Synthesis of a fusion-isomeric cellobionoimidazole and its evaluation against the syn-protonating glycosidase Cel7A

Article abstract of DOI:10.1002/hlca.200590260

The fusion-isomeric cellobinoimidazole 2, a potential inhibitor of the syn-protonating β-glycosidase Cel7A, was synthesised by Koenigs-Knorr glycosylation of the α-D-arabinopyranoside 32, followed by selective hydrolysis. Glycosylation of 32 with acetobromoglucose 6 proceeded with poor diastereoselectivity, giving the desired 1,3-linked β-D-disaccharide 35 as minor product, besides the major 1,3-linked α-D-disaccharide 36. Hg ²⁺-Promoted glycosylation of 32 led predominantly to the 1,2-ortho ester 33. Sequential removal of the silyl, acetyl, and allyl groups of 35 led to a 45:55 equilibrium mixture 2 and the manno-configured isomer 39. Similarly, deprotection of 36 gave a mixture of the maltonoimidazole 42 and the manno-configured isomer 43. According to a known protocol, the glycosyl acceptor 32 was synthesised in eleven steps and an overall yield of 8-13% from D-lyxose. The silylated arabinopyranosyl moiety of the α-D-glucosides 13-19, 33, 34, and 36 adopts a ⁴C₁ conformation, while the arabinopyranosyl moiety of the β-D-glucosides 17 and 35 exists as a 1:3 mixture of ⁴C₁ and ¹C₄ conformers, as a result of the combined preferred axial orientation of bulky vicinal substituents and the anomeric effect. MM3* Modelling evidences a preferred ⁴C₁ conformation of 35 and 36, and stronger steric interactions between the pyranosyl moieties of 35. The equilibrium mixture 2/39 proved a poor inhibitor of Cel7A with an IC₅₀ value of ca. 4 mM.

Full text of DOI:10.1002/hlca.200590260

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Helvetica Chimica Acta – Vol. 88 (2005)
Synthesis of a Fusion-Isomeric Cellobionoimidazole and Its Evaluation against
the syn-Protonating Glycosidase Cel7A
by Narinder Mohal, Bruno Bernet, and Andrea Vasella*
Laboratorium für Organische Chemie, ETH-Hönggerberg, HCI, CH-8093 Zürich
The fusion-isomeric cellobinoimidazole 2, a potential inhibitor of the syn-protonating b-glycosidase Cel7A,
was synthesised by Koenigs–Knorr glycosylation of the a-
ysis. Glycosylation of 32 with acetobromoglucose 6 proceeded with poor diastereoselectivity, giving the desired
1,3-linked b- -disaccharide 35 as minor product, besides the major 1,3-linked a-
-disaccharide 36. Hg2+-Pro-
D-arabinopyranoside 32, followed by selective hydrol-
D
D
moted glycosylation of 32 led predominantly to the 1,2-ortho ester 33. Sequential removal of the silyl, acetyl,
and allyl groups of 35 led to a 45 :55 equilibrium mixture 2 and the manno-configured isomer 39. Similarly,
deprotection of 36 gave a mixture of the maltonoimidazole 42 and the manno-configured isomer 43. According
to a known protocol, the glycosyl acceptor 32 was synthesised in eleven steps and an overall yield of 8–13%
from
D
-lyxose. The silylated arabinopyranosyl moiety of the a-
D
-glucosides 13–19, 33, 34, and 36 adopts a 4C1
-glucosides 17 and 35 exists as a 1:3 mixture of
conformation, while the arabinopyranosyl moiety of the b-
D
4C1 and 1C4 conformers, as a result of the combined preferred axial orientation of bulky vicinal substituents
and the anomeric effect. MM3* Modelling evidences a preferred 4C1 conformation of 35 and 36, and stronger
steric interactions between the pyranosyl moieties of 35. The equilibrium mixture 2/39 proved a poor inhibitor
of Cel7A with an IC50 value of ca. 4 mM.
Introduction. – We have recently disclosed the synthesis of fusion-isomeric gluco-
configured imidazoles of type 1 [1]. As predicted, they do not inhibit anti-protonating
b-glycosidases from family 1 [2] being devoid of a ‘glycosidic heteroatom’ that could
interact with the catalytic acid of an anti-protonating b-glycosidase [3–15]. The imida-
zole 1 does not inhibit Cel7A (formerly named CBH I), a syn-protonating b-glycosidase
from family 7 [16] and one of the industrially most important cellulase components of
Trichoderma reesei [17]. The inhibitory inactivity may be due to the requirement of
Cel7A for di- or oligosaccharide substrates, and/or to an unsuitable position of the gly-
cosidic heteroatom. An appreciation of these factors requires the synthesis of at least a
disaccharide analogue 2 of 1 [18]. As the isomeric cellobionoimidazole 3 [19] is a potent
inhibitor of the anti-protonating b-glycosidase Cel5A of family 5, a comparison of the
inhibitory activity of 2 and 3 promised to be meaningful. We decided to synthesise this
fusion-isomeric cellobionoimidazole 2.
© 2005 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 88 (2005)
3233
We considered that 2 – a tautomer of the corresponding hemiacetal A – should be
accessible by regioselective hydrolysis, or acetolysis and deacetylation, of a suitably
masked b-linked disaccharide which, in turn, should be available by standard glucosy-
lation of the acceptor B with a glucosyl donor C (Scheme 1). The a-
side B is accessible by oxidoreduction of the a- -lyxopyranoside D; a representative
-lyxose in eleven steps and in
D
-arabinopyrano-
D
of B (4 in Scheme 2) has already been prepared from
ca. 9–12% overall yield [1].
D
Scheme 1
Results and Discussion. – We first attempted to glucosidate the branched-chain a-
D-
arabinopyranoside 4 [1] with 2,3,4,6-tetra-O-acetyl-a-
D
-glucopyranosyl bromide (6)
[20] under Koenigs–Knorr conditions [21] but met with considerable difficulties1)
(Scheme 2). AgOTf-Promoted glucosidation of 4 with 6 in CH2Cl2 resulted in an insep-
arable 2 :1 mixture of disaccharides, which were de-bocylated and then separated by
chromatography into 13 (26%) and 17 (19%). The unexpected preferential formation
of the undesired a-
anomerisation of the initially formed b-
D
-glucopyranoside 13 was rationalised by postulating an in situ
-glucopyranoside 17 (cf. [22][23]). However,
D
glucosidation in the presence of an acid scavenger such as N,N,N’,N’-tetramethyl
urea (TMU) [24][25] led exclusively to the 1,2-ortho ester 18 that was isolated in ca.
90% yield. Similarly, glucosidation of 4 with 6 in the presence of Hg(CN)2/HgBr2 in
CH2Cl2 under Helferich conditions [26] gave exclusively 18 by preferred exo-attack
on the intermediate 1,3-dioxolenium cation [27–30].
We investigated several glucosyl donors to improve the stereoselectivity of the glu-
cosidation of 4 in favour of the desired b- -anomer (Scheme 2). Koenigs–Knorr-type
D
glucosidation by the more reactive perbenzoylated bromide 7 [31] provided a mixture
of 14 (30%) and N-debocylated 15 (29%) that was transformed into 14 by treatment
with Boc2O and DMAP in MeCN. There was no evidence of the desired b-linked
anomer. Glucosidation of 4 by 7 in the presence of TMU led exclusively to the 1,2-
ortho ester 19 (86%). It was stable to chromatography and stored for months without
1
)
A range of solvents and promoters were tested without success in search of a diastereoselective glycosida-
tion. Glycosidation at temperatures between ꢀ20 and 108 led to mixtures, with the 1,2-ortho ester 18 as
main product.

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Helvetica Chimica Acta – Vol. 88 (2005)
Scheme 2
a) i. 6, AgOTf (Tf=CF3SO2), 4-Å mol. sieves, CH2Cl2. ii. CF3COOH/CH2Cl2 1:9; 26% of 13, 19% of 17,
and 18% of 4. b) 7, AgOTf, 4-Å mol. sieves, CH2Cl2; 30% of 14, 29% of 15. c) 11, TMSOTf (TMS=Me3Si),
CH2Cl2; 99% of 5. d) 12, Zn(OTf)2, 4-Å mol. sieves, CH2Cl2; 30% of 16 and 27% of 4. e) AgOTf, N,N,N’N’-
tetramethylurea (TMU), 4-Å mol. sieves, CH2Cl2; 96% of crude 18 (ca. 90% pure); 86% of 19.
noticeable decomposition. Attempts to rearrange the ortho esters 18 and 19 under well-
precedented conditions (BF3 ·Et2O in CH2Cl2, TMSOTf in THF, or HgBr2 in CH2Cl2
[32][33]) led either to hydrolysis to the corresponding glucopyranoses or to recovery
of starting material. In an exploratory experiment, 4 was glucosidated with the pivaloyl-
ated bromide 8 [34] under Koenigs–Knorr conditions. The 1,2-ortho ester was the only
isolable product, besides the glycosyl acceptor 4. Yields were rather poor due to the
limited stability of the ortho ester to chromatography. Almost no reaction occurred
under Helferich conditions, and only traces of the pivaloylated ortho ester were
observed.
Treatment of 4 with the thioglucoside 9 [35], benzenesulfinyl piperidine (BSP), and
Tf2O [36] led to a ca. 3 :2 mixture of N-Boc-disaccharides that were transformed to 13
and 17 (Scheme 2). Similarly, glucosidation of 4 with the phenyl sulfoxide 10 [37] in the
presence of Tf2O and 2,6-di(tert-butyl)-4-methylpyridine (DTBMP) [38] provided only
the ortho ester 18 in poor yield; in the absence of DTBMP, a complex mixture of Boc-
disaccharides was isolated as major product. Treatment with CF3COOH (TFA) trans-
formed these disaccharides to 13 and 17. Schmidt glycosidation [39] of 4 with the tri-
chloroacetimidate 11 [40][41] and TMSOTf as promoter led only to silylation of 4 to
5 (99%). No disaccharide was formed. A similar glycosidation in the presence of
BF3 ·OEt3 induced extensive decomposition of the glycosyl acceptor 4. Treatment of
4 with the benzylated trichloroacetimidate 12 [42] in CH2Cl2, Et2O, MeCN, or toluene
led only to intractable mixtures, presumably due to decomposition of 4. The Zn(OTf)2-

Helvetica Chimica Acta – Vol. 88 (2005)
3235
promoted glucosidation of 4 with 12 in CH2Cl2 gave the a-
D
-glucopyranoside 16 in 30%
yield without any indication of the b- -anomer.
D
Unfortunately, all experiments directed at a regioselective hydrolysis [43] of the
C(1)–OMe bond of 17 failed. No reaction was observed when 17 was treated at low
temperature with BCl3 in CH2Cl2, Me3SiI in MeCN, or Me3SiCl and NaI in MeCN,
while higher temperatures and prolonged treatment led to intractable mixtures without
any indication of the desired product. There is precedent for regioselective acetolysis
[44–50], but acetolysis of 17 (cat. H2SO4 in Ac2O or FeCl3 in Ac2O) gave a complex
mixture of monomers.
In view of these results, we decided to replace the MeO group of 4 by an allyloxy
group. We preferred preparing the corresponding allyl glycoside 32 from
hydrolysing 4 and glycosidation of the resulting hemiacetal with allyl alcohol
(Scheme 3). Accordingly, Fischer glycosidation of -lyxose with 1% of H2SO4 in allyl
alcohol gave crude 20 in high yields. Isopropylidenation of crude 20 with Amberlyst-15
in acetone followed by chromatography provided the a- and b- -lyxopyranosides 21
and 22 in 59 and 6% yield, respectively, from -lyxose. Tosylation of 21 to 23 (89%) fol-
lowed by deisopropylidenation in 80% aqueous AcOH at 1108 gave the diol 24. Treat-
ment of 24 with t-BuOK gave the 3,4-anhydro-b- -ribopyranoside 25 (71% from 23)
D
-lyxose to
D
D
D
L
which was silylated with triisopropyl trifluoromethanesulfonate (TIPSOTf) to 26
(83%). With Et2AlCN [51][52], the oxirane ring of 26 underwent ring opening with
complete control of regioselectivity to provide the 4-cyano-a- -lyxopyranoside 27 in
D
78% yield. As described for the analogous methyl lyxoside [1], 27 was treated with a
1:1 mixture of NH2CH2CH(OMe)2 and Me3Al in toluene at 808 to yield 67% of the imi-
dazole 28 that was N-bocylated to 29. Dess–Martin periodinane [53] oxidised 29 to the
desired a-
D
-threo-pentopyranosid-3-ulose 30 (68% from 28) and its doubly-epimerised
b- -erythro-pentopyranosid-3-ulose 31 (10% from 28; cf. [1]) that is presumably formed
D
by elimination followed by addition of allyl alcohol during purification. Luche reduc-
tion of 30 with NaBH4 and CeCl3 ·7 H2O [54] proceeded highly stereoselectively to
yield the a- -arabinopyranoside 32 (80%). The stereoselectivity is presumably the
D
result of a complexation of CeIII with O=C(3) and the axial allyloxy group of 30.
The flattened 4C1 conformation of 21–23 is consistent with J(1,2)=1.5–3.3, J(2,3)=6.0–6.3, J(3,4)=5.4–
6.6, J(4,5ax)=6.6–9.9, and J(4,5eq)=4.5–4.8 Hz (Table 3 in the Exper. Part). The [a]2D5 values (21: +62.6, 22:
ꢀ86.5) are in accordance with Hudson’s rule. The b-
L
-riboside 25 adopts predominantly the 1Ho conformation,
as evidenced by J(1,2)=2.4, J(2,3)=4.5, J(3,4)=4.5, J(4,5ax)ꢁ1, and J(4,5eq)=1.5 Hz, whereas the silylated b-
L-
riboside 26 exists as ca. 1:1 mixture of 1Ho and oH1 conformers, as indicated by J(1,2)=2.4, J(2,3)=3.0,
J(3,4)=3.9, J(4,5ax)=1.5, and J(4,5eq)=1.5 Hz. The carbonitrile 27 shows the CꢂN s at 118.34 ppm, and a char-
acteristic td for HꢀC(4) at 3.01 ppm with J(3,4)=J(4,5ax)=10.8 and J(4,5eq)=5.1 Hz. Together with J(1,2)=2.4
and J(2,3)=3.0 Hz, these values evidence the predominant 4C1 conformation of 27. The imidazolyl moiety of 28
gives rise to a br. s at 6.99 for HꢀC(4’) and HꢀC(5’), a br. d at 121.2 ppm for C(4’) and C(5’), and a s at 146.4 for
C(2’), whereas the imidazolyl moiety of 29–32 shows two ds (J=1.5–2.1 Hz) for HꢀC(4’) at 6.86–6.90 and Hꢀ
C(5’) at 7.31–7.34, two ds for C(4’) at 127.2–128.9 and C(5’) at 118.6–119.0, and a s for C(2’) at 143.7–148.3
ppm. These values evidence a tautomeric equilibrium of the N-unprotected imidazole 28 (cf. [1][55][56]).
The a-
J(2,3)=2.4–3.0, J(3,4)=10.8, and J(4,5ax)=11.4, J(4, 5eq)=3.6–4.8 Hz. The C=O group of 30 and 31 resonates
at 201.0–201.3 ppm. Characteristic shifts are observed for C(1) of the a- -configured 30 (102.5 ppm) and 32
D
-lyxo-configuration and the 4C1 conformation of 28 and 29 agree well with J(1,2)=1.5–1.8,
D
(99.2 ppm) and the b-D-configured 31 (105.4 ppm; Table 4 in the Exper. Part). The a-D-threo-configuration of
30, the a-
D
-arabino-configuration of 32, and their 4C1 conformation is evidenced by J(1,2)ꢃ1.8,
J(4,5ax)=11.4, J(4,5eq)=4.2–6.6 Hz, and corroborated for 32 by J(2,3)=3.0, J(3,4)=2.1, and J(3,5eq)=1.2 Hz.

