Synthesis of an L-fucose-derived cyclic nitrone and its conversion to α-L-fucosidase inhibitors

Article abstract of DOI:10.1002/(SICI)1522-2675(19990707)82:7<1044::AID-HLCA1044>3.0.CO;2-3

The L-fuco-nitrone 1 has been synthesized from allyl 4,6-O-benzylidene- α-D-glucopyranoside (4) in 11 steps and an overall yield of 18%. The key step is the intramolecular alkylation of an intermediary 1,1- bis(hydroxylamine) derived from the tosyloxy oximes (E/Z)-2. The nitrone 1 has been transformed into the diamine 30, the indolizidines 39 and 40, the indolizidinones 34 and 35, and the imidazole 44, all inhibiting bovine epididymis α-L-fucosidase with IC₅₀ values between 105 nM and 240 μM.

Full text of DOI:10.1002/(SICI)1522-2675(19990707)82:7<1044::AID-HLCA1044>3.0.CO;2-3

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Helvetica Chimica Acta ± Vol. 82 (1999)
Synthesis of an l-Fucose-Derived Cyclic Nitrone and its
Conversion to a-l-Fucosidase Inhibitors1)
by Andreas Peer and Andrea Vasella*
Laboratorium für Organische Chemie, ETH-Zentrum, Universitätstrasse 16,
CH-8092 Zürich
The l-fuco-nitrone 1 has been synthesized from allyl 4,6-O-benzylidene-a-d-glucopyranoside (4) in 11
steps and an overall yield of 18%. The key step is the intramolecular alkylation of an intermediary 1,1-
bis(hydroxylamine) derived from the tosyloxy oximes (E/Z)-2. The nitrone 1 has been transformed into the
diamine 30, the indolizidines 39 and 40, the indolizidinones 34 and 35, and the imidazole 44, all inhibiting bovine
epididymis a-l-fucosidase with IC50 values between 105 nm and 240 mm.
Introduction. ± In spite of the importance of nitrones in organic synthesis [1 ± 4],
only a few carbohydrate-derived cyclic nitrones are known. Such nitrones have been
prepared as intermediates in the synthesis of pyrrolizidines [5][6], indolizidines [7],
pyrrolidinose C-disaccharides [8], and nucleoside analogues [9][10]; they have also
been used to establish the configuration of esperamicins [11]. Their restricted use is
surprising in view of the versatile character of nitrones and of their potential for the
preparation of carbohydrate-derived heterocycles. Presumably, the restricted applica-
tion is related to the difficulties of preparing such cyclic nitrones in a regioselective
manner [7][12].
We have developed a regioselective synthesis of the protected l-fucose-derived
nitrone 1 in view of the synthesis of a-l-fucosidase inhibitors. Although there are many
inhibitors of a-l-fucosidases with micromolar or better inhibition constants [13 ± 28],
relatively little is known about the details of their mechanism of action.
White et al. have shown that human liver a-l-fucosidase is a retaining glycosidase
[29]. Most likely, two carboxylic groups are involved in catalysis [30] of which one is
protonated at the pH optimum and the other deprotonated, similar to what is known
for other glycosidases [31]. There is evidence for a protein-bound intermediate [32].
Among the a-l-fucosidases from human liver, rat liver, dog lysosomes, Caenorhabditis
elegans, and Dictyostelium discoideum, there is a high amino-acid-sequence homology,
characterizing them as members of family 292) according to Henrissatꢀs classification of
glycosidases [33 ± 35]. A crystal structure of an a-l-fucosidase has yet to be reported.
We planned to prepare 1 by an intramolecular nucleophilic substitution of a
sulfonyloxy oxime (Scheme 1). This transformation is precedented by the synthesis of a
1
)
Part of this work is taken from the Diploma Thesis of A.P., which was presented at the ꢁRoyal Society of
Chemistry, Carbohydrate Group Spring Meetingꢀ, Birmingham, 30.3. ± 1.4.1998.
Compare with recent information on the internet at the address http://www.expasy.ch/cgi-bin/
lists?glycosid.txt
2
)

Helvetica Chimica Acta ± Vol. 82 (1999)
1045
steroidal five-membered nitrone [36] and of a carbohydrate-derived dihydropyrrole-N-
oxide [9]. We planned to convert 1 to three representative heterocycles, piperidines,
indolizidines, and fused imidazoles, each incorporating a major structural motif typical
for glycosidase inhibitors. The oxime 2, required for the synthesis of 1, should be readily
accessible from the 6-deoxyaltropyranose 3, and ultimately from d-glucose.
Scheme 1
Synthesis of the Nitrone 1. ± To prepare the 6-deoxyaltropyranose 3, we intended to
use the established procedure for the synthesis of altrosides from glucose [37],
replacing the intermediary methyl by allyl glycosides (Scheme 2).
The crystalline dimesylate 5 was obtained in 80% yield from allyl 4,6-O-
benzylidene-a-d-glucopyranoside (4) [38] and treated with excess NaOBn for 15 h at
958. This gave the monobenzylated altroside 7 (82%), obviating the isolation of the
epoxide 6. Minor amounts of 10 were formed by a well-precedented diequatorial
epoxide opening [37]. Yields were comparable to those reported for the two-step
procedure [37]. Benzylation of 7 afforded 94% of the dibenzyl ether 8. Reductive
opening of the 1,3-dioxane ring of 8 led mostly (AlCl3/LiAlH4) or exclusively (AlCl3/
LiAlH4/BuLi) to the undesired 6-O-benzylated 11 in yields of up to 80%. This
regioselectivity is in agreement with the dominating formation of 6-O-benzyl ethers
i
upon treatment of other altropyranosides with Bu2AlH [39]. The regioselectivity of
the reductive acetal opening is rationalised by the preferred formation of the benzylic
C(6)-oxycarbenium cation via a complex of the Lewis acid with OC(4) and the cis-
oriented OC(3) rather than with OC(6). Treating 8 with the non-chelating Me3SiCl in
the presence of LiAlH4 at 238 led indeed to a mixture of 11 and the 4-O-benzyl ether 12
(12/11 2 :1); replacing Me3SiCl by Me3SiBr and conducting the reaction in boiling Et2O
improved the 12/11 ratio to 7:1. Column chromatography yielded 75% of the desired
primary alcohol 12.
Tosylation of 12 to 13, followed by deoxygenation with LiAlH4, yielded the 6-
deoxyaltropyranoside 14. The synthesis of 14 from 8 was also carried out without
purification of the intermediates, resulting in an overall yield of 65%.
The allyl glycoside 14 was isomerized to the enol ether 15 using {Ir(cod)(PPh2-
Me)2}PF6 (cod ˆ cycloocta-1,5-diene) [40]. This procedure worked well on a scale of up
to 2 g of 14, but failed on a larger scale, possibly due to sulfur-containing impurities in
the starting material. Only starting material was isolated. The isomerization of 14 to 15
with KOtBu in DMSO at 1008 [41], however, proceeded well on a scale of up to 20 g,
and yielded almost exclusively the propenyl ether (Z)-15. It was hydrolyzed with HgO/
HgCl2 in aqueous acetone, resulting in overall yields of 82 ± 85% of 3 from 14.

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 2
a) MsCl (2 equiv.), pyridine; 80%. b) NaOBn (12 equiv.), BnOH; 82% of 7. c) BnBr (1.5 equiv.), NaH
(1.1 equiv.), BnBr, Bu4NI; 94%. d) Ac2O, cat. 4-(dimethylamino)pyridine (DMAP), pyridine; 75%. e) TMSBr
(5 equiv.), LiAlH4 (2 equiv.), Et2O; 75% of 12, 11% of 11. f) TsCl (2 equiv.), pyridine; 93%. g) LiAlH4
(2 equiv.), Et2O; 92%. h) KOtBu (4 equiv.), DMSO 1008 ( ! (Z)-15). i) HgCl2/HgO acetone/H2O; 83%. j)
t
NH2OSiPh2 Bu, cat. pyridinium p-toluenesulfonate (PPTA); 83% of (E)-16; 13% of (Z)-16. k) TsCl
(1.2 equiv.), pyridine; 80% of (E)-17; 13% of (Z)-17. l) Neat at room temperature, 4 d; 75% of (E/Z)-17 and
16% of (E/Z)-18. m) Et3N ´ 3 HF, THF. n) NH2OH ´ HCl (8 equiv.), Et3N (8 equiv.). o) Column
chromatography (silica gel); 60 ± 66% of 1 and 20 ± 24% (E/Z)-19. p) FeCl3, H2O, CH2Cl2; 44%.
Treatment of 3 with O-[(tert-butyl)diphenylsilyl]hydroxylamine3) led to the diaste-
reoisomeric silyl ethers (E)-16/(Z)-16 which were separated by chromatography,
yielding 83% of (E)-16 and 13% of (Z)-16.
Tosylation of the hydroxy oxime (E)-16 with 1.2 equiv. of TsCl yielded 80% of the
expected (E)-17, besides 13% of (Z)-17. Similarly, tosylation of (Z)-16 led to a mixture,
chromatography affording 69% of (E)-17 and 21% of (Z)-17/(E)-17 4 :1. Isomer-
ization of oximes by reversible addition of chloride to the CˆN bond is known [43].
3
)
Freshly prepared according to [42]. Under otherwise identical conditions, the commercially available
NH2OSitBuMe2 led to desilylated oximes.

Helvetica Chimica Acta ± Vol. 82 (1999)
1047
Tosylation of (E)-16 with 2 equiv. of TsCl led to a mixture of (E/Z)-17 (64%) and
the tetrahydrofurans (E/Z)-18 (30%). The tetrahydrofurans 18 were also formed when
the oxime sulfonates (E/Z)-17 were kept at room temperature for a few days.
Neighbouring group participation of BnO groups is well-known and has been used for
the synthesis of C-furanosides [44].
Desilylation of the oxime silyl ethers (E)-17 or (Z)-17 proceeded with retention of
configuration and led to a mixture of the tosyloxy oxime 2 and the tetrahydrofuran 19
as pure (E)- or (Z) diastereoisomers. Et3N ´ 3 HF (08, THF) was most satisfactory
among the reagents tested (Bu4NF, HF ´ pyridine, KF, [18]-crown-6, AcOH or Et3N ´
3 HF), yielding 80% of (E)-2 and 13% of (E)-19 from (E)-17.
The crude desilylation product (E)-2 was treated with excess NH2OH ´ HCl and
Et3N in THF followed by aqueous workup. This led to the bona fide bis(hydroxyl-
amines) 204) that were converted to the nitrone 1 (60 ± 66% from 17) by chrom-
tography on silica gel5). The major by-product was the tetrahydrofuran (E)-19 (20 ±
24% from 17). Similarly, treatment of (Z)-2 with NH2OH gave the nitrone 1 in about
the same yields. Hydroxylamine is required for the transformation of 2; heating of (E)-
and (Z)-2 in THF alone led to recovered starting material, besides small amounts of
(E/Z)-19. Hydroxylamine did not, however, lead to a transformation of the silylated
oximes (E/Z)-17; heating 17 in THF in the presence of NH2OH ´ HCl and Et3N again
resulted in recovered starting material. These observations are in agreement with a
nucleophilic addition of NH2OH to the CˆN bond of the oximes, followed by
intramolecular nucleophilic substitution of the TsO group by a C(1) hydroxylamino
group. In keeping with this mechanism, treatment of (E)-2 with N-methylhydroxyl-
amine in THF under reflux also led to the nitrone 1 (36%).
At room temperature, the nitrone 1 is slowly transformed into a complex mixture of
polar and apolar products that were not investigated. At 788, however, 1 proved
stable for several weeks. Treatment with acid (FeCl3 in aq. CH2Cl2; or AcOH in
AcOEt) transformed 1 into the unsymmetric dimer 21. Acid-catalyzed dimerization of
nitrones in aprotic solvents is well precedented [46][47].
This synthesis of 1 required eleven steps from 5 and proceeded in an overall yield of
ca. 18% on a scale of 10 to 30 g for the conversion of 5 to (E/Z)-16. Considering the
limited stability of the tosylates (E/Z)-17 and of the nitrone 1, the last three steps were
only performed on a 1-g scale.
A sample of 7 was acetylated. J(2,3) ˆ 3.2 Hz, and J(3,4) ˆ 2.1 Hz (d(H C(3)) at 5.31 ppm) of the
resulting acetate 9 confirm the altro-configuration. The H C(3) t of 10 appears at 3.85 ppm with a large
coupling constant (J ꢀ 9.3 Hz), evidencing the gluco-configuration. H C(2) gives rise to a complex signal at
3.73 ppm, which changes upon the addition of D2O. The OH group of 12 gives rise to a t (J ꢀ 5.6 Hz) at 1.95 ppm
and an IR band at 3512 cm 1 and that of 11 to a d (J ˆ 8.7 Hz) at 2.50 ppm. H C(4) of 11 resonates as a dt (J ˆ
3.1, 8.7 Hz) at 3.79 ppm. Tosylation of 12 to 13 resulted in a downfield shift of the H C(6) signals, resonating at
4.30 ppm. The Me group of 14 resonates as a d (J ˆ 6.5) at 1.29 ppm, and as a q at 17.84 ppm. The hemiacetal 3
(in CDCl3) is a b-d/a-d 3 : 2 mixture. The 1H-NMR signals of the minor component were assigned to the a-d-
anomer on the basis of a comparison with the spectrum of 14, the chemical shift of H C(5) being revealing
(4.28 ppm for 14, 4.24 ppm for a-d-3 and 4.01 ppm for b-d-3). H C(1) of both anomers of 3 resonate at ca.
4
)
)
A 1H-NMR spectrum (CDCl3) of the crude product showed no sign of 1, but broad signals at 5.2 ± 5.4 and
5.6 ± 5.7 ppm.
For a similar conversion of geminal bis(hydroxylamines) to nitrones, see [45].
5

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Helvetica Chimica Acta ± Vol. 82 (1999)
5.0 ppm. The OH group gives rise to a large d at 4.98 ppm (J ˆ 11.4) for a-d- and at 3.44 ppm (J ˆ 12.2) for b-d-
3, in keeping with the expected stronger intramolecular C(1)OH OH(3) H-bond of a-d-3. By comparison,
HO C(3) of 7 resonates at 3.01 ppm with J ˆ 7.6 Hz. (E)-16 is characterized by a H C(1) d (J ˆ 8.1 Hz) at
7.81 ppm, while H C(1) of (Z)-16, hidden by the ArH signals (7.18 ± 7.42 ppm), resonantes at higher field
[48][49]. The C(1) d of (Z)-16 (157.64 ppm) is shifted downfield relative to the corresponding signal of (E)-16
(154.81 ppm). The structure of the tosylated oximes (E/Z)-17 is evidenced by a Me s at 2.36 ppm for the (E)-
and at 2.41 ppm for the (Z)-oxime. C(1) resonates as a d at 154.96 ppm for (E)-17 and at 158.47 ppm for (Z)-17.
The nitrone 1 is characterized by lmax 247 nm (e 7940 m 1 cm 1) and a strong IR band at 1588 cm 1. C(1)
resonates as a d at 133.68 ppm and H C(1) as a dd at 7.05 ppm (J ˆ 1.9, 2.5 Hz), the smaller coupling
corresponding to a long range interaction with H C(5). The coupling constants (see below, Table 2) evidence a
3H4-conformation. The dimer 21 has a FAB-MS peak at m/z 863. The C1 symmetry was evidenced by the signals
for H C(1) at 5.85 ppm (J ˆ 3.3 Hz) and for H C(1') at 4.42 ppm (J ˆ 8.3 Hz).
Synthesis of a-l-Fucosidase Inhibitors. ± The versatile character of cyclic carbo-
hydrate-derived nitrones as advanced intermediates for the synthesis of glycosidase
inhibitors was illustrated by a nucleophilic addition, a cycloaddition to an acrylate, and
a transformation into a thiolactam. Thus, 1 was converted to the piperidine 30, the
indolizidines 39 and 40, and the thiolactam 41 that was further transformed into the
imidazole 44.
A range of piperidines are known a-l-fucosidase-inhibitors [50]. Deoxyfuconojir-
imycin and the hydroxymethylene analogue 22 are among the strongest inhibitors of
bovine epididymis a-l-fucosidase [14][15]. We prepared the piperidine methanamine
bis(hydrochloride) 30 to further investigate the influence of the substituent at the
anomeric center.
Similarly to piperidines, many indolizidines inhibit a-glycosidases efficiently [50].
We converted nitrone 1 to the indolizidine 39 and 40. Although there are indolizidines
possessing a OH group at the five-membered ring in the same position as 39 and 40,
they have not been tested as glycosidase inhibitors [7][51][52]. To the best of our
knowledge, 23 is the only indolizidine that has so far been tested against a-l-fucosidases
[14].
Tetrahydroimidazopyridines, such as 24, are potent inhibitors of b-glycosidases
[53][54][55]. To the best of our knowledge, only one imidazole has been shown to
inhibit an a-glycosidase, viz. 24, that inhibits brewers yeast a-glucosidase (Ki ˆ 59 mm)
[53]. The inhibitory power of compounds with an sp2-hybridized anomeric center
against a-glycosidases has been related to their basicity; while neutral lactone-type
inhibitors are selective for b-glycosidases, their basic analogues are less selective
[56][57]. This rule appears to be valid also for a-l-fucosidases. The l-fucono-1,5-
lactone and -lactam are weak inhibitors of bovine epididymis a-l-fucosidase (Ki ˆ 8.5
and 340 mm, resp.) [58], whereas the corresponding amidrazone 25 strongly inhibits
recombinant human lysosomal a-l-fucosidase (Ki ˆ 820 nm) [17].
The AlMe2Cl-promoted addition of trimethylsilyl cyanide (TMSCN) [59] to 1 gave
the diastereoisomeric N-[(silyloxy)amino] nitriles 26/28 and the desilylated 27 and 29

