From methyl mannosides to methyl octosides by a stepwise homologation with Grignard C1 reagents

Article abstract of DOI:10.1016/S0008-6215(01)00103-3

A four-step procedure for homologation of methyl α-D-manno furanoside and α-D-manno pyranoside was examined. The reactions consisted in (i) oxidation of the terminal hydroxymethyl group in a protected sugar derivative to an aldehyde; (ii) reaction with allyloxymethylmagnesium chloride (or (phenyldimethyl)silylmethyl-magnesium chloride); (iii) protection of the newly formed secondary alcohol group; (iv) deprotection of the terminal CH₂OR (or oxidation of the CH₂SiMe₂Ph) group. From methyl α-D-mannosides, stereoisomeric DαD and LαD methyl heptosides and from them, methyl octosides of D-threo- and L-erythro-α-D-manno configuration were obtained.

Full text of DOI:10.1016/S0008-6215(01)00103-3

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Carbohydrate Research 332 (2001) 429–438
Note
From methyl mannosides to methyl octosides by a
stepwise homologation with Grignard C1 reagents
Halszka Ste˛powska, Aleksander Zamojski*
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, PL-01224 Warsaw, Poland
Received 5 February 2001; accepted 2 April 2001
Abstract
A four-step procedure for homologation of methyl a-
D
-mannofuranoside and a-D-mannopyranoside was examined.
The reactions consisted in (i) oxidation of the terminal hydroxymethyl group in a protected sugar derivative to an
aldehyde; (ii) reaction with allyloxymethylmagnesium chloride (or (phenyldimethyl)silylmethyl–magnesium chloride);
(iii) protection of the newly formed secondary alcohol group; (iv) deprotection of the terminal CH2OR (or oxidation
of the CH2SiMe2Ph) group. From methyl a-
D
-mannosides, stereoisomeric
D
a
D and LaD methyl heptosides and from
them, methyl octosides of
Ltd. All rights reserved.
D
-threo- and
L
-erythro-a- -manno configuration were obtained. © 2001 Elsevier Science
D
Keywords: Methyl 5-O-benzyl-2,3-O-isopropylidene-a-
D-manno-hexodialdo-1,4-furanoside; Methyl 4-O-benzyl-2,3-O-isopropyli-
dene-a- -manno-hexodialdo-1,5-pyranoside; Methyl LaD- and DaD-manno-heptosides; Methyl octosides
D
OH group, liberation of the primary OH
group, etc. The problems to be answered con-
cerned the yields, stereoselectivity, separation
of stereoisomers, and protection of newly
formed secondary alcohol groups. Homologa-
Chain elongation of monosaccharide termi-
nalaldehydes(protectedpentodialdo-1,4-furan-
oses or hexodialdo-1,5-pyranoses) with
alkoxymethylmagnesium chlorides has proved
to be a practical method for homologation
reactions.1–5 We became interested in homolo-
gation of methyl mannosides in furanose and
pyranose forms protected with the same
groups: 2,3-O-isopropylidene and 5 (or 4)-O-
benzyl. The question was posed on how far
the homologation method can be continued
using a simple sequence of reactions consisting
of oxidation of the primary hydroxyl group to
aldehyde, reaction with C1 Grignard, separa-
tion of stereoisomers, protection of the new
tion of methyl 2,3,4-tri-O-benzyl-a- -manno-
D
hexodialdo-1,5-pyranoside using the Dondoni
2-trimethylsilyl-thiazole approach6,7 was per-
formed by Aspinall.8 The homologation of
sugar chain from the aldehyde group (C-1,
ascending synthesis) is well known.9
Methyl 5-O-benzyl-2,3-O-isopropylidene-a-
-mannofuranoside (1) was oxidized to the
D
6-aldehyde (2) and reacted with ally-
loxymethylmagnesium chloride to afford 78%
of methyl 7-O-allyl-5-O-benzyl-2,3-O-iso-
propylidene-heptofuranosides of
D
- and
L
-
glycero-a- -manno configuration (3 and 4) in
D
* Corresponding author. Tel.: +48-22-6323221; fax: +48-
22-6326681.
E-mail address: awzam@icho.edu.pl (A. Zamojski).
ca. 3.3:1 ratio. This result differs from an
analogous chain elongation reaction of 2 with
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00103-3

430
H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
was benzylated at C-6 to yield 11, and 11 was
oxidized at C-7 to heptoside 12, oxidized in
turn to aldehyde 13. Chain elongation was
achieved with the silyl Grignard reagent to
furnish methyl 5,6-di-O-benzyl-8-deoxy-2,3-
O-isopropylidene-8-(phenyldimethyl)silyl-octo-
benzyloxymethylmagnesium chloride where
two stereoisomeric heptofuranosides obtained
were of the
unexpected
Stereoisomers 3 and 4 were separated and the
major product 3 was benzylated to yield
D
-glycero-a-
D
-manno and of the
L
-glycero-b-
L
-gulo configuration.10
methyl
propylidene-
7-O-allyl-5,6-di-O-benzyl-2,3-O-iso-
-glycero-a- -manno-heptofura-
furanosides of
D
-threo- and
L
-erythro-a- -
D
D
D
manno configuration (14 and 15, 74.5%, 4.5:1).
Successful oxidation of the silyl group in 14
yielded a derivative of the corresponding
methyl octofuranoside (16) (Scheme 1).
noside (5). De-allylation of 5 with the
Wilkinson’s catalyst proceeded smoothly and
yielded alcohol 6 for the Swern oxidation. In
turn, reaction of the aldehyde 7 with ally-
loxymethylmagnesium chloride yielded 71% of
an inseparable mixture of stereoisomeric
Repetition of the benzylation procedure on
the octoside 14 afforded the 7-O-benzyl
derivative 17 in a low yield (18%). The main
product was an olefin (18, 78%) stemming
from the Peterson elimination. A number of
modifications of the benzylation procedure
was examined (cf. Section 1), however no
improvement was achieved.
methyl octofuranosides (8) of supposed
thro-a- -manno and -threo-a- -manno
configuration.
D
-ery-
D
L
D
An analogous series of reactions was per-
formed next starting with aldehyde 2 and
(phenyldimethyl)silylmethylmagnesium chlor-
ide.11 Two stereoisomeric methyl 5-O-benzyl-
7-deoxy-2,3-O-isopropylidene-7-(phenyldimeth-
Homologation in the pyranoside series
started with methyl 4-O-benzyl-2,3-O-
isopropylidene-a-
which was oxidized to methyl 4-O-benzyl-
2,3-O-isopropylidene-a- -manno-hexodialdo-
1,5-pyranoside (20). Its reaction with
D
-mannopyranoside
(19),
yl)silyl-
L
- and
D
-glycero-a-manno-heptofura-
nosides (9 and 10) were obtained (83%, 4:1).
After separation, the major stereoisomer 9
D
Scheme 1.

H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
431
Scheme 2.
allyloxymethylmagnesium chloride afforded
71% of an inseparable mixture of methyl 7-O-
allyl-4-O-benzyl-2,3-O-isopropylidene-hep-
Peterson olefin 30 (78%), and under two-phase
conditions (BnBr, Bu4NBr, 50% NaOH) to the
7-deoxy-heptoside 31.
topyranosides of
L
- and
D
-glycero-a- -manno
D
The configuration of the new secondary al-
cohol grouping in: 9, 14, 15, 24, 28 and 29 was
unequivocally determined by the CD spectra
with rhodium12 and in 16 with molybdenum
complexes.13 Configuration of 5 could be es-
tablished by comparison of its NMR spectral
data with the data of an analogous com-
pound.10 Also configurations of 21 were as-
signed similarly2 (Scheme 2).