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Helvetica Chimica Acta – Vol. 88 (2005)
Scheme 3
a) Allyl alcohol/conc. H2SO4 99 :1; 958. b) Amberlyst-15, 4-Å mol. sieves, acetone; 59% of 21, 6% of 22,
and 13% of 21/22. c) TsCl, pyridine; 89%. d) AcOH/H2O 4 :1, 1108. e) t-BuOK, THF; 71% from 23. f)
TIPSOTf (TIPS=(i-Pr)3Si), 2,6-lutidine, DMF; 83%. g) Et2AlCN, Et2O, toluene; 78%. h) Me3Al, NH2-
CH2CH(OMe)2, toluene; 67%. i) Boc2O, 4-(dimethylamino)pyridine (DMAP), MeCN. j) Dess–Martin per-
iodinane, CH2Cl2; 68% of 30 and 10% of 31 from 28. k) NaBH4, CeCl3 ·7 H2O, MeOH; 80%.
The downfield shift of the br. d (J=6.0 Hz) for HOꢀC(3) of 32 at 4.73 ppm hints to an intramolecular H-bond to
N(3’) of the imidazoyl moiety. J(1,2)=7.5, J(4,5ax)=11.7, and J(4,5eq)=6.3 Hz of 31 are consistent with the b-
erythro-configuration and a flattened 4C1 conformation.
D-
Glucosidation of 32 with 6 in the presence of Hg(CN)2 and HgBr2 led to the 1,2-
ortho ester 33 (39%; Scheme 4). Similarly, the AgOTf-promoted glucosidation of 32
with the benzoylated bromide 7 gave 70% of the 1,2-ortho ester 34. AgOTf-Promoted
glucosidation of 32 with 6 in CH2Cl2 gave 27% of recovered 32 and a ca. 7:3 mixture of
anomeric N-Boc-disaccharides, which could only be separated after their conversion to
the desired b-
D
-glucopyranoside 35 (13%) and the a-
D
-anomer 36 (31%). We were not
-anomer 35, and thus pro-
successful in improving the a/b ratio in favour of the b-
D
ceeded to deprotect 35 and 36. Desilylation of 35 to 37 and deacetylation gave the
deprotected allyl glycoside 38 (78% overall yield) that was heated in the presence of
Pd on charcoal for 24 h. Isomerisation of 38 to the (E)/(Z)-propenyl glycosides2) was
1
evident from the disappearance of the H-NMR signals of the allyl group and the
appearance of Me doublets (J=6.9 Hz) at 1.8 and 1.6 ppm in a ca. 4 :1 ratio. This mix-
ture was hydrolysed in acidic MeOH to yield 45% of a 45 :55 equilibrium mixture of the
2
)
In several experiments, it was necessary to replace the catalyst to drive the isomerisation to completion; we
assume that the catalyst was deactivated by the imidazole moiety.

Helvetica Chimica Acta – Vol. 88 (2005)
3237
Scheme 4
a) 6, Hg(CN)2, HgBr2, 4-Å mol. sieves, CH2Cl2; 39% of 33 and 21% of 32. b) 7, AgOTf, TMU, 4-Å mol.
sieves, CH2Cl2; 70% of 34. c) i. AgOTf, 3-Å mol. sieves, CH2Cl2. ii. CF3COOH/CH2Cl2 1:20; 13% of 35,
31% of 36, and 27% of 32. d) Bu4NF·3 H2O, THF; 92% of 37; 92% of 40. e) NH3, MeOH; 85% of 38;
82% of 41. f) 10% Pd/C, MeOH, reflux. g) 10% aq. HCl, MeOH; 45% of 2/39 45 :55; 64% of 42/43 ca. 1 :1.
cellobionoimidazole 2 and its manno-analogue 39. In an analogous sequence, the a- -
D
glucopyranoside 36 was transformed via 40 and 41 to a ca. 1:1 mixture of the maltono-
imidazole 42 and its manno-analogue 43 (48% overall yield).
A 3S5 conformation of the a-
the vicinal coupling constants J(1II,2II)=5.1–5.4, J(2II,3II)=2.7–3.0, J(3II,4II)=1.6–2.1, and J(4II,5II)=8.5–9.6
D-glucopyranosyl ring of the 1,2-ortho esters 18, 19, 33, and 34 is evidenced by

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Helvetica Chimica Acta – Vol. 88 (2005)
Hz, and by a long-range w-coupling of ꢃ1.2 Hz between HꢀC(2II) and HꢀC(4II) (see Table 1 in the Exper. Part).
HꢀC(1II) and HꢀC(2II) of the phenyl ortho esters 19 and 34 resonate 0.40–0.57 ppm downfield to HꢀC(1II) and
HꢀC(2II) of the methyl ortho esters 18 and 33 (5.52/5.55 and 4.04/4.25 ppm, resp.) whereas C(1II) of these four
ortho esters resonates in the narrow range of 96.8–97.5 ppm (see Table 2 in the Exper. Part). The b-D-configu-
ration of 17, 35, 37–39, and 2, and the a-D
-configuration of 13–16, 36, and 41–43 are evidenced by J(1II,2II) of
7.5–7.8 and 3.2–3.9 Hz, respectively, and by the upfield shift of HꢀC(1II) of the b-
D-anomers (Dd=0.54–0.67
ppm). The large J(2,3)=J(3,4)=J(4,5)=9.0–10.5 Hz reveal the 4C1 conformation of the glucopyranosyl moiety
of these disaccharides.
Sterically demanding 1,2-disilyl ethers and related vicinal sterically demanding sub-
stituents prefer a diaxial orientation (see [57–59] and refs. cit. therein). This preference
and the anomeric effect should force the a-
D
-arabinopyranosyl ring of the TIPS-pro-
tected disaccharides to prefer a 4C1 conformation. This is indeed found for the silylated
arabinopyranosyl moiety of the a- -glucosides 13–19, 33, 34, and 36 that adopt exclu-
D
sively the C1 conformation, as evidenced by J(1I,2I)<1, J(2I,3I)=J(3I,4I)=2.1–3.0,
4
J(4I,5axI)=10.5–12.0, and J(4I,5eqI)=3.0–4.3 Hz (see Table 1 in the Exper. Part). In con-
tradistinction, the silylated arabinopyranosyl moiety of the b- -glucosides 17 and 35
D
exists as a ca. 1:3 mixture of C1 and C4 conformers, as shown by J(1I,2I)=4.4–5.1,
J(2I,3I)=6.8–6.9, J(3I,4I)=3.0–3.8, J(4I,5axI)=5.1–6.3, and J(4I,5eqI)=3.0–3.8 Hz.
This observation suggests destabilising steric interactions between the glycosyl units
4
1
of the b- -glucosides. Indeed, MM3* modelling (programme Macromodel V. 6.0
D
4
[60]) of 35 and 36 confirmed this hypothesis. Minimisation of the C1 conformers of
35 and 36 led to a single favoured conformer, with the one of 36 by 1.2 kcal/mol
more stable than the one of 35 (Fig.). The C4 conformer of 36 (DE=5.1 kcal/mol) is
1
more destabilised than the one of 35 (DE=2.3 kcal/mol). The higher stability of the
4C1 conformer of 36 may contribute to the preferred formation of this unwanted
anomer in the glucosidation. Replacing the TIPS group of 32 by the sterically less
1
demanding Bn group may lead to ring inversion to the C4 conformer; conceivably it
would preferentially lead to the desired b- -glucopyranoside.
D
The desilylated b-
D
-glucopyranoside 37 and the a- -glucopyranoside 40 adopt
D
exclusively the 1C4 conformation (J(1I,2I)=6.6–7.2, J(2I,3I)=9.0, J(3I,4I)=5.6–5.7,
J(4I,5axI)=J(4I,5eqI)=1.8–2.7 Hz; see Table 1 in the Exper. Part). The deacetylated b-
D
-glucoside 38 in CD3OD (J(1I,2I)=6.0, J(2I,3I)=8.7, J(3I,4I)=5.4, J(4I,5axI)=3.6 Hz)
1
also prefers the C4 conformation to about 85% and the a-
D
-glucopyranoside 41
(J(1I,2I)=1.8, J(2I,3I)=4.8, J(3I,4I)=3.9, J(4I,5axI)=10.8, J(4I,5eqI)=3.9 Hz) flips to
4
about 80% back into the C1 conformation. These conformational changes are also
reflected by the chemical shift of C(1I) (13–18, 33–36, and 41: 98.3–101.6 ppm; 37,
38, and 40: 102.3–103.6 ppm) and C(3I) (13–18, 33–36, and 41: 70.2–77.4 ppm; 37,
38, and 40: 80.1–82.5 ppm; Table 2 in the Exper. Part).
Remarkably, the dts of HꢀC(5II) of 13, 14, 36 (each resonating at 2.73 ppm), 15 (3.20
ppm), and 41 (2.40 ppm) are strongly shifted to higher fields (compare their chemical
shift with 3.70–4.10 ppm for the other disaccharides; Table 1 in the Exper. Part). A
weaker upfield shift (ꢃ0.2 ppm) is observed for the signals of both HꢀC(6II). These
H-atoms are located in the p-plane of the imidazolyl moiety, with HꢀC(5II) nearly in
4
the centre of the ring (see modelled C1 conformer of 36 in the Fig.), and the upfield
shifts reflect its anisotropy. The strong shift difference for HꢀC(5II) of the benzoates
14 and 15 (0.47 ppm) suggests a different orientation of the imidazolyl ring; an elec-

Helvetica Chimica Acta – Vol. 88 (2005)
3239
Figure. Relative stability of the MM3*-calculated 4C1 and 1C4 conformers of the TIPS protected disaccharides
35 and 36 (for enhanced clarity, the H-atoms of the allyl, TIPS, and Ac groups are omitted).
tronic influence of the Boc group can be excluded since HꢀC(5II) of the bocylated 14
and the unbocylated 13 resonate at 2.73 ppm. The strongest upfield shift for HꢀC(5II)
of 41 (2.40 ppm) is due to the deacetylation and the change of the solvent to CD3OD.
There is precedent for such upfield shifts of HꢀC(5) and HꢀC(6) of an a-linked disac-
charide, as reported by our group [61]. Also shielded is C(1II) of the N-unprotected a-
-
D
glucosides 13, 15, and 16 (92.0–92.7 ppm), and the b-
ppm; compare with 94.8–96.2 and 103.6–105.1 ppm of 3-O-glucosylated a-
ranosides [62]). The MeO signal of the benzoylated a- -glucopyranosides 14 and 15
D
-glucosides 17 and 35 (97.3–97.9
D
-altropy-
D
is shifted upfield to 2.95 and 2.70 ppm, respectively, due to an anisotropy effect of
BzOꢀC(2II). The more flexible BnOꢀC(2II) group of the parent benzyl ether 16 can
avoid such a close contact; hence, MeO of 16 resonates at 3.30 ppm.
The
-gluco-configuration and the 7H6 conformation of the imidazopyridine moiety
D
of 2 and 42 agree with J(5,6)=6.6 Hz. The -manno-epimers 39 and 43 also prefer the
D
7H6 conformation and show a smaller J(5,6) value of 3.6 Hz.
Inhibition Studies. The cellobionoimidazole 2 and its manno-configured epimer
39 are very weak inhibitors of the syn-protonating Cel7A from T. reesi (family 7;