Helvetica Chimica Acta ± Vol. 82 (1999)
1049
(Scheme 3). Addition of TMSCN followed by desilylation (TsOH, MeOH) led
predominantly to the axial nitrile 29 (86%), besides 5% of the equatorial 27.
The reduction and hydrogenolysis of 29 with H2 over Pd/C in MeOH/HCl yielded
75% of the bis(hydrochloride) 30. Exploratory reductions of 29 with H2 over Pd/C in
MeOH/AcOH or in MeOH/HCO2H led to mixtures, due to incomplete cleavage of the
BnO groups. The bis(hydrochloride) 30 was not stable to storage at 238, rapidly turning
yellow. Addition of 0.01n HCl in Et2O to a methanolic solution of the crude reduction
product precipitated 30 as a slightly yellow solid that contained only traces of impurities
(1H-NMR spectroscopy) and proved stable at 48.
Scheme 3
a) TMSCN (2 equiv.), cat. AlMe2Cl, CH2Cl2. b) 3% TsOH ´ H2O, MeOH; 86% of 29, 5% of 27. c) 10% Pd/C,
H2, HCl, MeOH; 75% of 30.
For the synthesis of the indolizidines 39 and 40 (Scheme 4), we treated 1 with
methyl acrylate, following a known method [7]. As expected, the 1,3-dipolar
cycloaddition proceeded regioselectively [60][61] and led to a 3 :2 mixture of the
diasteroisomeric isoxazolidines 31 (55%) and 32 (34%) by exclusively axial C,C bond
formation. As often observed [4], the major product 31 derives from an exo-addition.
Reductive cleavage of the N O bond (Zn/AcOH) converted the isoxazolidine
carboxylates 31 and 32 into the corresponding hydroxy lactams 33 and 34, respectively
(78%). The major diastereoisomer 33 was converted into the minor 34 by a Mitsunobu
reaction with PhCOOH followed by transesterification in MeOH, confirming that 33/
34 and 31/32 differ only by the configuration at C(2). The lactam 34 was debenzylated
by Pd(OH)2/C-catalyzed hydrogenolysis in MeOH, yielding 84% of 36, while
debenzylation of the isomeric 33 to 35 (87%) only proceeded in MeOH/AcOH.
The lactams 33 and 34 were reduced with BH3 in THF to the indolizidines 37 (74%)
and 38 (85%), respectively. Hydrogenolytic debenzylation in MeOH/HCl afforded
the indolizidines 39 and 40 as their hydrochlorides. Purification by ion-exchange
chromatography gave the free amines 39 and 40 in 78 and 75% yield, respectively.
Tetrahydroimidazopyridines of the type 24 [62][53] have been most efficiently
prepared by condensation of thiolactams with aminoacetaldehyde dimethyl acetal
followed by acid-promoted cyclization. Thiolactams are available from nitrones by
fragmentation of their cycloadducts6) to thiocarbonyl compounds, 1,1'-carbonothioyl-
bis[1H-imidazole] and 1,1'-carbonothioylbis[1H-1,2,4-triazole] being particularly well
suited for this purpose [64].
Treatment of the nitrone 1 with 1,1'-carbonothioylbis[1H-1,2,4-triazole] in pyridine/
toluene 1:1 at ambient temperature yielded 84% of the thiolactam 41, while the less
6
)
For the isolation of cycloadducts that cannot undergo the fragmentation, see [63].

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 4
a) Methyl acrylate (10 equiv.), toluene; 55% of 31, 34% of 32. b) Zn (8 equiv.), AcOH; 78%. c) 10% Pd(OH)2/
C, H2 , MeOH, AcOH; 84%. d) 10% Pd(OH)2/C, H2 , MeOH; 87%. e) Ph3P (1.5 equiv.), diethyl
diazenedicarboxylate (DEAD) (1.5 equiv.), PhCOOH (1.5 equiv.). f) 1% soln. NaOMe in MeOH; 71% (two
steps). g) BF3 ´ THF (2.7 equiv.), THF; 74% (33 ! 37), 85% (34 ! 38). h) 10% Pd(OH)2, MeOH, 1m HCl in
Et2O; 78% (37 ! 39), 75% (38 ! 40).
reactive 1,1'-carbonothioylbis[1H-imidazole] led to only low yields of 41 (Scheme 5). It
was not possible to detect any intermediates by TLC, suggesting that fragmentation of
the cycloadducts is faster than their formation.
The thiolactam 41 reacted with aminoacetaldehyde dimethyl acetal in the presence
of Hg(OAc)2 to the amidine 42 which was cyclized by exposure to TsOH ´ H2O in
toluene/H2O. The imidazole 43 was isolated in a yield of 75% and debenzylated to
yield 76% of 44.
‡
The structure of 29 is evidenced by FAB-MS signals at m/z 459 ([M ‡ H] ) and at m/z 432 ([M ‡ H
‡
CN] ) and by a CN s at 115.48 ppm. The axial orientation of the CN group is evidenced by J ˆ 5.0 Hz of the
H
C(2) d at 4.36 ppm. HO N exchanges with D2O and resonates as a s at 5.30 ppm. The equatorial isomer 27
is characterized by J ˆ 10.0 Hz for the d at 3.50 ppm of the H C(2), a s at 5.73 ppm for HO N and a s at
117.78 ppm for the CN group. The bis(hydrochloride) 30 is characterized by a C(7) t at 38.83 ppm and by two
1
H
C(7) dd at 3.40 (J ˆ 4.4, 14.0 Hz) and 3.71 ppm (J ˆ 8.4, 14.0 Hz). The H-NMR spectrum ((D6)DMSO)
shows 3s for NH at 9.56 (1 H), 9.23 (1 H), and 8.35 ppm (3 H). The 1H-NMR spectrum of 31 exhibits broad
signals. The MeOCO group is evidenced by 13C-NMR signals at 51.99 (q) and 171.35 ppm (s), and by an IR band
‡

Helvetica Chimica Acta ± Vol. 82 (1999)
1051
Scheme 5
a) 1,1'-Carbonothioyl[1H-1,2,4-triazole] (1.2 equiv.), pyridine/toluene 1:1; 84%. b) Aminoacetaldehyde
dimethyl acetal (5 equiv.), Hg(OAc)2 (1.5 equiv.), THF. c) TsOH ´ H2O (0.5 equiv.), toluene, H2O, 75%
(2 steps). d) 10% Pd(OH)2/C, AcOEt, MeOH, H2O, 76%.
at 1742 cm 1. The spectra of 32 are better resolved, particularly at higher temperature. Ha C(3) of 32
((D5)PhCl, 758) resonates at 2.30 (ddd, J ˆ 6.2, 8.7, 12.8 Hz), Hb C(3) at 2.52 ppm (td, J ꢀ 8.7, 12.5 Hz), and
H
C(2) at 4.31 ppm (t, J ꢀ 8.7 Hz).
The lactams 33 and 34, and hence the isoxazolidines 31 and 32, differ only by the configuration at C(2), as
shown by the conversion of 33 to 34. The 4,5-cis-configuration is deduced from J(4,5) ꢀ 5.5 Hz for 31, 32, 39, and
40 and J(4,5) ꢀ 2 Hz for 33 ± 37, excluding a 4,5-trans-diaxial arrangement (Table 1). As evidenced by the
coupling constants, 31, 32, 39, and 40 adopt a 4C7 conformation of the piperidine ring and 33 ± 38 a flattened 7C4
conformation. Force-field calculations (macromodel MM3) of the lactams 35 and 36 confirm a flattened 7C4
7
conformation ). The configuration at C(2) was deduced by comparing the coupling constants of the lactams 35
and 36 to those corresponding to the calculated conformers (Table 1) and to those of related hydroxy lactams
[65][66][67]. Similarly, the coupling constants of the indolizidine 39, correspond to those of a related
indolizidin-2-ol [7]. The assignment is in keeping with the D[M]D values for 33/34 in CHCl3 ( 2568) and 35/36 in
MeOH ( 958) relative to those of the enantiomeric 3-hydroxypyrrolidin-2-ones in CHCl3 ([M]D(S)
[M]D(R) ˆ 2288) [68][69].
The thiolactam 41 is characterized by a C(1) s at 202.34 ppm and a broad NH signal at 7.81 ppm. J(H,H) of
41 evidence a 3H4 conformation (Table 2). The protected imidazole 43 is a flattened 7H6 conformation and the
1
unprotected 44 a 7H6 one (cf. [53]). An IR band at 3608 cm for 38 (free OH group), absent for 37, hints at an
intramolecular H-bond, further evidenced by a downfield shift of the OH signal (37: 2.60 ppm, 38: 1.98 ppm),
and only compatible with a cis-annulation of 37. MM3* Calculations suggest a cis-annulation for 37 and a trans-
annulation for 38.
Inhibition of Bovine Epididymis a-l-Fucosidase. ± The piperidine 30, the
indolizidines 39 and 40, the indolizidinones 35 and 36, and the imidazole 44 were
tested as inhibitors of bovine epididymis a-l-fucosidase (Table 3).
The diamine 30 (IC50 ˆ 105 nm) is about as strong an inhibitor as the deoxy-l-
fuconojirimycin (IC50 ˆ 90 nm [14], Ki ˆ 6.2 nm [15] against bovine epididymis a-l-
fucosidase), evidencing that the primary amino group does not contribute to the
binding of the enzyme.
7
)
Calculations showed an energy difference of 3.7 kcal/mol between the 7C4 and the next stable NS2
conformers of 36. The same analysis of 35 resulted in an energy difference of 2.6 kcal/mol in favour of
the C4 conformation.
7

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Helvetica Chimica Acta ± Vol. 82 (1999)
Table 1. Coupling Constants J [Hz] of the Protected Lactams 33 and 34, of the Deprotected Lactams 35 and 36,
and of the Indolizidines 37 ± 40, and Calculated Coupling Constants for 35 and 36 (carbohydrate numbering)
33
34
35
36
calc. 35
calc. 36
37
38
39
6.2
ꢁ0
4.7
7.4
12.4
5.9
40
4.7
6.5
7.2
J(1a,2)
J(1b,2)
J(2,3a)
J(2,3b)
J(3a,4)
J(3b,4)
J(4,5)
J(5,6)
J(6,7)
J(7,8)
±
±
±
±
±
±
±
±
±
±
±
±
±
±
4.7
6.2
7.8
1.9
8.1
6.9
5.3
8.7
5.0
7.8
2.8
3.4
2.8
6.5
7.7
9.0
9.3
1.3
2.2
3.7
2.8
6.5
7.5
8.7
7.5
7.2
2.2
3.7
3.1
6.9
7.5
8.7
9.3
1.9
1.9
3.7
3.4
6.5
7.3
9.4
6.1
10.9
2.2
3.6
3.1
6.1
7.8
8.6
8.8
1.7
2.2
3.5
3.4
5.9
ꢁ 0
6.2
ꢁ 0
6.8
8.7
2.2
3.1
3.1
5.9
12.1
6.5
5.3
8.1
3.1
2.7
a
)
5.6
2.7
3.1
5.3
7.5
a
)
1.9
a) Not determined.
Table 2. Coupling Constants J [Hz] of the Nitrone 1, the Thiolactam 41, and the Imidazoles 43 and 44
(carbohydrate numbering)
1
41
43
44
J(2,3)
J(3,4)
J(4,5)
6.8
1.9
3.7
8.4
2.2
2.5
5.6
1.9
4.7
9.0
2.2
2.2
Table 3. IC50 Values of the Inhibitors against Bovine Epididymis a-l-Fucosidase
30
39
40
35
36
44
IC50
105 nM
580 nM
5 mM
240 mM
100 mM
150 mM
The indolizidine 39 (IC50 ˆ 580 nm) is about as strong an inhibitor as the related 23
(Ki ˆ 240 nm) [14], whereas 40 is 10 times weaker (IC50 ˆ 5 mm). Overlay of the three
indolizidines shows that C(3) of 23 corresponds to the Me group of 39 and 40. Thus, 39
and 40 are the equivalent of two rotamers of 1-(2-hydroxyethyl)-N-methyldeoxyfu-
conojirimycin and 23 is the equivalent of N-ethyldeoxyfuconojirimycin. This compar-
ison shows that substitution at C(1) has a minor effect on the inhibition by N-
alkyldeoxyfuconojirimycin, but that the exact orientation of the hydroxyethyl group is
relevant.
The imidazole 44 (IC50 ˆ 150 mm, pKHA ˆ 5.6) is a weak inhibitor of bovine
epididymis a-l-fucosidase. The corresponding amidrazone 25 is a stronger inhibitor
(Ki ˆ 820 nm against recombinant human lysosomal a-l-fucosidase) [17]. The differ-
ence may be attributed to the expected higher pKHA value of the amidrazone8), i.e., to a
complete protonation of the amidrazone and the ensuing in a charge/charge interaction
with the catalytical nucleophile, but only a partial protonation of the imidazole
that apparently cannot form a H-bond with the catalytic acid [70]. In keeping with
the importance of a basic center, the indolizidinones 35 (IC50 ˆ 240 mm) and 36
(IC50 ˆ 100 mm) are only weak inhibitors of bovine epididymis a-l-fucosidase.
8
)
pKHA ˆ 8.5 for the corresponding glucose-derived analogue [57].

Helvetica Chimica Acta ± Vol. 82 (1999)
1053
We thank the Swiss National Science Foundation and F. Hoffmann-La Roche AG, Basel, for generous
support, and Dr. B. Bernet for checking the experimental part. A. Peer thanks S. Pitsch for help during his
Diploma Thesis.
Experimental Part
General. a-l-Fucosidase was purchased from Böhringer Mannheim as a suspension. Solvents were distilled
before use. Normal workup implies distribution of the crude product between the org. layer and the indicated
aq. layer, drying of the org. layer (Na2SO4), filtration, and evaporation of the filtrate. TLC: Merck silica gel 60
F254 plates; if not otherwise indicated, detection by treating the plates with an anisaldehyde soln. (10 ml of
anisaldehyde, 10 ml of conc. H2SO4 soln., 2 ml of AcOH, 180 ml of EtOH) followed by heating. Flash
chromatography (FC): silica gel (Fluka or Merck 60; 0.040 ± 0.063 mm). HPLC: Spherisorb ꢂ SiO2 (5 mm)
column (20 Â 250 mm); detection at 254 nm; tR in min. M.p.: uncorrected. NMR Spectra: chemical shifts d in
ppm and coupling constants J in Hz. FAB- and CI-MS: 3-nitrobenzyl alcohol and NH3 as matrix, resp., unless
indicated otherwise.
Allyl 4,6-O-Benzylidene-2,3-bis-O-(methanesulfonyl)-a-d-glucopyranoside (5). A soln. of 4 [71] (18 g,
63.3 mmol) in pyridine (110 ml) was cooled to 08, treated dropwise with MsCl (12.1 ml, 155 mmol), and stirred
at 218 for 6 h ( ! yellowish soln. and formation of a white precipitate). After addition of H2O (200 ml) and
extraction of the aq. layer with CH2Cl2, the org. layer was worked up in the usual way (sat. aq. NH4Cl soln.,
H2O). Residual pyridine was removed by co-evaporation with toluene. The resulting yellow powder was
recrystallized in CH2Cl2/Et2O 1 : 1 to give 5 (22.3 g, 80%). Colourless powder. M.p. 1328. Rf (AcOEt/hexane
1 : 1) 0.58. [a]2D5 ˆ 67.9 (c ˆ 0.8, CHCl3). IR (CHCl3): 2980m, 2940m, 2873m, 1731w, 1457m, 1415m, 1368s, 1178s,
1098s, 1049s, 1018s, 974s, 962s, 934m, 841s, 590w, 529m, 509m. 1H-NMR (300 MHz, CDCl3): 2.98 (s, MsO); 3.17
(s, MsO); 3.74 (t, J ꢀ 9.3, H C(4)); 3.78 (t, J ꢀ 10.0, H C(6)); 4.06 (dt, J ꢀ 5.0, 10.0, H C(5)); 4.13 (tdd, J ꢀ
1.3, 6.2, 12.8, 1 H, CH2ˆCHCH2); 4.26 (tdd, J ꢀ 0.9, 5.6, 12.7, 1 H, CH2ˆCHCH2); 4.33 (dd, J ˆ 5.0, 10.0,
H
C(6)); 4.64 (dd, J ˆ 3.7, 9.3, H C(2)); 5.11 (t, J ꢀ 9.3, H C(3)); 5.18 (d, J ˆ 3.7, H C(1)); 5.28 (qd, J ꢀ 0.9,
10.3, 1 olef. H); 5.37 (qd, J ꢀ 0.9, 16.5, 1 olef. H); 5.56 (s, PhCH); 5.93 (dddd, J ꢀ 5.6, 6.2, 10.3, 16.5, 1 olef. H);
7.26 ± 7.47 (m, 5 arom. H). 13C-NMR (75 MHz, CDCl3): 38.94 (q, MsO); 39.05 (q, MsO); 62.61 (d, C(5)); 68.81
(t,C(6)); 69.69 (t, CH2ˆCHCH2); 75.99 (d, C(3)); 77.40 (d, C(2)); 79.30 (d, C(4)); 97.07 (d, C(1)); 102.26
(d, PhCH); 119.10 (t, 1 olef. C); 126.30 (d, 2 arom. C); 128.74 (d, 2 arom. C); 129.83 (d, 1 arom. C); 133.00
‡
(d, 1 olef. C); 136.56 (s, 1 arom. C). FAB-MS: 465 (100, [M ‡ 1] ), 205 (14), 154 (23), 149 (19), 137 (31), 136
(27), 127 (12), 109 (14), 107 (21), 105 (27). Anal. calc. for C18H24O10S2 (464.51): C 46.54, H 5.21, O 34.44,
S 13.81; found: C 46.38, H 5.21, O 34.42, S 13.80.
Allyl 2-O-Benzyl-4,6-O-benzylidene-a-d-altropyranoside (7). A soln. of Na (9.6 g, 420 mmol) in PhCH2OH
(320 ml) was treated portionwise with 5 (12 g, 25.9 mmol) and stirred for 30 min at 218 and then for 15 h at 908.
The brown soln. was cooled to 218, diluted with AcOEt (500 ml), and worked up in the usual way (sat. aq. NH4Cl
soln., H2O). The residual PhCH2OH was removed by distillation at 1008/0.5 Torr. FC (hexane/AcOEt 1:0 !
4 : 1) gave 7 (8.4 g, 82%) and 10 (0.85 g, 8%; m.p. ˆ 134 ± 1358 and [a]2D5 ˆ 79.1 (c ˆ 1.2, CHCl3)) in accordance
with those reported in [72], both as colourless solids. Recrystallization of 7 in AcOEt/hexane 1 : 2 gave a
colourless powder.
Data of 7: M.p. 1408. Rf (toluene/CH2Cl2/Et2O 4 :1:1) 0.55. [a]2D5 ˆ 32.0 (c ˆ 0.75, CHCl3). IR (CHCl3):
3521m, 3068m, 3008m, 2936m, 2872m, 1955w, 1880w, 1813w, 1723w, 1647w, 1604w, 1497w, 1468w, 1455m, 1382m,
1313m, 1282m, 1248m, 1165m, 1135s, 1098s, 1029s, 939m, 917m, 887w, 858m, 828w, 640w, 618w, 599w, 556w, 521w,
512w. 1H-NMR (500 MHz, CDCl3): 3.01 (d, J ˆ 7.6, addition of D2O ! exchange, OH); 3.76 (dd, J ˆ 1.3, 3.4,
H
C(2)); 3.86 (t, J ꢀ 10.0, H C(6)); 4.01 (dd, J ˆ 10.0, 2.8, H C(4)); 4.03 (tdd, J ꢀ 1.3, 6.2, 13.1, 1 H,
CH2ˆCHCH2); 4.18 ± 4.29 (m, 1 H of CH2ˆCHCH2, H C(3), H C(5)); 4.34 (dd, J ˆ 5.0, 10.0, H C(6)); 4.63
(d, J ˆ 12.1, PhCH); 4.68 (d, J ˆ 11.8, PhCH); 4.91 (br. s, H C(1)); 5.23 (qd, J ꢀ 1.3, 10.3, 1 olef. H); 5.28
(qd, J ꢀ 1.3, 16.3, 1 olef. H); 5.66 (s, PhCH); 5.88 (dddd, J ˆ 5.3, 6.2, 10.3, 16.5, 1 olef. H); 7.09 ± 7.41
(m, 10 arom. H). 13C-NMR (75 MHz, CDCl3): 58.66 (d, C(5)); 67.30 (d, C(3)); 68.77 (t, C(6)); 69.31
(t, CH2ˆCHCH2); 72.78 (t, PhCH2); 76.93, 76.96 (2d, C(2), C(4)); 98.13 (d, C(1)); 102.47 (d, PhCH); 118.55
(t, 1 olef. C); 126.54 ± 129.38 (several d, 10 arom. C); 133.39 (d, 1 olef. C); 137.56 (s, 1 arom. C); 137.64
(s, 1 arom. C). FAB-MS: 399 (34, [M ‡ 1] ), 341 (100, [M OAll] ), 339 (23), 281 (37), 249 (26), 235 (23),
221 (36), 207 (34), 181 (35), 175 (23), 149 (32), 136 (25), 133 (37), 131 (32), 107 (38), 105 (48). Anal. calc. for
C23H26O6 (398.45): C 69.33, H 6.58, O 24.09; found: C 69.14, H 6.47, O 23.80.
‡
‡
Data of Allyl 3-O-benzyl-4,6-O-benzylidene-a-d-glucopyranoside (10): Rf (toluene/CH2Cl2/Et2O 4 :1 :1)
0.31. IR (CHCl3): 3569m, 3068m, 3008m, 2935m, 2870m, 1954w, 1880w, 1813w, 1648w, 1497m, 1454m, 1371s,