Stepwise homologation of hexosides to
higher sugars is based on a four-step proce-
dure: reaction of allyloxymethyl Grignard
with terminal aldehyde, protection of the new
secondary alcohol group, deprotection at the
primary alcohol position, Swern oxidation to
the aldehyde and the next Grignard reaction.
Although experimentally not complicated, it
experiences difficulties in separation of the
stereoisomeric homologs formed. In the reac-
tions performed, a preference for the forma-
configuration (21) in ca. 2:1 ratio. Benzylation
of this mixture led to three products isolated
by chromatography: two stereoisomeric 6-O-
benzylated products of
D
- and
L
-glycero-a- -
D
manno configuration (22 and 23) and a
non-benzylated substrate which proved to be
pure
L
aD
stereoisomer (24). The major
stereoisomer was de-allylated and the primary
alcohol 25 was oxidized to aldehyde 26. Unex-
pectedly, Grignard reaction of 26 with
AllOCH2MgCl was very inefficient and
yielded — besides the unreacted alde-
hyde — only negligible amounts of the oc-
tosides 27 which were identified only by the
1H NMR spectrum.
Elongation of the aldehyde 20 with silyl
Grignard led, as expected, to 77% of methyl 4
-O-benzyl-7-deoxy-2,3-O-isopropylidene-7-
(phenyldimethyl)silyl-
heptopyranoside (28) and a slight amount
(9%) of inverted product 29 of -glycero-b- -
L
-glycero-a- -manno-
D
tion of the
D
configuration at the new
D
L
secondary alcohol center is noted. This re-
mains in accord with our earlier observations
on domination of the Felkin–Anh pathway in
reactions of alkoxymethyl Grignard reagents
with sugar aldehydes.4,5 A single exception is
the chain-elongation of the aldehyde 20 where
gulo configuration. It must be added that for-
mation of an inverted product was observed
also earlier;4 silyl Grignard usually furnishes
normal products, without inversion of a
configuration to the aldehyde group.
As in the previous case in the furanoside
series, benzylation (BnBr, NaH, DMF, with
and without Bu4NBr) of 28 led only to the
L
a
D
heptopyranoside dominated over the
DaD
stereoisomer.

432
H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
JASCO J715 spectropolarimeter using hexane
For
the
stepwise
homologation,
or CHCl3 solution in cells of 0.1 or 0.2 path
length (spectral band width 1 nm, sensitivity
10×10−6DA unit/nm). CD spectra of heptose
and octose derivatives having free hydroxyl
group at C-6 or C-7 (6–8 mg) with
(CF3COO)4Rh2 complex (3–4 mg) were mea-
sured in chloroform (10 mL, Spectrograde). A
positive E band at 342–358 nm indicated the
(phenyldimethyl)silylmethylmagnesium chlor-
ide may also be conveniently used. This
reagent displays a preference for the forma-
tion of
L
-configurated secondary alcohol when
-manno-
reacting with protected methyl a-
D
hexodialdo-1,4-furanoside or -1,5-pyranoside.
The stereoisomeric homologs can be readily
separated but successful protection of the new
secondary alcohol group strongly depends on
reaction conditions employed. The usual ben-
zylation may fail due to Peterson elimination.
It is remarkable that on passing from heptose
to octose system (13“14+15) a preference
D
configuration.12 The shift of the E band to
401–413 nm in the CD spectra of 9 and 14 is
due to the presence of the dimethylphenylsilyl
group next to the secondary alcohol group-
ing.14 The configuration of 16 was determined
with Mo(AcO)4 complex in Me2SO solution; a
for the
Aspinall8 obtained derivatives of
glycero-a- -manno-heptopyranosides in ca.
D
configuration at C-7 was noted.
positive band at 312.5 nm indicated a
D
L
- and
D
-
configuration.13 Substrates were obtained ac-
cording to published methods: methyl 5-O-
D
55:37 ratio. Allyloxymethyl Grignard route
leads to the corresponding derivatives of
heptopyranosides in a ratio of 47:24 and to a
reverse proportion (3:10) of heptofuranosides.
The best stereoselectivity leading to the most
benzyl-2,3-O-isopropylidene-a-
D
-manno-hexodi-
aldo-1,4-furanoside (2)15 and methyl 4-O-ben-
zyl-2,3-O-isopropylidene-a- -manno-hexodi-
D
aldo-1,5-pyranoside (20)16 were obtained from
the corresponding primary alcohols 1 and 19
by Swern oxidation.
desired
L
-glycero- -manno-heptoside can be
D
obtained with the silyl Grignard introduced by
van Boom.11 This is also confirmed in the
experiments described here.
Methyl
7-O-allyl-5-O-benzyl-2,3-O-iso-
- and -glycero-h- -manno-hep-
propylidene-
D
L
D
tofuranosides (3 and 4).—To the Grignard
reagent AllOCH2MgCl, prepared at −30 °C
according to Ref. 4 from magnesium (0.86 g,
36.8 mmol) and freshly distilled ally-
loxymethyl chloride (3.91g, 36.8 mmol) in abs
THF (8 mL), was added dropwise a solution
of 2 (2.96 g, 9.2 mmol) in abs THF (8 mL)
and stirring at −30 °C was continued for 2 h.
Afterwards, the reaction mixture was allowed
to attain rt and was additionally stirred for 12
h. The mixture was cooled to 0 °C, poured
into cold aq ammonium chloride (50 mL) and
extracted with Et2O. The extract was dried
over MgSO4 and concentrated in vacuo to
dryness. The residue was separated on a sil-
icagel column with 8:3“4:1 hexane–EtOAc
as eluent. First eluted was 3 (2.16 g, 59.7%),
followed by 4 (0.66 g, 18.4%)
1. Experimental
Reactions were performed under strictly an-
hydrous conditions under Ar. For TLC, plates
covered with Silica Gel 60F254, E. Merck were
used. Tetrahydrofuran was distilled from
potassium–benzophenone ketyl. Products
were separated and purified by column chro-
matography (E. Merck Silica Gel 60, 230–400
mesh ASTM). Solvents used for elution were
of technical grade and were distilled over
CaH2 before use. 1H NMR spectra were
recorded with a Varian AC-200 (200 MHz) or
Bruker AM-500 (500 MHz) spectrometers us-
ing CDCl3 as solvent and Me4Si as internal
standard. 13C NMR spectra were recorded in
the DEPT mode. High-resolution mass spec-
tra (HR-MS) were measured in the LSIMS
mode with an AMD-604 mass spectrometer.