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Helvetica Chimica Acta – Vol. 88 (2005)
IC50 =4 m
M
at 508). This weak inhibition strongly suggests that N(1) cannot interact
with the flexible catalytic acid. Not surprisingly, the maltonoimidazole 42 and its
manno-analogue 43 are also weak inhibitors of Cel7A.
We thank the Swiss National Science Foundation and F. Hoffmann-La Roche AG, Basel, for generous sup-
port, and Dr. Anu Koivula, VTT Biotechnology and Food Research, VTT, Espoo, Finland, for a generous gift of
Cel7A.
Experimental Part
General (including inhibition experiments). See [1].
Glycosylation of 4 with 6. a) A suspension of 4 [1] (200 mg, 0.425 mmol), AgOTf (200 mg, 0.78 mmol) and
4-Å mol. sieves (400 mg) in CH2Cl2 (10 ml) was cooled to ꢀ108, treated slowly with a suspension of 6 [20] (200
mg, 0.486 mmol) and 4-Å mol. sieves (200 mg) in CH2Cl2 (2 ml) over 30 min, stirred for 16 h at 0 ! 168, treated
with sat. aq. NaHCO3 soln. (10 ml), and extracted with AcOEt (3×35 ml). The combined org. layers were
washed with sat. aq. NaHCO3 soln. (10 ml) and dried (Na2SO4). Evaporation and FC (25 g of silica gel; hex-
ane/AcOEt 3 :2) gave an inseparable mixture of Boc-disaccharides (120 mg, ca. 90% pure, traces of impurity
derived from 6) and 4 (36 mg, 18%). The soln. of these Boc-disaccharides (120 mg) in CH2Cl2 (10 ml) was cooled
to 08, treated with CF3COOH (0.1 ml), stirred for 4 h, neutralised with sat. aq. NaHCO3 soln. (5 ml), and
extracted with AcOEt (30 ml). The org. layer was washed with H2O and brine, dried (Na2SO4), and evaporated.
FC (4 g of silica gel, AcOEt/hexane 1:1 ! AcOEt ! AcOEt/MeOH 49 :1) gave 13 (90 mg, 26%) and 17 (66
mg, 19%).
b) A suspension of 4 (22.5 mg, 0.048 mmol) and 6 (22 mg, 0.053 mmol) in CH2Cl2 (2 ml) was treated with
4-Å molecular sieves (141 mg), stirred for 1 h, cooled to 28, treated with AgOTf (27 mg, 0.105 mmol) and
N,N,N’,N’-tetramethylurea (TMU, 20 ml, 0.16 mmol), stirred for 2 h at 2 ! 238 (complete consumption of 4),
and treated with sat. aq. NaHCO3 soln. (2 ml). After extraction with dil. AcOEt (20 ml), the org. layer was
washed with H2O (5 ml) and brine (5 ml), dried (Na2SO4), and evaporated. FC (2 g of silica gel; AcOEt/hexane
2 :3) gave crude 18 (37 mg, 96%; ca. 90% pure).
Methyl 2,3,4,6-Tetra-O-acetyl-a-
D
-glucopyranosyl-(1 ! 3)-4-deoxy-4-(1H-imidazol-2-yl)-2-O-(triisopropyl-
silyl)-a-
D
-arabinopyranoside (13). Colourless solid. Rf (AcOEt) 0.48. M.p. 174.2–174.58. [a]2D5 =+155.4
(c=0.35, CHCl3). IR (CHCl3): 3457w, 3233w, 3028w, 2947m, 2868w, 1750s, 1549w, 1464w, 1367m, 1236s,
1123m, 1075m, 1039s, 988w, 883m, 845m. 1H-NMR (300 MHz, CDCl3; assignments based on a DQFCOSY
and a HSQC spectrum): see Table 1; additionally, 9.44 (br. s, exchanged with D2O, NH); 7.06 (br. s, HꢀC(4’),
HꢀC(5’)); 3.37 (s, MeO); 2.09, 2.06, 2.04, 1.98 (4s, 4 AcO); 1.23–1.00 (m, (Me2CH)3Si). 13C-NMR (75 MHz,
CDCl3; assignment based on a HSQC spectrum): see Table 2; additionally, 170.46, 170.31, 169.75, 169.35 (4s,
4 C=O); 145.35 (s, C(2’)); 128.0 (br. d, C(4’)); 116.5 (br. d, C(5’)); 55.70 (q, MeO); 20.90 (q, 2 Me); 20.82,
20.73 (2q, 2 Me); 18.18 (q, (Me2CH)3Si); 12.39 (d, (Me2CH)3Si). HR-MALDI-MS: 723.3119 ([M+Na]+, C32H52-
N2NaO13Si+; calc. 723.3131). Anal. calc. for C32H52N2O13Si·0.5 H2O (709.854): C 54.14, H 7.53, N 3.92; found: C
54.26, H 7.42, N 3.95.
Methyl 2,3,4,6-Tetra-O-acetyl-b-
D
-glucopyranosyl-(1 ! 3)-4-deoxy-4-(1H-imidazol-2-yl)-2-O-(triisopropyl-
silyl)-a-
D
-arabinopyranoside (17). Colourless syrup. Rf (AcOEt) 0.22. [a]2D5 =ꢀ25.4 (c=0.5, CHCl3). IR
(CHCl3): 3428w, 3027w, 2945m, 2867w, 1755s, 1602w, 1545w, 1463m, 1368s, 1256m, 1140m, 1066s, 1041s, 968w,
864m, 845m. 1H-NMR (300 MHz, CDCl3; assignments based on a DQFCOSY and a HSQC spectrum): see
Table 1; additionally, 9.50 (br. s, exchanged with D2O, NH); 6.97 (br. s, HꢀC(4’), HꢀC(5’)); 3.46 (s, MeO);
2.07, 2.02, 1.98, 1.84 (4s, 4 AcO); 1.23–1.00 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3; assignments based
on a HSQC spectrum): see Table 2; additionally, 170.54, 170.07, 169.35, 169.13 (4s, 4 C=O); 145.34 (s, C(2’));
130–120 (br. hump; C(4’), C(5’)); 56.64 (q, MeO); 20.87, 20.82, 20.80, 20.71 (4q, 4 Me); 18.26, 18.23 (2q,
(Me2CH)3Si); 12.57 (d, (Me2CH)3Si). HR-MALDI-MS: 723.3139 ([M+Na]+, C32H52N2NaO13Si+; calc.
723.3131). Anal. calc. for C32H52N2O13Si (700.854): C 54.84, H 7.48, N 4.00; found: C 54.58, H 7.40, N 4.04.
Crude Methyl (S)-3,4,6-Tri-O-acetyl-1,2-O-(methylmethanediyl)-a-
butoxy)carbonyl]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-a-
D
-glucopyranose-(12 ! 3)-(4-{1-[(tert-
D
-arabinopyranoside (18; ca. 90%
pure). Colourless oil. Rf (AcOEt/hexane 4 :1) 0.31. [a]2D5 =+102.1 (c=0.9, CHCl3). IR (CHCl3): 2960m,
2947m, 2868m, 1755m, 1463w, 1371s, 1335w, 1306s, 1260s, 1140s, 1094s, 1042s, 986m, 926w, 883w, 844w. 1H-
NMR (300 MHz, CDCl3; impurity was not assigned): see Table 1; additionally, 7.24 (d, J=1.8, HꢀC(5’)); 6.83
(d, J=1.8, HꢀC(4’)); 3.30 (s, MeO); 2.08, 2.06, 2.04 (3s, 3 AcO); 1.58 (s, t-Bu); 1.22 (s, Me); 1.14–1.08 (m,

Helvetica Chimica Acta – Vol. 88 (2005)
3241
(Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally, 170.47, 169.36, 169.62 (3s, 3 OC=O); 148.64
(s, NC=O); 147.27 (s, C(2’)); 127.47 (d, C(4’)); 120.86 (s, C(OR)3); 117.96 (d, C(5’)); 85.01 (s, Me3C); 55.15 (q,
MeO); 27.77 (q, Me3C); 20.78 (q, 3 MeC=O); 19.72 (q, Me); 18.03 (q, (Me2CH)3Si); 12.33 (d, (Me2CH)3Si). HR-
MALDI-MS: 723.3121 ([M – Boc+Na]+, C32H52N2NaO13Si+; calc. 723.3131).
Glycosidation of 4 with 7. a) A suspension of 4 (112 mg, 0.24 mmol), 7 [31] (182 mg, 0.445 mmol), and 4-Å
mol. sieves (520 mg) in CH2Cl2 (2 ml) was stirred for 45 min at 248, cooled to 28, treated with AgOTf (126 mg,
0.49 mmol), warmed to 248, stirred further for 24 h, treated with sat. aq. NaHCO3 soln. (1 ml), and extracted
with AcOEt (3×15 ml). The combined org. layers were washed with sat. aq. NaHCO3 soln. (10 ml) and dried
(Na2SO4). Evaporation and FC (8 g of silica gel; hexane/AcOEt 7:3 !11 :9) gave 14 (76 mg, 30%) and 15
(65 mg, 29%).
b) A suspension of 4 (120 mg, 0.255 mmol) and 7 (274 mg, 0.42 mmol) in CH2Cl2 (6 ml) was treated with
4-Å mol. sieves, stirred at 278 for 1 h, cooled to 28, treated with AgOTf (192 mg, 0.75 mmol) and TMU (100
ml, 0.835 mmol), stirred for 14 h at 2 ! 238 (disappearance of 4), diluted with AcOEt (50 ml), washed with H2O
(5 ml) and brine (5 ml), dried (Na2SO4), and evaporated. FC (5 g of silica gel; CH2Cl2/hexane 1:19) gave 19
(229 mg, 86%).
Methyl 2,3,4,6-Tetra-O-benzoyl-a-
D
-glucopyranosyl-(1 ! 3)-4-{1-[(tert-butoxy)carbonyl]imidazol-2-yl}-4-
deoxy-2-O-(triisopropylsilyl)-a- -arabinopyranoside (14). Colourless oil. Rf (hexane/AcOEt 4 :1) 0.21, Rf (hex-
D
ane/AcOEt 7:3) 0.32. [a]2D5 =+168.8 (c=1.05 CHCl3). IR (CHCl3): 2946m, 2868w, 1762m, 1728s, 1602w, 1585w,
1494w, 1452m, 1373m, 1334m, 1304s, 1271s, 1141s, 1104s, 1070m, 1039s, 1028s, 991m, 882w, 843m. 1H-NMR (300
MHz, CDCl3): see Table 1; additionally, 8.04–8.01 (m, 4 arom. H); 7.92–7.86 (m, 4 arom. H); 7.56–7.24 (m, (12
arom. H); 7.33 (d, J=2.1, HꢀC(5’)); 6.97 (d, J=1.5, HꢀC(4’)); 2.95 (s, MeO); 1.58 (s, t-Bu); 1.10–1.00 (m, (Me2-
CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally, 166.05, 166.03, 165.03, 164.88 (4s, 4 OC=O);
149.06 (s, NC=O); 147.06 (s, C(2’)); 133.18, 133.03, 132.87, 132.81 (4s); 130.08–128.61 (several d); 127.71 (d,
C(4’)); 118.53 (d, C(5’)); 85.77 (s, Me3C); 54.55 (q, MeO); 27.86 (q, Me3C); 18.09, 18.02 (2q, (Me2CH)3Si);
12.24 (d, (Me2CH)3Si). HR-MALDI-MS: 1071.4290 ([M+Na]+, C57H68N2NaO15Si+; calc. 1071.4281).
Methyl 2,3,4,6-Tetra-O-acetyl-b-
D
-glucopyranosyl-(1 ! 3)-4-(1H-imidazol-2-yl)-4-deoxy-2-O-(triisopropyl-
silyl)-a-
D
-arabinopyranoside (15). Colourless oil. Rf (hexane/AcOEt 3 :2) 0.20. [a]2D5 =+160.4 (c=1.0,
CHCl3). IR (CHCl3): 3457w, 3226w, 2947m, 2868w, 1728s, 1602w, 1585w, 1548w, 1452m, 1370m, 1334m,
1
1316m, 1271s, 1111s, 1104s, 1070m, 1038s, 1028s, 882w, 846w. H-NMR (300 MHz, CDCl3; ca. 90% pure): 9.98
(br. s, exchanged with D2O, NH); see Table 1; additionally, 8.07–7.99 (m, 4 arom. H); 7.92–7.85 (m, 4 arom.
H); 7.55–7.28 (m, 12 arom. H); 7.22 (br. s, HꢀC(5’)); 6.97 (br. s, HꢀC(4’)); 2.70 (s, MeO); 1.05–1.00 (m, (Me2-
CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally, 166.30 165.99, 165.46, 164.79 (4s, 4 C=O); 145.70
(s, C(2’)); 133.40 (s, 2 C); 133.37, 133.01 (2s); 129.77–128.37 (several d); 128.09 (d, C(4’)); 116.35 (d, C(5’)); 55.10
(q, MeO); 18.15 (q, (Me2CH)3Si); 12.35 (d, (Me2CH)3Si). HR-MALDI-MS: 971.3745 ([M+Na]+, C52H60N2-
NaO13Si+; calc. 971.3757).
Methyl
(S)-3,4,6-Tri-O-benzoyl-1,2-O-(phenylmethanediyl)-a-
D
-glucopyranose-(12 ! 3)-(4-{1-[(tert-
butoxy)carbonyl]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-a-
D-arabinopyranoside (19). Colourless oil
solidifying upon storage. Rf (CH2Cl2/MeOH 4 :1) 0.31. M.p.: 143.3–144.18. [a]2D5 =+63.9 (c=0.38, MeOH).
IR (CHCl3): 3017s, 2976m, 2945m, 2895m, 2868m, 1762m, 1725s, 1602w, 1584w, 1522w, 1476m, 1451w, 1421w,
1372w, 1337w, 1307s, 1228s, 1142s, 1096s, 1043s, 970w, 880m, 848m. 1H-NMR (500 MHz, CDCl3; assignments
based on a DQFCOSY and a HSQC spectrum): see Table 1; additionally, 8.07 (br. dq, J=8.2, 1.2, 2 arom.
H); 7.96 (br. dq, J=8.3, 1.2, 2 arom. H); 7.72 (br. dq, J=8.3, 1.2, 2 arom. H); 7.55–7.44 (m, 4 arom. H); 7.50
(tt, J=7.5, 1.3, 1 arom. H); 7.32–7.26 (m, 7 arom H); 7.20–7.18 (m, 2 arom H); 7.17 (d, J=1.7, HꢀC(5’));
6.89 (d, J=1.7, HꢀC(4’)); 3.31 (s, MeO); 1.38 (s, t-Bu); 1.05–1.00 (m, (Me2CH)3Si). 13C-NMR (75 MHz,
CDCl3; assignments based on a HSQC spectrum): see Table 2; additionally, 166.08, 165.13, 164.44 (3s, 3 OC=
O); 148.91 (s, NC=O); 146.74 (s, C(2’)); 135.19, 133.62, 133.33, 133.06 (4s); 129.94–127.80 (several d); 127.56
(d, C(4’)); 126.41 (d); 121.12 (s, (PhCO3); 118.22 (d, C(5’)); 84.35 (s, Me3C); 55.14 (q, MeO); 27.68 (q, Me3C);
18.09, 18.06 (2q, (Me2CH)3Si); 12.19 (d, (Me2CH)3Si). HR-MALDI-MS: 1071.4279 ([M+Na]+, C57H68N2-
NaO15Si+; calc. 1071.4281). Anal. calc. for C57H68N2O15Si (1048.44): C 65.25, H 6.53, N 2.67; found: C 65.33,
H 6.40, N 2.64.
Attempted Glycosidation of 4 with 11. A mixture of 4 (40 mg, 0.085 mmol), 11 [40][41] (43.7 mg, 0.088
mmol), and 4-Å molecular sieves (92 mg) in dry CH2Cl2 (3 ml) was cooled to ꢀ788, treated with trimethylsilyl
triflate (TMSOTf; twice 3 ml, 0.033 mmol), stirred for 2 h at ꢀ308, treated with sat. aq. NaHCO3 soln. (3 ml), and
diluted with AcOEt (20 ml). The org. layer was separated, washed with H2O (25 ml), dried (Na2SO4), and evapo-
rated. FC (4 g of silica gel; hexane/AcOEt 4 :1) provided 5 (18 mg, 99%) and a mixture of 4 and 11 (42 mg).