1054
Helvetica Chimica Acta ± Vol. 82 (1999)
1
1345m, 1312m, 1171m, 1129s, 1074s, 1041s, 1005s, 934m, 656m, 577w, 524w. H-NMR (500 MHz, CDCl3): 2.31
(d, J ˆ 8.0, addition of D2O ! exchange, OH); 3.64 (t, J ꢀ 9.4, H C(4)); 3.73 (m, addition of D2O ! change,
H
C(2)); 3.74 (t, J ꢀ 10.3, H C(6)); 3.85 (t, J ꢀ 9.3, H C(3)); 3.88 (dt, J ꢀ 4.8, 9.8, H C(5)); 4.06 (tdd, J ꢀ
1.3, 6.3, 12.8, 1 H, CH2ˆCHCH2); 4.23 (tdd, J ꢀ 1.5, 5.4, 12.8, 1 H, CH2ˆCHCH2); 4.28 (dd, J ˆ 4.9, 10.2,
C(6)); 4.80 (d, J ˆ 11.6, PhCH); 4.96 (d, J ˆ 11.6, PhCH); 4.96 (d, J ˆ 3.9, H C(1)); 5.23 (qd, J ꢀ 1.2, 10.4,
H
1 olef. H); 5.32 (qd, J ꢀ 1.5, 17.2, 1 olef. H); 5.56 (s, PhCH); 5.94 (dddd, J ˆ 5.4, 6.4, 10.4, 17.1, 1 olef. H); 7.24 ±
7.50 (m, 10 arom. H). 13C-NMR (75 MHz, CDCl3): 62.40 (d, C(5)); 68.37, 68.56 (2t, C(6), CH2ˆCHCH2);
72.05 (d); 74.46 (t, PhCH2); 78.65 (d); 81.57 (d), 97.64 (d, C(1)); 100.91 (d, PhCH); 117.95 (t, 1 olef. C);
125.70 ± 128.65 (several d, 10 arom. C); 133.09 (d, 1 olef. C); 137.42 (s, 1 arom. C); 139.01 (s, 1 arom. C).
Allyl 3-O-Acetyl-2-O-benzyl-4,6-O-benzylidene-a-d-altropyranoside (9). A soln. of 7 (120 mg, 0.30 mmol)
in pyridine/Ac2O 1 :1 (1 ml) was treated with 4-(dimethylamino)pyridine (3 mg) and stirred for 12 h at 218,
diluted with CH2Cl2, and worked up in the usual way (sat. aq. NH4Cl soln.). The remaining pyridine was
removed by evaporation with toluene. FC (hexane/AcOEt 1 :0 ! 2 : 1) gave 9 (25 mg, 75%). Colourless oil. Rf
(hexane/AcOEt 2 : 1) 0.62. 1H-NMR (300 MHz, CDCl3): 2.10 (s, Ac); 3.80 (t, J ꢀ 11.8, 1 H C(6)); 3.84 (d, J ˆ
3.1, H C(2)); 3.92 (tdd, J ꢀ 1.3, 5.6, 13.4, 1 H, (CH2ˆCHCH2); 4.12 (dd, J ˆ 2.1, 9.0, H C(4)); 4.21 (tdd, J ꢀ
1.6, 4.7, 13.4, 1 H, CH2ˆCHCH2); 4.18 ± 4.38 (m, H C(5), 1 H C(6)); 4.66 (d, J ˆ 11.8, PhCH); 4.77 (d, J ˆ
11.8, PhCH); 4.77 (s, H C(1)); 5.22 (qd, J ꢀ 1.2, 10.6, 1 olef. H); 5.27 (qd, J ꢀ 1.6, 17.4, 1 olef. H); 5.31 (dd, J ˆ
1.6, 3.2, H C(3)); 5.61 (s, PhCH); 5.88 (dddd, J ˆ 4.7, 5.6, 10.3, 17.4, 1 olef. H); 7.26 ± 7.50 (m, 10 arom. H).
Allyl 2,3-Di-O-benzyl-4,6-O-benzylidene-a-d-altropyranoside (8). A soln. of 7 (15.6 g, 39.2 mmol) in anh.
THF (120 ml) was treated slowly at 238 with NaH (1.1 g, 45.8 mmol). The suspension was heated to 608, treated
dropwise with BnBr (5.5 ml, 46.3 mmol), followed by Bu4NI (0.8 g, 2.1 mmol), and stirred at 608 for 12 h. After
dilution with CH2Cl2, the orange soln. was worked up in the usual way (brine). FC (hexane/AcOEt 1:0 ! 4 : 1)
gave 8 (18.0 g, 94%). Colourless oil. Rf (hexane/AcOEt 4 : 1) 0.41. [a]2D5 ˆ 35.5 (c ˆ 1.1, CHCl3). IR (CHCl3):
3089w, 3068m, 3008m, 2934m, 2869m, 1953w, 1878w, 1814w, 1731m, 1644w, 1603w, 1469m, 1455m, 1382m, 1311m,
1269m, 1248m, 1167m, 1140s, 1100s, 1029s, 916m, 859w, 644w, 606w, 548w, 520w, 504w. 1H-NMR (300 MHz,
CDCl3): 3.75 (dd, J ˆ 0.6, 2.8, H C(2)); 3.81 (t, J ꢀ 10.3, 1 H C(6)); 4.00 (t, J ꢀ 2.8, H C(3)); 4.06 (dd, J ˆ 2.8,
10.0, H C(4)); 4.00 ± 4.10 (m, 1 H, CH2ˆCHCH2); 4.27 (tdd, J ꢀ 1.6, 4.7, 13.4, 1 H, CH2ˆCHCH2); 4.34
(dd, J ˆ 5.3, 10.3, 1 H C(6)); 4.47 (dt, J ˆ 5.3, 10.3, H C(5)); 4.55 (s, PhCH2); 4.71 (d, J ˆ 12.5, PhCH); 4.83
(d, J ˆ 12.5, PhCH); 4.86 (d, J ˆ 0.6, H C(1)); 5.20 (qd, J ꢀ 1.6, 10.6, 1 olef. H); 5.32 (qd, J ꢀ 1.6, 17.4,
1 olef. H); 5.60 (s, PhCH); 5.93 (dddd, J ˆ 4.7, 5.9, 10.6, 17.4, 1 olef. H); 7.26 ± 7.57 (m, 15 arom. H). 13C-NMR
(75 MHz, CDCl3): 58.81 (d, C(5)); 68.28 (t, C(6)); 69.57 (t, CH2ˆCHCH2); 72.67 (t, PhCH2); 72.88 (t, PhCH2);
73.03 (d, C(3)); 76.59, 77.57 (2d, C(2), C(4)); 98.05 (d, C(1)); 102.47 (d, PhCH); 117.34 (t, 1 olef. C); 126.58 ±
129.28 (several d, 15 arom. C); 134.28 (d, 1 olef. C); 137.69 (s, 1 arom. C); 138.13 (s, 1 arom. C); 139.05
‡
(s, 1 arom. C). FAB-MS: 489 (36, [M ‡ 1] ), 327(17), 325 (15), 281 (24), 221 (46), 207 (61), 193 (23), 191
(22), 181 (21), 154 (26), 147 (100), 136 (74), 133 (58), 107 (47). Anal. calc. for C30H32O6 (488.58): C 73.75,
H 6.60, O 19.65; found: C 73.47, H 6.82, O 19.43.
Reductive Acetal Cleavage of 8. A soln. of LiAlH4 (5.14 g, 135 mmol) in anh. Et2O (50 ml) was treated
dropwise with Me3SiBr (43.7 ml, 338 mmol) at 08. The suspension was stirred for 30 min at 238, heated to reflux
and then treated dropwise during 20 min with a soln. of 8 (32.0 g, 67 mmol) in anh. Et2O (50 ml). The mixture
was refluxed for another 30 min, until TLC (hexane/AcOEt 2 :1) indicated the complete conversion of the
reactant. The suspension was cooled to 08. AcOEt was added dropwise followed by H2O, until the residual
LiAlH4 was destroyed. The mixture was worked up in the usual way (1n HCl, sat. aq. NaHCO3 soln., H2O).
Removing the solvent in vacuo gave a colourless oil (32.5 g). Thereof, 1 g (3.1 %) was separated by FC (hexane/
AcOEt 1:0 ! 1 : 1) to give 12 (0.75 g, 75%) and 11 (0.11 g, 11%).
Allyl 2,3,4-Tri-O-benzyl-a-d-altropyranoside (12): Colourless oil. Rf (hexane/AcOEt 2 :1) 0.38. [a]2D5 ˆ 66.3
(c ˆ 1.1, CHCl3). IR (CHCl3): 3512m (br.), 3070m, 3008s, 2932s, 2894m, 2860s, 1956w, 1886w, 1816w, 1731w,
1603w, 1590w, 1497m, 1472m, 1454s, 1428m, 1393m, 1363m, 1306m, 1267w, 1248w, 1115s, 1068s, 1028m, 924s,
824m, 613m, 556w, 536w, 504s. 1H-NMR (300 MHz, CDCl3): 1.95 (t, J ꢀ 5.6, addition of D2O ! exchange, OH);
3.75 (dd, J ˆ 0.9, 3.1, H C(2)); 3.77 ± 3.86 (m, H C(3), H C(4), 2 H C(6)); 3.99 (tdd, J ꢀ 1.3, 5.9, 13.4, 1 H,
CH2ˆCHCH2); 4.19 ± 4.21 (m, H C(5)); 4.22 (tdd, J ꢀ 1.6, 6.2, 13.4, 1 H, CH2ˆCHCH2); 4.42 (d, J ˆ 12.1,
PhCH); 4.45 (d, J ˆ 11.5, PhCH); 4.52 (d, J ˆ 12.1, PhCH); 4.53 (d, J ˆ 11.8, PhCH); 4.54 (d, J ˆ 12.1, PhCH);
4.65 (d, J ˆ 12.1, PhCH); 4.83 (s, H C(1)); 5.15 (qd, J ꢀ 1.6, 10.6, 1 olef. H); 5.32 (qd, J ꢀ 1.6, 17.4, 1 H,
CH2ˆCHCH2); 5.89 (dddd, J ˆ 5.9, 6.2, 10.6, 17.5, 1 H, CH2ˆCHCH2); 7.26 ± 7.57 (m, 15 arom. H). 13C-NMR
(75 MHz, CDCl3): 62.90 (t, C(6)); 67.85 (d, C(5)); 68.21 (t, CH2ˆCHCH2); 71.56 (t, PhCH2); 72.03 (t, PhCH2);
72.69 (t, PhCH2); 72.82 (d, C(4)); 73.02 (d, C(3)); 75.36 (d, C(2)); 98.33 (d, C(1)); 117.02 (t, 1 olef. C); 127.81 ±
128.75 (several d, 15 arom. C); 134.43 (d, 1 olef. C); 138.02 (s, 1 arom. C); 138.40 (s, 1 arom. C); 138.65

