The arabinofuranoside method, a convenient substitute of the fucofuranoside method for determining the absolute configuration of the secondary alcohols

Article abstract of DOI:10.1016/S0040-4020(02)01248-6

As a simple substitute of the fucofuranoside method, a recently devised technique for determining the absolute configuration of secondary alcohols by ¹³C NMR, the arabinofuranoside method is proposed. Unlike fucose, the derivatizing agent arabi

Full text of DOI:10.1016/S0040-4020(02)01248-6

Tetrahedron 58 (2002) 9365–9371
The arabinofuranoside method, a convenient substitute of the
fucofuranoside method for determining the absolute configuration
of the secondary alcohols
*
Masaru Kobayashi
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Sapporo 060-0812, Japan
Received 27 August 2002; accepted 27 September 2002
Abstract—As a simple substitute of the fucofuranoside method, a recently devised technique for determining the absolute configuration of
secondary alcohols by 13C NMR, the arabinofuranoside method is proposed. Unlike fucose, the derivatizing agent arabinofuranose
tetraacetate is available quantitatively by acid treatment of arabinose followed by acetylation. Application to the ten alcohols, previously
tested for fucofuranoside method, showed essentially the identical DdC and DdH values, indicating that the arabinofuranoside method is
equally useful for determining the absolute configuration of the secondary alcohols. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
In the preceding works the author proposed the fucofurano-
side method for determining the absolute configuration of
the secondary alcohols, by converting to b-D- and b-L-
fucofuranosides.1–3 The judgment, drawn by the 13C NMR
1
rule, can be substantiated simultaneously by the H NMR
rule. In the 13C NMR analyses, it utilizes the difference of
the glycosidation shifts on the a- and b-carbon of the
Figure 1. Side view of the glycosidic linkages of the a-arabinofuranoside
and b-fucofuranoside.
1
aglycon, and on the anomeric carbon.4 For the H NMR
analyses, it utilizes the uneven paramagnetic effect of the
solvent pyridine (pyridine-induced shift),5 which solvates to
the polar and chiral fucofuranosyl moiety. These two effects
the 6-demethyl analog of fucose, is also commercially
are influenced by the conformation of the glycosidic
available both in D- and L-form. Unlike fucose, it has been
linkage, which depends on the steric environment of the
known that, by the same acid treatment, it changes into the
hydroxyl group, and cause the difference of the chemical
furanose form predominantly.6 Owing to the nomenclature
shifts, both in 1H and 13C NMR, between the diastereomeric
rule, however, the b-D-fucofuranose corresponds to a-L-
two fucofuranosides. These explanations have been
arabinofuranose, and the b-L-fucofuranose corresponds to
described in detail in the previous papers.1–3 The efficacy
a-D-arabinofuranose (Fig.1). The present paper shows that
of the method was proved for nineteen compounds,
the arabinofuranoside method is equally applicable as
including monohydroxy secondary alcohols,1 1,2-glycols
fucofuranoside method for determining the absolute con-
consisting of secondary and tertiary hydroxyl groups,3 and
figuration of secondary alcohols.
for the simple tertiary alcohols substituted with methyl and
two methylene groups.2
Preparation of the derivatizing agent fucofuranose tetra-
2. Results and discussion
acetate is, however, time-consuming, since the acid
treatment (1% methanolic HCl) of fucose gives the pyranose
In the fucofuranoside method the Dd values are obtained,
and furanose forms in almost equal amounts.1 Arabinose,
both in 13C and 1H NMR, by subtracting the chemical shift
of the b-D-isomer from the corresponding chemical shift of
Keywords: alcohol; arabinofuranoside; glycosidation shift; pyridine-
induced shift; 13C NMR; 1H NMR; absolute configuration.
the b-L-isomer. For the secondary alcohols, when the
glycoside is viewed fixing the a-proton below and the sugar
moiety in front, there are following rules.1,3
*
Tel.: þ81-011-706-3242; fax: þ81-011-706-4989; e-mail:
masark@pharm.hokudai.ac.jp
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01248-6

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M. Kobayashi / Tetrahedron 58 (2002) 9365–9371
Figure 2. The DdC (upper) and DdH (lower) values of the symmetrical (1), R-type (2) and S-type (3) secondary alcohols, and the tertiary alcohol 4 reported
previously using the fucofuranoside method (in ppm).
13C NMR (Fig. 2, upper part).
bulkier b-position (c) less bulky b-position. If it is
clockwise (R-type) as in l-menthol (2), the DdC values
of the anomeric, a-, and the right b-carbon are positive
while that of the left b-carbon is small (mostly
positive). In the counterclockwise (S-type) case, as in
4,4-dimethylcolesterol (3), the DdC values of the
anomeric, a-, and the left b-carbon (C-2) are negative
while that of the right b-carbon is small (mostly
negative).
(a) When the two b-carbons bear symmetrical steric
hindrances, as in cholesterol (1), the DdC value of the
right b-carbon is positive and that of the left b-carbon
is negative while those of the anomeric and a-carbon
are negligible.
(b) When the steric hindrances are unsymmetrical, see
the order of (a) fucofuranosyl group (b) sterically
Figure 3. The DdC (dDC2dCL ) values observed for the carbons of the a-D- and a-L-arabinofuranoside derivatives of the symmetrical (1, 5, 6), R-type (2, 7, 8) and
S-type (3, 9, 10) secondary alcohols, and the tertiary alcohol 4 (125 MHz, in ppm).

M. Kobayashi / Tetrahedron 58 (2002) 9365–9371
9367
Figure 4. The DdH (dDH2dHL ) values observed for the protons of the a-D- and a-L-arabinofuranoside derivatives of the symmetrical (1, 5, 6), R-type (2, 7, 8) and
S-type (3, 9, 10) secondary alcohols, and the tertiary alcohol 4 (500 MHz, in ppm).