3242
Helvetica Chimica Acta – Vol. 88 (2005)
Table 1. Selected 1H-NMR Chemical-Shift Values [ppm] and Coupling Constants [Hz] of the Ortho Esters 18, 19,
33, and 34, the a-
D
-Glucopyranosides 13–16, 36, 40, and 41, and b-
D-Glucopyranosides 17, 35, 37, and 38 in
a
CDCl3
)
18b)
4.55
33
4.71
19c)
4.56
34b)
13c)
14b)
4.46
15
4.44
16
4.64
HꢀC(1I)
HꢀC(2I)
HꢀC(3I)
HꢀC(4I)
HaꢀC(5I)
HbꢀC(5I)
HꢀC(1II)
HꢀC(2II)
HꢀC(3II)
HꢀC(4II)
HꢀC(5II)
HaꢀC(6II)
HbꢀC(6II)
J(1I,2I)
4.71
4.25
4.10–4.04
4.10–4.04
4.67
3.72
5.98
4.74
5.58
5.36
4.10
4.53
4.34
4.57
3.92
4.00
3.87
4.25
3.67
5.44
4.77
5.29
4.96
2.73
4.01
3.82
<1.0
3.0
3.3
12.0
4.2
10.8
3.8
3.91
4.33
4.17
4.48
3.71
5.52
4.04
5.06
4.84
3.80
4.16
4.09
<1.0
2.7
2.7
11.1
3.6
10.8
5.1
3.96
4.35
4.22
4.54
3.71
5.55
4.25
5.10
4.86
3.80
4.18
4.09
<1.0
3.0
3.0
11.4
3.6
10.8
5.4
4.16
4.10
4.08
4.62
3.71
5.92
4.61
5.55
5.37
4.04
4.49
4.32
3.71
4.47
4.24
4.76
3.67
5.49
5.03
6.08
5.67
2.73
4.16
4.00
<1.0
2.1
3.0
11.1
4.3
10.8
3.8
3.71
4.15
3.94
4.30
3.67
5.72
5.15
5.99
5.68
3.20
4.35
4.23
0.9
3.0
2.7
10.8
4.2
10.8
3.6
10.1
9.9
4.07
4.395
4.27
4.755
3.79
5.11
3.48
3.75
3.59
2.54
3.47
3.23
<1.0
<1.0
<1.0
J(2I,3I)
3.0
)
)
2.4
3.0
11.7
3.9
11.4
3.2
9.3
9.3
9.6
1.8
1.8
10.8
–
d
d
J(3I,4I)
)
d
J(4I,5aI)
J(4I,5bI)
J(5aI,5bI)
J(1II,2II)
J(2II,3II)
J(3II,4II)
J(4II,5II)
J(5II,6aII)
J(5II,6bII)
J(6aII,6bII)
4J(2II,4II)
11.2
3.7
11.2
5.2
3.0
1.5
8.7
2.7
5.6
12.1
0.8
10.5
3.0
10.5
5.1
3.0
1.6
8.5
2.7
5.6
12.0
1.2
2.7
2.1
9.6
4.8
3.0
12.1
<0.5
3.0
1.9
9.6
4.7
2.7
12.0
1.2
10.5
9.6
9.6
3.3
2.1
10.1
9.9
9.9
3.3
2.1
9.7
3.0
3.0
12.3
–
12.3
–
12.3
–
36b)
40c)
41a)
17c)
35b)
37b)
38a)
HꢀC(1I)
HꢀC(2I)
HꢀC(3I)
HꢀC(4I)
HaꢀC(5I)
HbꢀC(5I)
HꢀC(1II)
HꢀC(2II)
HꢀC(3II)
HꢀC(4II)
HꢀC(5II)
HaꢀC(6II)
HbꢀC(6II)
J(1I,2I)
4.74
4.39
4.68
4.32
4.51
4.35
4.41
3.67–3.57
4.05
3.42–3.23
4.36
3.67–3.57
4.55
3.42–3.23
3.67–3.57
3.42–3.23
3.42–3.23
3.86
3.89
4.02
3.88
4.32
3.67
5.40
4.76
5.28
4.96
2.73
3.99
3.82
3.63
3.88
3.58
4.37
3.72
5.45
4.89
5.33
5.07
4.19
4.28
4.16
6.6
3.75
4.05
3.60
4.39
3.74
4.94
3.23
3.39
3.21
2.40
3.45
3.32
1.8
3.79
4.12
3.72
4.20
3.66
4.90
4.96
5.17
5.11
3.71
4.21
4.16
5.1
3.645
3.89
3.72
4.17
3.64
4.85
4.97
5.18
5.11
3.71
4.23
4.14
4.4
3.54
3.94
3.45
4.44
3.64
4.78
5.02
5.30
5.06
3.78
4.20
4.14
7.2
3.73
6.0
8.7
5.4
<1.0
3.0
4.8
J(2I,3I)
9.0
5.6
4.8
3.9
6.9
4.5
6.8
4.5
9.0
5.7
J(3I,4I)
J(4I,5aI)
J(4I,5bI)
J(5aI,5bI)
J(1II,2II)
J(2II,3II)
12.0
3.8
10.8
3.6
2.7
2.7
12.0
3.6
10.8
5.1
3.0
11.1
7.8
9.0
6.3
3.8
11.4
7.8
9.0
1.8
2.1
12.0
7.5
9.3
3.6
)
12.6
d
3.9
10.8
3.6
7.5
d
10.4
10.2
9.6
)

Helvetica Chimica Acta – Vol. 88 (2005)
3243
Table 1 (cont.)
36b)
9.6
9.9
3.3
40c)
9.9
9.9
3.0
41a)
9.6
9.6
3.6
17c)
9.3
9.9
3.9
35b)
9.3
9.3
3.6
37b)
9.3
9.6
4.2
38a)
J(3II,4II)
)
)
d
J(4II,5II)
d
J(5II,6aII)
J(5II,6bII)
J(6aII,6bII)
2.1
2.6
12.0
2.1
12.4
2.1
12.0
2.4
12.0
2.6
12.0
2.6
12.3
2.4
13.2
a) 38 and 41 in CD3OD. b) Assignments based on selective homodecoupling experiments. c) Assignments based
on a DQFCOSY and a HSQC spectrum. d) Not assigned.
Table 2. Selected 13C-NMR Chemical-Shift Values [ppm] of the Ortho Esters 18, 19, 33, and 34, the a-
D-Gluco-
a
pyranosides 13–16, 36, 40, and 41, and b-
D-Glucopyranosides 17, 35, 37, and 38 in CDCl3
)
18
33
19b)
34
13b)
14
15
16
C(1I)
C(2I)
C(3I)
C(4I)
C(5I)
C(1II)
C(2II)
C(3II)
C(4II)
C(5II)
C(6II)
101.39
66.69
70.25
35.47
56.82
96.80
72.81
69.95
68.29
68.29
62.90
99.55
101.65
67.41
70.18
35.27
57.01
97.37
72.50
69.40
68.47
67.73
61.14
101.21
67.51
70.19
35.29
57.17
97.45
72.37
68.83
68.33
67.75
64.26
101.32
64.48
72.78
36.86
56.66
92.03
71.06
69.71
67.52
67.74
61.21
101.46
66.98c)
76.04
36.02
56.42
95.79
72.63
70.31
67.18c)
68.99c)
62.62
101.01
64.39
72.91
35.90
56.47
92.36
72.25
71.20
68.13
68.42
62.33
101.45
65.25
71.85
35.67
56.78
94.15
79.44
81.39
76.66
70.39
67.84
66.67
70.42
35.48
57.09
96.98
73.03
69.88
68.35
68.47
63.02
36
40b)
41a)
17b)
35
37
38a)
C(1I)
C(2I)
C(3I)
C(4I)
C(5I)
C(1II)
C(2II)
C(3II)
C(4II)
C(5II)
C(6II)
98.32
65.05
73.38
36.86
56.62
92.65
70.94
69.76
67.48
67.69
61.14
102.26
71.04
80.79
40.51
64.36
97.88
71.39
70.05
68.04
68.12
61.88
101.34
73.99
77.48
37.27
58.86
99.67
75.61
73.50
70.33
70.64
61.90
104.32
70.65
77.01
36.82
61.74
97.37
71.64
73.21
68.33
71.84
61.87
101.59
70.30
77.35
36.65
61.16
97.88
71.72
73.22
69.44
71.87
61.79
102.52
70.50
82.50
39.11
61.69
100.04
71.01
72.34
68.27
72.07
63.92
103.60
71.48
80.10
38.95
62.75
103.06
75.05
78.34
71.08
78.13
62.96
a) 38 and 41 in CD3OD. b) Assignments based on a HSQC spectrum. c) Assignments may be interchanged.
Methyl 4-{1-[(tert-Butoxy)carbonyl)]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-3-O-(trimethylsi-
lyl)a-D
-arabinopyranoside (5). Colourless oil. Rf (hexane/AcOEt 7:3) 0.10. [a]2D5 =+154.3 (c=0.5, CHCl3).
IR (CHCl3): 2947m, 2867m, 1762m, 1500w, 1463w, 1372w, 1333w, 1306s, 1262m, 1141s, 1100m, 1119m, 1055m,
1
1036m, 991w, 898m, 843w. H-NMR (300 MHz, CDCl3): 7.27 (d, J=1.5, HꢀC(5’)); 6.87 (d, J=1.5 HꢀC(4’));
4.59 (t, J=11.4, Hax–C(5)); 4.58 (br. s, HꢀC(1)); 4.39 (br. t, J ꢁ 3.6, HꢀC(3)); 4.15 (dt, J ꢁ 11.1, 3.6, Hꢀ
C(4)); 3.74 (br. d, J=3.6, HꢀC(2)); 3.70 (br. dd, J ꢁ 10.8, 3.6, Heq–C(5)); 3.36 (s, MeO); 1.59 (s, t-Bu); 1.13
(br. s, (Me2CH)3Si); 0.18 (s, Me3Si). 13C-NMR (75 MHz, CDCl3): 149.50 (s, C=O); 147.36 (s, C(2’)); 127.62
(d, C(4’)); 117.91 (d, C(5’)); 102.02 (d, C(1)); 84.78 (s, Me3C); 70.63, 69.73 (2d, C(2), C(3)); 56.58 (t, C(5));
55.20 (q, MeO); 37.01 (d, C(4)); 27.95 (q, Me3C); 18.25, 18.19 (q, (Me2CH)3Si); 12.49 (d, Me2CH)3Si); ꢀ0.29
(q, Me3Si).