Helvetica Chimica Acta ± Vol. 82 (1999)
1055
(s, 1 arom. C). FAB-MS: 461 (10), 355 (29), 341 (34), 327 (35), 325 (28), 281 (78), 267 (35), 221 (99), 207
(100), 193 (31), 181 (53), 154 (55), 147 (95), 137 (47). Anal. calc. for C30H34O6 (490.60): C 73.45, H 6.99; found:
C 73.19, H 7.15.
Allyl 2,3,6-Tri-O-benzyl-a-d-altropyranoside (11): Colourless oil. Rf (hexane/AcOEt 2 :1) 0.50. IR
(CHCl3): 3552w, 3068w, 3008m, 2962m, 2908m, 2868m, 1952w, 1698w, 1602w, 1496m, 1454s, 1397m, 1351m,
1
1262s, 1098s, 1050s, 1017s, 931m, 865m, 818s, 652w, 629w, 601w. H-NMR (300 MHz, CDCl3): 2.50 (d, J ˆ 8.7,
OH); 3.69 (dd, J ˆ 5.6, 10.6, 1 H C(6)); 3.76 ± 3.80 (m, H C(2), H C(3) 1 H C(6)); 3.79 (dt, J ꢀ 3.1, 8.7,
H
C(4)); 3.98 (tdd, J ꢀ 1.6, 5.9, 13.1, 1 olef. H); 4.06 (ddd, J ˆ 3.2, 5.6, 8.7, H C(5)); 4.27 (tdd, J ꢀ 1.3, 5.0, 13.1,
1 H, CH2ˆCHCH2); 4.43 (d, J ˆ 11.5, PhCH); 4.56 (d, J ˆ 12.1, PhCH); 4.60 (s, PhCH2); 4.66 (d, J ˆ 11.8,
PhCH); 4.69 (d, J ˆ 11.2, PhCH); 4.90 (s, H C(1)); 5.15 (qd, J ꢀ 1.3, 10.4, 1 olef. H); 5.27 (qd, J ꢀ 1.6, 16.5,
1 olef. H); 5.92 (dddd, J ˆ 5.0, 5.6, 10.6, 16.5, 1 olef. H); 7.25 ± 7.36 (m, 15 arom. H). 13C-NMR (75 MHz,
CDCl3): 65.44 (d, C(4)); 69.49 (d, C(5)); 68.26 (t, CH2ˆCHCH2); 70.43 (t, C(6)); 72.24 (t, PhCH2); 72.82
(t, PhCH2); 73.52 (t, PhCH2); 74.58 (d); 76.19 (d); 98.19 (d, C(1)); 117.07 (t, 1 olef. C); 127.70 ± 128.67 (several
d, 15 arom. C); 134.49 (d, 1 olef. C); 137.90 (s, 1 arom. C); 138.45 (s, 1 arom. C); 138.65 (s, 1 arom. C). FAB-
‡
MS: 400 (7), 355 (28), 327 (39), 281 (36), 267 (36), 136 (51), 91 (100, Bn ).
Allyl 2,3,4-Tri-O-benzyl-6-O-[(4-methylphenyl)sulfonyl]-a-d-altropyranoside (13). A soln. of crude 12
(31.5 g) in pyridine (56 ml) was treated with TsCl (25.3 g, 133 mmol) at 08 and stirred at 228 for 4 h when TLC
(hexane/AcOEt 2 :1) indicated complete conversion of the reactant. The mixture was poured on H2O and
extracted with CH2Cl2. The org. layer was worked up in the usual way (sat. aq. NaHCO3 soln., H2O).
Evaporation left a yellow oil which was filtered through silica gel (hexane/AcOEt 2 :1). After evaporation,
recrystallization in Et2O/pentane 2 :3 gave 13 (31 g, 75% from 8). Colourless powder. M.p. 69 ± 708. Rf (hexane/
AcOEt 2 :1) 0.56. [a]2D5 ˆ 61.2 (c ˆ 0.73, CHCl3). IR (CHCl3): 3089w, 3067m, 3008m, 2927m, 2872m, 1953w,
1809w, 1730w, 1644w, 1600m, 1496m, 1454s, 1365s, 1308m, 1266s, 1177s, 1143s, 1098s, 1045s, 1029s, 976s, 843m,
658m, 606m, 572m, 555s, 524m, 512w, 504w. 1H-NMR (300 MHz, CDCl3): 2.41 (s, Me); 3.73 (dd, J ˆ 1.2, 3.1,
H
C(3)); 3.75 ± 3.80 (m, H C(5)); 3.80 (dd, J ˆ 3.1, 9.1,
H
C(4)); 3.92 (tdd, J ꢀ 1.6, 5.9, 13.4, 1 H,
C(2)); 4.30 ± 4.36
CH2ˆCHCH2); 4.17 (tdd, J ꢀ 1.6, 5.0, 13.4, 1 H, CH2ˆCHCH2); 4.28 (d, J ˆ 1.3,
H
(m, 2 H C(6)); 4.35 (d, J ˆ 11.5, PhCH); 4.43 (d, J ˆ 12.5, PhCH); 4.44 (d, J ˆ 11.5, PhCH); 4.48 (d, J ˆ 12.1,
PhCH); 4.55 (d, J ˆ 12.1, PhCH); 4.61 (d, J ˆ 12.1, PhCH); 4.78 (s, H C(1)); 5.15 (qd, J ꢀ 1.6, 10.6, 1 olef. H);
5.27 (qd, J ꢀ 1.6, 17.1, 1 olef. H); 5.87 (dddd, J ˆ 4.7, 5.9, 10.6, 17.1, 1 olef. H); 7.01 ± 7.41 (m, 17 arom. H);
7.82 (td, J ꢀ 1.8, 8.4, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 21.68 (q, Me); 65.91 (d, C(5)); 68.14 (t,
CH2ˆCHCH2); 69.97 (t, C(6)); 71.28 (t, PhCH2); 71.94 (t, PhCH2); 72.25, 72.38 (2d,C(3), C(4)); 72.62
(t, PhCH2); 74.93 (d, C(2)); 97.93 (d, C(1)); 117.06 (t, 1 olef. C); 128.03 ± 129.54 (several d, 17 arom. C); 129.97
(d, 2 arom. C); 133.37 (d, 1 olef. C); 134.29 (s, 1 arom. C); 138.01 (s, 1 arom. C); 138.08 (s, 1 arom. C); 138.47
‡
‡
(s, 1 arom. C); 144.86 (s, 1 arom. C). FAB-MS: 667 (30, [M ‡ Na] ), 645 (18, [M ‡ 1] ), 643 (92), 587 (25), 527
(20), 496 (28), 495 (88), 405 (24), 271 (29), 253 (56), 181 (45), 90 (100). Anal. calc. for C37H40O8S (644.78):
C 68.92, H 6.25, O 19.85; found: C 68.78, H 6.22, O 19.80.
Allyl 2,3,4-Tri-O-benzyl-6-deoxy-a-d-altropyranoside (14). A soln. of 13 (23 g, 35.7 mmol) in anh. Et2O
(55 ml) was treated with LiAlH4 (2.7 g, 71.1 mmol) in small portions at 228. The resulting suspension was heated
for 2 h to reflux, cooled to 08, and treated dropwise with AcOEt followed by H2O. Usual workup (1n HCl, sat.
aq. NaHCO3 soln., H2O) and FC (hexane/Et2O 1 :0 ! 3 : 1) gave 14 (15.6 g, 92%). Colourless oil. Rf (hexane/
AcOEt 2 : 1) 0.77. [a]D25
ˆ
19.1 (c ˆ 0.79, CHCl3). IR (CHCl3): 3088w, 3066w, 3007m, 2929m, 2871m, 1952w,
1875w, 1814w, 1727w, 1692w, 1659w, 1643w, 1603m, 1548w, 1496m, 1454s, 1369m, 1266m, 1146s, 1091s, 1028s,
992s, 911m, 840w, 606m, 542w, 535w, 526m, 514w. 1H-NMR (300 MHz, CDCl3): 1.29 (d, J ˆ 6.5, 3 H C(6)); 3.52
(dd, J ˆ 2.5, 8.7, H C(4)); 3.78 ± 3.82 (m, H C(2), H C(3)); 4.04 (tdd, J ꢀ 1.3, 5.9, 13.1, 1 H, CH2ˆCHCH2);
4.28 (qd, J ˆ 6.5, 8.7, H C(5)); 4.20 ± 4.40 (m, 1 H, CH2ˆCHCH2); 4.48 (d, J ˆ 11.8, PhCH); 4.49 (d, J ˆ 12.1,
PhCH); 4.55 (d, J ˆ 11.8, 2 PhCH); 4.60 (d, J ˆ 11.8, PhCH); 4.68 (d, J ˆ 12.1, PhCH); 4.80 (s, H C(1)); 5.18
(qd, J ꢀ 1.6, 10.6, 1 olef. H); 5.33 (qd, J ꢀ 1.6, 17.1, 1 olef. H); 5.94 (dddd, J ˆ 5.0, 5.9, 10.6, 16.8, 1 olef. H); 7.20 ±
7.40 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 17.84 (q, C(6)); 64.49 (d, C(5)); 68.47 (t, CH2ˆCHCH2);
71.60 (t, PhCH2); 72.00 (t, PhCH2); 72.88 (t, PhCH2); 73.06, 75.78 (2d, C(3), C(4)); 77.77 (d, C(2)); 98.07
(d, C(1)); 116.87 (t, 1 olef. C); 126.56 ± 129.38 (several d, 15 arom. C); 134.63 (d, 1 olefin. C); 138.27
‡
(s, 1 arom. C); 138.65 (s, 1 arom. C); 138.77 (s, 1 arom. C). FAB-MS: 417 (5, [M OAll] , 5), 281 (10), 253
(24), 181 (100), 154 (36), 147 (44), 136 (55), 107 (46), 105 (36). Anal. calc. for C30H32O5 (474.60): C 75.92,
H 7.22, O 16.86; found: C 75.78, H 7.19, O 17.09.
2,3,4-Tri-O-benzyl-6-deoxy-d-altropyranose (3). a) A soln. of 14 (25 g, 52.7 mmol) in anh. DMSO (115 ml)
was treated with KOtBu (25.7 g, 229 mmol) at 218 and stirred at 1008 for 1.5 h until complete isomerization of 14
to (Z)-15 (evidenced by 1H-NMR). The brown soln. was cooled to 258 and treated with a sat. aq. NH4Cl soln.

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Helvetica Chimica Acta ± Vol. 82 (1999)
The aq. layer was extracted with CH2Cl2, and the combined organic layers were worked up in the usual way
(brine). The resulting brown oil was dissolved in acetone/H2O 10 :1 (340 ml), treated with yellow HgO (11.8 g,
52.7 mmol) and a soln. of HgCl2 (13 g, 47.8 mmol) in acetone/H2O 10 :1 (120 ml), and stirred for 15 min at 218.
After evaporation in vacuo to a volume of 70 ml, addition of CH2Cl2 and usual workup (sat. aq. KI soln., H2O),
the resulting brown oil was filtered through silica gel (50 g, hexane/AcOEt 1:1). Evaporation and crystallization
from hexane/AcOEt 1:1 gave 3 (19.0 g, 83%). Colourless crystals.
b) A soln. of 14 (2.6 g, 5.6 mmol) in anh. THF (13 ml) was treated with {Ir(cod)[PMePh2]2}PF6 (cod ˆ
cycloocta-1,5-diene; 50 mg, 60 mmol), and the resulting red suspension was stirred at 218 under H2, until the
colour changed to yellow. H2 was replaced by Ar and stirring was continued for 2.5 h until the isomerization of
14 to (E/Z)-15 was complete (1H-NMR control). After evaporation, the residue was dissolved in acetone/H2O
10 : 1 (35 ml), treated with yellow HgO (1.22 g, 5.6 mmol) and a soln. of HgCl2 (0.97 g, 4.5 mmol) in acetone/
H2O 10 : 1 (11 ml), and stirred for 15 min at 218. After concentration to a volume of ca. 10 ml, addition of
CH2Cl2, usual workup (sat. aq. KI soln., H2O), and crystallization from hexane/AcOEt 1 : 1 gave 3 (2 g, 85%).
Colourless crystals. Rf (hexane/AcOEt 2 : 1) 0.48. M.p. 1058. IR (CHCl3): 3571m, 3068m, 3008m, 2934m, 2870m,
1956w, 1602w, 1497w, 1454s, 1371s, 1345m, 1312m, 1266m, 1172m, 1130s, 1074s, 1041s, 1003s, 933m, 653m, 575m,
526m, 513w, 503w. 1H-NMR (500 MHz, CDCl3, a-d/b-d 2 : 3): 1.29 (d, J ˆ 6.2, 1.8 H), 1.34 (d, J ˆ 6.2, 1.2 H,
3 H C(6)); 3.36 (dd, J ˆ 2.8, 9.5, 0.6 H), 3.51 (dd, J ˆ 2.7, 9.4, 0.4 H, H C(4)); 3.44 (d, J ˆ 12.2, addition of
D2O ! exchange, 0.6 H), 5.04 (d, J ˆ 11.4, addition of D2O ! exchange, 0.4 H, OH); 3.49 (dd, J ˆ 1.7, 3.7,
0.6 H); 3.61 (dd, J ˆ 1.2, 3.8, 0.4 H, H C(2)); 3.88 (t, J ꢀ 3.3, 0.6 H), 3.88 ± 3.89 (ddd, J ꢀ 1.5, 2.5, 3.5, H C(3));
4.01 (qd, J ˆ 6.2, 9.5, 0.6 H), 4.24 (qd, J ꢀ 6.2, 9.7, 0.4 H, H C(5)); 4.40 (d, J ˆ 12.2, 0.4 H, 4.40 (s, 1.2 H), 4.44
(d, J ˆ 12.0, 0.6 H), 4.45 (d, J ˆ 12.2, 0.4 H), 4.46 (d, J ˆ 11.6, 0.6 H), 4.47 (d, J ˆ 12.2, 0.6 H), 4.49 (d, J ˆ 11.6,
0.4 H), 4.53 (d, J ˆ 11.8, 0.4 H), 4.54 (d, J ˆ 12.3, 0.4 H), 4.63 (d, J ˆ 12.2, 0.6 H), 4.71 (d, J ˆ 11.8, 0.4 H,
6 PhCH); 4.98 (br. td, J ꢀ 1.5, 11.7, addition of D2O ! br. s, 0.4 H), 5.03 (dd, J ˆ 1.7, 12.2, addition of D2O ! br.
s, 0.6 H, H C(1)); 7.19 ± 7.36 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3, a-d/b-d 2 : 3): signals of a-d-3:
17.74 (q, C(6)); 68.34 (d, C(5)); 71.74 (t, PhCH2); 71.81 (d, C(4)); 73.49 (t, PhCH2); 74.47 (t, PhCH2); 77.41 (d);
77.52 (d); 92.53 (d, C(1)); 128.19 ± 128.99 (several d, 15 arom. C); signals of b-d-3: 17.74 (q, C(6)); 62.63
(d, C(5)); 71.55 (d, C(4)); 71.65 (t, PhCH2); 72.72 (t, PhCH2); 73.04 (t, PhCH2); 77.33 (d); 77.55 (d); 91.20
(d, C(1)); 128.19 ± 128.99 (several d, 15 arom. C); 135.22 (s, 1 arom. C); 135.69 (s, 1 arom. C); 135.85
‡
‡
(s, 1 arom. C). FAB-MS: 435 (3, [M‡ 1] ), 433 (49), 417 (49, [M OH] ), 325 (22), 253 (20), 181 (78), 91 (100).
(Z)-Prop-1-enyl 2,3,4-Tri-O-benzyl-6-deoxy-a-d-altropyranose (15). In an additional exper., FC (hexane/
Et2O 1:0 ! 3 : 1) of the crude product obtained by the conversion of 14 (90 mg, 0.19 mmol) with KOtBu
(100 mg, 0.89 mmol) in DMSO (0.5 ml) as described above gave (Z)-15 (82 mg, 91%). Colourless oil. Rf
(hexane/AcOEt 2 : 1) 0.77. IR (CHCl3): 3089w, 3066m, 3008m, 2924m, 2870m, 1952w, 1877w, 1812w, 1731m,
1672m, 1605w, 1496w, 1454s, 1374s, 1318m, 1248m, 1154m, 1091s, 1028s, 911m, 868w, 818m, 609w. 1H-NMR
(300 MHz, CDCl3): 1.27 (d, J ˆ 6.5, 3 H C(6)); 1.59 (dd, J ˆ 1.9, 6.8, Me); 3.49 (dd, J ˆ 3.1, 8.4, H C(4)); 3.81
(t, J ꢀ 3.1, H C(3)); 3.85 (dd, J ˆ 1.6, 3.1, H C(2)); 4.27 (qd, J ˆ 6.5, 8.4, H C(5)); 4.47 (d, J ˆ 11.8, PhCH);
4.48 (d, J ˆ 12.1, PhCH); 4.54 (d, J ˆ 12.5, PhCH); 4.56 (d, J ˆ 12.5, PhCH); 4.58 (d, J ˆ 12.1, PhCH); 4.68
(d, J ˆ 12.1, PhCH); 4.94 ± 5.04 (m, 1 vinyl. H); 4.97 (br. s, H C(1)); 6.13 (qd, J ˆ 1.9, 6.1, 1 olef. H); 7.23 ± 7.39
(m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 9.36 (q, Me); 17.78 (q, C(6)); 64.68 (d, C(5)); 71.60 (t, PhCH2);
71.93 (t, PhCH2); 72.85 (t, PhCH2); 72.57 (d, C(4)); 74.56, 77.43 (2d, C(2), C(3)); 98.54 (d, C(1)); 103.72
(t, 1 olef. C); 127.84 ± 128.75 (9d, 15 arom. C); 138.02 (s, 1 arom. C); 138.47 (s, 1 arom. C); 138.58 (s, 1 ar-
om. C); 142.35 (d, 1 olef. C).
(E)- and (Z)-2,3,4-Tri-O-benzyl-6-deoxy-d-altrose O-[(tert-Butyl)diphenylsilyl]oxime ((E)-16 and (Z)-16,
resp.). A soln. of 3 (7.2 g, 16.6 mmol) in CH2Cl2 (26 ml) was treated with pyridinium p-toluenesulfonate
(170 mg, 0.68 mmol), O-[(tert-butyl)diphenylsilyl]hydroxylamine (9.14 g, 33.6 mmol), and molecular sieves 3 Š
(50 mg, powder (Union Carbide)). The resulting suspension was stirred at 228 under Ar for 3 d until complete
conversion (TLC (toluene/Et2O 9 :1) control). Addition of CH2Cl2, usual workup (sat. aq. NaHCO3 soln.,
H2O), and FC (hexane/Et2O 1:0 ! 1 : 1) gave (E)-16 (9.4 mg, 83%) and (Z)-16 (1.5 g, 13%), both as colourless
oils.
Data of (E)-16: Rf (toluene/Et2O 9 :1) 0.40. IR (CHCl3): 3592w, 3068m, 3008s, 2929s, 2872m, 1954w, 1876w,
1814w, 1711m, 1658w, 1602m, 1548w, 1496m, 1454s, 1428m, 1364s, 1266s, 1248m, 1097s, 1040s, 1028s, 990s, 932s,
844w, 610m, 544w, 533m, 523m, 512m, 504s. 1H-NMR (300 MHz, CDCl3): 1.21 (s, tBu); 1.21 (d, J ˆ 6.2,
3 H C(6)); 2.65 (d, J ˆ 4.4, addition of D2O ! exchange, OH); 3.46 (dd, J ˆ 5.0, 6.5, H C(4)); 3.84 (t, J ꢀ 5.0,
H
C(3)); 4.11 (m, addition of D2O ! change, H C(5)); 4.25 (dd, J ˆ 5.0, 8.1, H C(2)); 4.36 (d, J ˆ 11.8,
PhCH); 4.52 (d, J ˆ 11.2, PhCH); 4.58 (d, J ˆ 11.2, PhCH); 4.63 (d, J ˆ 11.8, PhCH); 4.69 (d, J ˆ 11.5, PhCH);
4.77 (d, J ˆ 11.5, PhCH); 7.16 ± 7.43 (m, 21 arom. H); 7.68 ± 7.73 (m, 4 arom. H); 7.81 (d, J ˆ 8.1, H C(1)).