1H NMR (Fig. 2, lower part).
reported procedure, with arabinofuranose tetraacetate,
TMSOTf and 4A molecular sieve, followed by hydroly-
sis.1,7a The tertiary alcohol 4 was glycosidated using the
1-bromosugar and silver zeolite.2,7b,c Under these
conditions, the arabinofuranosides formed are exclusively
a-anomers, as confirmed by the characteristic small
coupling constant (less than 2.0 Hz) of the anomeric proton.
The a-D- and a-L-arabinofuranosides obtained showed the
NOE between the anomeric and a-proton, in common with
the corresponding b-L- and b-D-fucofuranoside,
respectively.
(a) When the two b-carbons bear symmetrical steric
hindrances, the DdH values are positive for the right
segment protons and negative for the left segment
protons while that of the a-proton is negligible (Fig. 2,
1).
(b) In the unsymmetrical compounds, the DdH values
are also positive for the right segment protons and
negative for the left segment protons. However, the
DdH value of the a-proton is negative in the R-type
compounds (Fig. 2, 2), but that is positive in the
S-type compounds (Fig. 2, 3).
The DdC and DdH values, obtained by subtracting the
chemical shift of the a-L-isomer from the corresponding
chemical shift of the a-D-isomer, are shown in Figs. 3 and 4.
The results are indeed consistent with the rule shown above
in the fucofuranoside method. In the symmetrical com-
pounds 1, 5 and 6, the DdC value of the right b-carbon is
positive and that of the left b-carbon is negative while those
of the anomeric and a-carbon are quite small (Fig. 3). In the
R-type compounds 2, 7 and 8, the DdC values of the
anomeric, a-, and the right b-carbon are positive while that
of the left b-carbon is small. In contrast, in the S-type
compounds 3, 9 and 10, the DdC values of the anomeric, a-,
To confirm that these rules also hold good in arabinofurano-
side, three secondary alcohols having methylene group at
both b-position (1, 5, 6), each three unsymmetrically
substituted R-type (2, 7, 8) and S-type (3, 9, 10) secondary
alcohols, and one tertiary alcohol (4), substituted with
methyl and two methylene groups, were chosen. The DdC
and DdH values of these compounds in the fucofuranoside
method have previously been shown.1–3 These alcohols
were converted to arabinofuranosides, using the previously

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M. Kobayashi / Tetrahedron 58 (2002) 9365–9371
and the left b-carbon are negative while that of the right
b-carbon is small.
evaporated off. The residue was dissolved, with cooling, in
40 ml of pyridine and 15 ml of Ac2O and kept at room
temperature overnight. The mixture was added into ice-
water and stirred for 1 h. The mixture was extracted with
CHCl3 and the extract was thoroughly washed with
saturated NaHCO3 solution, H2O and saturated NaCl
solution, and then the solvent was evaporated off. It was
dissolved in a mixture of AcOH (50 ml) and Ac2O (12.5 ml)
and treated, with cooling, with conc. H2SO4 (2.5 ml), and
kept at room temperature overnight. The mixture was added
with ice-water (75 ml), stirred for 50 min, and extracted
with CHCl3. The extract was washed with H2O, saturated
NaHCO3 solution, H2O and saturated NaCl solution, and the
solvent was evaporated giving crude arabinofuranoside
(6.9 g). A portion (2.5 g) of the product was purified by flash
chromatography over a column of silica gel with ethyl-
acetate–hexane (1.3:2) to remove the trace amount of the
more polar by-product. The arabinofuranoside tetraacetate
obtained is a ca. 10:1 mixture of a-anomer and b-anomer
but gives the a-furanoside exclusively in the following
glycosidation condition.
1
The H NMR showed also the results, consistent with the
rule (Fig. 4). The significant DdH values, caused by the
pyridine-induced shift, are positive for the right segment
protons and negative for the left segment protons. The DdH
values of the a-proton in the symmetrical compounds 1, 5
and 6 are negligible. In contrast, they are significant and
negative in the R-type compounds 2, 7 and 8, but are
positive in the S-type compounds 3, 9 and 10. The
diastereomeric glycosides generally show small difference
of the chemical shifts, unrelated to the pyridine-induced
anisotropy, so that the DdH values up to a magnitude of
0.02 ppm should be regarded as meaningless.
The fucofuranoside method has been shown to be effective
for the six-membered cyclic tertiary alcohols substituted
with methyl and two methylene groups.2 However, it was
not in the 13C NMR of the five-membered 4-norcholestane
type alcohol 4 (Fig. 2). The 40-oxygen atom of the furanose
unit influences on one of the b-carbons of the six-membered
compounds causing small difference between the dia-
stereomeric two glycosides. Probably, this effect is lost in
the five-membered compound due to the increased distance
between the two positions. It was also the case in the present
3.3. Preparation of a-D- and a-L-arabinofuranosides
TMSOTf (10 ml) was added to the mixture of the
arabinofuranose tetraacetate (75 mg, 0.24 mmol) and
powdered and freshly dried 4A molecular sieve (250 mg)
in dry CH2Cl2 (1.5 ml) and stirred for 3 min. The starting
alcohol (0.1 mmol) was added and the mixture was stirred at
room temperature for 30–60 min. Excess TMSOTf was
quenched with one drop of triethylamine and the mixture
was filtered. The filtrate was evaporated to dryness and
dissolved in 1 ml of MeOH and one drop of 28% NaOMe in
MeOH and kept at 608C for 30 min. After usual work-up,
the mixture was subjected to flash chromatography over a
column of silica gel with 2–4% MeOH in CHCl3 giving the
a-arabinofuranoside (20–50% yield).
1
study as shown in Fig. 3 but, in contrast, in the H NMR
(Fig. 4) it showed substantial DdH values due to the 3b-H
(right, þ0.27 ppm) and the 1b-H (left, 20.23 ppm).
