3.7
Hz, H-5%b), 5.69 (dd, 1 H, J3%,4% 7.7, J2%,3% 5.5
Hz, H-3%), 5.79 (dd 1 H J2%,3% 5.5 J1%,2% 2.6 Hz,
H-2%), 7.32–8.10 (m, 15 H, Ph); 13C NMR
(CDCl3): l 63.1, 65.7 (C-2,5%), 66.7, 67.0, 70.8,
72.2, 73.9, 74.3, 78.5, 81.4 (C-3,4,5,6,1%,2%,3%,
4%), 128.3–133.4 (Ph), 165.4, 165.8, 166.4
(CꢀO). FABMS (nitrobenzyl alcohol as ma-
trix): Calcd for C31H31O11; [MH] 579.1866.
Found: [MH]+ m/z 579.1908.
(3R,4S,5S)-3,4,5-Trihydroxy-(6S)-6-(i- -
D
ribofuranosyl)tetrahydropyran (8a). Yield:
1
71%; [h]D +3.8° (c 0.43, MeOH); H NMR
(CD3OD): l 3.58 (dd, 1 H, J2a,2b 12.0, J2a,3 5.1
Hz, H-2a), 3.66 (m, 3 H, H-4%,5%), 3.73 (dd, 1
H, J2a,2b 12.0, J2b,3 3.1 Hz, H-2b), 3.79–3.92
(m, 5 H, H-3,4,5,6,1%), 4.14 (dd, 1 H, J2%,3% 4.8,
J3%,4% 2.8 Hz, H-3%), 4.27 (dd, 1 H, J1%,2%=J2%,3%
4.8 Hz, H-2%); 13C NMR (CD3OD): l 63.8,
67.9 (C-2,5%), 67.0, 71.4, 71.6, 72.2, 73.1, 76.7,
84.9, 85.7 (C-3,4,5,6,1%,2%,3%,4%). FABMS (tri-
ethanolamine as matrix): Calcd for C10H17O8;
[M−H] 265.0923. Found: [M−H]− m/z
265.0882.
General procedure for the deprotection.—
Sufficient methanolic sodium carbonate (0.5
mL, 0.4 mmol) was added to the protected
C-nucleoside (0.04 mmol) in MeOH (2 mL).
The mixture was kept at rt for 5 h and evapo-
rated under reduced pressure. The residue was
(3S,4R,5R)-3,4,5-Trihydroxy-(6S)-6-(i- -
D
ribofuranosyl)tetrahydropyran (8b). Yield:
1
67%; [h]D +37.2 (c 0.45, MeOH); H NMR

M. Yuasa et al. / Carbohydrate Research 315 (1999) 98–105
105
265.0923. Found; [M−H]− m/z 265.0960.
(CD3OD): l 3.10 (t, 1 H, J2a,2b=J2a,3 10.7 Hz,
H-2a), 3.28 (m, 1 H, H-6), 3.56 (dd, 1 H,
J5%a,5%b 11.7, J4%,5%a 5.4 Hz, H-5%a), 3.72 (dd, 1 H,
J5%a,5%b 11.7, J4%,5%b 2.9 Hz, H-5%b), 3.81 (m, 2 H,
H-1%,4%), 3.91–4.03 (m, 4 H, H-2b,3,5,2%), 4.14
(dd, 1 H, J2%,3% 5.4, J3%,4% 3.9 Hz, H-3%); 13C
NMR (CD3OD): l 63.4, 71.5 (C-2,5%), 68.3,
70.3, 72.7, 73.8, 76.3, 80.9, 83.6, 84.6 (C-
3,4,5,6,1%,2%,3%,4%). FABMS (triethanolamine as
matrix): Calcd for C10H17O8; [M−H]
265.0923. Found: [M−H]− m/z 265.0806.
(3R,4R,5R)-3,4,5-Trihydroxy-(6R)-6-(i-
D
-ribofuranosyl)tetrahydropyran (8e). Yield:
1
82%; [h]D −20.5° (c 1.00, MeOH); H NMR
(CD3OD): l 3.52–3.69 (m, 7 H, H-2,5,6,4%,5%),
3.83 (m, 1 H, H-3), 3.94 (dd, 1 H, J6,1%=J1%,2%
5.1 Hz, H-1%), 4.09 (m, 3 H, H-4,2%,3%); 13C
NMR (CD3OD): l 64.0, 66.6 (C-2,5%), 68.6,
68.7, 72.5, 73.1, 73.2, 75.2, 82.6, 85.6 (C-
3,4,5,6,1%,2%,3%,4%). FABMS (triethanolamine as
matrix): Calcd for C10H17O8; [M−H]