Helvetica Chimica Acta ± Vol. 82 (1999)
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13C-NMR (75 MHz, CDCl3): 19.37 (s, Me3C); 19.48 (q, C(6)); 27.16 (q, Me3C); 68.34 (d, C(5)); 71.22
(t, PhCH2); 73.77 (t, PhCH2); 74.37 (t, PhCH2); 77.62 (d, C(2)); 81.62 (d); 83.56 (d); 127.87 ± 128.72 (several d,
19 arom. C); 130.04 (d, 2 arom. C); 133.59 (s, 1 arom. C); 133.73 (s, 1 arom. C); 135.90 (d, 4 arom. C); 137.50
‡
(s, 1 arom. C); 138.05 (s, 1 arom. C); 138.52 (s, 1 arom. C); 154.81 (d, C(1)). FAB-MS: 688 (100, [M ‡ 1] ), 580
(9), 199 (14), 181 (9), 137 (9), 136 (7), 105 (6). Anal. calc. for C30H32NO5 (687.95): C 75.07, H 7.18, N 2.04;
found: C 75.19, H 7.23, N 2.03.
Data of (Z)-16: Rf (toluene/Et2O 9 :1) 0.28. IR (CHCl3): 3498m, 3070m, 3008s, 2961m, 2933s, 2860s, 1955w,
1886w, 1815w, 1590w, 1548w, 1497m, 1472m, 1454s, 1428m, 1392m, 1363m, 1336m, 1306m, 1263m, 1115s, 1070s,
1028s, 911s, 823m, 650w, 613m, 533w, 503s. 1H-NMR (300 MHz, CDCl3): 1.14 (s, tBu); 1.24 (d, J ˆ 6.2,
3 H C(6)); 2.51 (d, J ˆ 4.4, addition of D2O ! exchange, OH); 3.71 (dd, J ˆ 5.0, 6.8, H C(4)); 4.06 (dd, J ˆ
3.1, 6.9, H C(3)); 4.09 ± 4.15 (m, addition of D2O ! change, H C(5)); 4.47 (d, J ˆ 11.5, PhCH); 4.49 (d, J ˆ
11.5, PhCH); 4.56 (d, J ˆ 11.5, PhCH); 4.60 (d, J ˆ 12.1, PhCH); 4.65 (d, J ˆ 12.2, PhCH); 4.66 (d, J ˆ 11.8,
PhCH); 5.35 (dd, J ˆ 3.1, 6.2, H C(2)); 7.18 ± 7.42 (m, 21 arom. H, H C(1)); 7.69 ± 7.76 (m, 4 arom. H).
13C-NMR (75 MHz, CDCl3): 18.48 (s, Me3C); 19.42 (q, C(6)); 27.17 (q, Me3C); 68.67 (d, C(5)); 72.53
(t, PhCH2); 72.59 (d, C(2)); 73.87 (t, PhCH2); 74.76 (t, PhCH2); 81.02 (d); 82.61 (d); 127.71 ± 128.77 (several d,
19 arom. C); 130.17 (d, 2 arom. C); 133.29 (s, 1 arom. C); 133.31 (s, 1 arom. C); 135.87 (d, 4 arom. C); 137.45
‡
(s, 1 arom. C); 137.81 (s, 1 arom. C); 138.76 (s, 1 arom. C); 157.64 (d, C(1)). FAB-MS: 688 (73, [M ‡ 1] ),
417(15), 325 (18), 271 (13), 253 (48), 181 (50), 91 (100).
(E)- and (Z)-2,3,4-Tri-O-benzyl-6-deoxy-5-O-[(4-methylphenyl)sulfonyl]-d-altrose O-[(tert-Butyl)diphe-
nylsilyl]oxime ((E)-17 and (Z)-17). a) At 08 a soln. of (E)-16 (1.77 g, 2.6 ml) in pyridine (1.8 ml) was treated
with TsCl (590 mg, 3.1 mmol) and stirred at 228 for 48 h ( ! precipitation of a white solid). After completion of
the conversion (TLC (toluene/Et2O 9 : 1) control), H2O was added to the mixture. The aq. layer was extracted
with CH2Cl2, and the combined org. layers were worked up in the usual way (brine). FC (hexane/Et2O 1 : 0 !
1 : 1) gave (E)-17 (1.73 g, 80%) and (Z)-17 (0.28 g, 13%), both as colourless oils.
b) The same procedure was applied to (Z)-16 (1.40 g, 2.03 mmol) with TsCl (450 mg, 2.33 mmol) in
pyridine (1.6 ml) to yield (E)-17 (1.17 g, 69%) and (Z)-17/(E)-17 4 :1 (0.35 g, 21%).
Data of (E)-17: Rf (toluene/Et2O 9 :1) 0.70. IR (CHCl3): 3090w, 3069m, 3008m, 2933m, 2860m, 1956w,
1888w, 1816w, 1730m, 1602m, 1591w, 1497m, 1472m, 1455m, 1428s, 1393w, 1363w, 1337w, 1306w, 1265m, 1115s,
1070s, 1028m, 1010m, 930s, 866w, 823m, 640w, 616m, 558m. 1H-NMR (300 MHz, CDCl3): 1.21 (s, tBu); 1.27
(d, J ˆ 6.5, irrad. at 5.02 ! s, 3 H C(6)); 2.36 (s, Me); 3.45 (dd, J ˆ 4.4, 8.4, H C(3)); 3.85 (dd, J ˆ 1.9, 8.4,
irrad. at 5.02 ! d, J ˆ 8.4, irrad. at 3.45 ! d, J ˆ 1.9, H C(4)); 4.20 (dd, J ˆ 5.0, 8.0, irrad. at 3.45 ! d, J ˆ 8.1,
H
C(2)); 4.21 (d, J ˆ 12.0, PhCH); 4.23 (d, J ˆ 11.8, PhCH); 4.49 (d, J ˆ 11.6, 2 PhCH); 4.64 (d, J ˆ 11.8,
PhCH); 4.68 (d, J ˆ 11.2, PhCH); 5.02 (dq, J ˆ 1.7, 6.3, H C(5)); 7.14 ± 7.48 (m, 23 arom. H); 7.69 ± 7.80
(m, 6 arom. H, H C(1)). 13C-NMR (75 MHz, CDCl3): 15.10 (q, C(6)); 19.48 (s, Me3C); 21.76 (q, Me); 27.30
(q, Me3C); 71.14 (t, PhCH2); 73.64 (t, PhCH2); 74.24 (t, PhCH2); 77.84 (d, C(2)); 79.91 (d, C(5)); 80.17 (d);
81.09 (d); 127.76 ± 128.82 (several d, 21 arom. C); 130.17 (d, 2 arom. C); 130.24 (d, 1 arom. C); 130.27
(d, 1 arom. C); 133.59 (s, 1 arom. C); 133.76 (s, 1 arom. C); 134.48 (s, 1 arom. C); 136.04 (d, 4 arom. C);
137.91 (s, 1 arom. C); 138.02 (s, 1 arom. C); 138.26 (s, 1 arom. C); 144.91 (s, 1 arom. C); 154.96 (d, C(1)). FAB-
‡
MS: 688 (100, [M ‡ 1] ), 580 (9), 199 (14), 181 (9), 137 (9), 136 (7), 105 (5).
Data of (Z)-17: Rf (toluene/Et2O 9 :1) 0.64. IR (CHCl3): 3070w, 3008m, 2932m, 2860m, 1957w, 1889w, 1731s,
1599w, 1497m, 1472m, 1455m, 1428m, 1374m, 1361m, 1248s, 1176s, 1156m, 1114s, 1069s, 1046m, 1029m, 1008m,
917m, 869w, 818s, 634w, 607m, 568m, 556m, 504m. 1H-NMR (300 MHz, CDCl3): 1.14 (s, tBu); 1.10 ± 1.17
(m, 3 H C(6)); 2.41 (s, Me); 3.87 (dd, J ˆ 1.9, 9.3, H C(3)); 4.11 (dd, J ˆ 0.9, 9.3, H C(4)); 4.31 (d, J ˆ 11.5,
PhCH); 4.35 (d, J ˆ 12.1, PhCH); 4.39 (d, J ˆ 12.1, PhCH); 4.53 (d, J ˆ 11.8, PhCH); 4.58 (d, J ˆ 11.5, PhCH);
4.82 (d, J ˆ 11.5, PhCH); 5.01 (dq, J ˆ 0.9, 6.2,
H
C(5)); 4.20 (dd, J ˆ 1.9, 5.3,
H C(2)); 7.14 ± 7.48
(m, 23 arom. H, H C(1)); 7.69 ± 7.80 (m, 6 arom. H). 13C-NMR (75 MHz, CDCl3): 14.32 (q, C(6)); 19.35
(s, Me3C); 21.70 (q, Me); 27.09 (q, Me3C); 72.72 (t, PhCH2); 72.84 (d, C(2)); 74.03 (t, PhCH2); 74.76 (t, PhCH2);
78.64 (d, C(5)); 79.18 (d); 81.35 (d); 127.58 ± 128.73 (several d, 21 arom. C); 130.06 (d, 2 arom. C); 130.19
(d, 1 arom. C); 130.22 (d, 1 arom. C); 133.18 (s, 1 arom. C); 133.25 (s, 1 arom. C); 134.49 (s, 1 arom. C); 135.81
(d, 4 arom. C); 137.58 (s, 2 arom. C); 138.55 (s, 1 arom. C); 144.76 (s, 1 arom. C); 158.47 (d, C(1)).
Decomposition of (E)-17. (E)-17 (50 mg, 73 mmol) was allowed to stand for 4 d at 238. FC of the resulting
yellow oil gave (E)-17 (37 mg, 75%) and (E)-(18) (7 mg, 16%), both as colourless oils.
Data of (E)-2,5-Anhydro-3,4-di-O-benzyl-6-deoxy-l-galactose O-[(tert-Butyl)diphenylsilyl]oxime ((E)-
18): Rf (toluene/Et2O 9 :1) 0.71. IR (CHCl3): 3089w, 3071m, 3007s, 2960s, 2933s, 2892m, 2860m, 1957w, 1887w,
1819w, 1743w, 1599m, 1590m, 1497m, 1472s, 1454s, 1428s, 1392m, 1362m, 1308w, 1263m, 1176s, 1115s, 1068s,
1028s, 932s, 823s, 610w, 556w, 507m. 1H-NMR (300 MHz, CDCl3): 1.10 (s, tBu); 1.33 (d, J ˆ 6.5, 3 H C(6)); 3.88

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Helvetica Chimica Acta ± Vol. 82 (1999)
(t, J ꢀ 4.0, H C(4)); 4.08 (dq, J ˆ 4.0, 6.2, H C(5)); 4.22 (dd, J ˆ 4.1, 7.5, H C(3)); 4.45 (d, J ˆ 12.1, PhCH);
4.54 (d, J ˆ 12.5, PhCH); 4.61 (dd, J ˆ 7.2, 8.4, H C(2)); 4.65 (d, J ˆ 11.8, PhCH); 4.92 (d, J ˆ 12.1, PhCH);
7.20 ± 7.43 (m, 16 arom. H); 7.62 ± 7.75 (m, 4 arom. H); 7.87 (d, J ˆ 8.4, H C(1)). 13C-NMR (75 MHz, CDCl3):
15.94 (q, C(6)); 19.42 (s, Me3C); 27.18 (q, Me3C); 72.42 (t, PhCH2); 73.63 (t, PhCH2); 76.07 (d); 76.59 (d); 79.00
(d); 81.67 (d); 127.62 ± 129.88 (several d, 14 arom. C); 130.11 (d, 2 arom. C); 133.89 (s, 1 arom. C); 134.02
(s, 1 arom. C); 135.87 (d, 4 arom. C); 138.60 (s, 1 arom. C); 138.92 (s, 1 arom. C); 156.23 (d, C(1)). FAB-MS:
‡
‡
1159 (1, [2M ‡ 1] ), 580 (100, [M ‡ 1] ), 578 (9), 522 (10), 199 (10), 154 (12), 91 (47).
1,5-Anhydro-2,3,4-tri-O-benzyl-1,6-dideoxy-1-imino-l-galactitol N-Oxide (1) and (E)-2,5-Anhydro-3,4-di-
O-benzyl-6-deoxy-l-galactose Oxime ((E)-19). A soln. of (E)-17/(Z)-17 6 :1 (1.86 g, 2.21 mmol) in anh. THF
(75 ml) was treated at 08 dropwise with Et3N ´ 3 HF (4.4 ml), stirred for 2.5 h at 08, diluted with Et2O, and
worked up in the usual way (H2O). The crude intermediate was dissolved in anh. THF (19 ml), treated with
NH2OH ´ HCl (1.23 g, 17.7 mmol) and Et3N (2.5 ml, 17.7 mmol), and heated to 608 for 36 h. Cooling to 258,
dilution with Et2O, workup in the usual way (H2O) and FC (hexane/AcOEt 3 : 1 ! 0 : 1) gave (E)-19 (150 mg,
20%) and 1 (590 mg, 62%), both as colourless oils.
Data of 1: Rf (AcOEt/hexane 3 :1) 0.11. UV (MeOH): 247 (3.90). IR (CHCl3): 3090w, 3068w, 3007s, 2941m,
2871m, 1952w, 1811w, 1716w, 1588s, 1497m, 1455s, 1352m, 1311w, 1248w, 1147m, 1069s, 1028s, 912w, 823w, 603w,
531w, 507w. 1H-NMR (300 MHz, CDCl3): 1.55 (d, J ˆ 6.5, 3 H C(6)); 3.87 (dd, J ˆ 1.9, 6.9, irrad. at 4.51 !
d, J ˆ 1.9, H C(3)); 3.90 ± 4.02 (m, irrad. at 1.55 ! dd, J ˆ 1.9, 3.7, irrad. at 7.05 ! change, H C(5)); 4.00
(dd, J ˆ 2.2, 3.7, H C(4)); 4.51 (ddd, J ˆ 1.9, 3.1, 6.8, irrad. at 7.05 ! dd, J ˆ 1.9, 6.8, H C(2)); 4.64 (d, J ˆ 11.5,
PhCH); 4.65 (d, J ˆ 11.5, PhCH); 4.67 (d, J ˆ 11.5, PhCH); 4.69 (d, J ˆ 11.5, PhCH); 4.76 (s, PhCH2); 7.05
(dd, J ˆ 1.9, 2.5, H C(1)); 7.24 ± 7.37 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 14.54 (q, C(6)); 66.90
(d, C(5)); 70.00 (t, PhCH2); 72.63 (t, PhCH2); 73.14 (d, C(2)); 75.05 (t, PhCH2); 75.24 (d); 78.56 (d); 127.87 ±
128.86 (several d, 15 arom. C); 133.68 (d, C(1)); 137.60 (s, 1 arom. C); 137.94 (s, 1 arom. C); 138.05
‡
‡
(s, 1 arom. C). FAB-MS: 863 (49, [2M ‡ 1] ), 432 (100, [M ‡ 1] ), 391 (11).
Data of (E)-19: Rf (toluene/Et2O 8 :2) 0.16. IR (CHCl3): 3538m, 3089w, 3067w, 3008s, 2977w, 2930m,
2872m, 1952w, 1879w, 1813w, 1711w, 1587w, 1496m, 1454s, 1417m, 1365m, 1318m, 1248m, 1165m, 1086s, 1028s,
1009s, 910m, 871w, 822w, 603m, 554w, 503m. 1H-NMR (300 MHz, CDCl3): 1.33 (d, J ˆ 6.5, 3 H C(6)); 3.90
(t, J ꢀ 4.1, H C(4)); 4.10 (dq, J ˆ 4.1, 6.5, H C(5)); 4.3 (dd, J ˆ 4.1, 7.2, H C(3)); 4.56 (d, J ˆ 12.1, PhCH);
4.60 ± 4.67 (m, H C(2)); 4.63 (d, J ˆ 12.1, PhCH); 4.64 (d, J ˆ 12.1, PhCH); 4.83 (d, J ˆ 12.1, PhCH); 7.20 ± 7.38
(m, 10 arom. H); 7.71 (d, J ˆ 8.4, H C(1)).
Desilylation of (E)-17/(Z)-17. In an additional exper., FC of the crude after desilylation of (E)-17/(Z)-17
6 :1 (53 mg, 63 mmol), which was carried out as described above (75 ml Et3N ´ 3 HF, 1.5 ml THF), gave (E)-2
(26 mg, 69%), (Z)-2 (4 mg, 11%), and (E)-19 (3 mg, 16%), all as colourless oils.
Data of (E)-2: Rf (toluene/Et2O 8 :2) 0.35. IR (CHCl3): 3581m, 3333w, 3090w, 3067w, 3008m, 2928m,
2872m, 1732w, 1599w, 1497s, 1455m, 1399w, 1358s, 1307m, 1292m, 1262w, 1177s, 1095s, 1071s, 1028m, 917s, 872m,
1
818m, 556m, 534w, 525w. H-NMR (300 MHz, CDCl3): 1.16 (d, J ˆ 6.5, 3 H C(6)); 2.40 (s, Me); 3.64 (dd, J ˆ
4.4, 8.4, H C(3)); 3.94 (dd, J ˆ 1.6, 8.4, H C(4)); 4.23 (dd, J ˆ 4.4, 7.8, H C(2)); 4.27 (d, J ˆ 11.2, PhCH); 4.32
(d, J ˆ 11.5, PhCH); 4.50 (d, J ˆ 11.2, PhCH); 4.59 (d, J ˆ 11.8, PhCH); 4.96 (d, J ˆ 11.2, 2 PhCH); 5.00 (dq, J ˆ
1.6, 6.5, H C(5)); 7.21 ± 7.35 (m, 17 arom. H, OH); 7.43 (d, J ˆ 7.8, H C(1)); 7.72 (td, J ꢀ 1.9, 8.7, 2 arom. H).
13C-NMR (75 MHz, CDCl3): 14.72 (q, C(6)); 21.51 (q, Me); 72.18 (t, PhCH2); 73.41 (t, PhCH2); 74.01
(t, PhCH2); 77.44 (d); 79.35 (d); 79.95 (d); 80.81 (d); 127.60 ± 128.48 (several d, 17 arom. C); 129.82
(d, 2 arom. C); 134.14 (s, 1 arom. C); 137.56 (s, 2 arom. C); 137.94 (s, 1 arom. C); 144.61 (s, 1 arom. C);
‡
153.08 (d, C(1)). FAB-MS: 604 (27, [M ‡ 1] ), 601 (30), 587 (33), 543 (34), 522 (27), 432 (64), 342 (46),
327 (32), 207 (29), 181 (42), 154 (58), 136 (88), 107 (42).
Data of (Z)-2: Rf (toluene/Et2O 8 :2) 0.38. IR (CHCl3): 3581m, 3325m, 3090m, 3067m, 3008m, 2930m,
2872m, 1952w, 1734w, 1599m, 1497m, 1454s, 1397m, 1359s, 1308m, 1261m, 1177s, 1153m, 1095s, 1070s, 1028s,
917m, 874m, 818m, 598w, 556m, 521w, 505w. 1H-NMR (300 MHz, CDCl3): 1.11 (d, J ˆ 6.5, 3 H C(6)); 2.39
(s, Me); 3.69 (dd, J ˆ 2.8, 8.7, H C(3)); 4.01 (dd, J ˆ 1.3, 8.6, H C(4)); 4.25 (d, J ˆ 11.5, PhCH); 4.32 (d, J ˆ
11.5, PhCH); 4.45 (d, J ˆ 11.5, PhCH); 4.57 (d, J ˆ 11.5, PhCH); 4.66 (d, J ˆ 11.2, PhCH); 4.72 (d, J ˆ 11.2,
PhCH); 4.98 (dq, J ˆ 1.6, 6.5, H C(5)); 5.01 (dd, J ˆ 2.8, 5.9, H C(2)); 6.96 (d, J ˆ 5.9, H C(1)); 7.19 ± 7.35
(m, 17 arom. H); 7.73 (td, J ꢀ 1.9, 8.7, 2 arom. H); 7.99 (br. s, addition of D2O ! exchange, OH). 13C-NMR
(75 MHz, CDCl3): 14.55 (q, C(6)); 21.68 (q, Me); 72.20 (d, C(2)); 72.34 (t, PhCH2); 73.74 (t, PhCH2); 74.05
(t, PhCH2); 78.48 (d); 79.44 (d); 81.33 (d); 127.79 ± 128.67 (several d, 17 arom. C); 130.00 (d, 2 arom. C); 134.22
(s, 1 arom. C); 137.64 (s, 2 arom. C); 138.41 (s, 1 arom. C); 144.53 (s, 1 arom. C); 153.08 (d, C(1)). FAB-MS:
‡
604 (27, [M ‡ 1] ), 432 (41), 327 (60), 281 (100), 221 (60), 206 (80), 91 (100).