The magnitude of the DdC and DdH values, observed in the
present study, are virtually identical with the corresponding
values found in the fucofuranosides (Fig. 2). This indicates
that the conformation of the each glycosidic linkage in
compounds 1 to 10 is also virtually identical with that of the
corresponding fucofuranoside. In summary, the arabino-
furanoside method is shown to be equal to the fucofuranoside
method and more convenient because of the easier preparation
of the derivatizing agent arabinofuranose tetraacetate.6
3.3.1. Cholest-5-en-3b-ol 3-O-a-D-arabinofuranoside
(1a). Mp 240–2428C (from acetone); [a]2D3¼þ44.28 (c
2.34, pyridine); dH 0.66 (3H, s, 18-H3), 0.98 (3H, s, 19-H3),
1.77 (1H, dt, J¼13.5, 3.5 Hz, 1b-H), 1.91 (1H, dddd,
J¼17.5, 5.5, 5.5, 2.5 Hz, 7b-H), 1.98 (2H, m, 2a, 12b-H),
2.57 (1H, br t, J¼13.5 Hz, 4b-H), 2.74 (1H, ddd, J¼13.5,
5.0, 2.0 Hz, 4a-H), 3.80 (1H, m, 3a-H), 5.32 (1H, m, 6-H),
5.70 (1H, d, J¼2.0 Hz, 10-H) [0.95 (9a-H), 1.00 (1a-H),
1.39 (8b-H), 1.39 (11b-H), 1.46 (11a-H), 1.53 (7a-H) and
1.60 (2b-H) detected by HSQC spectrum]; dC 12.0 (C-18),
19.5 (C-19), 21.3 (C-11), 24.5 (C-15), 28.5 (C-16), 28.6
(C-2), 32.1 (C-8), 32.2 (C-7), 36.9 (C-10), 37.5 (C-1), 40.0
(C-12), 41.1 (C-4), 42.5 (C-13),0 50.4 (C-9), 56.4 (C-17),
56.9 (C-14), 77.3 (C-3), 62.9 (C-5 ), 78.8 (C-30), 84.2 (C-20),
85.4 (C-40), 107.8 (C-10), 121.8 (C-6), 141.2 (C-5). [Found:
MNaþ, m/z 541.3884. C32H54O5Na requires 541.3869].
3. Experimental
3.1. General
Mps were determined on a Kofler hot stage and are
uncorrected. The optical rotations were determined on a
JASCO DIP-370 digital polarimeter. NMR spectra were
determined in pyridine-d5 on a JEOL ALPHA 500
spectrometer at 500 MHz (1H) and at 125 MHz (13C) and
were referenced to the residual proton of the solvent
(7.20 ppm) or the solvent carbon (123.50 ppm) as internal
standards. J values are given in Hz. Mass spectra were
determined on a JEOL JMS DX 303 (EI) and JEOL JMS HX
110 (FAB) mass spectrometer. Flash column chromato-
graphy was performed on silica gel (Wako gel C-300,
200–300 mesh, Wako Pure Chemical Industries).
3.3.2. Cholest-5-en-3b-ol 3-O-a-L-arabinofuranoside
(1b). Mp 201–2038C (from acetone); [a]2D3¼299.18 (c
2.32, pyridine); dH 0.66 (3H, s, 18-H3), 0.97 (3H, s, 19-H3),
1.76 (1H, m, 2b-H), 1.92 (1H, br d, J¼17.5 Hz, 7b-H), 2.16
(1H, m, 2a-H), 2.39 (1H, br t, J¼13.0 Hz, 4b-H), 2.57 (1H,
ddd, J¼13.0, 5.0, 2.0 Hz, 4a-H), 3.80 (1H, m, 3a-H), 5.34
(1H, m, 6-H), 5.71 (1H, d, J¼2.0 Hz, 10-H) [0.95 (9a-H),
1.02 (1a-H), 1.38 (8b-H), 1.54 (7a-H), 1.39 (11b-H), 1.46
3.2. D- and L-arabinofuranose tetraacetates
D-Arabinose or L-arabinose (5 g) was dissolved in a mixture
of H2SO4 (0.9 ml) in 130 ml of dry MeOH and stirred at 38C
for 1 d. Pyridine (40 ml) was added and the solvent was

M. Kobayashi / Tetrahedron 58 (2002) 9365–9371
9369
(11a-H), and 1.75 (1b-H) detected by HSQC spectrum]; dC
12.0 (C-18), 19.5 (C-19), 21.3 (C-11), 24.5 (C-15), 28.5
(C-16), 30.5 (C-2), 32.1 (C-8), 32.2 (C-7), 37.0 (C-10), 37.6
(C-1), 39.3 (C-4), 40.0 (C-12), 402.5 (C-13), 50.4 (C-9), 560.4
(C-17), 56.8 (C-14), 62.9 (C-5 ), 77.0 (C-3), 78.7 (C-3 ),
84.2 (C-20), 85.3 (C-40), 107.7 (C-10), 121.9 (C-6), 141.0
(C-5). [Found: MNaþ, m/z 541.3870. C32H54O5Na requires
541.3869].
(1H, dd, J¼4.0, 3.0 Hz, 6-H) [0.90 (9a-H), 1.02 (1a-H),
1.48 (8b-H), 1.64 (1b-H) and 1.66 (7a-H) detected by
HSQC spectrum]; dC 12.0 (C-18), 20.9 (C-11), 21.6 (C-19),
24.4 (C-15), 25.2 (4b-Me), 26.7 (C-2), 27.4 (4a-Me), 28.6
(C-16), 31.2 (C-8), 32.9 (C-7), 36.8 (C-10), 37.0 (C-1), 40.0
(C-12), 42.1 (C-4), 42.5 (C-13), 051.2 (C-9),0 56.3 (C-17),
57.5 (C-14), 62.9 (C-50), 78.7 (C-3 ), 84.1 (C-2 ), 86.0 (C-3),
85.2 (C-40), 111.9 (C-10), 120.2 (C-6), 150.4 (C-5). [Found:
MNaþ, m/z 569.4160. C34H58O5Na requires 569.4182].