3244
Helvetica Chimica Acta – Vol. 88 (2005)
Glycosidation of 4 with 12. A suspension of 4 (15 mg, 0.031 mmol), 12 [42] (41 mg, 0.67 mmol), and 4-Å mol.
sieves (198 mg) in CH2Cl2 (2 ml) was stirred for 45 min at 238, cooled to ꢀ208, treated with Zn(OTf)2 (15 mg,
0.041 mmol), stirred for 2 h, warmed to 238, stirred for another 2 h, treated with sat. aq. NaHCO3 soln. (2
ml), and extracted with AcOEt (3×5 ml). The combined org. layers were washed with sat. aq. NaHCO3 soln.
(2 ml) and dried (Na2SO4). Evaporation and FC (2 g of silica gel, hexane/AcOEt 9 :1 ! 17:3) gave 16 (12
mg, 30%) and 4 (4 mg, 27%).
Methyl
2,3,4,6-Tetra-O-benzyl-a-
D
-glucopyranosyl-(1 ! 3)-4-{1-[(tert-butoxy)carbonyl]-2H-imidazol-2-
yl}-4-deoxy-2-O-(triisopropylsilyl)-a-
D-arabinopyranoside (16). Colourless oil. Rf (hexane/AcOEt 4 :1) 0.60.
1H-NMR (300 MHz, CDCl3): see Table 1; additionally, 7.44–7.39 (m, 2 arom. H); 7.35–7.22 (m, 16 arom. H);
7.20–7.15 (m, 2 arom. H); 7.17 (d, J=1.8, HꢀC(5’)); 6.84 (d, J=1.8, HꢀC(4’)); 4.91, 4.64 (2d, J=10.8,
PhCH2); 4.82, 4.42 (2d, J=11.8, PhCH2); 4.81, 4.65 (2d, J=12.0, PhCH2); 4.52, 4.44 (2d, J=12.3, PhCH2);
3.30 (s, MeO); 1.51 (s, t-Bu); 1.14–1.10 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally,
148.98 (s, NC=O); 147.38 (s, C(2’)); 139.41, 138.96, 138.86, 137.94 (4s); 128.40–126.86 (several d including d of
C(4’)); 118.14 (d, C(5’)); 85.02 (s, Me3C); 75.70, 73.97, 73.64, 71.68 (4t, 4 PhCH2); 55.06 (q, MeO); 27.81 (q,
Me3C); 18.13, 18.10 (2q, (Me2CH)3Si); 12.30 (d, (Me2CH)3Si). HR-MALDI-MS (complete debocylation during
the measurement): 915.4584 (94, [M+Na]+, C52H68N2NaO9Si+; calc. 915.4586), 893.4697 (93, [M+H]+, C52H69N2-
O9Si+; calc. 893.4767), 861.4439 (100, [MꢀMeO]+, C51H65N2O9Si+; calc. 861.4505).
Allyl a/b-
was treated dropwise with conc. H2SO4 (1.8 ml, 14.08 mmol), warmed to 238, heated to 958 for 3 h (disappear-
ance of -lyxose), cooled, neutralised with Ag2CO3 (ca. 4.8 g, pH ca. 7), filtered, and evaporated. Filtration
through a short plug of silica gel (25 g; MeOH/CH2Cl2 1:4) and evaporation gave crude 20 (60 g), which was
used for the next step without further purification. A pure sample of a- -20 was obtained by FC (silica gel;
D-Lyxopyranoside (20). An ice cold soln. of D-lyxose (41.63 g, 277 mmol) in anh. AllOH (180 ml)
D
D
MeOH/CH2Cl2 1:4). Thick oil solidifying upon storage. Rf (CH2Cl2/MeOH 4 :1) 0.55. M.p.: 76–798.
[a]2D5 =+60.7 (c=1.3, MeOH). IR (ATR): 3301m, 2989w, 2943w, 2892w, 2864w, 1646w, 1466w, 1409w, 1375w,
1300m, 1149w, 1129m, 1103m, 1084m, 1070s, 1008s, 921m, 883m, 856w. 1H-NMR (300 MHz, D2O): 5.85
(dddd, J=16.8, 10.5, 6.3, 5.7, CH2 =CH); 5.26 (dq, J=17.1, 1.5), 5.12 (dq, J=10.2, 1.2) (CH2=CH); 4.72 (d,
J=3.0, HꢀC(1)); 4.13 (ddt, J=12.9, 5.6, 1.5), 3.96 (ddt, J=12.9, 6.3, 1.5) (CH2=CHCH2); 3.80–3.66 (m, Hꢀ
C(2), HꢀC(3), HꢀC(4), Heq–C(5)); 3.43 (dd, J=10.6, 8.4, Hax–C(5)). 13C-NMR (75 MHz, D2O): 133.05 (d,
CH2=CH); 118.36 (t, CH2=CH); 99.16 (d, C(1)); 70.50, 69.47 (2d, C(2), C(3)); 68.64 (t, CH2=CHCH2); 66.74
(d, C(4)); 62.50 (t, C(5)). Anal. calc. for C8H14O5·0.1 H2O (191.99): C 50.09, H 7.49; found: C 49.64, H 6.95.
Isopropylidenation of Crude 20. A soln. of crude 20 (60 g, 54.7 mmol) in anh. acetone (400 ml) was treated
with powdered 4-Å mol. sieves (73 g) and Amberlyst-15 (H+ form, 13.2 g). The resulting suspension was stirred
at 238 for 20 h (disappearance of 20) and filtered through a short plug of Celite (4×4 cm; washing with additional
100 ml of acetone). Evaporation and FC (156 g of silica gel; hexane/AcOEt 4 :1 ! 2 :1 ! 1:1) gave 21 (37.5 g,
59% from
D
-lyxose), 21/22 (8.3 g, 13%), and 22 (4.2 g, 6%).
-lyxopyranoside (21). Viscous oil solidifying to a colourless solid upon stor-
Allyl 2,3-O-Isopropylidene-a-
D
age. Rf (hexane/AcOEt 1:1) 0.62. M.p. 43.1–44.48. [a]2D5 =+62.6 (c=0.81, CHCl3). IR (CHCl3): 3591w (sh),
3454w, 3017s, 2991w, 2939w, 1457w, 1384m, 1375m, 1234m, 1164m, 1141m, 1075s, 1005m, 936m, 908w, 873w,
856w. 1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 5.90 (dddd, J=17.4, 10.5, 6.3, 5.7, CH2=CH);
5.32 (dq, J=17.1, 1.5), 5.23 (dq, J=10.5, 1.5) (CH2=CH); 4.28 (ddt, J=12.9, 5.1, 1.5), 4.07 (ddt, J=12.9, 6.3,
1.5) (CH2=CHCH2); 3.08 (d, J=7.8, exchanged with D2O, HOꢀC(4)); 1.50, 1.36 (2s, Me2C). 13C-NMR (75
MHz, CDCl3): see Table 4; additionally, 133.40 (d, CH2=CH); 118.20 (t, CH2=CH); 109.57 (s, Me2C); 68.86
(t, CH2=CHCH2); 27.54, 25.62 (2q, Me2C). Anal. calc. for C11H18O5 (230.26): C 57.38, H 7.88; found: C 57.50,
H 8.04.
Allyl 2,3-O-Isopropylidene-b-D-lyxopyranoside (22). Colourless oil. Rf (hexane/AcOEt 1:1) 0.43.
[a]2D5 =ꢀ86.5 (c=4.5, CHCl3). IR (CHCl3): 3458w, 2991w, 2939w, 1457w, 1384w, 1375w, 1263m, 1163m,
1140m, 1073s, 1009s, 937m, 856w, 823w. 1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 5.89 (dddd,
J=17.1, 10.2, 6.6, 5.1, CH2=CH); 5.29 (dq, J=17.1, 1.5), 5.16 (dq, J=10.5, 1.5) (CH2=CH); 4.30 (ddt,
J=12.6, 4.8, 1.5), 4.08 (ddt, J=12.6, 6.6, 1.5) (CH2=CHCH2); 3.08 (d, J=4.5, exchanged with D2O, HOꢀ
C(4)); 1.50, 1.39 (2s, Me2C). 13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 133.92 (d, CH2=CH);
117.97 (t, CH2=CH); 110.50 (s, Me2C); 68.86 (t, CH2=CHCH2); 27.04, 25.96 (2q, Me2C). Anal. calc. for C11H18O5
(230.26): C 57.38, H 7.88; found: C 57.50, H 8.04.
Allyl 2,3-O-Isopropylidene-4-O-[4-methylphenylsulfonyl]-a-D-lyxopyranoside (23). A soln. of 21 (8.5 g, 36.9
mmol) in dry pyridine (20 ml, 245 mmol) was treated with TsCl (9.65 g, 50.79 mmol; ! thick slurry), stirred at
238 for 20 h, diluted with Et2O (500 ml), washed with 10% aq. HCl (2×50 ml), H2O (2×50 ml), and brine (25
ml), dried (Na2SO4), and evaporated. FC (ca. 120 g of silica gel; 600 ml of hexane/AcOEt 9 :1 and 300 ml of hex-

Helvetica Chimica Acta – Vol. 88 (2005)
3245
1
Table 3. Selected H-NMR Chemical-Shift Values [ppm] and Coupling Constants [Hz] of the Monosaccharides
21–32 in CDCl3
21
22a)
23
24
25a)
26
HꢀC(1)
HꢀC(2)
HꢀC(3)
HꢀC(4)
HaꢀC(5)
HbꢀC(5)
J(1,2)
4.81
4.17
4.26
3.80–3.78
3.80–3.78
3.70
2.7
6.3
4.74
4.88
4.77
4.53
4.44
4.20
4.07
3.87
3.96
3.25
3.3
4.08
4.17
4.40
3.77
3.66
1.5
4.01–3.92
4.01–3.92
4.62
3.75
3.49b)
3.34
3.98b)
3.90
2.4
3.97
3.36c)
3.41
4.04
3.92c)
4.4
3.67–3.58
3.67–3.58
2.7
d
J(2,3)
6.0
6.3
)
4.5
2.9
J(3,4)
5.4
)
6.9
12.9
5.4
4.5
6.6
10.8
6.6
5.0
9.8
11.4
8.1
6.3
8.1
4.5
1.5
0.9
13.4
3.9
2.4
1.0
13.4
d
J(4,5a)
J(4,5b)
J(5a,5b)
d
)
27
28
29
30
31a)
32
HꢀC(1)
HꢀC(2)
HꢀC(3)
HꢀC(4)
HaꢀC(5)
HbꢀC(5)
J(1,2)
4.61
4.87
4.86
4.09
4.26–4.23
4.26–4.23
4.02
5.02
4.12
–
5.28
4.56
4.28
2.0
–
4.48
4.44
–
4.63
4.51
4.13
7.5
–
4.79
3.98
4.03
3.01
3.87
3.79
2.4
4.02
4.08
3.32
4.28
3.90
2.0
3.97
4.27e)
4.19
4.35
3.70e)
1.2
3.82
1.8
J(2,3)
J(3,4)
3.0
9.6
3.3
10.8
2.5
3.0
2.1
d
)
–
–
J(4,5a)
J(4,5b)
J(5a,5b)
5.1
9.6
11.3
4.8
10.8
11.4
10.8
3.6
10.8
11.1
6.6
11.1
6.3
11.7
11.4
11.4
4.1
11.4
a) Assignments based on selective homodecoupling experiments. b) 4J(3,5a)=0.5 Hz. c) 4J(3,5b)=1.0 Hz. d) Not
4
assigned. e) J(3,5b)=1.2 Hz.
Table 4. Selected 13C-NMR Chemical Shift Values [ppm] of the Monosaccharides 21–32 in CDCl3
21
22
23
24
25
97.70
26
C(1)
C(2)
C(3)
C(4)
C(5)
97.63
74.44
77.26
67.17
63.12
96.14
72.93
77.97
67.91
62.91
96.53
74.60
75.68
77.00
58.61
98.35
99.73
69.51
54.18a)
53.07a)
60.66
69.05
70.45
77.28
59.83
64.84
51.92a)
51.37a)
57.98
27
28
29
30
31
32
C(1)
C(2)
C(3)
C(4)
C(5)
98.93
99.17
99.83
102.47
76.53
201.28
47.84
62.82
105.43
79.81
201.01
51.21
63.65
99.16
69.94a)
67.62a)
32.53
70.73a)
69.37a)
38.43
71.30a)
70.99a)
38.62
69.92a)
69.10a)
36.15
59.06
61.12
61.92
57.02
a) Assignments may be interchanged.

3246
Helvetica Chimica Acta – Vol. 88 (2005)
ane/AcOEt 3 :1) gave 23 (12.6 g, 89%). Colourless oil. Rf (hexane/AcOEt 4 :1) 0.38. [a]2D5 =ꢀ0.7 (c=0.92,
CHCl3). IR (CHCl3): 2992w, 2937w, 1599w, 1495w, 1451w, 1375m, 1308w, 1190m, 1141m, 1081m, 1015m,
994m, 964w, 927m, 829s. 1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 7.83 (d, J=8.4, 2 arom. H);
7.34 (d, J=9.3, 2 arom. H); 5.87 (dddd, J=17.1, 10.5, 6.0, 5.1, CH2=CH); 5.29 (dq, J=17.1, 1.5), 5.21 (dq,
J=10.5, 1.2) (CH2=CH); 4.25 (ddt, J=12.9, 4.8, 1.5), 3.98 (ddt, J=12.6, 6.3, 1.5) (CH2=CHCH2); 2.44 (s,
Me); 1.25, 1.17 (2s, Me2C). 13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 145.06 (s); 133.33 (d,
CH2=CH); 133.14 (s); 129.82 (d, 2 C); 128.37 (d, 2 C); 118.20 (t, CH2=CH); 109.76 (s, Me2C); 68.48 (t, CH2=
CHCH2); 27.45, 26.21 (2q, Me2C); 21.72 (q, Me). Anal. calc. for C18H24O7S (384.45): C 56.24, H 6.29; found:
C 56.11, H 6.19.
Allyl 4-O-(4-methylphenylsulfonyl)-a-D-lyxopyranoside (24). A soln. of 23 (56 g, 145.8 mmol) in glacial
AcOH (240 ml) was heated to 1108, stirred for 5 min, treated with H2O (60 ml), stirred for 40 min at 1108 (dis-
appearance of 23), and evaporated without any further heating. The resulting thick oil was dissolved in Et2O
(600 ml), washed with H2O (50 ml), sat. aq. NaHCO3 soln. (2 × 50 ml), and dried (Na2SO4). Evaporation
gave crude 24 (51 g, 89%), which was used for next step without further purification. A pure sample of 24
was obtained by FC (silica gel; hexane/AcOEt 3 :2). Colourless oil. Rf (hexane/AcOEt 1:1) 0.34.
[a]2D5 =ꢀ106.0 (c=0.38, EtOH). IR (CHCl3): 3574w, 3382w (sh), 3019w, 2925w, 1598m, 1495w, 1405w, 1365m,
1292w, 1190m, 1176s, 1132m, 1099m, 1065m, 1016s, 988m, 956m, 880m, 824m, 814m. 1H-NMR (300 MHz,
CDCl3): see Table 3; additionally, 7.82 (d, J=8.4, 2 arom. H); 7.35 (d, J=8.4, 2 arom. H); 5.86 (dddd,
J=17.1, 10.5, 6.3, 5.1, CH2=CH); 5.29 (dq, J=17.1, 1.5), 5.19 (dq, J=10.2, 1.5) (CH2=CH); 4.17 (ddt,
J=12.9, 5.1 1.5), 3.96 (ddt, J=13.2, 6.9, 1.5) (CH2=CHCH2); 2.99 (d, J=3.9, exchanged with D2O), 2.68 (d,
J=3.3, exchanged with D2O) (HOꢀC(2), HOꢀC(3)); 2.46 (s, Me). 13C-NMR (75 MHz, CDCl3): see Table 4;
additionally, 145.54 (s); 133.40 (d, CH2=CH); 133.40 (s); 130.12 (d, 2 C); 128.11 (d, 2 C); 117.93 (t, CH2=
CH); 68.57 (t, CH2=CHCH2); 21.78 (q, Me). HR-MALDI-MS: 367.0823 ([M+Na]+, C15H22NaO7S+; calc.
367.0822). Anal. calc. for C15H20O7S (344.38): C 52.31, H 5.85; found: C 52.13, H 5.85.
Allyl 3,4-Anhydro-b-L-ribopyranoside (25). A suspension of t-BuOK (2.77 g, 24.7 mmol) in anh. THF (50
ml) was cooled to 38, treated dropwise with a soln. of 24 (6.45 g, 20.6 mmol) in anh. THF (200 ml) over a period
of 35 min, stirred for 45 min (during this time the stirring became sluggish), and poured into sat. aq. NH4Cl soln.
(60 ml). After stirring for 30 min, the liquor was decanted and filtered through a short pad of Celite (2×2 cm).
The residue in the flask was treated with AcOEt (150 ml) and filtered. Evaporation of the combined filtrates and
FC (ca. 240 g of silica gel; hexane/AcOEt 2 :3) gave 25 (18.2 g, 71% from 23). Low-melting colourless solid. Rf
(hexane/AcOEt 1:1) 0.40. M.p. <258. [a]2D5 =+189.9 (c=0.64, CHCl3). IR (CHCl3): 3553w, 3085w, 2959m,
2920m, 2870w, 1448w, 1406w, 1342m, 1322w, 1246m, 1148s, 1097s, 1045s, 1069s, 1023m, 996s, 936m, 866m,
802m. 1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 5.99 (dddd, J=17.1, 10.5, 6.3, 5.1, CH2=CH);
5.30 (dq, J=17.1, 1.5), 5.21 (dq, J=10.5, 1.5) (CH2=CH); 4.19 (ddt, J=12.6, 5.1, 1.5), 4.00 (ddt, J=12.9, 6.6,
1.5) (CH2=CHCH2); 2.51 (d, J=9.9, exchanged with D2O, HOꢀC(2)). 13C-NMR (75 MHz, CDCl3): see Table
4; additionally, 133.46 (d, CH2=CH); 117.95 (t, CH2=CH); 68.74 (t, CH2=CHCH2). Anal. calc. for C8H12O4
(172.18): C 55.81, H 7.02; found: C 55.56, H 7.00.
Allyl 3,4-Anhydro-2-O-(triisopropylsilyl)-b-L-ribopyranoside (26). A soln. of 25 (18.0 g, ca. 104 mmol) in
anh. DMF (30 ml) was treated with 2,6-lutidine (26 ml, 238 mmol), cooled to 08, treated dropwise with TIPS-
OTf (28 ml, 103 mmol) over a period of 5 min, and stirred at 08 until disappearance of 25 (ca. 4 h). The mixture
was diluted with Et2O (500 ml) and washed with 10% aq. HCl (2×30 ml), H2O (50 ml), and brine (25 ml), dried
(Na2SO4), and evaporated. FC (ca. 180 g of silica gel; hexane/AcOEt 19 :1 ! 9 :1) gave 26 (28.3 g, 83%). Col-
ourless oil. Rf (hexane/AcOEt 1:1) 0.80. [a]2D5 =+99.9 (c=0.7, CHCl3). IR (CHCl3): 2946s, 2894m, 2868s, 1464m,
1
1384w, 1318w, 1129s, 1092m, 1046m, 996s, 956w, 882m. H-NMR (300 MHz, CDCl3): see Table 3; additionally,
5.89 (dddd, J=17.4, 10.2, 6.3, 5.1, CH2=CH); 5.29 (dq, J=17.1, 1.5), 5.19 (dq, J=10.5, 1.5) (CH2=CH); 4.21
(ddt, J=12.9, 5.1, 1.5), 3.96 (ddt, J=12.9, 6.6, 1.5) (CH2=CHCH2); 1.08–1.03 (m, (Me2CH)3Si). 13C-NMR (75
MHz, CDCl3): see Table 4; additionally, 133.98 (d, CH2=CH); 117.60 (t, CH2=CH); 68.84 (t, CH2=CHCH2);
18.04 (q, (Me2CH)3Si); 12.39 (d, (Me2CH)3Si). Anal. calc. for C17H32O4Si (328.51): C 62.15, H, 9.82; found: C
62.09, H, 9.92.
Allyl 4-Cyano-4-deoxy-2-O-(triisopropylsilyl)-a-
D-lyxopyranoside (27). A soln. of 26 (13.8 g, 42.07 mmol) in
anh. Et2O (250 ml) was cooled to 08, treated portionwise with ca. 1
M
Et2AlCN in toluene (46.5 ml, 46.5 mmol),
allowed to warm up, and refluxed for ca. 4 h until complete disappearance of 26. The mixture was cooled to ꢀ408
and treated dropwise with sat. aq. NH4Cl soln. (ca. 50 ml; caution: exothermic reaction!). After stirring for 2 h,
the liquor was decanted, and the solid was thoroughly washed with AcOEt (2×25 ml). After evaporation of the
combined filtrate and washings, FC (220 g of silica gel; hexane/AcOEt 21:4 ! 17:3) gave 27 (9.6 g, 78%). Col-
ourless solid. Rf (hexane/AcOEt 9 :1) 0.33. M.p. 43.3–44.28 (hexane). [a]2D5 =0.7 (c=0.86, CHCl3). IR (CHCl3):