Helvetica Chimica Acta ± Vol. 82 (1999)
1059
2,3,4-Tri-O-benzyl-5,6-dideoxy-5-(hydroxyamino)-a-l-galactopyranose 2',3',4'-Tri-O-benzyl-5',6'-dideoxy-5'-
(hydroxyamino)-b-l-galactopyranose 1,N':1',N-Dianhydride (ˆ(1R,2S,3S,4R,4aS,7R,8S,9S,10R,10aR)-2,3,4,8,
9,10-Hexakis(benzyloxy)octahydro-1,7-dimethyl-1H,7H-dipyrido[1,2-b:1',2'-e][1,4,2,5]dioxadiazine; 21). A soln.
of 1 (80 mg, 0.19 mmol) in CH2Cl2 (1 ml) was treated with an aq. FeCl3 soln. (1.9 ml, 0.2 mm) and stirred at 218
for 2 d. Addition of CH2Cl2, usual workup (H2O), and FC (hexane/AcOEt 1 : 0 ! 1 : 1) gave 21 (35 mg, 44%).
Colourless solid. M.p. 178 ± 179 (dec.) Rf (pentane/AcOEt 5 : 1) 0.70. IR (CHCl3): 3089w, 3067w, 3007s, 2938m,
2875m, 1952w, 1877w, 1812w, 1604w, 1497m, 1454s, 1356m, 1284w, 1265m, 1153s, 1118s, 1048s, 1028s, 965m, 911m,
856w, 818w, 631w, 600w, 536w, 526w, 516w, 508w. 1H-NMR (500 MHz, CDCl3): 1.18 (d, J ˆ 6.2, 3 H C(6')); 1.20
(d, J ˆ 6.3, 3 H C(6)); 2.69 (dq, J ˆ 2.0, 6.2,
H
C(5')); 3.49 (dd, J ˆ 3.0, 9.8,
H C(3')); 3.67 ± 3.70
(m, H C(3), H C(5), H C(4')); 3.72 (br. s, H C(4)); 3.96 (dd, J ˆ 8.3, 9.8, H C(2')); 4.21 (dd, J ˆ 3.3,
10.0, H C(2)); 4.42 (d, J ˆ 8.3, H C(1')); 4.60 (d, J ˆ 11.4, PhCH); 4.66 (d, J ˆ 11.6, PhCH); 4.67 (d, J ˆ 11.8,
PhCH); 4.69 (d, J ˆ 11.6, PhCH); 4.70 (d, J ˆ 10.8, PhCH); 4.74 (d, J ˆ 11.9, PhCH); 4.76 (d, J ˆ 11.3, PhCH);
4.82 (d, J ˆ 11.7, PhCH); 4.83 (d, J ˆ 11.8, PhCH); 4.88 (d, J ˆ 10.8, PhCH); 4.94 (d, J ˆ 11.3, PhCH); 4.96
‡
(d, J ˆ 11.3, PhCH); 5.85 (d, J ˆ 3.3, H C(1)); 7.27 ± 7.35 (m, 30 arom. H). FAB-MS: 863 (20, [M ‡ 1] ), 518
(25), 459 (29), 432 (92), 401 (27), 342 (34), 281 (60), 267 (30), 221 (50), 207 (66), 147 (100), 136 (58).
Treatment of 1 with Me3SiCN. A soln. of 1 (110 mg, 0.26 mmol) in anh. CH2Cl2 (2.1 ml) was treated
dropwise with freshly distilled Me3SiCN (0.05 ml, 0.39 mmol) and a 1m soln. of Me2AlCl in hexane (0.26 ml,
0.26 mmol) at 08 under Ar and stirred for 1.5 h. Addition of CH2Cl2 and usual workup (sat. aq. NaHCO3 soln.,
H2O) gave a crude mixture, which was treated with a 3% soln. of TsOH ´ H2O in MeOH (3 ml) and stirred at 238
for 20 min. After addition of a sat. aq. soln. of NaHCO3, evaporation of the org. solvent, and extraction of the
aq., layer with CH2Cl2, usual workup (sat. aq. NaHCO3 soln., H2O) and FC (hexane/AcOEt 1 : 0 ! 1 : 1) gave 29
(101 mg, 86%) and 27 (6 mg, 5%).
2,6-Anhydro-3,4,5-tri-O-benzyl-2,7-dideoxy-2-(hydroxyamino)-l-glycero-d-gluco-heptononitrile (29). Col-
ourless solid. M.p. 144 ± 1458. Rf (AcOEt/hexane 1 :1) 0.26. [a]D25
3355m, 3090m, 3067m, 3007m, 2941m, 2873m, 1952w, 1876w, 1812w, 1605w, 1497m, 1454s, 1368m, 1347m, 1315m,
1292m, 1262s, 1145s, 1112s, 1055s, 1028s, 1012s, 911m, 818m, 607m, 536w, 504w. H-NMR (300 MHz, CDCl3):
ˆ
6.1 (c ˆ 0.91, CHCl3). IR (CHCl3): 3561m,
1
1.17 (d, J ˆ 6.5, 3 H C(7)); 3.00 ± 3.11 (m, H C(6)); 3.71 (t, J ꢀ 2.9, H C(5)); 4.25 (dd, J ˆ 2.8, 9.6, H C(4));
4.15 (dd, J ˆ 5.0, 10.0, H C(3)); 4.36 (d, J ˆ 5.0, H C(2)); 4.60 (d, J ˆ 11.2, PhCH); 4.62 (d, J ˆ 11.5, PhCH);
4.75 (d, J ˆ 11.5, PhCH); 4.82 (d, J ˆ 11.8, PhCH); 4.86 (d, J ˆ 11.2, PhCH); 4.94 (d, J ˆ 11.5, PhCH); 5.30
(s, addition of D2O ! exchange, OH); 7.24 ± 7.40 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 15.15
(q, C(7)); 60.28, 62.01 (2d, C(2), C(6)); 73.81 (t, PhCH2); 74.00 (t, PhCH2); 74.13 (d, C(4)); 75.89 (t, PhCH2);
77.10 (d); 81.44 (d); 115.48 (s, C(1)); 127.89 ± 128.91 (several d, 15 arom. C); 137.79 (s, 1 arom. C); 138.16
‡
‡
(s, 1 arom. C); 138.52 (s, 1 arom. C). FAB-MS: 459 (21, [M ‡ 1] ), 432 (21 [M CN] ), 355 (20), 342 (45), 327
(44), 281 (100), 267 (44), 221 (54), 207 (50), 147 (50).
2,6-Anhydro-3,4,5-tri-O-benzyl-2,7-dideoxy-2-(hydroxyamino)-l-glycero-d-manno-heptononitrile (27).
1
Colourless oil. Rf (hexane/AcOEt 1:1) 0.28. H-NMR (300 MHz, CDCl3): 1.20 (d, J ˆ 5.9, 3 H C(7)); 2.50 ±
2.55 (m, H C(6)); 3.43 (dd, J ˆ 2.8, 10.0, H C(4)); 3.50 (d, J ˆ 10.0, H C(2)); 3.72 (br. s, H C(5)); 4.29
(t, J ꢀ 10.0, H C(3)); 4.67 (d, J ˆ 11.5, PhCH); 4.74 (d, J ˆ 11.5, PhCH); 4.79 (d, J ˆ 11.8, PhCH); 4.92 (d, J ˆ
12.0, PhCH); 4.97 (d, J ˆ 12.0, PhCH); 4.99 (d, J ˆ 11.5, PhCH); 5.73 (s, addition of D2O ! exchange, OH);
7.26 ± 7.43 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 15.60 (q, C(7)); 63.45, 63.60 (2d, C(2), C(6)); 73.52
(t, PhCH2); 75.64 (t, PhCH2); 76.23 (t, PhCH2)); 76.39 (d); 77.35 (d); 83.71 (d); 117.78 (s, C(1)); 127.83 ± 128.91
(several d, 15 arom. C); 137.51, 138.08 (2s, 3 arom. C).
Isolation of Me3Si Adduct 28. In an additional experiment FC of the crude after Me3SiCN addition at 1
(110 mg, 0.26 mmol), which was carried out as described above (0.05 ml of Me3SiCN, 0.26 ml of 1m Me2AlCl in
hexane, 2.1 ml of CH2Cl2), gave 26/28 ca. 1:15 (35 mg, 26%) and 27/29 ca. 1:15 (4 mg, 11%).
2,6-Anhydro-3,4,5-tri-O-benzyl-2,7-dideoxy-2-{[(trimethylsilyl)oxy]amino}-l-glycero-d-gluco-heptononi-
trile (28). Colourless oil. Rf (hexane/AcOEt 1:1) 0.62. 1H-NMR (300 MHz, CDCl3): 0.08 (s, Me3Si); 1.13 (d, J ˆ
6.2, 3 H C(7)); 2.98 ± 3.02 (m, H C(6)); 3.69 (dd, J ˆ 1.9, 2.1, H C(5)); 3.77 ± 3.83 (m, H C(4)); 4.09 ± 4.15
(m, H C(2)); 4.29 (t, J ꢀ 10.0, H C(3)); 4.59 (d, J ˆ 11.5, PhCH); 4.65 (d, J ˆ 12.1, PhCH); 4.77 (d, J ˆ 11.8,
PhCH); 4.87 (d, J ˆ 11.5, PhCH); 4.94 (d, J ˆ 11.5, PhCH); 4.98 (d, J ˆ 11.5, PhCH); 7.26 ± 7.43 (m, 15 ar-
om. H). 13C-NMR (75 MHz, CDCl3): 0.37 (q, Me3Si); 15.96 (q, C(7)); 61.52, 63.02 (2d, C(2), C(6)); 73.92
(t, PhCH2); 73.96 (t, PhCH2); 74.68 (d, C(4)); 75.67 (t, PhCH2); 77.74 (d); 81.31 (d); 115.79 (s, C(1)); 127.73 ±
128.86 (d, 15 arom. C); 138.02 (s, 1 arom. C); 138.76 (s, 1 arom. C); 139.05 (s, 1 arom. C).
2,7-Diamino-2,6-anhydro-1,2,7-trideoxy-l-glycero-d-galacto-heptitol Bis(hydrochloride) (30). A soln. of
29 (54 mg, 0.13 mmol) in MeOH (10 ml) was treated with 1n HCl in Et2O (0.5 ml) and 10% Pd/C (54 mg), and
hydrogenated at 6 bar for 2 d. The mixture was filtered through Celite and evaporated ( ! slightly yellow

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Helvetica Chimica Acta ± Vol. 82 (1999)
colour). The residue was dissolved in MeOH and treated with 0.01n HCl in Et2O leading to precipitation of 30
(18 mg, 75%). Slightly yellow solid. Rf (CH2Cl2/MeOH/20% aq. NH3 soln. 5 : 4 : 1, developed with ninhydrin)
0.23. [a]2D5
ˆ
3.40 (c ˆ 1.0, MeOH). IR (KBr): 3389m (br.), 2928m, 1627w, 1457m, 1160w, 1076s, 1049m, 960w,
877w, 575m. 1H-NMR (300 MHz, D2O): 1.37 (d, J ˆ 6.5, 3 H C(1)); 3.40 (dd, J ˆ 4.4, 14.0, 1 H C(7)); 3.60
(dq, J ˆ 1.6, 6.5, H C(2)); 3.71 (dd, J ˆ 8.4, 14.0, 1 H C(7)); 3.87 (dd, J ˆ 3.1, 9.7, irrad. at 4.24 ! d, J ˆ 3.1,
H
C(4)); 4.00 ± 4.06 (m, irrad. at 4.24 ! change, H C(3), H C(6)); 4.24 (dd, J ˆ 5.6, 9.7, H C(5)).
13C-NMR (75 MHz, D2O): 16.42 (q, C(1)); 38.83 (t, C(7)); 54.23, 54.91 (2d, C(2), C(6)); 68.65 (d, C(4)); 71.62
‡
(d); 72.06 (d). ESI-MS (CH3OH): 177 (100, [M HCl2] ), 160 (81), 130 (18), 100 (32), 57 (45), 56 (31), 44
(89).
Cycloaddition of 1 and Methyl Acrylate. A soln. of 1 (255 mg, 0.6 mmol) in anh. toluene (2.6 ml) was
treated with methyl acrylate (0.51 ml, 6 mmol) and stirred for 15 h at 228. Evaporation and FC (hexane/AcOEt
2 :1 ! 1 : 1) gave 31 (168 mg, 55%) and 32 (115 mg, 34%).
Methyl
2,N:4,8-Dianhydro-5,6,7-tri-O-benzyl-3,4,9-trideoxy-4-(hydroxyamino)-l-threo-d-ido-nononate
(31): Colourless oil. Rf (hexane/Et2O 1:1). 0.11. [a]2D5 ˆ 20.2 (c ˆ 1.00, CHCl3). IR (CHCl3): 3067w, 3008s,
2929s, 2856m, 1742s, 1602m, 1497m, 1454s, 1438m, 1352s, 1261m, 1152s, 1116s, 1058s, 1028s, 912w, 649w, 603w,
514w. 1H-NMR (300 MHz, CDCl3): 1.35 (d, J ˆ 6.2, 3 H C(9)); 2.19 ± 2.26 (m, 2 H C(3)); 2.40 ± 2.48
(m, H C(8)); 3.32 (s, MeO); 3.41 ± 3.44 (m, H C(6), H C(7)); 4.13 (td, J ꢀ 6.5, 11.5, H C(4)); 4.28
(d, J ˆ 11.8, PhCH); 4.43 (d, J ˆ 11.5, PhCH); 4.45 ± 4.53 (m, H C(2), H C(5)); 4.54 (d, J ˆ 11.8, PhCH); 4.62
(d, J ˆ 12.1, PhCH); 4.69 (d, J ˆ 12.2, PhCH); 4.94 (d, J ˆ 11.2, PhCH); 7.24 ± 7.39 (m, 15 arom. H). 13C-NMR
(75 MHz, CDCl3): 14.82 (q, C(9)); 32.85 (t, C(3)); 51.99 (q, MeO); 56.37, 62.34 (2d, C(4), C(8)); 72.63
(t, PhCH2); 73.07 (t, 2 PhCH2); 74.34, 75.36, 76.79 (3d, C(5), C(6), C(7)); 79.14 (br. d, C(2)); 127.07 ± 128.03
(several d, 15 arom. C); 137.86 (s, 1 arom. C); 137.99 (s, 1 arom. C); 138.08 (s, 1 arom. C); 171.35 (s, C(1)).
‡
FAB-MS: 518 (100, [M ‡ 1] ), 502 (11), 458 (9), 426 (13), 410 (8), 91 (39). Anal. calc. for C31H35NO6 (517.62):
C 71.93, H 6.82, N 2.71 found: C 71.67, H 6.99, N 2.49.
Methyl 2,N:4,8-Dianhydro-5,6,7-tri-O-benzyl-3,4,9-trideoxy-4-(hydroxyamino)-l-threo-d-gulo-nononate
(32): Colourless oil. M.p. 119 ± 1208. Rf (hexane/Et2O 1:1) 0.16. [a]2D5 ˆ 27.1 (c ˆ 1.00, CHCl3). IR (CHCl3):
3067w, 3008s, 2929s, 2856m, 1741s, 1602m, 1497m, 1454s, 1438m, 1352s, 1261m, 1152s, 1116s, 1058s, 1028s, 912w,
1
649w, 603w, 514w. H-NMR (300 MHz, C5D5Cl, 758): 1.54 (d, J ˆ 5.9, 3 H C(9)); 2.30 (ddd, J ˆ 6.2, 8.7, 12.8,
1 H C(3)); 2.52 (td, J ꢀ 8.7, 12.5, 1 H C(3)); 3.15 (dq, J ˆ 1.7, 5.9, H C(8)); 3.36 (s, MeO); 3.50 ± 3.57
(m, H C(7)); 3.56 (dd, J ˆ 2.8, 9.7, H C(6)); 3.81 (td, J ˆ 5.9, 8.2, H C(4)); 4.31 (t, J ꢀ 8.7, H C(2)); 4.44
(dd, J ˆ 5.9, 9.7, H C(5)); 4.50 (d, J ˆ 11.5, PhCH); 4.51 (d, J ˆ 11.8, PhCH); 4.53 (d, J ˆ 12.1, PhCH); 4.54
1
(d, J ˆ 12.1, PhCH); 4.57 (d, J ˆ 12.5, PhCH); 4.87 (d, J ˆ 11.2, PhCH); 7.06 ± 7.38 (m, 15 arom. H). H-NMR
(300 MHz, CDCl3): 1.23 (d, J ˆ 6.2, 3 H C(9)); 2.44 (td, J ˆ 9.0, 12.8, 1 H C(3)); 2.60 (ddd, J ˆ 6.8, 8.4, 13.1,
1 H C(3)); 2.86 ± 3.00 (m, H C(8)); 3.68 (dd, J ˆ 2.8, 9.7, H C(6)); 3.68 ± 3.76 (m, H C(7)); 3.73 (s, MeO);
3.80 ± 3.90 (m, H C(4)); 4.51 (t, J ꢀ 9.0, H C(2)); 4.42 ± 4.52 (m, H C(5)); 4.65 (d, J ˆ 11.5, PhCH); 4.70
(d, J ˆ 11.5, PhCH); 4.73 (d, J ˆ 11.8, PhCH); 4.74 (d, J ˆ 11.2, PhCH); 4.82 (d, J ˆ 11.8, PhCH); 4.92 (d, J ˆ
11.5, PhCH); 7.24 ± 7.39 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 15.29 (br. q, C(9)); 33.64 (t, C(3));
52.45 (q, MeO); 57.48, 64.31 (2d, C(4), C(8)); 73.16 (t, PhCH2); 73.78 (t, PhCH2); 75.04 (t, PhCH2); 75.77,
77.30, 77.59 (3d, C(5), C(6), C(7)); 80.30 (br. d, C(2)); 127.66 ± 128.77 (several d, 15 arom. C); 138.65
‡
‡
(s, 2 arom. C); 138.78 (s, 1 arom. C); 173.88 (s, C(1)). FAB-MS: 1035 (1, [2M ‡ 1] ), 518 (100, [M ‡ 1] ), 502
(3), 458 (7), 426 (13), 410 (9), 91 (33).
4-Amino-4,8-anhydro-5,6,7-tri-O-benzyl-3,4,9-trideoxy-l-threo-d-ido-nonono-1,4-lactam (33). A soln. of
31 (115 mg, 0.22 mmol) in AcOH (1.2 ml) was treated with Zn (110 mg, 1.68 mmol) at 218 and stirred at 608 for
4 h until complete conversion (TLC (hexane/AcOEt 1:2) control). Filtration, dilution with Et2O, usual work-up
(sat. aq. NaHCO3 soln., H2O), and FC (hexane/AcOEt 1:0 ! 1 : 2) gave 33 (84 mg, 78%). Colourless oil. Rf
(hexane/AcOEt 1 : 2, developed with mostain) 0.11. [a]D25
ˆ
58.9 (c ˆ 0.98, CHCl3). IR (CHCl3): 3470m,
3090m, 3067m, 3007m, 2961m, 2872m, 1952w, 1685s, 1497m, 1455s, 1439m, 1366m, 1287s, 1262s, 1169m, 1104s,
1028s, 910w, 865w, 818m, 640w, 602w, 575w, 540w, 530w, 516w, 504w. 1H-NMR (300 MHz, CDCl3): 1.39 (d, J ˆ
7.2, 3 H C(9)); 1.86 (td, J ꢀ 5.0, 13.4, 1 H C(3)); 2.32 (td, J ꢀ 8.1, 13.4, 1 H C(3)); 3.04 (d, J ˆ 7.5, addition of
D2O ! exchange, OH); 3.45 (dd, J ˆ 2.8, 3.4, H C(5)); 3.76 (dd, J ˆ 2.8, 6.5, H C(7)); 3.95 (t, J ꢀ 3.1,
H
H
C(6)); 4.07 (ddd, J ˆ 2.8, 5.0, 7.8, H C(4)); 4.21 (ddd, J ˆ 5.3, 7.5, 8.7, addition of D2O ! dd, J ˆ 5.0, 8.4,
C(2)); 4.36 (d, J ˆ 11.5, PhCH); 4.40 (d, J ˆ 12.8, PhCH); 4.44 (d, J ˆ 12.8, PhCH); 4.58 (d, J ˆ 11.8,
PhCH); 4.64 (quint., J ꢀ 6.8,
H
C(8)); 4.68 (d, J ˆ 12.1, PhCH); 4.86 (d, J ˆ 12.1, PhCH); 7.12 ± 7.16
(m, 2 arom. H); 7.26 ± 7.41 (m, 13 arom. H). 13C-NMR (75 MHz, CDCl3): 12.88 (q, C(9)); 28.62 (t, C(3));
45.64, 49.44 (2d, C(4), C(8)); 70.49 (d); 71.40 (t, PhCH2); 72.79 (t, PhCH2); 73.61 (d); 73.90 (t, PhCH2); 74.79
(d); 75.78 (d); 127.73 ± 128.96 (several d, 15 arom. C); 136.84 (s, 1 arom. C); 138.41 (s, 1 arom. C); 138.65