3.3.3. (2)-Menthol 3-O-a-D-arabinofuranoside (2a). Mp
113–1148C (from acetone); [a]2D3¼þ43.78 (c 1.58,
pyridine); dH 0.74 (1H, m, 6b-H), 0.76 (3H, d, J¼7.0 Hz,
9-H3), 0.79 (3H, d, J¼7.0 Hz, 7-H3), 0.81 (3H, d, J¼7.0 Hz,
10-H3), 0.88 (1H, dq, J¼3.5, 12.5 Hz, 5a-H), 1.19 (1H, br q,
J¼11.5 Hz, 2b-H), 1.24 (1H, m, 1a-H), 1.32 (1H, ddt,
J¼12.0, 10.5, 3.0 Hz, 4b-H), 1.50 (1H, m, 5b-H), 1.50 (1H,
m, 6a-H), 2.40 (1H, d sept, J¼2.0, 7.0 Hz, 8-H), 2.50 (1H,
m, 2a-H), 3.50 (1H, dt, J¼4.5, 10.5 Hz, 3a-H), 5.58 (1H, d,
J¼2.0 Hz, 10-H); dC 16.4 (C-9), 21.2 (C-10), 22.4 (C-7),
23.6 (C-5), 25.7 (C-8), 31.8 (C-1), 34.6 (C-6), 44.0 (C-2),
49.1 (C-4), 62.8 (C-50), 78.5 (C-30), 79.6 (C-3), 83.9 (C-20),
85.4 (C-40), 111.0 (C-10). [Found: MHþ, m/z 289.1995.
C15H29O5 requires 289.2015].
3.3.7. 2a-Methyl-4-nor-5a-cholestan-2b-ol 2-O-a-D-ara-
binofuranoside (4a). Colorless oil; [a]2D3¼þ34.78 (c 1.85,
pyridine); dH 0.64 (3H, s, 18-H3), 0.69 (1H, dt, J¼3.5,
11.2 Hz, 9a-H), 1.07 (3H, s, 19-H3), 1.51 (3H, s, 2a-Me),
1.74 (1H, dd, J¼13.0, 6.0 Hz, 3a-H), 2.10 (1H, d,
J¼13.0 Hz, 1b-H), 2.33 (1H, dd, J¼12.5, 13.0 Hz, 3b-H),
5.69 (1H, d, J¼2.4 Hz, 10-H) [0.84 (7a-H), 1.16 (1a-H),
1.25 (11a-H), 1.28 (6b-H), 1.29 (5a-H), 1.28 (8b-H), 1.40
(11b-H), 1.47 (6a-H), 1.63 (7b-H) detected by HSQC
spectrum]; dC 12.4 (C-18), 14.0 (C-19), 23.6 (C-11), 24.6
(C-15), 25.1 (C-6), 28.5 (C-16), 29.7 (2a-Me), 32.4 (C-7),
35.4 (C-8), 40.2 (C-12), 43.2 (C-13), 44.3 (C-10), 44.8
(C-3), 49.5 (C-5), 54.3 (C-1), 55.4 (C-9), 56.3 (C-14), 56.5
(C-17), 62.8 (C-50), 78.0 (C-30), 84.2 (C-20), 84.6 (C-2), 84.8
(C-40), 105.1 (C-10). [Found: MNaþ, m/z 543.4036.
C32H56O5Na requires 543.4025].
3.3.4. (2)-Menthol 3-O-a-L-arabinofuranoside (2b). Mp
135–1378C (from acetone); [a]2D3¼21628 (c 1.58,
pyridine); dH 0.74 (1H, m, 6b-H), 0.79 (3H, d, J¼7.0 Hz,
7-H3), 0.84 (1H, br q, J¼11.5 Hz, 2b-H), 0.86 (3H, d,
J¼7.0 Hz, 10-H3), 0.91 (1H, m, 5a-H), 0.95 (3H, d,
J¼7.0 Hz, 9-H3), 1.17 (1H, m, 1a-H), 1.32 (1H, ddt,
J¼12.5, 10.5, 2.5 Hz, 4b-H), 1.51 (2H, br d, J¼11.0 Hz, 5b,
6a-H), 2.14 (1H, m, br d, J¼12.0 Hz, 2a-H), 2.59 (1H, d
sept, J¼2.0, 7.0 Hz, 8-H), 3.69 0 (1H, dt, J¼2.0, 7.0 Hz,
3a-H), 5.65 (1H, d, J¼2.0 Hz, 1 -H); dC 15.9 (C-9), 21.2
(C-10), 22.4 (C-7), 23.4 (C-5), 25.6 (C-8), 31.5 (C-1), 34.8
(C-6), 40.2 (C-2), 48.4 (C-4), 62.7 (C-50),0 74.5 (C-3), 79.0
(C-30), 84.5 (C-20), 85.4 (C-40), 105.5 (C-1 ). [Found: MHþ,
m/z 289.2018. C15H29O5 requires 289.2015].
3.3.8. 2a-Methyl-4-nor-5a-cholestan-2b-ol 2-O-a-L-ara-
binofuranoside (4b). Colorless oil; [a]2D3¼229.18 (c 1.46,
pyridine); dH 0.64 (3H, s, 18-H3), 0.68 (1H, dt, J¼3.5,
11.2 Hz, 9a-H), 1.05 (3H, s, 19-H3), 1.52 (3H, s, 2a-Me),
1.72 (1H, dd, J¼12.5, 6.0 Hz, 3a-H), 2.06 (1H, dd, J¼12.0,
12.5 Hz, 3b-H), 2.33 (1H, d, J¼13.0 Hz, 1b-H), 5.68 (1H,
d, J¼2.4 Hz, 10-H) [0.84 (7a-H), 1.16 (1a-H), 1.28 (6b-H),
1.27 (5a-H), 1.25 (11a-H), 1.28 (8b-H), 1.41 (11b-H), 1.47
(6a-H), 1.63 (7b-H) detected by HSQC spectrum]; dC 12.4
(C-18), 14.0 (C-19), 23.6 (C-11), 24.6 (C-15), 25.1 (C-6),
28.5 (C-16), 29.7 (2a-Me), 32.4 (C-7), 35.4 (C-8), 40.2
(C-12), 43.2 (C-13), 44.3 (C-10), 44.8 (C-3), 49.5 (C-5),
54.3 (C-1)0, 55.4 (C-9), 56.3 (C-14), 56.5 (C-17), 84.1 (C-2),
62.80 (C-5 ), 78.0 (C-30), 84.6 (C-20), 84.8 (C-40), 105.1
(C-1 ). [Found: MNaþ, m/z 543.4025. C32H56O5Na requires
543.4025].