Optical rotation were measured with a JASCO
DIP-360 automatic polarimeter at 2492 °C
for solutions in CHCl3. CD spectra were
recorded between 280 and 750 nm at rt with a
In a similar manner were synthesized the
7-O-allyl derivatives of methyl DaD and
LaD
heptopyranosides and 8-O-allyl derivatives of
octofuranosides and -pyranosides. The
phenyldimethylsilylmethyl Grignard reagent
was obtained according to Fleming et al.17
using the procedure of van Boom et al.18 Its

H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
433
reactions with aldehydes 2, 7, 13, and 20 were
performed at −30 °C according to prescrip-
tion for 2“3+4. Unmasking of the silyl
group from compounds 11 and 14 was accom-
plished with HOOAc–NaBr–NaOAc19 to fur-
nish heptofuranosides 12 and 16.
mmol) in DMF (15 mL) cooled to −10 °C,
sodium hydride (50% suspension, 0.317 g, 6.63
mmol) was added and the mixture was stirred
for 30 min. Benzyl bromide (1.13 g, 6.63
mmol) was added dropwise. After 15 min the
mixture was allowed to attain rt and stirring
was continued for 3 h. Water (25 mL) was
slowly added and the product was extracted
with ether (3×30 mL). The combined organic
extracts were washed with water (25 mL),
dried over Na2SO4 and concentrated to dry-
ness. Column chromatography of the residue
with 4:1 hexane–EtOAc gave 5 (1.73 g,
80.5%) as a colorless oil, [h]D +26.6° (c 3.1,
Methyl
7-O-allyl-5-O-benzyl-2,3-O-iso-
-glycero-h- -manno-heptofuran-
propylidene-
D
D
oside (3).—Colorless oil, 2.16 g, (59.7%); [h]D
+39.7° (c 1.9, CHCl3); CD: 355 nm (De%
1
0.0087, c 0.00106 M); H NMR: l 7.35–7.31
(m, 5 H, Ph), 5.93 (m, 1 H, CHꢀ), 5.28, 518 (2
q, 2 H, CH2ꢀ), 4.88 (s, 1 H, H-1) 4.79 (dt, 1 H,
J3,4 2.8 Hz, H-3) 4.52 (d, 1 H, J2,3 5.9 Hz,
H-2), 4.15 (m, 1 H, J5,6 1.6 Hz, H-5), 4.05 (dt,
1 H, J4,5 9.3 Hz, H-4), 3.98 (m, 1 H, J6,7 7.00
Hz, H-6), 3.64 (bs, 2 H, OCH2), 3.32 (AB, 1
H, 2 H, J7a,7b 10.0 Hz), 3.29 (s, 3 H, OCH3),
2.82 (bs, 1 H, OH), 1.47, 1.33 [2 s, 6 H,
(CH3)2C].
1
CHCl3); H NMR (CDCl3); l 7.37–7.28 (m, 5
H, Ph), 5.90 (m, 1 H, CHꢀ), 5,25, 5.15 (2 q, 2
H, CH2ꢀ), 4.86 (s, 1 H, H-1), 4.78 (dd, 1 H,
J3,4 3.8 Hz, H-3), 4.82, 4.65 (2 d, 4 H, CH2Ph),
4.51 (d, 1 H, J2,3 5.8 Hz, H-2), 4.13 (dd, 1 H,
J5,6 1.4 Hz, H-5), 4.05 (dd, 1 H, J4,5 9.5 Hz,
H-4), 4.01 (m, 1 H, J6,7a 1.8, J6,7b 5.2 Hz, H-6),
3.94 (m, 2 H, H-7a, H-7b), 3.27 (s, 3 H,
OCH3), 1.44, 1.32 [2 s, 6 H, (CH3)2C]. 13C
NMR (CDCl3): l 134.9 (CHꢀ), 128.1–127.2
(2×Ph), 116.5 (CH2ꢀ), 107.2 (C-1), 84.5 (C-
2), 80.0, 79.7, 78.2 (C-3,4,5), 77.4 (C-6), 74.0,
72.5 (2×CH2Ph), 72.1 (OCH2), 70.4 (C-7),
54.4 (OCH3), 26.2, 25.1 (CH3)2C]. LSIMS
(HRMS): m/z 507.2360 [M+Na]+. Calcd for
C28H36NaO7 507.2358. Anal. Calcd for
C28H36O7: C, 69.40; H, 7.49. Found: C, 69.27;
H, 7.51.
13C NMR (CDCl3): l 134.7 (CHꢀ), 128.2–
127.5 (Ph), 117.1 (CH2ꢀ), 107.5 (C-1), 84.3
(C-2), 80.0, 79.2, 76.9 (C-3,4,5), 74.1 (CH2Ph),
72.3 (OCH2), 72.2 (C-6), 70.5 (C-7), 54.6
(OCH3), 26.2, 24.9 [(CH3)2C]. LSIMS
(HRMS): m/z 417.1899 [M+Na]+. Calcd for
C21H30NaO7: 417.1889. Anal. Calcd for
C21H30O7·1/2 H2O: C, 62.52; H, 7.74. Found:
C, 62.57; H, 7.67.
Methyl
propylidene-
7-O-allyl-5-O-benzyl-2,3-O-iso-
-glycero-h- -manno-heptofuran-
L
D
oside (4).—Colorless oil, 0.66 g (18.4%); [h]D
1
+31.6° (c 1.6, CHCl3); H NMR (CDCl3): l
Methyl
dene- -glycero-h-
5,6-di-O-benzyl-2,3-O-isopropyli-
-manno-heptofuranoside
7.48–7.36 (m, 5 H, Ph), 5.89 (m, 1 H, CHꢀ),
5.32, 5.18 (2 q, 2 H, CH2ꢀ), 4.89 (s, 1 H, H-1),
4.81 (dd, 1 H, J3,4 2.9 Hz, H-3), 4.74 (d, 2 H,
CH2Ph), 4.56 (d, 1 H, J2,3 5.9 Hz, H-2), 4.13
(dd, 1 H, J4,5 9.8 Hz, H-4), 4.01 (dd, 1 H, J5,6
2.8 Hz, H-5), 3.98 (m, 2 H, OCH2), 3.52 (AB,
2 H, J7a,7b 10 Hz, H-7a, H-7b), 3.30 (s, 3 H,
OCH3), 1.45, 1.34 [2 s, 6 H, (CH3)2C]. 13C
NMR (CDCl3): l 134.6 (CHꢀ), 128.4–127.6
(Ph), 116.9 (CH2ꢀ), 107.2 (C-1), 84.9 (C-2),
79.9, 78.3, 75.6 (C-3,4,5), 74.1 (CH2Ph), 72.2
(OCH2), 71.5 (C-7), 70.2 (C-6), 54.5 (OCH3),
26.2, 25.0 [(CH3)2C]. LSIMS (HRMS): m/z
417.1899 [M+Na]+. Calcd for C21H30NaO7:
417.1891.
D
D
(6).—To a solution of 5 (1.64 g, 3.38 mmol)
in 9:3:1 EtOH–benzene–water (26 mL) were
added the Wilkinson’s catalyst (0.148 g) and
1,4-diazabicyclo[2.2.2]octane (52 mg) and the
mixture was refluxed until the reaction was
complete (4 h). The mixture was filtered and
the solvents were evaporated under dimin-
ished pressure. The residue was dissolved in
10:1 acetone–water (22 mL), HgCl2 (0.75 g)
and HgO (0.59 g) were added and the mixture
was stirred for 1 h. Then, it was filtered
through a Celite layer, washed with aq 50%
KI, aq 1% NaHSO3 and 1% NaHCO3, dried
and concentrated. The residue was purified by
chromatography with 4:1 hexane–EtOAc to
give 6 (1.02 g, 67.8%), oil, [h]D +36.3° (c 1.7,
Methyl 7-O-allyl-5,6-di-O-benzyl-2,3-O-iso-
propylidene-
D
-glycero-h- -manno-heptofuran-
D
1
oside (5).—To a solution of 3 (1.75 g, 4.44
CHCl3); H NMR (CDCl3): l 7.36–7.25 (m,

434
H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
H, 2×CH2Ph), 4.58 (d, 1 H, J2,3 5.8 Hz, H-2),
4.20 (m, 1 H, J6,7 7.1 Hz, H-6), 4.08 (dd, 1 H,
J4,5 9.2 Hz, H-4), 3.78 (dd, 1 H, J5,6 2.3 Hz,
H-5), 3.28 (s, 3 H, OCH3), 2.38 (d, 1 H, OH),
1.46, 1.31 [2 s, 6 H, (CH3)2C], 1.20 (m, 2 H,
H-7a, H-7b), 0.36, 0.35 [2 s, 6 H, (CH3)2Si].