265.0923. Found: [M−H]− m/z 265.0914.
(3S,4S,5S)-3,4,5-Trihydroxy-(6S)-6-(i- -
D
ribofuranosyl)tetrahydropyran (8c). Yield:
1
70%; [h]D +9.1° (c 1.11, MeOH); H NMR
Acknowledgements
(CD3OD): l 3.50–3.66 (m, 6 H, H-2a,3,5,6,5%),
3.72 (dd, 1 H, J2a,2b 12.0, J2b,3 3.2 Hz, H-2b),
3.83 (m, 1 H, H-4%), 3.89 (dd, 1 H, J6,1% 5.7.
J2%,1% 4.8 Hz, H-1%), 4.03 (m, 1 H, H-4), 4.11
(dd, 1 H, J2%,3% 4.8, J3%,4% 2.3 Hz, H-3%), 4.19 (dd,
1 H, J1%,2%=J2%,3% 4.8 Hz, H-2%); 13C NMR
(CD3OD): l 63.8, 66.3 (C-2,5%), 68.7, 69.7,
72.2, 72.3, 73.1, 75.7, 85.0, 85.6 (C-
3,4,5,6,1%,2%,3%,4%). FABMS (triethanolamine as
matrix): Calcd for C10H17O8: [M−H]
265.0923. Found: [M−H]− m/z 265.0902.
This work was partly supported by the
Ministry of Education Science, Sports and
Culture of Japan (High-Tech Research Center
Project).
References
[1] P. Lalegerie, G. Legler, J.M. Yon, Biochimie, 64 (1982)
977–1000.
[2] E. Truscheit, W. Frommer, B. Junge, L. Muller, D.D.
Schmidt, W. Wingender, Angew. Chem., Int. Ed. Engl., 20
(1981) 744–761.
[3] (a) S.J. Danishefsky, C.J. Maring, M.R. Barbachyn, B.E.
Segmuller, J. Org. Chem., 49 (1984) 4564–4565. (b) R.W.
Armstrong, B.R. Teegarden, J. Org. Chem., 57 (1992)
915–922. (c) A. Dondoni, L. Kniezo, M. Martinkova, J.
Chem. Soc., Chem. Commun., (1994) 1963–1964. (d)
A.L.J. Byerley, A.M. Kenwright, P.G. Steel, Tetrahedron
Lett., 37 (1996) 9093–9096. (e) G.V.M. Sharma, L. Hy-
mavathi, P.R. Krishna, Tetrahedron Lett., 38 (1997)
6929–6932.
(3S,4R,5R)-3,4,5-Trihydroxy-(6R)-6-(i- -
D
ribofuranosyl)tetrahydropyran (8d). Yield:
1
71%; [h]D −22.2° (c 0.32, MeOH); H NMR
(CD3OD): l 3.58 (m, 2 H, H-2a,5%a), 3.67 (m,
2 H, H-4%,5%b), 3.73 (dd, 1 H, J2a,2b 12.2, J2a,3
2.9 Hz, H-2b), 3.83 (m, 2 H, H-5,6), 3.92 (dd,
1 H, J6,1%=J1%,2% 3.2 Hz, H-1%), 3.99 (m, 2 H,
H-3,4), 4.11 (m, 2 H, H-2%,3%); 13C NMR
(CD3OD): l 63.0, 68.2 (C-2,5%), 65.8, 71.4,
71.6, 72.5, 72.7, 75.8, 82.6, 85.5 (C-
3,4,5,6,1%,2%,3%,4%). FABMS (triethanolamine as
matrix): Calcd for C10H17O8; [M−H]
[4] I. Maeba, T. Takeuchi, T. Iijima, H. Furukawa, J. Org.
Chem., 53 (1988) 1401–1405.
[5] N. Morishita, S. Honmi, C. Ito, I. Maeba, J. Chem. Soc.,
Perkin Trans. 1, (1992) 791–795.
.