3.3.5. 4,4-Dimethylcholest-5-en-3b-ol 3-O-a-D-arabino-
furanoside (3a). Mp 183–1888C (from acetone);
[a]2D3¼þ5.68 (c 2.28, pyridine); dH 0.67 (3H, s, 18-H3),
1.12 (3H, s, 19-H3), 1.30 (3H, s, 4b-Me), 1.45 (3H, s, 4a-
Me), 1.95 (1H, dq, J¼13.5, 3.5 Hz, 2a-H), 2.08 (1H, dt,
J¼18.5, 5.0 Hz, 7b-H), 3.59 (1H, dd, J¼12.0, 5.5 Hz, 3a-
H), 5.67 (1H, d, J¼1.0 Hz, 10-H), 5.64 (1H, br dd, J¼4.0,
3.0 Hz, 6-H) [0.90 (9a-H), 0.96 (1a-H), 1.48 (8b-H), 1.67
(1b-H), 1.66 (7a-H) and 1.73 (2b-H) detected by HSQC
spectrum]; dC 12.1 (C-18), 20.9 (C-11), 21.6 (C-19), 22.7
(C-2), 24.4 (C-15), 25.3 (4b-Me), 27.8 (4a-Me), 28.6
(C-16), 31.2 (C-8), 32.9 (C-7), 36.8 (C-1), 37.0 (C-10), 40.1
(C-12), 41.4 (C-4), 42.5 (C-13), 51.2 (C-9), 56.3 (C-17),
57.5 (C-14), 63.0 (C-50), 79.0 (C-30), 80.3 (C-3), 84.2 (C-20),
85.6 (C-40), 106.1 (C-10), 120.2 (C-6), 150.4 (C-5). [Found:
MNaþ, m/z 569.4182. C34H58O5Na requires 569.4182].
3.3.9. 5a-Cholestan-3b-ol 3-O-a-D-arabinofuranoside
(5a). Mp 168–1738C (from acetone); [a]2D3¼þ46.68 (c
2.37, pyridine); dH 0.54 (1H, dt, J¼3.5, 11.2 Hz, 9a-H),
0.64 (3H, s, 18-H3), 0.73 (3H, s, 19-H3), 3.80 (1H, m, 3a-H),
5.51 (1H, d, J¼2.0 Hz, 10-H) [0.83 (1a-H), 0.85 (7a-H),
0.96 (5a-H), 1.14 (6-H2), 1.20 (11b-H), 1.24 (8b-H), 1.43
(11a-H), 1.50 (2b-H), 1.54 (4b-H), 1.58 (7b-H), 1.61 (1b-
H), 1.86 (4a-H), 1.97 (1H, br d, J¼14.0 Hz, 2a-H) detected
by HSQC spectrum]; dC 12.2 (C-18/19), 12.3 (C-19/18),
21.5 (C-11), 24.4 (C-15), 28.3 (C-2), 28.5 (C-16), 29.0
(C-6), 32.3 (C-7), 35.6 (C-8), 35.7 (C-10), 36.9 (C-4), 37.2
(C-1), 40.2 (C-12), 42.8 (C-13), 45.0 (C-5), 54.4 (C-9), 56.5
(C-14, C-17), 76.3 (C-3), 62.9 (C-50), 78.7 (C-30), 84.1
(C-20), 85.4 (C-40), 107.8 (C-10). [Found: MNaþ, m/z
543.4006. C32H56O5Na requires 543.4025].
3.3.6. 4,4-Dimethylcholest-5-en-3b-ol 3-O-a-L-arabino-
furanoside (3b). Mp 225–2308C (from acetone);
[a]2D3¼297.18 (c 1.92, pyridine); dH 0.67 (3H, s, 18-H3),
1.11 (3H, s, 19-H3), 1.26 (3H, s, 4b-Me), 1.27 (3H, s,
4a-Me), 2.01 (1H, m, 2b-H), 2.06 (1H, dt, J¼18.5, 5.5 Hz,
7b-H), 2.27 (1H, dq, J¼13.5, 4.0 Hz, 2a-H), 3.34 (1H, dd,
J¼12.0, 4.0 Hz, 3a-H), 5.58 (1H, d, J¼2.0 Hz, 10-H), 5.58
3.3.10. 5a-Cholestan-3b-ol 3-O-a-L-arabinofuranoside
(5b). Mp 188–1948C (from acetone); [a]2D3¼240.78 (c 2.42,
pyridine); dH 0.53 (dt, J¼3.5, 11.2 Hz, 9a-H), 0.64 (3H, s,

9370
M. Kobayashi / Tetrahedron 58 (2002) 9365–9371
18-H3), 0.73 (3H, s, 19-H3), 2.08 (1H, br d, J¼14.0 Hz, 2a-
H), 3.82 (1H, m, 3a-H), 5.71 (1H, br s, 10-H) [0.85 (7a-H),
0.86 (1a-H), 1.14 (6-H2), 0.92 (5a-H), 1.20 (11b-H), 1.24
(8b-H), 1.30 (4b-H), 1.43 (11a-H), 1.59 (7b-H), 1.60 (1b-
H), 1.65 (2b-H), 1.70 (4a-H), detected by HSQC spectrum];
dC 12.2 (C-18/19), 12.3 (C-19/18), 21.4 (C-11), 24.4 (C-15),
28.5 (C-16), 30.2 (C-2), 29.1 (C-6), 32.3 (C-7), 35.6 (C-8),
35.8 (C-10), 34.7 (C-4), 37.3 (C-1), 40.2 (C-12), 42.8
(C-13), 44.8 (C-5), 54.5 (C-9), 56.5 (C-14, 17), 76.1 (C-3),
62.90 (C-50), 78.7 (C-30), 84.2 (C-20), 85.2 (C-40), 107.2
(C-1 ). [Found: MNaþ, m/z 543.4050. C32H56O5Na requires
5543.4025].