13C NMR (CDCl3): l 128.5–127.2 (2×Ph),
107.3 (C-1), 84.6 (C-2), 79.9, 79.1, 78.7 (C-
3,4,5), 74.1 (CH2Ph), 69.3 (C-6), 54.6 (OCH3),
26.2, 24.9 [(CH3)2C], 20.9 (C-7), −1.9, −2.5
[(CH3)2Si]. LSIMS (HRMS): m/z 459.2177
2×Ph), 4,87 (s, 1 H, H-1), 4.81 (dd, 1 H, J3,4
3.5 Hz, H-3), 4.53 (d, 1 H, J2,3 5.9 Hz, H-2),
4.20 (dd, 1 H, J5,6 1.9 Hz, H-5), 4.78, 4.68
(2×AB, 4 H, 2×CH2Ph), 4.02 (dd, 1 H, J4,5
9.5 Hz, H-4), 3.92–3.80 (m, 3 H, H-6, H-7a,
H-7b), 3.28 (s, 3 H, OCH3), 2.62 (d, 1 H, OH),
1.46, 1.39 [2 s, 6 H, (CH3)2C]. 13C NMR
(CDCl3): l 128.4–127.6 (2×Ph), 107.4 (C-1),
84.5 (C-2), 79.91, 79.90, 78.3 (C-3,4,5), 77.6
(C-6), 74.5, 71.9 (2×CH2Ph), 61.5 (C-7), 54.6
(OCH3), 26.2, 25.0 [(CH3)2C]. Anal. Calcd for
C25H32O7: C, 67.56; H, 7.20. Found: C, 67.31;
H, 7.23.
[M+Na]+.
Calcd
for
C26H36NaO6Si
495.2179.
Methyl 5-O-benzyl-7-deoxy-2,3-O-isopropy-
Methyl 8-O-allyl-5,6-di-O-benzyl-2,3-O-iso-
lidene-7-(phenyldimethy)lsilyl-
D
-glycero-h- -
D
propylidene-
D
-erythro-h- -manno-octofuran-
D
manno-heptofuranoside (10).—White foam,
0.474 g (16.6%); [h]D+47.8° (c, 1.1, CHCl3);
1H NMR (CDCl3): l 7.55–7.35 (m, 2×Ph),
4.91 (s, 1 H, H-1), 4.70 (dd, 1 H, J3,4 3.5 Hz,
H-3), 4.87, 4.65 (AB, 2 H, CH2Ph), 4.52 (d, 1
H, J2,3 5.8 Hz, H-2), 4.22 (dd, 1 H, J4,5 9.0 Hz,
H-4), 3.98 (dd, 1 H, J5,6 3.0 Hz, H-5), 3.76 (m,
1 H, J6,7a 8.4, J6,7b 2.8 Hz, H-6), 3.29 (s, 3 H,
OCH3), 1.27–1.19 (m, 2 H, H-7a, H-7b), 1.95
(d, 1 H, OH), 1.28, 1.16 [2 s, 6 H, (CH3)2C],
0.31, 0.29 [2 s, 6 H, [(CH3)2Si]. 13C NMR
(CDCl3): l 133.8–127.6 (2×Ph), 107.1 (C-1),
84.7 (C-2), 82.4, 81.2, 79.9 (C-3,4,5), 74.0
[(CH2Ph), 69.5 (C-6), 54.3 (OCH3), 23.0 (C-7),
26.0, 24.7 [(CH3)2C], −2.1, −2.8 [(CH3)2Si].
Anal. Calcd for C26H36O6Si: C, 66.10; H, 7.62.
Found: C, 65.92; H, 7.71.
osides (8).—Colorless syrup, 0.226 g (70.8%),
obtained from 7 [0.28 g, obtained from 6 (0.37
g, 76.5%) by Swern oxidation]. NMR data
were taken from the spectra of a 6:1 mixture
stereoisomeric octosides. The
D
-erythro-a- -
D
manno configuration was assigned to the dom-
inating stereoisomer on the basis of similarity
of the NMR data with those of methyl 5,7-di-
O-benzyl-2,3-O-isopropylidene-
D
-glycero-a- -
D
manno-heptofuranoside.10 1H NMR (CDCl3):
l 7.31–7.25 (m, 2×Ph), 5.85 (m, 1 H, CHꢀ),
5.26, 5.15 (2g, 2 H, CH2ꢀ), 4.85 (s, 1 H, H-1),
4.78, 4.58 (2×AB, 4 H, 2×CH2Ph), 4.81 (dd,
1 H, J3,4 3.0 Hz, H-3), 4.52 (d, 1 H, J2,3 5.8
Hz, H-2), 4.27 (dd, 1 H, J5,6 2.9 Hz, H-5), 4.20
(dd, 1 H, J4,5 9.5 Hz, H-4), 4.14–4.06 (m, 3 H,
H-6, OCH2), 4.01–3.95 (m, 1 H, J7,8a 7.8, J7,8b
1.1 Hz, H-7), 3.88, 3.54 (AB, 2 H, H-8a,
H-8b), 3.27 (s, 3 H, OCH3), 2.82 (d, 1 H, OH),
1.45, 1.33 [2 s, 6 H, (CH3)2C]. 13C NMR
(CDCl3): l 134.7 (CHꢀ), 128.3–127.4 (2×
Ph), 117.0 (CH2ꢀ), 107.3 (C-1), 84.4 (C-2),
80.3, 79.4, 78.0 (C-3,4,5), 77.6 (C-6), 70.5 (C-
7), 71.0 (C-8), 73.7, 71.7 (2×CH2Ph), 72.2
(OCH2), 54.5 (OCH3), 26.3, 25.1 [(CH3)2C].
LSIMS (HRMS): m/z 537.2467 [M+Na]+.
Calcd for C29H38NaO8 537.2464.
Methyl 5-O-benzyl-7-deoxy-2,3-O-isopropy-
lidene-7-(phenyldimethy)lsilyl-
D
-glycero-h- -
D
manno-heptofuranoside (11).—Obtained from
9 (1.7 g), colorless oil, 1.46 g (72.2%); [h]D
1
+22.1° (c 2.4, CHCl3); H NMR (CDCl3): l
7.38–7.27 (m, 3×Ph), 4.86 (s, 1 H, H-1), 4.76
(dd, 1 H, J3,4 3.2 Hz, H-3), 4.54 (d, 1 H, J2,3
5.9 Hz, H-2), 4.65, 4.52 (AB, 4 H, 2×
CH2Ph), 4.18 (dd, 1 H, J4,5 9.2 Hz, H-4), 3.88
(m, 1 H, J6,7a 7.6 Hz, H-6), 3.77 (dd, 1 H, J5,6
2.6 Hz, H-5), 3,21 (s, 3 H, OCH3), 1.47, 1.31
[2 s, 6 H, (CH3)2C], 1.41 (dd, 1 H, J7a,7b 14.7
Hz, H-7a), 1.14 (dd, 1 H, J7b,6 6.3 Hz, H-7b),
0.29, 0.28 [2 s, 6 H, (CH3)2Si]. 13C NMR
(CDCl3): l 133.6–127.4 (3×Ph), 107.4 (C-1),
84.9 (C-2), 80.2, 78.9, 78.8 (C-3,4,5), 77.1 (C-
6), 73.8, 71.6 (2×CH2Ph), 54.7 (OCH3), 26.4,
25.1 [(CH3)2C], 18.1 (C-7), −1.9, −2.3
[(CH3)2Si]. LSIMS (HRMS): m/z 585.2646
[M+Na]+. Calcd for C33H42NaO6Si 585.2648.