Helvetica Chimica Acta ± Vol. 82 (1999)
1061
‡
‡
(s, 1 arom. C); 173.56 (s, C(1)). FAB-MS: 975 (12, [2M ‡ 1] ), 488 (100, [M ‡ 1] ), 181 (7), 133 (12), 91 (96).
Anal. calc. for C30H33NO5 ´ 1.125 H2O (507.87): C 70.95, H 6.94, N 2.76; found: C 70.85, H 6.69, N 2.66.
4-Amino-4,8-anhydro-5,6,7-tri-O-benzyl-3,4,9-trideoxy-l-threo-d-gulo-nonono-1,4-lactam (34). The proce-
dure for the conversion of 31 to 33 was applied to 32 (69 mg, 0.13 mmol) in AcOH (0.7 ml) with Zn (70 mg,
1.1 mmol) to give 34 (51 mg, 78%). Colourless oil. Rf (hexane/AcOEt 1:2, developed with mostain) 0.11.
[a]2D5
ˆ
15.6 (c ˆ 0.94, CHCl3). IR (CHCl3): 3571m, 3369m, 3090w, 3067m, 3008m, 2961m, 2872m, 1952w,
1812w, 1681s, 1496m, 1455s, 1439m, 1367m, 1354m, 1289s, 1262s, 1100s, 1027s, 908m, 886m, 818m, 605m, 560w.
1H-NMR (300 MHz, CDCl3): 1.43 (d, J ˆ 7.2, 3 H C(9)); 1.94 (ddd, J ˆ 7.7, 9.3, 13.4, H C(3)); 2.15 (ddd, J ˆ
1.3, 9.0, 13.4, H C(3)); 2.94 (s, OH); 3.46 (dd, J ˆ 2.2, 3.7, H C(5)); 3.67 (dd, J ˆ 2.8, 6.5, H C(7)); 3.90
(t, J ꢀ 3.1, H C(6)); 4.13 (td, J ꢀ 1.8, 9.3, H C(4)); 4.31 (d, J ˆ 11.5, PhCH); 4.39 ± 4.45 (m, H C(2)); 4.43
(d, J ˆ 11.8, PhCH); 4.45 (d, J ˆ 11.8, PhCH); 4.50 (d, J ˆ 12.1, PhCH); 4.59 (quint., J ꢀ 6.9, H C(8)); 4.67
(d, J ˆ 11.8, PhCH); 4.86 (d, J ˆ 11.8, PhCH); 7.10 ± 7.14 (m, 2 arom. H); 7.22 ± 7.40 (m, 13 arom. H). 13C-NMR
(75 MHz, CDCl3): 12.47 (q, C(9)); 29.23 (t, C(3)); 45.64, 49.46 (2d, C(4), C(8)); 70.35 (d); 71.43 (t, PhCH2);
72.50 (t, PhCH2); 73.94 (t, PhCH2); 74.02 (d); 74.96 (d); 77.33 (d); 127.66 ± 128.85 (several d, 15 arom. C);
133.61 (s, 1 arom. C); 138.49 (s, 1 arom. C); 138.75 (s, 1 arom. C); 174.61 (s, C(1)). FAB-MS: 975 (2, [2M ‡
‡
‡
1] ), 488 (100, [M ‡ 1] ), 133 (18), 91 (23). Anal. calc. for C30H33NO5 ´ 0.5H2O (496.61): C 72.56, H 6.90,
N 2.82; found: C 72.63, H 6.92, N 2.75.
4-Amino-4,8-anhydro-2-O-benzoyl-5,6,7-tri-O-benzyl-3,4,9-trideoxy-l-threo-d-gulo-nonono-1,4-lactam
and Its Conversion to 34. A soln. of 33 (18 mg, 37 mmol) in anh. Et2O (0.15 ml) was treated with diethyl
diazenedicarboxylate (DEAD; 8.5 ml, 55.5 mmol), benzoic acid (7 mg, 55.5 mmol), and Ph3P (15 mg, 55.5 mmol)
and stirred for 18 h at 228. The mixture was filtered, diluted with Et2O and worked up as usual (H2O).
Preparative TLC (hexane/AcOEt 1 :2) gave the title compound (18 mg, 83%). Colourless oil. Rf (hexane/
AcOEt 1:2, developed with mostain) 0.46. IR (CHCl3): 3089w, 3067w, 3008m, 2942w, 2872w, 1694s, 1603w,
1586w, 1469w, 1453m, 1353m, 1353m, 1316m, 1296m, 1274s, 1116s, 1072s, 1027m, 904w, 868w, 818w, 603w, 572w,
524w, 513w, 502w. 1H-NMR (300 MHz, CDCl3): 1.48 (d, J ˆ 7.2, 3 H C(9)); 2.00 (ddd, J ˆ 7.7, 9.0, 13.4,
1 H C(3)); 2.45 (ddd, J ˆ 1.6, 9.0, 13.4, 1 H C(3)); 3.49 (dd, J ˆ 1.9, 3.4, H C(5)); 3.73 (dd, J ˆ 2.8, 6.2,
H
C(7)); 3.91 (t, J ꢀ 3.1, H C(6)); 4.20 (td, J ꢀ 1.9, 9.3, H C(4)); 4.38 (d, J ˆ 11.8, PhCH); 4.45 (d, J ˆ 11.5,
PhCH); 4.49 (d, J ˆ 12.5, PhCH); 4.57 (d, J ˆ 12.1, PhCH); 4.68 (d, J ˆ 11.8, PhCH); 4.70 (quint., J ꢀ 6.9,
H
C(8)); 4.87 (d, J ˆ 11.8, PhCH); 5.61 (dd, J ˆ 7.5, 9.0, H C(2)); 7.19 ± 7.22 (dd, J ˆ 1.6, 6.9, 2 arom. H);
7.26 ± 7.40 (m, 15 arom. H); 7.56 (tt, J ꢀ 1.3, 7.2, 1 arom. H); 8.08 (dd, J ˆ 1.6, 6.9, 2 arom. H). 13C-NMR
(75 MHz, CDCl3): 12.48 (q, C(9)); 28.92 (t, C(3)); 45.48, 49.11 (2d, C(4), C(8)); 70.98 (d); 71.90 (t, PhCH2);
72.05 (t, PhCH2)); 73.42 (t, PhCH2)); 73.45 (d); 74.28 (d); 76.64 (d); 127.66 ± 128.85 (several d, 20 arom. C);
132.78 (s, 1 arom. C); 137.34 (s, 1 arom. C); 138.06 (s, 1 arom. C); 138.24 (s, 1 arom. C); 169.42 (s, 1 CˆO);
‡
173.41 (s, C(1)). FAB-MS: 592 ([M ‡ 1] , 100), 281 (5), 207 (5), 147 (13), 136 (7), 104 (31).
A soln. of the 2-O-benzoyl derivative (see above) (10 mg, 17 mmol) in a 1% soln. of NaOMe in MeOH
(1 ml) was stirred for 2 h at 228. After addition of sat. aq. NH4Cl soln. and extraction with Et2O, the combined
org. layers were worked up in the usual way (brine). Prep. TLC (hexane/AcOEt 1:3) gave 34 (7 mg, 85%).
Colourless oil.
4-Amino-4,8-anhydro-3,4,9-trideoxy-l-threo-d-ido-nonono-1,4-lactam (35). A suspension of 33 (32 mg,
65.7 mmol) and 20% Pd(OH)2/C on charcoal (16 mg) in AcOH/MeOH 1:1 (1 ml) was hydrogenated at 6 bar for
2 d. Filtration through Celite, evaporation, FC (AcOEt/MeOH/H2O 20 :5 :2), and lyophilization yielded 35
(12 mg, 84%). Colourless amorphous solid. Rf (AcOEt/MeOH/H2O 13 :5 :2, developed with mostain) 0.63.
[a]2D5
ˆ
31.2 (c ˆ 0.7, MeOH). IR (KBr): 3371m (br.), 3009m, 2975m, 2932s, 1668s, 1455s, 1442m, 1384w,
1366w, 1355w, 1320w, 1301m, 1276m, 1112m, 1093m, 1066m, 1042m, 1030s, 994w, 958w, 886w, 868w, 827w, 771w,
742w, 682s, 668w, 527w, 544w, 440w, 414w. 1H-NMR (300 MHz, CD3OD): 1.26 (d, J ˆ 7.2, 3 H C(9)); 1.87
(td, J ꢀ 7.5, 13.1, 1 H C(3)); 2.36 (ddd, J ˆ 7.2, 8.7, 13.1, 1 H C(3)); 3.69 (dd, J ˆ 2.5, 3.7, H C(5)); 3.90
(dd, J ˆ 3.1, 6.9, H C(7)); 3.86 (t, J ꢀ 3.1, irrad. at 3.69 ! d, J ˆ 3.1, H C(6)); 3.97 (dt, J ꢀ 2.2, 7.2, irrad. at
3.69 ! t, J ꢀ 7.5, H C(4)); 4.22 (quint. J ꢀ 7.2, irrad. at 1.26 ! d, J ˆ 6.9, H C(8)); 4.26 (dd, J ˆ 7.5, 8.4,
H
C(2)). 13C-NMR (75 MHz, CD3OD): 13.11 (q, C(9)); 29.50 (t, C(3)); 49.65, 49.82 (2d, C(4), C(8)); 66.16
‡
(d); 70.72 (d); 71.80 (d); 74.43 (d, C(2)); 176.26 (s, C(1)). CI-MS (MeOH): 218 (2, [M ‡ 1] ), 217 (1), 145 (2),
127 (1), 110 (1), 100 (1), 100 (2), 45 (18), 43 (38), 33 (24), 32 (47), 31 (100), 29 (45), 28 (24).
4-Amino-4,8-anhydro-3,4,9-trideoxy-l-threo-d-gulo-nonono-1,4-lactam (36). A suspension of 34 (18 mg,
37 mmol) and 20% Pd(OH)2/C (9 mg) in MeOH (1 ml) was hydrogenated at 6 bar for 24 h at 228. Filtration
through Celite, evaporation, FC (AcOEt/MeOH/H2O 20 :5 :2), and lyophilization yielded 36 (7 mg, 87%).
Colourless amorphous solid. Rf (AcOEt/MeOH/H2O 13 :5 :2). [a]2D5 ˆ 14.0 (c ˆ 0.5, MeOH). 0.57. IR (KBr):
3389s, 2926m, 1669m, 1573m, 1441s, 1297m, 1277m, 1245w, 1199w, 1129w, 1076m, 1045m, 989w, 908w, 872w,