4-H), 1.65 (1H, m, 5-exo), 2.12 (1H, m, 3-exo), 2.26 (1H, m,
6-endo), 4.26 (1H, dt, J¼8.5, 2.5 Hz, 2-exo), 5.51 (1H, s,
10-H); dC 13.9 (C-10), 18.9 (C-8), 19.8 (C-9), 27.1 (C-6),
28.5 (C-5), 35.9 (C-3), 45.3 (C-4), 47.8 (C-7), 49.1 (C-1),
62.7 (C-50),078.7 (C-30), 80.5 (C-2), 84.1 (C-20), 85.2 (C-40),
107.7 (C-1 ). [Found: MHþ, m/z 287.1884. C15H27O5
requires 287.1858].
3.3.15. Cholestan-5a,6b-diol 6-O-a-D-arabinofurano-
side (8a). Mp 169–1728C; [a]2D3¼þ37.68 (c 1.32, pyridine);
dH 0.69 (3H, s, 18-H3), 1.34 (3H, s, 19-H3), 2.16 (1H, td,
J¼12.5, 3.0 Hz, 7a-H), 2.28 (1H, dt, J¼12.5, 2.5 Hz, 7b-
H), 2.44 (1H, td, J¼12.5, 4.0 Hz, 04b-H), 3.87 (1H, br t,
J¼2.5 Hz, 6a-H), 5.56 (1H, br s, 1 -H) [1.98 (1a-H), 1.40
(1b-H), 1.48 (2a-H), 1.37 (2b-H), 2.12 (3a-H), 1.52 (3b-
H), 1.42 (4a-H), 2.05 (8b-H), 1.87 (9a-H), 1.56 (11-H2)
detected by HSQC spectrum]; dC 12.3 (C-18), 16.8 (C-19),
21.1 (C-2/3), 21.2 (C-3/2), 21.7 (C-11), 24.6 (C-15), 28.6
(C-16), 31.5 (C-8), 32.2 (C-4), 33.6 (C-1), 34.0 (C-7), 39.5
(C-10), 40.6 (C-12), 42.9 (C-13), 45.9 (C-9), 56.5
(C-14/17), 56.6 (C-17/14), 73.5 (C-5), 805.0 (C-6), 620.6
(C-50), 78.9 (C-30), 84.3 (C-20), 85.3 (C-4 ), 111.7 (C-1 ).
[Found: MNaþ, m/z 559.3947. C32H56O6Na requires
559.3975].
3.3.11. 5a-Cholestan-3a-ol 3-O-a-D-arabinofuranoside
(6a). Mp 168–1698C (from acetone); [a]2D3¼þ58.88 (c 2.17,
pyridine); dH 0.65 (3H, s, 18-H3), 0.76 (3H, s, 19-H3), 1.70
(1H, m, 5a-H), 2.07 (1H, br d, J¼13.00 Hz, 2a-H), 4.13 (1H,
br s, 3b-H), 5.62 (1H, d, J¼2.0 Hz, 1 -H) [0.63 (9a-H), 0.79
(7a-H), 1.07 (12a-H), 1.14 (6-H2), 1.21 (11b-H), 1.27 (8b-
H), 1.34 (4b-H), 1.45 (1b-H), 1.48 (11a-H), 1.53 (1a-H),
1.57 (7b-H), 1.62 (2b-H) and 1.65 (4a-H) detected by
HSQC spectrum]; dC 11.6 (C-19), 12.3 (C-18), 21.1 (C-11),
24.4 (C-15), 28.2 (C-2), 28.6 (C-16), 28.9 (C-6), 32.3 (C-7),
33.0 (C-4), 33.3 (C-1), 35.6 (C-8), 36.2 (C-10), 39.8 (C-5),
40.30(C-12), 42.8 (C-13), 54.40(C-9), 56.7 (C-14, 17), 620.9
(C-5 ), 72.4 (C-3), 78.7 (C-3 ), 84.2 (C-20), 85.3 (C-4 ),
108.1 (C-10). [Found: MNaþ, m/z 543.4025. C32H56O5Na
requires 573.4025].
3.3.16. Cholestan-5a,6b-diol 6-O-a-L-arabinofuranoside
(8b). Colorless oil; [a]D23¼2748 (c 0.80, pyridine); dH 0.63
(3H, s, 18-H3), 1.34 (3H, s, 19-H3), 2.14 (1H, m, 3a-H), 2.63
(1H, td, J¼013.5, 4.0 Hz, 4b-H), 4.16 (1H, br s, 6a-H), 5.61
(1H, br s, 1 -H) [2.00 (1a-H), 1.40 (1b-H), 1.50 (2a-H), 1.36
(2b-H), 1.55 (3b-H), 1.68 (4a-H), 1.95 (7-H2), 1.86 (8b-H),
1.91 (9a-H), 1.58 (11-H2) detected by HSQC spectrum]; dC
12.4 (C-18), 16.5 (C-19), 21.1 (C-2/3), 21.2 (C-3/2), 21.7
(C-11), 24.4 (C-15), 28.5 (C-16), 31.2 (C-8), 32.3 (C-4),
33.6 (C-1), 30.0 (C-7), 39.4 (C-10), 40.6 (C-12), 42.9
(C-13), 46.0 (C-09), 56.5 (C-14, C-17), 73.3 (C-5), 790.2
(C-6), 63.0 (C-5 ), 79.5 (C-30), 84.3 (C-20), 85.7 (C-4 ),
106.3 (C-10). [Found: MNaþ, m/z 559.3989. C32H56O6Na
requires 559.3975].