Methyl 5-O-benzyl-7-deoxy-2,3-O-isopropy-
lidene-7-(phenyldimethyl)silyl-
L
-glycero-h- -
D
manno-heptofuranoside (9).—From 2 (1.95 g)
and (phenyldimethyl)silylmethylmagnesium
chloride, white foam, 1.89 g (66.4%); [h]D
+42.5° (c 1.6, CHCl3); CD: 413 nm (De%
1
−0.0367, c 0.0011 M); H NMR (CDCl3): l
7.36–7.24 (m, 2×Ph), 4.86 (s, 1 H, H-1), 4.76
(dd, 1 H, J3,4 3.3 Hz, H-3), 4.72, 4.54 (AB, 4

H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
435
1.35 [2 s, 6 H, (CH3)2C], 1.18 (dd, 1 H, J8a,7
5.6, J8a,8b 10.8 Hz, H-8a), 0.98 (dd, 1 H, J8b,7
3.8 Hz, H-8b), 0.31, 0.30 [2 s, 6 H, (CH3)2Si];
13C NMR (CDCl3): l 128.8–127.5 (3×Ph),
107.9 (C-1), 85.0 (C-2), 84.0, 80.0, 78.7 (C-
3,4,5), 75.2 (C-6), 74.0, 73.4 (2×CH2Ph), 68.7
(C-7), 55.1 (OCH3), 26.2, 25.1 [(CH3)2C], 20.8
(C-8), −2.0, −2.2 [(CH3)2Si]. Anal. Calcd
for C34H44O7Si: C 68.91, H 7.43. Found C
68.72, H 7.56.
Methyl
dene- -glycero-h-
5,6-di-O-benzyl-2,3-O-isopropyli-
-manno-heptofuranoside
L
D
(12).—Obtained from 11 (1.1 g), colourless
oil, 0.558 g (64.2%); [h]D +27.5° (c 2.5,
1
CHCl3); H NMR (CDCl3): l 7.38–7.24 (2×
Ph), 4.91 (s, 1 H, H-1), 4.86 (dd, 1 H, J3,4 3.2
Hz, H-3), 4.58 (d, 1 H, J2,3 5.8 Hz, H-2), 4.23
(dd, 1 H, J4,5 9.4 Hz, H-4), 4.82, 4.56 (AB, 4
H, 2×CH2Ph), 3.98 (dd, 1 H, J5,6 3.6 Hz,
H-5), 3.87 (m, 1 H, J6,7a 9.3, J6,7b 5.1 Hz, H-6),
3.74 (m, 2 H, H-7a, H-7b), 3.20 (s, 3 H,
OCH3), 2.40 (bs, 1 H, OH), 1.50, 1.36
[(CH3)2C]. 13C NMR (CDCl3): l 128.8–127.4
(2×Ph), 107.9 (C-1), 84.7 (C-2), 80.8, 80.0,
78.7 (C-3,4,5), 76.5 (C-6), 74.1, 73.3 (2×
CH2Ph), 61.8 (C-7), 55.1 (OCH3), 26.2, 25.0
[(CH3)2C]. LSIMS (HRMS): m/z 467.2048
[M+Na]+. Calcd for C25H32NaO7 467.2046.
Methyl 5,6-di-O-benzyl-8-deoxy-2,3-O-iso-
Methyl
5,6-di-O-benzyl-2,3-O-isopropyli-
- manno - octofuranoside
dene - - threo - h -
D
D
(16).—Obtained from 14 (0.13 g), colorless
oil, 0.076 g (72.7%); [h]D +28.6° (c 1.0,
CHCl3); CD: 355 nm (De% 0.0087, c 0.00106
1
M); H NMR: l 7.33–7.28 (m, 10H, Ph), 4.92
(s, 1 H, H-1), 4.86 (dd, 1 H, J3,4 3.6 Hz, H-3),
4.82, 4.68 (AB, 4 H, 2×CH2Ph), 4.58 (d, 1 H,
J2,3 5.9, H-2), 4.21 (dd, 1 H, J4,3 3.4, J4,5 9.3
Hz, H-4), 4.05 (dd, 1 H, J5,6 3.9 Hz, H-5), 3.93
(dd, 1 H, J7,8a 10.0 Hz, H-7), 3.73 (dd, 1 H,
J6,7 4.8 Hz, H-6), 3.54 (d, 2 H, J7,8b 5.2 Hz,
H-8a, H-8b), 3.31 (s, 3 H, OCH3), 2.85, 1.98
(2×bs, 2 H, OH), 1.50, 1.35 [2 s, 6 H,
(CH3)2C]. 13C NMR (CDCl3): l 128.5–127.8
(2×Ph), 108.2 (C-1), 84.7 (C-2), 80.0, 79.9,
79.3, 76.4 (C-3,4,5,6), 74.7, 74.0 (2×CH2Ph),
71.7 (C-7), 63.9 (C-8), 55.3 (OCH3), 26.3, 25.1
[(CH3)2C]. LSIMS (HRMS): m/z 497.2167
[M+Na]+. Calcd for C26H34NaO8 497.2154.
Anal. Calcd for C26H34O8·H2O: C, 63.40; H,
7.37. Found: C, 63.50; H, 7.31.
propylidene-8-(phenyldimethyl)silyl-
-manno-octofuranoside (14).—Obtained
from 13 (0.7 g), colorless oil, 0.572 g (60.9%);
[h]D +21.9° (c 1.1, CHCl3); CD: 401 nm (De%
0.0208, c 0.00105 M); H NMR (CDCl3): l
D
-threo-h-
D
1
7.38–7.27 (m, 3×Ph), 4.87 (s, 1 H, H-1), 4.82
(dd, 1 H, J3,4 3.1 Hz, H-3), 4.55 (d, 1 H, J2,3
5.8 Hz, H-2), 4.75, 4.62 (AB, 4 H, 2×
CH2Ph), 4.16 (dd, 1 H, J4,5 9.4 Hz, H-4), 4.02
(dd, 1 H, J5,6 3.9 Hz, H-5), 3.49 (m, 1 H, J6,7a
5.4, J6,7b 8.3 Hz, H-6), 3.20 (s, 3 H, OCH3),
1.49, 1.33 [2 s, 6 H, (CH3)2C], 1.16–0.89 (m, 2
H, H-7a, H-7b), 0.34, 0.32 [2 s, 6 H, (CH3)2Si].
13C NMR (CDCl3): l 136.8–127.2 (3×Ph),
108.2 (C-1), 86.2 (C-2), 84.7, 80.1, 79.3 (C-
3,4,5), 76.7 (C-6), 75.2, 74.2 (2×CH2Ph), 69.2
(C-7), 55.2 (OCH3), 26.3, 25.0 [(CH3)2C], 20.8
(C-8), −1.6, −2.3 [(CH3)2Si]. LSIMS
(HRMS): m/z 615.2748 [M+Na]+. Calcd for
C34H44NaO7Si 615.2752.