Helvetica Chimica Acta – Vol. 88 (2005)
3247
3562w, 3024w, 2946s, 2869s, 2247w, 1464m, 1389w, 1264w, 1126s, 1089s, 1024s, 997w, 883m. 1H-NMR (300 MHz,
CDCl3): see Table 3; additionally, 5.84 (dddd, J=16.8, 10.8, 6.6, 5.4, CH2=CH); 5.29 (dq, J=16.8, 1.5), 5.19 (dq,
J=10.5, 1.5) (CH2=CH); 4.16 (ddt, J=12.9, 5.1, 1.5), 3.95 (ddt, J=12.9, 6.3, 1.5, CH2=CHCH2); 2.44 (d, J=9.3,
exchanged with D2O, HOꢀC(3)); 1.07–1.02 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 4; addi-
tionally, 133.29 (d, CH2=CH); 118.34 (s, CN); 117.98 (t, CH2=CH); 68.30 (t, CH2=CHCH2); 18.18, 18.10 (2q,
(Me2CH)3Si); 12.65 (d, (Me2CH)3Si). Anal. calc. for C18H33NO4Si (355.55): C 60.81, H 9.35, N 3.94; found: C
60.96, H 9.26, N 3.94.
Allyl 4-Deoxy-4-(1H-imidazol-2-yl)-2-O-(triisopropylsilyl)-a-
20.56 mmol) in anh. toluene (85 ml) was treated with NH2CH2CH(OMe)2 (4 ml, 37.1 mmol), cooled to ꢀ188,
treated portionwise with 2 Me3Al in toluene (19 ml, 38 mmol), warmed slowly to 238, and heated to 808 for
D-lyxopyranoside (28). A soln. of 27 (7.3 g,
M
26 h. The mixture was allowed to cool and treated carefully with sat. aq. NH4Cl soln. (6 ml) to allow precipita-
tion of the aluminium salts. After filtration and washing with AcOEt (400 ml), the combined org. layers were
washed with H2O (2×40 ml) and brine, dried (Na2SO4), and evaporated. FC (ca. 150 g of silica gel; hexane/
AcOEt 85 :17 ! 2 :3) gave 28 (5.5 g, 67%). Yellow syrup. Rf (AcOEt) 0.34. [a]2D5 =+7.5 (c=0.56, CHCl3). IR
(CHCl3): 3551w, 3423m, 2946s, 2869s, 1541m, 1464m, 1436w, 1372w, 1218m, 1127s, 1111s, 1085m, 1016s, 997m,
967m, 910m, 884m, 838w. 1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 6.98 (br. s, HꢀC(4’), Hꢀ
C(5’)); 5.87 (dddd, J=16.8, 10.8, 6.6, 5.1, CH2=CH); 5.22 (dq, J=16.8, 1.5), 5.19 (dq, J=10.2, 1.5) (CH2=
CH); 4.18 (ddt, J=12.9, 5.1, 1.5), 3.97 (ddt, J=12.6, 6.3, 1.5) (CH2=CHCH2); 1.09–1.05 (m, (Me2CH)3Si); sig-
nals of NH and OH not observed. 13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 146.40 (s, C(2’)); 133.58
(d, CH2=CH); 121.22 (br. d, C(3’), C(4’)); 117.41 (t, CH2=CH); 67.72 (t, CH2=CHCH2); 18.06, 18.00 (2q,
(Me2CH)3Si); 12.57 (d, (Me2CH)3Si). Anal. calc. for C20H36N2O4Si (396.60): C 60.57, H 9.15, N 7.06; found: C
60.50, H 9.06, N 7.08.
Allyl 4-{1-[(tert-Butoxy)carbonyl]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-a-D-lyxopyranoside
(29). A soln. of 28 (1.45 g, 3.65 mmol) in anh. MeCN (7 ml) was treated with Boc2O (876 mg, 4.02 mmol) and
DMAP (47 mg, 0.385 mmol), stirred at 238 for 2 h (complete disappearance of 28), treated with sat. aq. NH4Cl
soln. (20 ml), and extracted with AcOEt (100 ml). The org. layer was washed with H2O (5 ml) and brine (5 ml),
dried (Na2SO4), and evaporated affording crude 29 (1.726 g of a thick oil), which was used for the next step with-
out further purification. An pure sample of 29 was obtained by FC (silica gel; hexane/AcOEt 4 :1). Colourless
oil. Rf (hexane/AcOEt 4 :1) 0.23. [a]2D5 =+26.6 (c=0.52, CHCl3). IR (CHCl3): 3555w, 2945m, 2868m, 1749s,
1464w, 1414w, 1372m, 1307s, 1263w, 1142s, 1124s, 1065m, 1017s, 934w, 883w, 854w. 1H-NMR (300 MHz,
CDCl3): see Table 3; additionally, 7.33 (d, J=2.1, HꢀC(5’)); 6.90 (d, J=1.8, HꢀC(4’)); 5.90 (dddd, J=17.1,
10.5, 6.3, 5.1, CH2=CH); 5.30 (dq, J=16.8, 1.5), 5.19 (dq, J=10.2, 1.5) (CH2=CH); 4.22 (ddt, J=12.9, 5.4,
1.5), 3.97 (ddt, J=12.9, 6.3, 1.5) (CH2=CHCH2); 2.84 (br. d, J=9.0, exchanged with D2O, HOꢀC(3)); 1.60 (s,
t-Bu); 1.14–1.08 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 149.04 (s, C=O);
148.27 (s, C(2’)); 133.92 (d, CH2=CH); 127.64 (d, C(4’)); 118.73 (d, C(5’)); 117.49 (t, CH2=CH); 85.70 (s,
Me3C); 67.90 (t, CH2=CHCH2); 28.01 (q, Me3C); 18.24, 18.21 (2q, (Me2CH)3Si); 12.76 (d, (Me2CH)3Si). HR-
MALDI-MS: 519.2855 ([M+Na]+, C25H44N2NaO6Si+; calc. 519.2861). Anal. calc. for C25H44N2O6Si (496.71):
C 60.45, H, 8.93, N 5.64; found: C 60.57, H, 8.93, N 5.64.
Oxidation of 29 with Periodinane. A soln. of crude 29 (1.722 g, ca. 3.54 mmol) in anh. CH2Cl2 (20 ml) was
cooled to 08, treated with a 15% soln. of Dess–Martin periodinane in CH2Cl2 (11.2 ml, 3.92 mmol), stirred for 4 h
(complete disappearance of 29), diluted with Et2O (200 ml), washed with sat. aq. NaHCO3 soln. (2×25 ml),
dried (Na2SO4), and evaporated. FC (50 g of silica gel, hexane/AcOEt 85 :15) gave 30 (1.225 g, 68% from 28)
and 31 (70 mg, 10% from 28).
Allyl 4-{1-[(tert-Butoxy)carbonyl]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-a-D-threo-pentopyra-
nosid-3-ulose (30). Colourless oil. Rf (hexane/AcOEt 4 :1) 0.21. [a]2D5 =+69.6 (c=0.67 CHCl3). IR (CHCl3):
3035w, 2945m, 2868m, 1762s, 1740m, 1499w, 1464m, 1412m, 1372m, 1338w, 1309s, 1264m, 1141s, 1116m,
1077m, 1036m, 1013m, 941w, 882m, 869w. 1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 7.31 (d,
J=1.8, HꢀC(5’)); 6.89 (d, J=1.8, HꢀC(4’)); 5.86 (dddd, J=17.1, 10.2, 6.3, 4.8, CH2=CH); 5.27 (dq, J=17.1,
1.5), 5.19 (dq, J=10.5, 1.5) (CH2=CH); 4.22 (ddt, J=12.9, 4.8, 1.5), 4.02 (ddt, J=12.9, 6.3, 1.5) (CH2=
CHCH2); 1.54 (s, t-Bu); 1.18–1.09 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 4; additionally,
147.33 (s, NC=O); 144.77 (s, C(2’)); 133.38 (d, CH=CH2); 128.87 (d, C(4’)); 118.78 (d, C(5’)); 118.11 (t,
CH2=CH); 85.09 (s, Me3C); 67.88 (t, CH2=CHCH2); 27.82 (q, Me3C); 17.9 (br. q, (Me2CH)3Si); 12.13 (d,
(Me2CH)3Si). HR-MALDI-MS: 517.2711 ([M+Na]+, C25H42N2NaO6Si+; calc. 517.2704). Anal. calc. for C25H42-
N2O6Si (494.69): C 60.70, H 8.56, N 5.66; found: C 60.54, H 8.42, N 5.76.
Allyl 4-{1-[(tert-Butoxy)carbonyl]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-b-D-erthyro-pento-
pyranosid-3-ulose (31). Colourless oil. Rf (hexane/AcOEt 4 :1) 0.12. [a]2D5 =ꢀ22.1 (c=0.65, CHCl3). IR