3.3.12. 5a-Cholestan-3a-ol 3-O-a-L-arabinofuranoside
(6b). Mp 179–1818C (from acetone); [a]2D3¼26.88 (c 2.28,
pyridine); dH 0.65 (3H, s, 18-H3), 0.76 (3H, s, 19-H3), 1.89
(1H, br d, J¼14.0 Hz, 2a-H), 4.15 (1H, br s, 3b-H), 5.61
(1H, d, J¼2.0 Hz, 10-H) [0.61 (9a-H), 0.84 (7a-H), 1.14
(6b-H), 1.19 (11b-H), 1.21 (6a-H), 1.26 (8b-H), 1.35
(1-H2), 1.42 (11a-H), 1.43 (2b-H), 1.48 (4b-H), 1.56 (7b-
H), 1.78 (4a-H) and 1.80 (5a-H) detected by HSQC
spectrum]; dC 11.6 (C-19), 12.3 (C-18), 21.0 (C-11), 24.4
(C-15), 25.4 (C-2), 28.6 (C-16), 28.9 (C-6), 32.3 (C-7), 32.9
(C-1), 35.1 (C-4), 35.6 (C-8), 36.1 (C-10), 40.0 (C-5), 400.3
(C-12), 42.8 (C-13), 54.3 (C-9), 56.6 (C-14, 17), 62.8 (C-5 ),
71.70 (C-3), 78.7 (C-30), 84.3 (C-20), 85.2 (C-40), 107.4
(C-1 ). [Found: MNaþ, m/z 543.4008. C32H56O5Na requires
543.4025].
3.3.17. Cholestan-4b,5a-diol 4-O-a-D-arabinofurano-
side (9a). Mp 215–2168C; [a]2D3¼þ1248 (c 1.89, pyridine);
dH 2.28 (1H, br tt, J¼12.0, 4.0 Hz, 3a-H), 4.15 (1H, br s,
4a-H), 2.51 (1H, td, J¼13.5, 4.5 Hz, 6b-H), 0.71 (3H, s, 18-
H3), 1.33 (3H, s, 19-H3), 5.54 (1H, br s, 10-H) [1.90 (1a-H),
1.38 (1b-H), 1.47 (2a-H), 1.88 (2b-H), 1.81 (3b-H), 1.67
(6a-H), 1.74 (7a-H), 1.46 (7b-H), 1.45 (8b-H), 1.93 (9a-H)
detected by HSQC spectrum]; dC 12.4 (C-18), 15.8 (C-19),
17.8 (C-2), 20.7 (C-11), 24.1 (C-3), 24.4 (C-15), 26.5 (C-7),
28.6 (C-16), 32.0 (C-6), 32.3 (C-1), 35.2 (C-8), 39.4 (C-10),
40.6 (C-12), 43.0 (C-13), 46.8 (C-9), 56.6 (C-14/17), 560.7
(C-17/14)0, 73.3 (C-5),0 79.4 (C-4), 603.0 (C-50), 79.6 (C-3 ),
84.6 (C-2 ), 85.6 (C-4 ), 106.5 (C-1 ). [Found: MNaþ, m/z
559.3988. C32H56O6Na requires 559.3975].
3.3.13. (1S)-endo]-(2)-Borneol 2-O-a-D-arabinofurano-
side (7a). Mp 150–1528C (from acetone); [a]2D3¼þ758 (c
1.68, pyridine); dH 0.76 (3H, s, 9-H3), 0.77 (3H, s, 8-H3),
0.87 (10-H3), 1.19 (1H, m, 6-exo), 1.25 (1H, m, 5-endo),
1.45 (1H, dd, J¼13.5, 3.5 Hz, 3-endo), 1.53 (1H, br t,
J¼4.5 Hz, 4-H), 1.63 (1H, m, 5-exo), 2.25 (1H, m, 6-endo),
2.32 (1H, m, 3-exo), 4.02 (1H, ddd, J¼10.0, 3.0, 2.0 Hz,
2-exo), 5.53 (1H, d, J¼2.0 Hz, 10-H); dC 14.0 (C-10), 18.8
(C-8), 19.8 (C-9), 27.1 (C-6), 28.6 (C-5), 38.3 (C-3), 45.3
(C-40), 47.5 (C-7), 49.6 (C-1), 62.7 (C-50),078.7 (C-30), 83.9
(C-2 ), 84.2 (C-2), 85.1 (C-40), 111.0 (C-1 ). [Found: MHþ,
m/z 287.1849. C15H27O5 requires 287.1858].
3.3.18. Cholestan-4b,5a-diol 4-O-a-L-arabinofuranoside
(9b). Mp 240–2428C (from acetone); [a]2D3¼þ3.28 (c 0.89,
pyridine); dH 2.11 (1H, qt, J¼12.5, 3.5 Hz, 2b-H), 2.52 (1H,
tt, J¼13.0, 4.0 Hz, 3a-H), 2.20 (1H, br d, J¼13.0 Hz, 3b-
H), 3.90 (1H, H, br s, 4a-H), 2.37 (1H, td, J¼13.0, 4.5 Hz,
6b-H), 1.73 (1H, qd, J¼12.5, 4.0 Hz, 7a-H), 0.69 (3H, s,
18-H3), 1.32 (3H, s, 19-H3), 5.57 (1H, d, J¼2.0 Hz, 10-H)
[1.90 (1a-H), 1.38 (1b-H), 1.55 (2a-H), 1.43 (6a-H), 1.46
3.3.14. (1S)-endo]-(2)-Borneol 2-O-a-L-arabinofurano-
side (7b). Mp 188–1948C (from acetone); [a]2D3¼21408 (c
1.62, pyridine); dH 0.75 (3H, s, 8-H3), 0.78 (9-H3), 0.98
(10-H3), 1.12 (1H, dd, J¼13.0, 3.5 Hz, 3-endo), 1.19 (1H,
m, 5-endo), 1.22 (1H, m, 6-exo), 1.55 (1H, t, J¼4.5 Hz,

M. Kobayashi / Tetrahedron 58 (2002) 9365–9371
9371
(7b-H), 1.42 (8b-H), 1.90 (9a-H), detected by HSQC
spectrum]; dC 12.3 (C-18), 15.7 (C-19), 18.2 (C-2), 20.7
(C-11), 28.1 (C-3), 24.5 (C-15), 26.6 (C-7), 28.6 (C-16),
31.9 (C-6), 32.1 (C-1), 35.1 (C-8), 39.5 (C-10), 40.5 (C-12),
42.9 (C-13), 46.7 (C-9), 56.5 (C-14/17), 56.6 (C-17/14),
73.6 (C-5), 85.0 (C-4), 62.8 (C-50), 78.8 (C-30), 84.3 (C-20),
85.3 (C-40), 111.8 (C-10). [Found: MNaþ, m/z 559.3960.