Methyl 5,6,7-tri-O-benzyl-8-deoxy-2,3-O-
isopropylidene-8-(phenyldimethyl)silyl-
h- -manno-octofuranoside
D
-threo-
D
(17).—Obtained
from 14 (0.5 g), colorless oil, 0.106 g (18.4%);
1
[h]D +21° (c 1.4, CHCl3); H NMR (CDCl3):
l 7.31–7.20 (m, 3×Ph), 4.86 (s, 1 H, H-1),
4.82 (dd, 1 H, J3,4 3.2 Hz, H-3), 4.76, 4.64,
4.56 (AB, 6 H, 3×CH2Ph), 4.58 (d, 1 H, J2,3
5.8 Hz, H-2), 4.34 (dd, 1 H, J4,5 9.3 Hz, H-4),
4.09 (dd, 1 H, J5,6 2.3 Hz, H-5), 3.91 (m, 1 H,
J7,8a 8.2, J7,8b 5.1 Hz, H-7), 3.21 (s, 3 H,
OCH3), 1.50 (dd, 1 H, J8a,8b 10.1 Hz, H-8a),
1.49, 1.33 [2 s, 6 H, (CH3)2C], 1.15 (dd, 1 H,
H-8a), 0.27, 0.25 [2 s, 6 H, (CH3)sSi]. 13C
NMR (CDCl3): l 128.7–127.0 (3×Ph), 107.9
(C-1), 85.2 (C-2), 83.7, 80.0, 78.9, 77.5 (C-
3,4,5,6), 75.9 (C-7), 74.9, 73.4, 72.8 (3×
CH2Ph), 55.2 (OCH3), 26.3, 25.1 [(CH3)2C],
19.1 (C-8), −1.2, −2.0 [(CH3)2Si]. LSIMS
Methyl 5,6-di-O-benzyl-8-deoxy-2,3-O-iso-
propylidene-8-(phenyldimethyl)silyl-
L
-erythro-
h- -manno-octofuranoside
D
(15).—Colorless
oil 0.127 g (13.6%); [h]D +34.2° (c 0.9,
CHCl3); CD: 353.5 nm (De% −0.1386, c
1
0.00107 M); H NMR (CDCl3): l 7.49–7.24
(m, 3×Ph), 4.84 (s, 1 H, H-1), 4.86 (dd, 1 H,
J3,4 3.0 Hz, H-3), 4.73, 4.66 (AB, 4 H, 2×
CH2Ph), 4.59 (d, 1 H, J2,3 5.9 Hz, H-2), 4.25
(dd, 1 H, J5,6 2.9 Hz, H-5), 4.20 (dd, 1 H, J4,5
9.1 Hz, H-4), 4.02 (m, 1 H, H-7), 3.48 (dd, 1
H, J6,7 5.8 Hz, H-6), 3.23 (s, 3 H, OCH3), 1.49,

436
H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
(HRMS) m/z 705.3225 [M+Na]+. Calcd for
C41H50NaO7Si 705.3223.
(CH2Ph), 71.3 (OCH2), 70.4 (C-7), 67.3 (C-5),
54.9 (OCH3), 27.9, 26.3 [(CH3)2C]. LSIMS
(HRMS): m/z 417.1893 [M+Na]+. Calcd for
C21H30NaO7 417.1889. Anal. Calcd for
C21H30O7·H2O: C, 61.15; H, 7.82. Found: C,
61.41; H, 7.49.
Methyl 5,6-di-O-benzyl-7,8-dideoxy-2,3-O-
isopropylidene-
L
-glycero-h- -manno-oct-7-
D
enofuranoside (18).—Colorless oil, 0.291 g
(78.3%); [h]D +41.6° (c 1.1, CHCl3); 1H
NMR (CDCl3): l 7.31–7.24 (m, 2×Ph), 6.01
(m, 1 H, J7,6 7.8, J7,8a 2.5, J7,8b 0.7 Hz, H-7),
5.35 (dq, 1 H, J8a,8b 14.6 Hz, H-8a), 5.26 (dq,
1 H, H-8b), 4.85 (s, 1 H, H-1), 4.82 (dd, 1 H,
J3,4 3.3 Hz, H-3), 4.55 (d, 1 H, J2,3 5.8 Hz,
H-2), 4.68, 4.52 (AB, 4 H, 2×CH2Ph), 4.30
(dd, 1 H, J4,5 9.5 Hz, H-4), 4.09 (dd, 1 H, J6,7
7.8 Hz, H-6), 3.83 (dd, 1 H, J5,6 2.6 Hz, H-5),
3.18 (s, 3 H, OCH3), 1.48, 1.32 [2 s, 6 H,
(CH3)2C]. 13C NMR (CDCl3): l 128.8–127.3
(2×Ph), 136.3 (C-7), 117.9 (C-8), 107.5 (C-1),
84.8 (C-2), 81.2, 80.0, 79.5 (C-3,4,5), 78.0 (C-
6), 74.7, 70.9 (2×CH2Ph), 54.5 (OCH3), 26.2,
24.9 [(CH3)2C]. LSIMS (HRMS) m/z 463.2079
[M+Na]+. Calcd for C26H32NaO6 463.2096.
Methyl 7-O-allyl-4-O-benzyl-2,3-O-isopro-
Methyl 7-O-allyl-4,6-di-O-benzyl-2,3-O-iso-
propylidene-
D
-glycero-h- -manno-heptopyran-
D
oside (22).—Colorless oil, 0.482 g (64.6%);
[h]D +56.2° (c 1.4, CHCl3); 1H NMR
(CDCl3): l 7.29–7.23 (m, 2×Ph), 5.89 (m, 1
H, CHꢀ), 5.26, 5.18 (dg, 2 H, CH2ꢀ), 4.97 (s,
1 H, H-1), 4.82, 4.60 (AB, 4 H, 2×CH2Ph),
4.24 (t, 1 H, J3,4 6.0 Hz, H-3), 4.12 (dd, 1 H,
J2,3 5.9 Hz, H-2) 4.08–3.98 (m, 3 H, OCH2,
H-6), 3.84–3.62 (m, 4 H, H-4, H-5, H-7a,
H-7b), 3.35 (s, 3 H, OCH3), 1.54, 1.37 [2 s, 6
H, [(CH3)2C]. 13C NMR (CDCl3): l 134.5
(CHꢀ), 128.1–127.4 (2×Ph), 116.8 (CHꢀ),
98.5 (C-1), 79.1, 75.6, 75.0, 74.9 (C-2,3,4,6),
73.4, 72.2 (2×CH2Ph), 72.0 (OCH2), 69.7 (C-
7), 67.8 (C-5), 54.9 (OCH3), 27.9, 26.3
[(CH3)2C]. LSIMS (HRMS): m/z 507.2356
[M+Na]+. Calcd for C28H36NaO7 507.2358.