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Helvetica Chimica Acta ± Vol. 82 (1999)
661w, 618w. 1H-NMR (300 MHz, CD3OD): 1.30 (d, J ˆ 7.2, 3 H C(9)); 1.87 (ddd, J ˆ 7.2, 9.3, 13.4, 1 H C(3));
2.36 (ddd, J ˆ 1.9, 8.7, 13.4, 1 H C(3)); 3.70 (dd, J ˆ 1.9, 3.7, H C(5)); 3.72 (dd, J ˆ 3.4, 6.5, H C(7)); 3.86
(t, J ꢀ 3.4, H C(6)); 4.09 (td, J ꢀ 1.9, 9.3, H C(4)); 4.22 (quint., J ꢀ 6.9, H C(8)); 4.40 (dd, J ˆ 7.5, 8.7,
H
C(2)). 13C-NMR (75 MHz, CD3OD): 12.95 (q, C(9)); 30.94 (t, C(3)); 49.65, 50.62 (2d, C(4), C(8)); 66.28
‡
(d); 71.69 (d); 72.84 (d); 74.50 (d, C(2)); 176.49 (s, C(1)). CI-MS (MeOH): 218 (100, [M ‡ 1] ), 217 (15), 200
(14), 145 (50), 127 (19), 100 (26), 44 (23), 33 (27), 32 (47), 29 (36), 28 (31). CI-MS: 218 (100, [M ‡ 1]), 199
(14), 145 (50), 128 (13), 127 (19), 110 (11), 100 (26), 72 (12), 70 (13), 44 (23), 31 (92).
1-Amino-1,4:4,8-dianhydro-5,6,7-tri-O-benzyl-1,3,9-trideoxy-l-threo-d-ido-nonitol (37).
A soln. of 33
(157 mg, 0.32 mmol) in H2O-free THF (1.0 ml) was treated with a 1m soln. of BH3 in THF (0.87 ml, 2.7 equiv.)
at 08. The resulting soln. was heated during 3 h to 608. After cooling to 238, MeOH (1 ml) was added, followed by
1n HCl in Et2O (0.17 ml). The resulting mixture was evaporated in vacuo at 238, the residue treated again with
MeOH (1 ml) and 1n HCl in Et2O (0.17 ml) and evaporated. After addition of Et2O, the residue was worked up
in the usual way (sat aq. NaHCO3 soln., brine). FC (AcOEt) gave 37 (113 mg, 74%). Colourless oil. Rf (AcOEt)
0.10. [a]2D5
ˆ
22.1 (c ˆ 1.1, CHCl3). IR (CHCl3): 3458w, 3089w, 3066m, 3007s, 2940s, 2870s, 2975m, 1951w,
1876w, 1811w, 1723w, 1605w, 1586w, 1496m, 1454s, 1402m, 1370m, 1310m, 1248m, 1159s, 1096s, 1066s, 1028s,
996m, 912m, 818w, 598m, 523w. 1H-NMR (300 MHz, CDCl3): 1.19 (d, J ˆ 6.5, 3 H C(9)); 1.67 (br. dd, J ˆ 6.9,
13.7, irrad. at 3.16 ! br. d, J ˆ 13.7, 1 H C(3)); 2.06 (ddd, J ˆ 6.2, 8.7, 13.7, irrad. at 3.16 ! dd, J ˆ 6.5, 13.7,
1 H C(3)); 2.60 (br. s, OH); 2.73 ± 2.81 (m, 2 H C(1)); 3.16 (ddd, J ˆ 1.9, 6.8, 8.7, irrad. at 3.43 ! change,
H
C(4)); 3.43 (dd, J ˆ 2.2, 3.1, irrad. at 3.16 ! d, J ˆ 3.1, H C(5)); 3.55 (quint., J ꢀ 6.5, irrad. at 1.19 ! d, J ˆ
5.7, H C(8)); 3.87 (t, J ꢀ 3.1, irrad. at 3.43 ! d, J ˆ 3.1, H C(6)); 3.94 (dd, J ˆ 3.1, 5.9, H C(7)); 4.10 ± 4.20
(br. s, irrad. at 2.78 ! d, J ˆ 5.6, H C(2)); 4.42 (d, J ˆ 11.8, PhCH); 4.49 (d, J ˆ 12.1, 2 PhCH); 4.54 (d, J ˆ 12.1,
PhCH); 4.63 (d, J ˆ 12.1, PhCH); 4.79 (d, J ˆ 12.1, PhCH); 7.22 ± 7.37 (m, 15 arom. H). 13C-NMR (75 MHz,
CDCl3): 6.67 (q, C(9)); 35.24 (t, C(3)); 51.32 (d); 52.41 (d, C(4), C(8)); 58.65 (t, C(1)); 70.25 (d); 71.04
(t, PhCH2); 72.85 (t, PhCH2); 73.43 (t, PhCH2); 75.31 (d); 75.75 (d); 76.22 (d); 127.47 ± 128.56 (several d,
‡
15 arom. C); 137.97 (s, 1 arom. C); 138.93 (s, 1 arom. C); 139.05 (s, 1 arom. C). FAB-MS: 474 (100, [M ‡ 1] ),
382 (29), 327 (11), 325 (13), 281 (13), 207 (13), 147 (17), 134 (13), 91 (35).
1-Amino-1,4:4,8-dianhydro-5,6,7-tri-O-benzyl-1,3,9-trideoxy-l-threo-d-gulo-nonitol (38). The procedure
for the conversion of 33 to 37 was applied to 34 (82 mg, 0.17 mmol) in H2O-free THF (0.6 ml) with a 1m soln. of
BH3 in THF (0.45 ml, 0.45 mmol) to give 38 (73 mg, 85%). Colourless oil. Rf (AcOEt) 0.10. [a]D25
ˆ
3.6 (c ˆ 1.1,
CHCl3). IR (CHCl3): 3608w, 3441w, 3088w, 3066m, 3008s, 2962s, 2866m, 1951w, 1875w, 1811w, 1722w, 1605w,
1496m, 1454s, 1398m, 1361m, 1311m, 1261s, 1159s, 1098s, 1028s, 915m, 865m, 818s, 598m, 509w. 1H-NMR
(300 MHz, CDCl3): 1.23 (d, J ˆ 6.8, irrad. at 3.45 ! s, 3 H C(9)); 1.46 (ddd, J ˆ 1.9, 6.9, 13.1, irrad. at 4.50 !
dd, J ˆ 6.9, 13.1, irrad. at 3.30 ! dd, J ˆ 1.9, 13.0, H C(3)); 1.98 (br. s, OH); 2.14 (ddd, J ˆ 7.8, 8.1, 13.0, irrad. at
4.50 ! dd, J ˆ 8.1, 13.1, irrad. at 3.30 ! dd, J ˆ 7.8, 13.0, H C(3)); 2.59 (dd, J ˆ 4.7, 9.6, irrad. at 4.50 ! d, J ˆ
9.3, irrad. at 3.30 ! d, J ˆ 5.3, 1 H C(1)); 3.30 (dd, J ˆ 6.2, 9.6, irrad. at 4.50 ! d, J ˆ 9.6, irrad. at 2.59 ! d, J ˆ
5.9, 1 H C(1)); 3.27 ± 3-32 (m, irrad. at 3.45 ! change, H C(4)); 3.34 ± 3.49 (m, irrad. at 1.23 ! change, irrad.
at 3.87 ! change, irrad. at 3.30 ! change, H C(5), H C(8)); 3.77 (t, J ꢀ 3.1, irrad. at 3.45 ! d, J ˆ 3.1, irrad. at
3.87 ! d, J ˆ 2.7, H C(6)); 3.87 (dd, J ˆ 3.1, 5.3, irrad. at 3.45 ! d, J ˆ 2.9, H C(7)); 4.39 (d, J ˆ 12.1, PhCH);
4.43 (d, J ˆ 11.8, PhCH); 4.44 ± 4-53 (m, irrad. at 2.59 ! change, irrad. at 3.30 ! change, H C(2)); 4.50 (d, J ˆ
11.7, PhCH); 4.52 (d, J ˆ 11.6, PhCH); 4.62 (d, J ˆ 12.1, PhCH); 4.74 (d, J ˆ 12.2, PhCH); 7.21 ± 7.38
(m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 14.85 (q, C(9)); 35.13 (t, C(3)); 51.55 (d), 52.33 (d, C(4),
C(8)); 58.54 (t, C(1)); 70.06 (d); 71.00 (t, PhCH2); 72.89 (t, PhCH2); 73.17 (t, PhCH2); 75.04 (d); 75.45 (d); 76.35
(d); 127.39 ± 129.53 (several d, 15 arom. C); 137.97 (s, 1 arom. C); 138.79 (s, 1 arom. C); 138.97 (s, 1 arom. C).
‡
FAB-MS: 474 (100, [M ‡ 1] ), 382 (40), 366 (14), 281 (6), 221 (6), 207 (6), 147 (8), 91 (62).
1-Amino-1,4:4,8-dianhydro-1,3,9-trideoxy-l-threo-d-ido-nonitol (39). A suspension of 37 (54 mg, 0.11 mmol)
and 10% Pd/C (54 mg) in MeOH (1.5 ml) was hydrogenated at 6 bar for 24 h at 228. Filtration through Celite and
‡
evaporation yielded crude 39 ´ HCl. Purification by ion-exchange chromatography (Amberlite CG-120, NH4
form, eluted with H2O ! 0.1m aq. NH3) and lyophilization yielded 39 (18 mg, 78%). Colourless hygroscopic
amorphous solid. Rf (AcOEt/MeOH/2m aq. NH3 6 : 3 : 1): 0.15. [a]D25
3450s, 3342s, 2944s, 2870m, 1636w, 1462m, 1428s, 1407m, 1386m, 1333m, 1303m, 1281m, 1259m, 1224w, 1191w,
1147s, 1100s, 1083s, 1008s, 973m, 932s, 882w, 852w, 836w, 748w, 712w, 645w, 516m. H-NMR (300 MHz, D2O):
ˆ
23.0 (c ˆ 0.1, MeOH). IR (KBr):
1
1.14 (d, J ˆ 6.5, 3 H C(9)); 1.72 (dt, J ꢀ 4.7, 13.1, H C(3)); 2.31 (td, J ꢀ 7.4, 13.6, H C(3)); 2.91 (dd, J ꢀ 6.2,
13.3, 1 H C(1)); 3.01 (br. d, J ꢀ 13.1, 1 H C(1)); 3.12 (dq, J ˆ 1.9, 6.8, H C(8)); 3.22 (td, J ꢀ 5.9, 12.4,
H
C(4)); 3.84 ± 3.88 (m, H C(6), H C(7)); 4.07 (dd, J ˆ 5.6, 7.5, H C(5)); 4.45 ± 4.66 (m, H C(2)).
13C-NMR (75 MHz, D2O): 15.60 (q, C(9)); 35.86 (t, C(3)); 56.29, 63.44 (d, C(4), C(8)); 60.93 (t, C(1)); 70.72

Helvetica Chimica Acta ± Vol. 82 (1999)
1063
‡
‡
(d); 73.58 (d); 73.77 (d); 74.60 (d). CI-MS: 204 (77, [M ‡ 1] ), 188 (100, [M Me] ), 186 (56), 132 (26), 131
‡
(46), 130 (27), 112 (20), 94 (22), 86 (96), 68 (26). HR-FAB-MS: 204.1238 ([M ‡ 1] ; calc. 204.1236).
1-Amino-1,4:4,8-dianhydro-1,3,9-trideoxy-l-threo-d-gulo-nonitol (40). The procedure for the conversion of
37 to 39 was applied to 37 (38 mg, 0.08 mmol) in MeOH (0.8 ml) with 10% Pd/C (38 mg). Purification by ion-
‡
exchange chromatography (Amberlite CG-120, NH4 form, eluted with H2O ! 0.1m aq. NH3) and lyophilization
yielded 40 (12 mg, 75%). Colourless hygroscopic amorphous solid. Rf (AcOEt/MeOH/2m aq. NH3 7: 2 : 1): 0.17.
[a]2D5
ˆ
25.2 (c ˆ 0.4, MeOH). IR (KBr): 3458w, 3089w, 3066m, 3007s, 2940s, 2870s, 2795m, 1951w, 1876w,
1811w, 1723w, 1605w, 1586w, 1496m, 1454s, 1402m, 1370m, 1310m, 1248m, 1159s, 1096s, 1066s, 1028s, 996m,
912m, 818w, 598m, 523w. 1H-NMR (300 MHz, D2O): 1.18 (d, J ˆ 6.5, 3 H C(9)); 1.83 (br. dd, J ꢀ 6.5, 14.0,
1 H C(3)); 2.16 (ddd, J ˆ 7.2, 12.1, 14.0, 1 H C(3)); 2.85 (dd, J ˆ 4.7, 12.7, 1 H C(1)); 3.00 (dq, J ˆ 2.5, 6.5,
H
C(8)); 3.51 (dd, J ˆ 6.5, 12.7, 1 H C(1)); 3.70 (td, J ꢀ 5.9, 12.1, H C(4)); 3.77 (dd, J ˆ 3.1, 8.1, H C(6));
3.84 (t, J ꢀ 2.7, H C(7)); 4.09 (dd, J ˆ 5.3, 8.1, H C(5)); 4.54 (br. q, J ꢀ 6.0, H C(2)). 13C-NMR (75 MHz,
D2O): 15.18 (q, C(9)); 35.45 (t, C(3)); 58.02, 62.80 (d,C(4), C(8)); 61.69 (t, C(1)); 69.96 (d); 70.86 (d); 73.00
‡
‡
(d); 73.35 (d). CI-MS: 204 (89, [M ‡ 1] ), 188 (100, [M Me] ), 186 (58), 147 (24), 132 (24), 86 (80), 68 (21),
31 (75). Anal. calc. for C9H17NO4 ´ 0.6H2O (214.05): C 50.50, H 8.57, N 6.54; found: C 50.29, H 8.41, N 6.41.
5-Amino-2,3,4-tri-O-benzyl-5,6-dideoxy-l-galactonothio-1,5-lactam (41). A soln. of 1 (150 mg, 0.35 mmol)
in toluene/pyridine 1 :1 (3 ml) was treated with 1,1'-carbonothioyl[1H-1,2,4-triazole] (73 mg, 0.41 mmol) and
stirred for 13 h at 238. Addition of CH2Cl2, usual workup (sat. NH4Cl soln., H2O), and FC (hexane/AcOEt
1:0 ! 1 : 1) gave 41 (130 mg, 84%). Colourless oil. Rf (hexane/AcOEt 1 : 1, developed with mostain) 0.68. IR
(CHCl3): 3360m, 3066m, 3008m, 2962s, 2857m, 1715m, 1674m, 1574w, 1513m, 1498m, 1454m, 1415m, 1356m,
1308m, 1262s, 1098s, 1014s, 910m, 864m, 599w, 580w, 572w, 544w, 529w, 514m, 503m. 1H-NMR (300 MHz,
CDCl3): 1.27 (d, J ˆ 6.5, 3 H C(6)); 3.57 (dq, J ˆ 2.5, 6.5, H C(5)); 3.81 (dd, J ˆ 2.2, 8.4, H C(3)); 3.82 ± 3.92
(m, H C(4)); 4.47 (d, J ˆ 8.4, H C(2)); 4.64 (d, J ˆ 11.5, PhCH); 4.65 (d, J ˆ 12.1, PhCH); 4.76 (d, J ˆ 11.8,
PhCH); 4.85 (d, J ˆ 10.3, PhCH); 4.92 (d, J ˆ 11.5, PhCH); 5.40 (d, J ˆ 10.6, PhCH); 7.26 ± 7.48 (m, 15 ar-
om. H); 7.81 (br. s, NH). 13C-NMR (75 MHz, CDCl3): 17.04 (q, C(6)); 54.14 (d, C(5)); 74.10 (t, PhCH2); 75.00
(t, PhCH2); 76.23 (d, C(2)); 76.82 (t, PhCH2); 80.39 (d); 81.43 (d); 127.83 ± 128.96 (several d, 15 arom. C);
138.24 (s, 1 arom. C); 138.42 (s, 1 arom. C); 138.45 (s, 1 arom. C); 202.34 (s, C(1)). FAB-MS: 448 (100, [M ‡
‡
1] ), 446 (21), 147 (15), 136 (11), 91 (64), 73 (32).
(5S,6R,7R,8R)-6,7,8-Tris(benzyloxy)-5,6,7,8-tetrahydro-5-methylimidazo[1,2-a]pyridine (43). A soln. of 41
(68 mg, 0.15 mmol) in anh. THF (8.5 ml) was treated with Hg(OAc)2 (73 mg, 0.23 mmol) and then dropwise
with aminoacetaldehyde dimethyl acetal (80 ml, 0.75 mmol) at 08. The soln., which slowly turned black, was
stirred for 3.5 h at 08. After dilution with CH2Cl2, usual workup (sat. NH4Cl soln., H2O), filtration through
Celite, and evaporation gave a residue which was dissolved in toluene (4.4 ml) and H2O (0.4 ml), treated with
TsOH ´ H2O (77 mg, 0.40 mmol) and stirred at 708 for 19.5 h. Dilution with CH2Cl2, work-up in the usual way
(H2O), evaporation, and FC (alumina, act. grade I, hexane/AcOEt 1 : 0 ! 1 : 2) gave 43 (52 mg, 75%).
Colourless oil. Rf (hexane/AcOEt 1 : 1, developed with mostain) 0.22. [a]D25
ˆ
29.0 (c ˆ 1.1, CHCl3). IR
(CHCl3): 3090w, 3067w, 3008s, 2929m, 2859m, 1953w, 1810w, 1671m, 1602m, 1520w, 1496s, 1485s, 1454s, 1380m,
1
1355s, 1296s, 1262s, 1090s, 1071s, 1028s, 910w, 820w, 601w, 530w. H-NMR (300 MHz, CDCl3): 1.56 (d, J ˆ 6.8,
Me); 4.08 (dd, J ˆ 1.9, 5.6, H C(7)); 4.16 (dd, J ˆ 1.9, 4.7, H C(6)); 3.86 (dq, J ˆ 4.7, 6.9, H C(5)); 4.64
(d, J ˆ 11.5, PhCH); 4.70 (d, J ˆ 12.1, PhCH); 4.76 (d, J ˆ 12.1, PhCH); 4.79 (d, J ˆ 11.8, PhCH); 4.82 (d, J ˆ
11.8, PhCH); 4.88 (d, J ˆ 5.6, H C(8)); 5.10 (d, J ˆ 11.8, PhCH); 6.88 (d, J ˆ 1.2), 7.11 (d, J ˆ 0.9, H C(2),
H
C(3)); 7.25 ± 7.38 (m, 15 arom. H). 13C-NMR (75 MHz, CDCl3): 17.86 (q, Me); 52.91 (d, C(5)); 72.69
(t, PhCH2); 73.06 (d); 73.11 (t, 2 PhCH2); 75.26 (d); 79.65 (d); 117.29 (d, C(3)); 129.77 (d, C(2)); 127.74 ± 128.93
(9d, 15 arom. C); 138.23 (s, 1 arom. C); 138.45 (s, 1 arom. C); 138.71 (s, 1 arom. C); 143.73 (s, C(8a)). FAB-
‡
MS: 455 (100, [M ‡ 1] ), 347 (10), 901 (11). Anal. calc. for C29H30N2O3 (454.57): C 76.63, H 6.65, N 6.16;
found: C 76.51, H 6.78, N 6.00.
(5S,6R,7R,8R)-5,6,7,8-Tetrahydro-5-methylimidazo[1,2-a]pyridine-6,7,8-triol (44). A soln. of 43 (65 mg,
0.14 mmol) in AcOEt/MeOH/H2O 5 :17:3 (4 ml) was treated with AcOH (1.7 ml) and 10% Pd(OH)2/C (65 mg)
and hydrogenated at 6 bar for 18 h at 228. Filtration through Celite, evaporation, FC (MeCN/H2O 1 :0 ! 7: 3),
and lyophilization gave 44 (20 mg, 76%). Colourless amorphous solid. Rf (MeCN/H2O 7: 3, developed with
mostain) 0.25. [a]D25
ˆ
14.3 (c ˆ 0.5, MeOH). IR (KBr): 3417m (br.), 2926s, 1622m, 1455s, 1261m, 1098s, 937w,
1
751m, 545m. H-NMR (300 MHz, D2O): 1.53 (d, J ˆ 6.5, Me); 3.96 (dd, J ˆ 2.2, 9.0, H C(7)); 4.19 (t, J ꢀ 2.2,
H
C(6)); 4.35 (dq, J ˆ 2.2, 6.5, H C(5)); 4.82 (d, J ˆ 9.0, H C(8)); 7.20, 7.24 (2s, H C(2), H C(3)).
13C-NMR (75 MHz, D2O): 15.36 (q, Me); 53.58 (d, C(5)); 66.62 (d, C(8)); 72.40 (d); 73.77 (d); 118.05 (d, C(3));
‡
127.76 (d, C(2)); 145.93 (s, C(8a)). CI-MS (MeOH): 185 (100, [M ‡ 1] ), 158 (69), 151 (67), 149 (62), 135

1064
Helvetica Chimica Acta ± Vol. 82 (1999)
(52), 132 (58), 97 (49), 69 (53), 44 (52). Anal. calc. for C8H12N2O3 ´ 0.5H2O (193.20): C 49.73, H 6.78, N 14.49;
found: C 50.01, H 7.01, N 13.23.
Inhibition of a-l-Fucosidase from Bovine Epidydimis. Determination of the IC50 was performed at 258 using
400 ml of a trisodium citrate buffer (pH 5.5), which contained the following assay components: 4-nitrophenyl a-
l-fucopyranoside (0.75 mm) as substrate, and the inhibitor in different concentrations which bracket the IC50
value. Measurements were started by addition of 200 ml of an aq. soln. of a-l-fucosidase (5 mg/ml). The reaction
was stopped after 10 min by addition of 400 ml of glycine buffer (pH 10) and the absorption was measured at
400 nm.
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Received April 1, 1999