C32H56O6Na requires 559.3975].
1.45 (1H, m, 15a-H), 1.82 (1H, m, 16b-H), 1.90 (1H, dt,
J¼12.5, 3.0 Hz, 12b-H), 2.15 (1H, m, 16a-H), 3.77 (1H, t,
J¼8.5 Hz, 17a-H), 5.59 (1H, d, J¼2.0 Hz, 10-H), 5.84 (1H,
br s, 4-H) [0.80 (14a-H), 0.80 (7a-H), 1.34 (11a-H), 1.34
(8b-H), 1.59 (7b-H) detected by HSQC spectrum]; dC 12.0
(C-18), 17.1 (C-19), 20.8 (C-11), 23.5 (C-15), 29.6 (C-16),
31.7 (C-7), 32.6 (C-6), 34.2 (C-2), 35.3 (C-8), 35.8 (C-1),
37.5 (C-12), 38.6 (C-10), 43.0 (C-13), 50.5 (C-14), 54.0
(C-9), 62.8 (C-50),078.8 (C-30), 84.1 (C-20), 87.1 (C-17), 85.3
(C-40), 109.9 (C-1 ), 123.8 (C-4), 170.5 (C-5), 198.3 (C-3).
[Found: MHþ, m/z 421.2600. C24H37O6 requires 421.2590].
3.3.19. Androst-4-en-17b-ol-3-one 17-O-a-D-arabino-
furanoside (10a). Mp 154–1568C (from acetone);
[a]2D3¼þ1608 (c 2.31, pyridine); dH 0.88 (3H, s, 18-H3),
0.98 (3H, s, 19-H3), 1.06 (1H, dt, J¼4.5, 13.0 Hz, 12a-H),
1.18 (1H, dq, J¼6.0, 12.0 Hz, 15b-H), 2.00 (1H, m, 16a-H),
2.13 (1H, dt, J¼13.0, 3.0 Hz, 12b-H), 3.80 (1H, t,
J¼8.5 Hz, 17a-H), 5.49 (1H, br s, 10-H), 5.84 (1H, br s,
4-H) [0.69 (9a-H), 0.80 (14a-H), 0.80 (7a-H), 1.24 (11b-
H), 1.34 (11a-H), 1.36 (8b-H), 1.45 (15a-H), 1.60 (7b-H)
and 1.62 (16b-H) detected by HSQC spectrum]; dC 12.1
(C-18), 17.1 (C-19), 20.8 (C-11), 23.4 (C-15), 27.7 (C-16),
31.7 (C-7), 32.7 (C-6), 34.3 (C-2), 35.4 (C-8), 35.8 (C-1),
36.9 (C-12), 38.7 (C-10), 42.6 (C-13), 50.7 (C-14), 54.1
(C-9), 62.8 (C-50),070 8.8 (C-30), 84.2 (C-20), 85.9 (C-17), 85.3
(C-40), 108.5 (C-1 ), 123.7 (C-4), 170.6 (C-5), 198.3 (C-3).
[Found: MHþ, m/z 421.2616. C24H37O6 requires 421.2590].
References
1. Kobayashi, M. Tetrahedron 1997, 53, 5973–5994.
2. Kobayashi, M. Tetrahedron 1998, 54, 10987–10998.
3. Kobayashi, M. Tetrahedron 2000, 56, 1661–1665.
4. (a) Kasai, R.; Suzuo, M.; Asakawa, J.; Tanaka, O. Tetrahedron
Lett. 1977, 175–178. (b) Tori, K.; Seo, S.; Yoshimura, Y.;
Arita, H.; Tomita, Y. Tetrahedron Lett. 1977, 79–182.
5. Demarco, P. V.; Farkas, E.; Doddrell, D.; Mylari, B. L.;
Wenkert, E. J. Am. Chem. Soc. 1968, 90, 5480–5486.
6. Backinowsky, L. V.; Nepogodev, S. A.; Shashkov, A. S.;
Kochetkov, N. K. Carbohydr. Res. 1985, 138, 41–54.
7. (a) Ogawa, T.; Beppu, K.; Nakabayashi, S. Carbohydr. Res.
1981, 93, C6. (b) Gaeregg, P. J.; Ossowski, P. Acta Chem.
Scand. Ser. B. 1983, 37, 249–250. (c) Gaeregg, P. J.;
Henrichson, C.; Norberg, T.; Ossowski, P. Carbohydr. Res.
1983, 119, 95–100.
3.3.20. Androst-4-en-17b-ol-3-one 17-O-a-L-arabino-
furanoside (10b). Mp 164–1668C (from acetone);
[a]2D3¼þ158 (c 2.34, pyridine); dH 0.69 (1H, dt, J¼4.5,
11.5 Hz, 9a-H), 0.87 (3H, s, 18-H3), 0.97 (3H, s, 19-H3),
1.06 (1H, dt, J¼4.5, 12.5 Hz, 12a-H), 1.17 (1H, dq, J¼6.0,
12.0 Hz, 15b-H), 1.24 (1H, dq, J¼3.5, 12.5 Hz, 11b-H),