Methyl 7-O-allyl-4,6-di-O-benzyl-2,3-O-iso-
pylidene-
L
-glycero and
D
-glycero-h- -manno-
D
heptopyranosides (21).—Obtained from 20
(1.7 g) and allyloxymethylmagnesium chlo-
ride, following the procedure for 3 and 4, as
propylidene-
L
-glycero-h- -manno-heptopyran-
D
oside (23).—Colorless oil, 0.263 g (35.3%);
[h]D +51.1° (c 1.9, CHCl3); 1H NMR
(CDCl3): l 7.35–7.27 (m, 2×Ph), 5.88 (m, 1
H, CHꢀ), 5.22, 5.14 (dq, 2 H, CH2ꢀ), 4.85 (s,
1 H, H-1), 4.78, 4.58 (AB, 4 H, 2×CH2Ph),
4.31 (t, 1 H, J3,4 6.2 Hz, H-3), 4.10 (d, 1 H, J2,3
5.8 Hz, H-2), 4.02 (dd, 1 H, J4,5 7.6 Hz, H-4),
3.98–3.80 (m, 4 H, H-5, H-6, OCH2), 3.67–
3.59 (m, 2 H, H-7a, H-7b), 3.37 (s, 3 H,
OCH3), 1.49, 1.36 [2 s, 6 H, (CH3)2C]. 13C
NMR (CDCl3): l 134.8 (CHꢀ), 128.3–127.3
(2×Ph), 116.5 (CH2ꢀ), 98.0 (C-1), 79.2, 77.7,
75.6, 75.5 (C-2,3,4,5), 72.6, 72.4 (2×CH2Ph),
72.1 (OCH2), 70.2 (C-7), 68.7 (C-6), 54.7
(OCH3), 27.9, 26.3 [(CH3)2C]. LSIMS
(HRMS): m/z 507.2360 [M+Na]+. Calcd for
C28H36NaO7 507.2358.
an inseparable mixture of stereoisomeric
L
a -
D
and -manno-heptopyranosides (1.48 g,
D D
a
71%, approx. 2:1). The proportion and
configuration of stereoisomers could be de-
duced after the benzylation experiment and
isolation of the pure
below).
L
a
D
stereoisomer 24 (see
Methyl
7-O-allyl-4-O-benzyl-2,3-O-iso-
-glycero-h- -manno-heptopyran-
propylidene-
L
D
oside (24).—Obtained from 21 (1.36 g),
colorless oil, 0.462 g (47.3%); [h]D +46.3° (c
1.4, CHCl3); CD: 352.5 nm (De% −0.0135, c
0.00107 M); CD: 355 nm (De% 0.0087, c
1
0.00106 M); H NMR (CDCl3): l 7.37–7.28
(m, Ph), 5.90 (m, 1 H, CHꢀ), 5.26, 5.18 (dq, 2
H, CH2ꢀ), 4.93 (s, 1 H, H-1), 4.82, 4.65 (AB,
2 H, CH2Ph), 4.32 (t, 1 H, J3,4 6.0 Hz, H-3),
4.18 (dd, 1 H, J4,5 7.3 Hz, H-4), 4.11 (d, 1 H,
J2,3 5.7 Hz, H-2), 4.02 (m, 2 H, OCH2), 3.72
(dd, 1 H, J5,6 6.8 Hz), 3.64–3.59 (m, 1 H,
H-6), 3.58–3.40 (m, 2 H, H-7a, H-7b), 3.34 (s,
3 H, OCH3), 2.20 (bs, 1 H, OH), 1.50, 1.36 [2
Methyl
4,6-di-O-benzyl-2,3-O-isopropyli-
-manno-heptopyranoside
dene- -glycero-h-
D
D
(25).—Obtained from 22 (0.39 g), colorless
oil, 0.289 g (80.4%); [h]D +61.5° (c 1.8,
1
CHCl3); H NMR (CDCl3): l 7.32–7.35 (m,
2×Ph), 4.98 (s, 1 H, H-1), 4.82, 4.50 (AB, 4
H, 2×CH2Ph), 4.34 (t, 1 H, J3,4 6.3 Hz, H-3),
4.14 (d, 1 H, J2,3 5.9 Hz, H-2), 3.96–3.30 (m,
3 H, J4,5 10.3, J5,6 3.0 Hz, H-4, H-5, H-6),
13
s, 6 H, (CH3)2C]. C NMR (CDCl3): l 134.4
(CHꢀ), 128.2–127.6 (Ph), 117.2 (CH2ꢀ), 98.4
(C-1), 78.8, 77.9, 75.5, 74.9 (C-2,3,4,6), 73.1

H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
437
H-4), 3.51 (s, 6 H, OCH3), 3.35 (dt, J5,6 7.6
Hz, H-5), 2.70 (bs, 1 H, OH), 1.47, 1.36 [2 s,
6 H, (CH3)2C], 0.87 (dd, 1 H, J7a,7b 14.3 Hz,
H-7a), 0.60 (dd, 1 H, H-7b), 0.31, 0.30 [2 s, 6
H, (CH3)2Si]. 13C NMR (CDCl3): l 128.6–
127.4 (Ph), 104.0 (C-1), 79.2 (C-2), 74.6, 73.7,
72.2 (C-3,4,5), 72.3 (CH2Ph), 68.1 (C-6), 56.8
(OCH3), 27.9, 26.0 [(CH3)2C, 19.1 (C-7), −
1.6, −2.5 [(CH3)2Si]. LSIMS (HRMS): m/z
495.2180 [M+Na]+. Calcd for C26H36NaO6Si
495.2178. Anal. Calcd for C26H36O6Si·1/2H2O:
C, 64.86; H, 7.69. Found: C, 64.88; H, 7.43
Methyl 4-O-benzyl-6,7-dideoxy-2,3-O-iso-
3.78–3.73 (m, 2 H, H-7a, H-7b), 3.39 (s, 3 H,
OCH3), 1.55, 1.37 [2 s, 6 H, (CH3)2C]. 13C
NMR (CDCl3): l 128.4–127.7 (2×Ph), 98.6
(C-1), 78.9, 76.4, 75.5, 75.2 (C-2,3,4,5), 73.0,
72.2 (2×CH2Ph), 69.6 (C-6), 62.6 (C-7), 55.3
(OCH3), 27.9, 26.3 [(CH3)2C]. LSIMS
(HRMS): m/z 467.2038 [M+Na]+. Calcd for
C25H32NaO7 467.2045
Methyl 8-O-allyl-4,6-di-O-benzyl-2,3-O-iso-
propylidene-
D
-erythro-
and
L
-threo-h- -
D
manno-octopyranosides (27).—Obtained from
26 (0.124 g) and allyloxymethylmagnesium
chloride, following the procedure for 3 and 4,
as an inseparable mixture of stereoisomeric
propylidene-h- -manno-hept-6-enopyranoside
D
D
-erythro- and
L
-threo-a- -manno-octopyran-
D
(30).—Obtained (BnBr, NaH, DMF) from 28
osides and together with some unreacted alde-
hyde (11 mg). H NMR (CDCl3): inter alia l
(3.81 g), 0.953 g (78.1%), white foam; [h]D
1
1
+34.4° (c 1.3, CHCl3); H NMR (CDCl3): l
9.41 (d, J 1.0 Hz, CHO), 5.85 (m, allyl ꢁCHꢀ),
7.35–7.27 (m, Ph), 5.98 (ddd, 1 H, J6,7a 17.3,
J6,7b 10.4 Hz, H-6), 5.44 (dq, 1 H, J7a,7b 17.5
Hz, H-7a), 5.26 (dq, 1 H, H-7b), 4.92 (s, 1 H,
H-1), 4.82, 4.61 (AB, 2 H, CH2Ph), 4.29 (t, 1
H, J3,4 7.0 Hz, H-3), 4.14 (d, 1 H, J2,3 5.8 Hz,
H-2), 4.01 (dd, 1 H, J5,6 5.7 Hz, H-5), 3.36
(dd, 1 H, J4,5 10.1 Hz, H-4), 3.32 (s, 3 H,
OCH3), 1.47, 1.36 [2 s, 6 H, (CH3)2C]. 13C
NMR (CDCl3): l 134.9 (C-6), 128.1–127.5
(Ph), 117.3 (C-7), 98.0 (C-1), 79.4, 78.6, 75.7,
68.8 (C-2,3,4,5), 72.9 (CH2Ph), 54.8 (OCH3),
27.8, 26.2 [(CH3)2C]. LSIMS (HRMS): m/z
343.1524 [M+Na]+. Calcd for C18H24NaO5
343.1521.