3248
Helvetica Chimica Acta – Vol. 88 (2005)
(ATR): 2942w, 2866m, 1753s, 1745s (sh), 1502w, 1463m, 1410m, 1370m, 1338m, 1306s, 1258m, 1136s, 1114s, 1101s,
1
1068s, 1017m, 995w, 917w, 882m, 845w. H-NMR (300 MHz, CDCl3): see Table 3; additionally, 7.34 (d, J=1.5,
HꢀC(5’)); 6.88 (d, J=1.5, HꢀC(4’)); 5.96 (dddd, J=16.8, 10.5, 6.0, 5.1, CH2=CH); 5.34 (dq, J=17.1, 1.5),
5.20 (dq, J=10.2, 1.5) (CH2=CH); 4.42 (ddt, J=12.6, 5.1, 1.5), 4.20 (ddt, J=12.6, 6.3, 1.5) (CH2=CHCH2);
1.55 (s, t-Bu); 1.12–1.05 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 4; additionally, 147.60 (s,
NC=O); 143.69 (s, C(2’)); 133.77 (d, CH2=CH); 127.85 (d, C(4’)); 119.03 (d, C(5’)); 117.95 (t, CH2=CH);
85.43 (s, Me3C); 70.89 (t, CH2=CHCH2); 27.83 (q, Me3C); 17.96, 17.93 (2q, (Me2CH)3Si); 12.48 (d, (Me2CH)3Si).
HR-MALDI-MS: 417.2865 ([MꢀBoc+Na]+, C25H42N2NaO6Si+; calc. 517.2861).
Allyl 4-{1-[(tert-Butoxy)carbonyl)]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-a-D-arabinopyrano-
side (32). A soln. of 30 (1.18 mg, 2.38 mmol) in dry MeOH (6 ml) was cooled to 08, treated with CeCl3 ·7 H2O
(896 mg, 2.40 mmol) and NaBH4 (79 mg, 2.14 mmol), stirred for 15 min (disappearance of 30), treated with sat.
aq. NH4Cl soln. (25 ml), and diluted with AcOEt (150 ml). The org. layer was separated, washed with H2O (25
ml), dried (Na2SO4), and evaporated. FC (45 g of silica gel; hexane/AcOEt 4 :1) provided 32 (954 mg, 80%).
Colourless oil. Rf (hexane/AcOEt 4 :1) 0.10. [a]2D5 =+78.8 (c=0.83, CHCl3). IR (CHCl3): 3507w, 3342w,
3014w, 2945m, 2868m, 1762m, 1462w, 1372w, 1353w, 1305s, 1264m, 1141s, 1100m, 1025m, 932w, 882w, 817w.
1H-NMR (300 MHz, CDCl3): see Table 3; additionally, 7.33 (d, J=2.1, HꢀC(5’)); 6.86 (d, J=2.1 HꢀC(4’));
5.91 (dddd, J=17.1, 10.8, 6.9, 5.1, CH2=CH); 5.30 (dq, J=17.1, 1.5), 5.20 (dq, J=10.8, 1.5) (CH2=CH); 4.73
(br. d, J=6.0, exchanged with D2O, HOꢀC(3)); 4.25 (ddt, J=12.9, 5.1, 1.5), 4.05 (ddt, J=12.9, 6.3, 1.5)
(CH2=CHCH2); 1.60 (s, t-Bu); 1.14–1.04 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 4; addition-
ally, 149.14 (s, C=O); 147.26 (s, C(2’)); 133.78 (d, CH2=CH); 127.16 (d, C(4’)); 118.60 (d, C(5’)); 117.96 (t, CH2=
CH); 85.62 (s, Me3C); 68.36 (t, CH2=CHCH2); 27.97 (q, Me3C); 18.19 (q, (Me2CH)3Si); 12.38 (d, Me2CH)3Si).
HR-MALDI-MS: 519.2865 ([M+Na]+, C25H44N2NaO6Si+; calc. 519.2861). Anal. calc. for C25H44N2O6Si
(496.71): C 60.45, H 8.93, N 5.64; found: C 60.54, H 8.42, N 5.73.
Glycosidation of 32 with 6. a) A suspension of 32 (64 mg, 0.13 mmol), 6 (68 mg, 0.164 mmol), and 4-Å mol.
sieves (260 mg) in CH2Cl2 (10 ml) was stirred for 1 h at 238, treated with Hg(CN)2 (35 mg, 0.14 mmol) and HgBr2
(17 mg, 0.047 mmol), heated to reflux for 8 h, cooled to r.t., diluted with AcOEt (40 ml), washed with sat. aq.
NaHCO3 soln. (5 ml) and brine (5 ml), and dried (Na2SO4). Evaporation and FC (6 g of silica gel; CH2Cl2/hex-
ane 1:19) gave 32 (14 mg, 21%) and 33 (42 mg, 39%).
b) At 248, a suspension of 32 (1.975 g, 3.98 mmol), 6 (2.1 g, 5.1 mmol) and 3-Å mol. sieves 3 (5.2 g) in CH2Cl2
(60 ml) was stirred for 30 min, cooled to 08, treated with AgOTf (1.7 g, 6.6 mmol), allowed to warm to 238, stir-
red for 17 h, treated with sat. aq. NaHCO3 soln. (10 ml), and extracted with AcOEt (300 ml). The combined org.
layers were washed with sat. aq. NaHCO3 soln. (30 ml) and dried (Na2SO4). Evaporation and FC (60 g of silica
gel; hexane/AcOEt 3 :2) gave 32 (552 mg, 27%) and an inseparable mixture of crude Boc-disaccharides (1.641
g; ca. 90% pure, contaminated with impurities derived from 6). A soln. of this mixture in CH2Cl2 (20 ml) was
cooled to 08, treated with CF3COOH (1 ml), stirred for 4 h (disappearance of the Boc-disaccharides), neutral-
ised with sat. aq. NaHCO3 soln. (10 ml), extracted with AcOEt (60 ml). The org. layer was washed with H2O (10
ml) and brine (10 ml), dried (Na2SO4) and evaporated. FC (40 g of silica gel; AcOEt/hexane 7 :3 ! 9 :1) gave 36
(892 mg, 31%) and 35 (360 mg, 13%).
Allyl (S)-3,4,6-Tri-O-acetyl-1,2-O-(methylmethanediyl)-a-
bonyl]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-a-
D
-glucopyranose-(12!3)-4-{1-[(tert-butoxy)car-
D
-arabinopyranoside (33). Colourless oil. Rf (hex-
ane/AcOEt 2 :3) 0.46. [a]2D5 =+88.9 (c=0.7, CHCl3). IR (CHCl3): 3014w, 2946m, 2868m, 1756s, 1462w, 1391w,
1372m, 1335w, 1306s, 1242s, 1140s, 1094s, 1059s, 1041s, 980m, 927w, 882w. 1H-NMR (300 MHz, CDCl3): see
Table 1; additionally, 7.26 (d, J=1.8, HꢀC(5’)); 6.85 (d, J=1.7, HꢀC(4’)); 5.86 (dddd, J=17.1, 10.5, 6.3, 5.1,
CH2=CH); 5.24 (dq, J=17.1, 1.8), 5.12 (dq, J=10.2, 1.2) (CH2=CH); 4.22 (ddt, J=12.3, 5.1, 1.5), 3.93 (ddt,
J=12.3, 6.3, 1.2) (CH2=CHCH2); 2.08, 2.07, 2.04 (3s, 3 AcO); 1.59 (s, t-Bu); 1.21 (s, Me); 1.15–1.09 (m,
(Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally, 170.79, 169.69, 168.82 (3s, 3 OC=O);
148.94 (s, NC=O); 147.56 (s, C(2’)); 134.50 (d, CH2=CH); 127.90 (d, C(4’)); 121.06 (s, MeCO3); 118.15 (d,
C(5’)); 117.26 (t, CH2=CH); 85.18 (s, Me2C); 68.25 (t, CH2=CHCH2); 27.83 (q, Me3C); 20.98, 20.94, 20.92
(3q, 3 MeC=O); 19.30 (q, Me); 18.20, 18.17 (2q, (Me2CH)3Si); 12.31 (d, (Me2CH)3Si). HR-MALDI-MS:
849.3812 ([M+Na]+, C39H62N2NaO15Si+; calc. 849.3812).
Allyl
silyl)-a-
2,3,4,6-Tetra-O-acetyl-b-
D
-glucopyranosyl-(1!3)-4-deoxy-4-(1H-imidazol-2-yl)-2-O-(triisopropyl-
D
-arabinopyranoside (35). Colourless oil. Rf (CH2Cl2/AcOEt 1 :4) 0.32. [a]2D5 =ꢀ12.2 (c=1.35,
CHCl3). IR (CHCl3): 3430w, 3029w, 2946m, 2867m, 1754s, 1545w, 1462w, 1367w, 1237s, 1139m, 1067s, 1040s,
909w, 883w. 1H-NMR (300 MHz, CDCl3): see Table 1; additionally, 9.50 (br. s, exchanged with D2O, NH);
6.99 (br. s, HꢀC(4’), HꢀC(5’)); 5.93 (dddd, J=17.1, 10.5, 6.0, 5.1, CH2=CH); 5.32 (dq, J=17.1, 1.5), 5.17 (dq,
J=10.5, 1.5) (CH2=CH); 4.31 (ddt, J=12.6, 4.8, 1.5), 4.03 (ddt, J=12.6, 6.0, 1.5) (CH2=CHCH2); 2.06, 2.02,

Helvetica Chimica Acta – Vol. 88 (2005)
3249
1.98, 1.86 (4s, 4 AcO); 1.08–1.01 (m, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally, 170.53,
170.09, 169.32, 169.03 (4s, 4 C=O); 145.39 (s, C(2’)); 134.01 (d, CH2=CH); 130–120 (2 br. d, C(4’), C(5’)); 117.13
(t, CH2=CH); 68.22 (t, CH2=CHCH2); 20.86, 20.15 (2q, 2 Me); 20.80 (q, 2 Me); 18.27, 18.24 (2q, (Me2CH)3Si);
12.58 (d, (Me2CH)3Si). HR-MALDI-MS: 749.3277 ([M+Na]+, C34H54N2NaO13Si+; calc. 749.3287). Anal. calc.
for C34H54N2O13Si (726.89): C 56.18, H 7.49, N 3.85; found: C 56.06, H 7.31, N 3.93.
Allyl 2,3,4,6-Tetra-O-acetyl-a-
D
-glucopyranosyl-(1 ! 3)-4-deoxy-4-(1H-imidazol-2-yl)-2-O-(triisopropyl-
silyl)-a-D-arabinopyranoside (36). Colourless solid. Rf (CH2Cl2/AcOEt 1:4) 0.59. M.p. 116–1188.
[a]2D5 =+135.8 (c=2.25, CHCl3). IR (2.2%, CHCl3): 3456w, 3233w, 2946m, 2868m, 1750s, 1548w, 1463m,
1
1368m, 1254s, 1120m, 1102s, 1071m, 1036s, 932w, 883m, 845m. H-NMR (300 MHz, CDCl3): see Table 1; addi-
tionally, 9.73 (br. s, exchanged with D2O, NH); 7.05, 7.01 (2 br. s, HꢀC(4’), HꢀC(5’)); 5.86 (dddd, J=17.1,
10.5, 6.3, 4.8, CH2=CH); 5.30 (dq, J=17.1, 1.5), 5.20 (dq, J=10.2, 1.5) (CH2=CH); 4.16 (ddt, J=13.5, 4.5,
1.5), 4.06 (ddt, J=13.5, 6.6, 1.5) (CH2=CHCH2); 2.06, 2.04, 2.02, 1.97 (4s, 4 AcO); 1.10–1.05 (m, (Me2CH)3Si).
13C-NMR (75 MHz, CDCl3): see Table 2; additionally, 170.63, 170.40, 169.99, 169.40 (4s, 4 C=O); 145.46 (s,
C(2’)); 134.01 (d, CH2=CH); 130–120 (br. d, C(4’), C(5’)); 117.96 (t, CH2=CH); 68.10 (t, CH2=CHCH2);
20.90 (q, 3 Me); 20.60 (q, Me); 18.02 (q, (Me2CH)3Si); 12.22 (d, (Me2CH)3Si). HR-MALDI-MS: 749.3276
([M+Na]+, C34H54N2NaO13Si+; calc. 749.3287). Anal. calc. for C34H54N2O13Si (726.89): C 56.18, H 7.49, N
3.85; found: C 56.31, H 7.47, N 3.97.
Glycosidation of 32 with 7. A suspension of 32 (30 mg, 0.06 mmol), 7 (71 mg, 0.42 mmol), and 4-Å mol.
sieves (71 mg) in CH2Cl2 (4 ml) was stirred for 1 h at 238, cooled to 28, treated with AgOTf (43 mg, 0.17
mmol) and TMU (40 ml, 0.334 mmol), stirred for 4 h (disappearance of 32), diluted with AcOEt (50 ml), washed
with H2O (5 ml) and brine (5 ml), and dried (Na2SO4). Evaporation and FC (6 g of silica gel; CH2Cl2/hexane
1:19) gave 34 (42 mg, 70%).
Allyl (S)-3,4,6-Tri-O-benzoyl-1,2-O-(phenylmethanediyl)-a-
carbonyl]-1H-imidazol-2-yl}-4-deoxy-2-O-(triisopropylsilyl)-a-
D
-glucopyranose-(12 ! 3)-4-{1-[(tert-butoxy)-
D
-arabinopyranoside (34). Colourless oil. Rf
(hexane/AcOEt 4 :1) 0.16. [a]2D5 =+70.1 (c=1.55, CHCl3). IR (CHCl3): 2945m, 2867m, 1761m, 1724s, 1602w,
1493w, 1452m, 1410w, 1372m, 1338w, 1307s, 1267s, 1142s, 1097s, 1071s, 1028s, 993m, 961m, 883w, 845w. 1H-
NMR (300 MHz, CDCl3): see Table 1; additionally, 8.08 (br. dq, J=8.4, 1.2, 2 arom. H); 7.96 (br. dq, J=8.4,
1.2, 2 arom. H); 7.63 (br. dq, J=8.4, 1.2, 2 arom. H); 7.59 (tt, J=6.0, 1.3, 1 arom. H); 7.51–7.42 (m, 5 arom.
H); 7.30–7.10 (m, 8 arom. H); 7.18 (d, J=1.7, HꢀC(5’)); 6.93 (d, J=1.7, HꢀC(4’)); 5.78 (ddt, J=17.1, 10.5,
6.0, CH2=CH); 5.06 (dq, J=17.1, 1.5), 4.73–4.67 (m) (CH2=CH); 4.19 (ddt, J=12.0, 6.0, 1.2), 3.84 (ddt,
J=12.0, 6.0, 1.2) (CH2=CHCH2); 1.38 (s, t-Bu); 1.05 (br. s, (Me2CH)3Si). 13C-NMR (75 MHz, CDCl3): see
Table 2; additionally, 166.09, 165.08, 164.26 (3s, 3 OC=O); 148.91 (s, NC=O); 144.67 (s, C(2’)); 135.12 (s);
134.11 (d, CH2=CH); 133.61, 133.24, 133.06 (3d); 130.06–128.18 (several d); 129.73, 129.18, 129.13 (3s);
127.68 (d, C(4’)); 126.41 (2d); 123.32 (s, PhCO3); 118.20 (d, C(5’)); 117.93 (t, CH2=CH); 84.40 (s, Me3C);
68.83 (t CH2=CHCH2); 27.70 (q, Me3C); 18.10, 18.06 (2q, (Me2CH)3Si); 12.21 (d, (Me2CH)3Si). HR-MALDI-
MS: 1097.4430 ([M+Na]+, C59H70N2NaO15Si+; calc. 1097.4438).
Allyl 2,3,4,6-Tetra-O-acetyl-b-
D-glucopyranosyl-(1!3)-4-deoxy-4-(1H-imidazol-2-yl)-a-
D-arabinopyrano-
side (37). A soln. of 35 (142 mg, 0.195 mmol) in THF (2 ml) was cooled to 08, treated with a soln. of TBAF·3
H2O (72 mg, 0.23 mmol) in THF (3 ml), stirred for 3 h (disappearance of 35), and evaporated to dryness. FC
(4.8 g of silica gel; AcOEt ! AcOEt/MeOH 24 :1) gave 37 (106 mg, 92%). Colourless solid. Rf (CH2Cl2/
MeOH 9 :1) 0.42. [a]2D5 =ꢀ55.5 (c=2.5, CHCl3). IR (CHCl3): 3516w, 3434w, 3029w, 3015w, 2957m, 2867m,
1756s, 1544w, 1437w, 1368m, 1258s, 1069s, 1040s, 998w, 960w, 909s. 1H-NMR (300 MHz, CDCl3): see Table 1;
additionally, 6.94 (br. s, HꢀC(4’), HꢀC(5’)); 5.92 (dddd, J=16.8, 10.8, 6.0, 5.1, CH2=CH); 5.30 (dq, J=17.1,
1.5), 5.17 (dq, J=10.2, 1.5) (CH2=CH); 4.34 (ddt, J=13.5, 5.1, 1.5), 4.12 (ddt, J=13.5, 6.0, 1.5) (CH2=
CHCH2); 2.06, 2.0, 1.97, 1.94 (4s, 4 AcO). 13C-NMR (75 MHz, CDCl3): see Table 2; additionally, 170.62,
170.06, 170.04, 169.41 (4s, 4 C=O); 144.51 (s, C(2’)); 133.84 (d, CH2=CH); 121.57 (br. hump, C(4’), C(5’));
117.88 (t, CH2=CH); 69.96 (t, CH2=CHCH2); 21.67, 20.58 (2q, 4 Me); NH and OH hidden by coalescence.
HR-MALDI-MS: 571.2127 ([M+H]+, C25H35N2Oþ13 ; calc. 571.2134). Anal. calc. for C25H34N2O13 ·0.5 H2O
(579.55): C 51.81, H 6.09, N 4.83; found: C 51.93, H 6.04, N 4.85.
Allyl b-
D
-Glucopyranosyl-(1 ! 3)-4-deoxy-4-(1H-imidazol-2-yl)-a-
D-arabinopyranoside (38). A soln. of 37
NH3 in MeOH (400 ml), stirred for 23 h at 248, and
(50 mg, 0.088 mmol) in MeOH (3 ml) was treated with ca. 7
M
evaporated to dryness. FC (3 g of silica gel, CHCl3/MeOH/NH4OH 15 :4 :1) gave 38 (30 mg, 85%). Colourless
hygroscopic solid. Rf (CHCl3/MeOH/NH4OH 15 :4 :1) 0.24. M.p. 211–2158 (dec.). [a]2D5 =ꢀ25.3 (c=1.49,
MeOH). IR (ATR): 3227m, 3092w, 2881m, 1662w, 1548w, 1444w, 1373w, 1247m, 1067s, 1039s, 996s, 963m,
922m, 894w. 1H-NMR (300 MHz, CD3OD): see Table 1; additionally, 7.04 (br. s, HꢀC(4’), HꢀC(5’)); 5.92
(dddd, J=17.1, 10.8, 6.0, 5.4, CH2=CH); 5.34 (dq, J=17.1, 1.8), 5.16 (dq, J=10.5, 1.8) (CH2=CH); 4.32 (ddt,