3.17, 3.15, 3.13 (3 s, 3×OCH3).
Methyl 4-O-benzyl-7-deoxy-2,3-O-isopropy-
lidene-7-(phenyldimethyl)silyl-
L
-glycero-h- -
D
manno-heptofuranoside (28).—Obtained from
20 (2.2 g), colorless oil, 2.49 g (77.3%); [h]D
+37.9° (c 1.7, CHCl3); CD: 360.5 nm (De%
−0.0238, c 0.00105 M); CD: 355 nm (De%
1
0.0087, c 0.00106 M); H NMR (CDCl3): l
7.47–7.24 (m, 2×Ph), 4.93 (s, 1 H, H-1),
4.58, 4.52 (AB, 4 H, 2×CH2Ph), 4.28 (dd, 1
H, J3,4 6.8 Hz, H-3), 4.16–4.02 (m, 1 H, H-6),
4.09 (d, 1 H, J2,3 5.7 Hz, H-2), 3.62 (dd, 1 H,
J4,5 10.0 Hz, H-4), 3.34 (dd, 1 H, J5,6 3.8 Hz,
H-5), 3.25 (s, 3 H, OCH3), 1.60 (dd, 1 H, J7a,6
3.8, J7a,7b 14.7 Hz, H-7a), 1.50, 1.36 [2 s, 6 H,
(CH3)2C], 0.92 (dd, 1 H, J7b,6 11.0 Hz, H-7b),
0.36, 0.35 [2 s, 6 H, (CH3)2Si]. 13C NMR
(CDCl3): l 128.3–127.6 (2×Ph), 98.4 (C-1),
78.9 (C-2), 75.9, 75.5, 71.7 (C-3,4,5), 73.2
(CH2Ph), 67.3 (C-6), 55.1 (OCH3), 27.9, 26.3
[(CH3)2C], 21.5 (C-7), −2.1, −2.4 [(CH3)2Si].
LSIMS (HRMS): m/z 495.2177 [M+Na]+.
Calcd for C26H36NaO6Si 495.2178.
Methyl 4,6-di-O-benzyl-7-deoxy-2,3-O-iso-
propylidene-
L
-glycero-h- -manno-heptofuran-
D
oside (31).—To methyl 4-O-benzyl-7-deoxy-
2,3-O-isopropylidene-7-(phenyldimethyl)silyl-
L
- glycero - a -
D
- manno - heptofuranoside (28)
(0.35 g, 0.74 mmol) was added 5 mL of aq
50% NaOH and the mixture was stirred at rt
for a few minutes. Benzyl bromide (1.5 mL)
and tetrabutylammonium bromide (30 mg)
were added, and vigorous stirring was con-
tinued for 1 h. The product was extracted
with Et2O (3×20 mL). Combined organic
extracts were washed with water (20 mL),
dried over Na2SO4 and concentrated to dry-
ness. Column chromatography of the residue
with 6:1 hexane–EtOAc gave 31 (0.267 g,
84.2%) as a colorless oil; [h]D +72.5° (c 1.2,
Methyl 4-O-benzyl-7-deoxy-2,3-O-isopropy-
lidene - 7 - (phenyldimethyl)silyl -
D
- glycero - i-
L
-gulo-heptopyranoside (29).—Colorless oil,
0.277 g (8.6%); [h]D +79.1° (c 3.1, CHCl3);
1
CD: 352 nm (De% 0.0462, c 0.00105 M); H
NMR (CDCl3): l 7.47–7.24 (m, 2×Ph), 4.58
(AB, 2 H, CH2Ph), 4.38 (dd, 1 H, J3,4 2.3 Hz,
H-3), 4.28 (d, 1 H, J1,2 7.0 Hz, H-1), 4.05 (m,
1 H, J6,7a 10.9, J6,7b 2.2 Hz, H-6), 3.97 (dd, 1
H, J2,3 5.8 Hz, H-2), 3.76 (t, 1 H, J4,5 1.9 Hz,
1
CHCl3); H NMR (CDCl3): l 7.36–7.27 (m,
Ph), 5.01 (s, 1 H, H-1), 4.83, 4.64 (AB, 4 H,

438
H. Ste˛powska, A. Zamojski / Carbohydrate Research 332 (2001) 429–438
3. Grzeszczyk, B.; Holst, O.; Mu¨ller-Loennies, S.; Zamojski,
A. Carbohydr. Res. 1998, 307, 55–67.
4. Ste˛powska, H.; Zamojski, A. Tetrahedron 1999, 55,
5519–5538.
5. Kim, M.; Grzeszczyk, B.; Zamojski, A. Tetrahedron 2000,
56, 9319–9337.
6. Dondoni, A. In Modern Synthetic Methods; Scheffold,
R., Ed. Carbohydrate Synthesis via Thiazoles.; VHCA
and VCH: Basel, 1992; pp. 377–437.
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347–355.
2×CH2Ph), 4.36 (dd, 1 H, J3,4 6.3 Hz, H-3),
4.30 (dd, 1 H, J5,6 1.2 Hz, H-5), 4.12 (d, 1 H,
J2,3 5.9 Hz, H-2), 4.00 (dg, 1 H, J6,7 6.6 Hz,
H-6), 3.81 (dd, 1 H, J4,5 10.0 Hz, H-4), 3.38 (s,
3 H, OCH3), 1.54, 1.37 [2 s, 6 H, (CH3)2C],
1.32 (d, 3 H7, CH3). 13C NMR (CDCl3): l
128.4–127.7 (2×Ph), 98.6 (C-1), 79.2 (C-2),
75.6, 75.5, 71.4, 71.3 (C-3,4,5,6), 72.4, 71.1
(2×CH2Ph), 54.9 (OCH3), 27.9, 26.3
[(CH3)2C], 15.8 (C-7). LSIMS (HRMS): m/z
451.2091 [M+Na]+. Calcd for C25H32NaO6
451.2096. Anal. Calcd for C25H32O6·H2O: C,
67.24; H, 7.67. Found: C, 67.13; H, 7.23.
11. Boons, G. J. P. H.; van der Marel, G. A; van Boom, J.
H. Tetrahedron Lett. 1989, 30, 299–302.
12. Frelek, J.; Pakulski, Z.; Zamojski, A. J. Carbohydr.
Chem. 1993, 12, 625–639.
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1999, 3, 145–174.
14. Frelek, J. unpublished observation.
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347–355.
Acknowledgements
Support of this work from Grant No. 3
TO9A 066 12, obtained from the State Com-
mittee for Scientific Research, is gratefully
acknowledged. We thank Dr Jadwiga Frelek
for CD measurements.
17. Fleming, J.; Henning, R.; Plaut, H. J. Chem. Soc., Chem.
Commun. 1984, 29–31.
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