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Helvetica Chimica Acta – Vol. 88 (2005)
J=12.6, 5.4, 1.5), 4.14 (ddt, J=12.6, 6.0, 1.5) (CH2=CHCH2). 13C-NMR (75 MHz, CD3OD): see Table 2; addi-
tionally, 146.31 (s, C(2’)); 135.38 (d, CH2=CH); 121.90 (d, C(4’), C(5’)); 117.47 (t, CH2=CH); 70.68 (t, CH2=
CHCH2). HR-MALDI-MS: 425.1535 ([M+Na]+, C17H26N2NaO9þ ; calc. 425.1531). Anal. calc. for C17H26N2O9·
0.5 H2O (411.40): C 49.63, H 6.62, N 6.81; found: C 49.63, H 6.62, N 6.63.
(5R/S,6R,7S,8S)-7-(b-D-Glucopyranosyloxy)-5,6,7,8-tetrahydro-8-(hydroxymethyl)imidazo[1,2-a]pyridine-
5,6-diol (2/39). A soln. of 38 (29 mg, 0.072 mmol) in MeOH (5 ml) was treated with 10% Pd/C (24 mg), heated to
reflux at 808 for 24 h, cooled to 248, and filtered over Celite. After evaporation of the filtrate, a soln. of the res-
idue (28 mg, 4 :1 mixture of propenyl acetals) in MeOH (5 ml) was cooled to 08, treated with 10% aq. HCl soln.
(100 ml), and stirred for 21 h at r.t. Evaporation and FC (5 g of silica gel; 100 ml of CH3Cl/MeOH/NH4OH
7:2 :1) gave 2/39 45 :55 (16 mg, 45%). Off-white solid. Rf (AcOEt/MeOH/NH4OH 7:2 :1) 0.20. M.p. 184–
1948 (dec.). [a]2D5= ꢀ34.9 (c=0.6, MeOH). IR (ATR): 3286m, 2884w, 1638w, 1528w, 1447w, 1367m, 1256m,
1
1098s, 1065s, 1019s, 909w. H-NMR (300 MHz, CD3OD; 2/39 45 :55): 7.15 (d, J=1.8, 0.45 H), 7.11 (d, J=1.5,
0.55 H), 6.99 (d, J=1.5, 0.45 H), 6.96 (d, J=1.5, 0.55 H) (HꢀC(2), HꢀC(3)); 5.93 (d, J=3.0, 0.55 H), 5.26 (d,
J=6.6, 0.45 H) (HꢀC(5)); 4.54 (d, J=7.8, HꢀC(1’)); 4.46 (d, J=3.0), 4.23 (dd, J=8.1, 5.7), 4.16 (t, J ꢁ 9.0),
4.15 (d, J=4.2), 4.08 (dd, J=8.1, 3.0), 3.90 (dd, J=12.0, 2.1), 3.86 (dd, J=12.0, 1.8), 3.82 (dd, J=9.0, 6.9),
3.68 (dd, J=12.0, 5.7), 3.45–3.20 (m) (HꢀC(6), HꢀC(7), CH2–C(8), HꢀC(2’), HꢀC(3’), HꢀC(4’), HꢀC(5’),
2 H2ꢀC(6’)); 3.14–3.04 (m, HꢀC(8)). 13C-NMR (75 MHz, CD3OD; 2/39 ca. 1:1): 145.02/144.38 (2s, C(8a));
129.22/128.88 (2d, C(2)); 118.78/117.75 (2d, C(3)); 104.85/104.82 (2d, C(1’)); 82.36/79.36 (2d, C(5)); 78.45,
78.30 (2 C), 77.99, 77.90, 77.83, 75.28, 75.03 (2 C), 71.28, 71.43, 71.35 (10d, C(6), C(7), C(2’), C(3’), C(4’),
C(5’)); 62.65/61.96, 62.49/60.32 (4t, C(6), CH2–C(8)); 45.20/44.64 (2d, C(8)). HR-ESI-MS: 363.1397
([M+H]+, C14H23N2Oþ9 ; calc. 363.1398).
Allyl 2,3,4,6-Tetra-O-acetyl-a-
D-glucopyranosyl-(1 ! 3)-4-deoxy-4-(1H-imidazol-2-yl)-a-
D-arabinopyrano-
side (40). A soln. of 36 (174 mg, 0.24 mmol) in THF (2 ml) was cooled to 08, treated with Bu4NF·3 H2O (138
mg, 0.44 mmol) stirred for 3 h (complete disappearance of 36), and evaporated to dryness. FC (4.8 g of silica
gel; AcOEt ! AcOEt/MeOH 24 :1) gave 40 (125 mg, 92%). Colourless syrup solidifying to an off-white pow-
der upon storage. Rf (AcOEt/MeOH 24 :1) 0.16. M.p. 106–1088 (at 97–988 becoming transparent). [a]2D5 =+76.7
(c=1.8, CHCl3). IR (CHCl3): 3431w, 3027w, 3016w, 1751s, 1602w, 1542w, 1433w, 1367m, 1250s, 1139m, 1074s,
1067s, 1038s, 959w, 939w, 909w. 1H-NMR (300 MHz, CDCl3; assignments based on a DQFCOSY and a
HSQC spectrum): see Table 1; additionally, 7.02 (br. s, HꢀC(4’), HꢀC(5’)); 5.92 (dddd, J=17.1, 11.4, 6.6, 5.1,
CH2=CH); 5.34 (dq, J=17.1, 1.5), 5.26 (dq, J=11.4, 1.5) (CH2=CH); 4.35 (ddt, J=12.3, 5.1, 1.5), 4.14 (ddt,
J=12.3, 6.6, 1.5) (CH2=CHCH2); 2.08, 2.03, 2.02, 2.00 (4s, 4 AcO); NH and OH hidden by coalescence. 13C-
NMR (75 MHz; CDCl3, assignments based on a HSQC spectrum): see Table 2; additionally, 170.68, 170.08,
169.82, 169.54 (4s, 4 C=O); 145.09 (s, C(2’)); 134.42 (d, CH2=CH); 123.0 (br. hump, C(4’), C(5’)); 118.42 (t,
CH2=CH); 70.24 (t, CH2=CHCH2); 20.92, 20.86 (2q, 2 Me); 20.84 (q, 2 Me). HR-MALDI-MS: 571.2135
([M+H]+, C25H35N2NaO1þ3 ; calc. 571.2134).
Allyl a-
D
-Glucopyranosyl-(1 ! 3)-4-deoxy-4-(1H-imidazol-2-yl)-a-
D-arabinopyranoside (41). A soln. of 40
NH3 in MeOH (650 ml), stirred for 17 h at 248 (com-
(87 mg, 0.15 mmol) in MeOH (5 ml) was treated with ca. 7
M
plete disappearance of 40), and evaporated to dryness. FC (ca. 2 g of silica gel; AcOEt/MeOH 24 :1 ! 4 :1) gave
41 (52 mg, 82%). Colourless solid. Rf (AcOEt/MeOH/NH4OH 7 :2.5 :0.5) 0.15. M.p. 184–1948 (dec.).
[a]2D5 =+69.6 (c=0.67, CHCl3). IR (ATR): 3381m, 2921w, 1162w, 1558w, 1452w, 1409w, 1250w, 1132m, 1067s,
1020s, 1000s, 943m, 880w. 1H-NMR (300 MHz, CD3OD, >90% pure): see Table 1; additionally, 6.99 (br. s,
HꢀC(4’), HꢀC(5’)); 5.93 (dddd, J=16.8, 10.5, 6.6, 5.4, CH2=CH); 5.28 (dq, J=16.8, 1.5), 5.18 (dq, J=10.5,
1.5) (CH2=CH); 4.24 (ddt, J=12.3, 5.7, 1.5), 4.08–4.02 (m) (CH2=CHCH2). 13C-NMR (75 MHz, CD3OD):
see Table 2; additionally, 147.17 (s, C(2’)); 135.18 (d, CH2=CH); 122.5 (br. hump, C(4’), C(5’)); 118.98 (t,
CH2=CH); 67.36 (t, CH2=CHCH2). HR-MALDI-MS: 425.1535 ([M+H]+, C17H26N2NaO1þ3 ; calc. 425.1531).
Anal. calc. for C17H26N2O9·0.25 H2O (411.40): C 50.18, H 6.56, N 6.90; found: C 50.11, H 6.44, N 6.90.
(5R/S,6R,7S,8S)-7-(a-D-Glucopyranosyloxy)-5,6,7,8-tetrahydro-8-(hydroxymethyl)imidazo[1,2-a]pyridine-
5,6-diol (42/43). A soln. of 41 (38 mg, 0.094 mmol) in MeOH (5 ml) was treated with 10% Pd/C (35 mg), heated
to reflux at 808 for 48 h, cooled to 248, filtered over Celite, and evaporated. A cold soln. of the residue (33 mg,
mixture of propenyl acetals) in MeOH (5 ml) was treated with 10% aq. HCl soln. (100 ml), slowly warmed to 278,
and stirred for 21 h. Evaporation and FC (5 g of silica gel, 100 ml of CH3Cl/MeOH/NH4OH 60 :32 :8) gave 42/43
ca. 1:1 (22 mg, 64%). Off-white solid. Rf (CH3Cl/MeOH/NH4OH 60 :32 :8) 0.17. M.p. 180–1958 (dec. ! brown
residue). [a]2D5 =+47.9 (c=0.45, MeOH). IR (ATR): 3258m, 2987w, 1653w, 1567w, 1449m, 1410m, 1343m,
1252m, 1139m, 1068s, 1018s, 910m, 823m. 1H-NMR (300 MHz, CD3OD; 42/43 ca. 1:1, >90% pure): 7.30,
7.28 (2d, J=1.8, HꢀC(2)); 7.20, 7.16 (2d, J=1.8, HꢀC(3)); 5.74 (d, J=3.3), 5.34 (d, J=6.0) (HꢀC(5)); 5.19
(d, J=3.6), 5.16 (d, J=3.9) (HꢀC(1’)); 4.39 (dd, J=7.8, 5.7, 0.5 H), 4.24–4.14 (m, 1.5 H), 4.08–3.98 (m, 1 H),

Helvetica Chimica Acta – Vol. 88 (2005)
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3.88–3.82 (m, 1 H), 3.75–3.45 (m, 6 H) (HꢀC(6), HꢀC(7), CH2–C(8), HꢀC(2’), HꢀC(3’), HꢀC(4’), HꢀC(5’), 2
HꢀC(6’)); 3.24–3.14 (m, HꢀC(8)). 1H-NMR (300 MHz, D2O; 42/43 ca. 1 :1, >90% pure): 7.09, 7.05 (2 br. s, Hꢀ
C(2)); 6.96, 6.94 (2 br. s, HꢀC(3)); 5.65 (d, J=3.6), 5.31 (d, J=6.3) (HꢀC(5)); 5.26 (d, J=3.9), 5.22 (d, J=3.6)
(HꢀC(1’)); 4.20 (t, J=8.1, 0.5 H), 4.18–4.03 (m, 2 H), 3.98–3.91 (m, 1.5 H), 3.78–3.49 (m, 5 H), 3.30 (t, J=9.0, 1
H) (HꢀC(6), HꢀC(7), CH2ꢀC(8), HꢀC(2’), HꢀC(3’), HꢀC(4’), HꢀC(5’), 2 HꢀC(6’)); 3.08–3.02 (m, HꢀC(8)).
1H-NMR (300 MHz, CD3OD; 42/43·HCl 7:3, ca. 90% pure): 7.62 (d, J=1.8), 7.66 (d, J=2.1) (HꢀC(2)); 7.55 (d,
J=1.8), 7.51 (d, J=2.1) (HꢀC(3)); 5.91 (d, J=3.0), 5.55 (d, J=6.0) (HꢀC(5)); 5.24, 5.18 (2d, J=3.9) (HꢀC(1’));
4.44–4.34 (m, 1 H), 4.26–3.96 (m, 3 H), 3.85 (br. t, J=8.1, 1 H), 3.76–3.46 (m, 5 H) (HꢀC(6), HꢀC(7), CH2ꢀ
C(8), HꢀC(2’), HꢀC(3’), HꢀC(4’), HꢀC(5’), 2 HꢀC(6’)); 3.37–3.24 (m, HꢀC(8)). 13C-NMR (75 MHz, CD3
OD; 42/43·HCl (7:3), ca. 90% pure): 144.74/144.24 (2s, C(8a)); 121.29, 120.84, 120.56, 120.35 (4d, C(2),
C(3)); 102.21/101.31 (2d, C(1’)); 83.74/80.30 (2d, C(5)); 77.19, 75.19, 74.87 (2 C), 74.75, 74.65, 73.53, 73.26,
71.55, 71.34, 69.22 (11d, C(6), C(7), C(2’), C(3’), C(4’), C(5’)); 62.57 (t, C(6’)); 61.80, 60.59 (2t, CH2–C(8));
44.37 (d, C(8)). HR-ESI-MS: 363.1394 ([M+H]+, C14H23N2O9þ ; calc. 363.1398).
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Received September 9, 2005