Studies on the synthesis of di- and trisaccharide analogues of moenomycin A. Modifications in unit E and in the lipid part

Article abstract of DOI:10.1002/hlca.200490161

Routes allowing the synthesis of moenomycin analogues with one modified sugar component and with new lipid parts were developed (see 10c, 12c, 16b, and 20b in Schemes 2-4). It is anticipated that such analogues will be useful for studying the mode of action of the moenomycin-type transglycosylase inhibitors in detail and for preparing analogues with improved pharmacokinetic properties.

Full text of DOI:10.1002/hlca.200490161

Helvetica Chimica Acta Vol. 87 (2004)
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Studies on the Synthesis of Di- and Trisaccharide Analogues of
Moenomycin A. Modifications in Unit E and in the Lipid Part
by Guangbin Yang, Madina Mansourova, Lothar Hennig, Matthias Findeisen, Ramona Oehme, Sabine Giesa,
and Peter Welzel*
Universit‰t Leipzig, Fakult‰t f¸r Chemie und Mineralogie, Johannisallee 29, D-04103 Leipzig
(fax: ‡‡ 49341 9736599; e-mail: welzel@chemie.uni-leipzig.de)
Routes allowing the synthesis of moenomycin analogues with one modified sugar component and with new
lipid parts were developed (see 10c, 12c, 16b, and 20b in Schemes 2 4). It is anticipated that such analogues will
be useful for studying the mode of action of the moenomycin-type transglycosylase inhibitors in detail and for
preparing analogues with improved pharmacokinetic properties.
Introduction. The objectives of the studies described in this and the preceding
communication [1] were twofold, i.e., to prepare oligosaccharide analogues of
moenomycin A with new lipid chains and to develop routes to oligosaccharide
(preferably trisaccharide) analogues of moenomycin A (1) containing a substituent at
C(6) of unit E (see formula 2) with orthogonal reactivity to all other functional groups
present in the molecule.
According to structure-activity-relationship (SAR) studies [2], the antibiotic
activity of the moenomycins relies on two features, i) anchoring of the antibiotics to the
cytoplasmic membrane via the lipid part and ii) highly selective binding via the C E F
trisaccharide part1) (see 1 and 2) to the glycosyl donor binding site of the enzyme that is
responsible for the formation of the sugar strands in peptidoglycan biosynthesis2).
Although membrane anchoring of the moenomycins [3] is essential for antibiotic
activity to be exposed, the structural features of the lipid part that are mandatory to
assist the proper interaction of the antibiotic with the membrane-bound enzyme are
largely unexplored. With one exception, namely hydrogenation, all modifications of the
lipid part of moenomycin caused a dramatic loss of antibiotic activity [3][4]. The
prerequisite for the chemical synthesis of lipid-modified moenomycin analogues, i.e.,
sufficiently convenient access to 2-O-alkylated glyceric acid building blocks, has been
satisfied only recently [5]. The second objective is based on the SAR result that the 6-
OH groups of units C and E are dispensable as far as antibiotic activity is concerned
(see dotted arrows in 2) [2]. Thus, moenomycin analogues with suitable substituents at
the 6-position of unit C and/or unit E should allow the study of the mode of action of
the moenomycin-type transglycosylase inhibitors in more detail [6] and the preparation
of analogues with improved pharmacokinetics.
1
)
)
The different building blocks of the compounds discussed in this paper are indexed exactly as in
moenomycin (1).
For a discussion of the SARs and the proposed mode of action, see preceding communication [1].
2

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Helvetica Chimica Acta Vol. 87 (2004)
Results.
Synthesis of the Carbohydrate Part of a Moenomycin Trisaccharide
Analogue. Koeller and Wong [7] have reported that coupling of 2,3,4,6-tetra-O-acetyl-
a-d-galactopyranosyl trichloroacetimidate (3a) with (tert-butyl)dimethylsilyl 6-O-
[(tert-butyl)diphenylsilyl]-2-deoxy-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-d-glu-
copyranoside (4) in CH2Cl2 solution with Me3SiOTf as promoter afforded the 1 ! 4-
linked disaccharide (50%, after deacetylation) (Troc ˆ (2,2,2-trichloroethoxy)carbon-
yl). The 1 ! 3-linked disaccharide was only a minor product (8%). When we treated
the related d-gluco-configurated donor 3b with the same acceptor 4 in CH2Cl2 using
Me3SiOTf as promoter, the 1 ! 3-linked disaccharide 5a was obtained as the main
product (76%) accompanied by small amounts of trisaccharide 5b (8%) (Scheme 1)3).
The desired 1 ! 4 disaccharide was not detected. When the reaction was performed in
Et2O solution, disaccharide 5a (46%) and trisaccharide 5b (29%) were obtained. The
structure of 5a was confirmed by analyzing the NMR spectra of 5c, which was obtained
from 5a by acetylation.
3
)
For a discussion of the influence of the configuration at C(4) on substiution reactions at the anomeric
center, see [8].

Helvetica Chimica Acta Vol. 87 (2004)
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Scheme 1
a) 3b ‡ 4, 4-ä molecular sieves, CH2Cl2, Me3SiOTf, 08; 76% of 5a, 8% of 5b. b) Conditions a, Et2O instead of
CH2Cl2; 46% of 5a, 29 % of 5b. c) Ac2O, pyridine, 208; 87%.
In view of the above results, we based our further synthetic efforts on to the C E F
trisaccharide precursor 6a of moenomycin analogues, the synthesis of which was
discussed in the preceding communication [1]. As described, removal of the N-
phthaloyl (PhthN) protecting group in the aminosugar moieties in later stages of the
trisaccharide synthesis turned out to be incompatible with the urethane function at
C(3) of unit F. Thus, in a new attempt, we replaced the N-phthaloyl groups in an early
phase of the synthesis by N-(2,2,2-trichloroethoxy)carbonyl (TrocN) groups, which we
expected to be easily convertible to N-Ac groups under mild conditions [9a] (see also
[9b]). To this end, 6a was treated with ethane-1,2-diamine in BuOH (Scheme 2).
Subsequent N-(trichloroethoxy)carbonylation followed by reacetylation furnished 6b.
Selective desilylation at the anomeric position with I2/MeOH [10], CF3COOH [11],
AcOH [11], KF [12] or Bu4NF [11] failed [13]. Fortunately, selective removal of the
tBuMe2Si group with [PdCl2(MeCN)2], a reagent known to leave tBuPh2Si ethers intact
1
[14], yielded compound 6c (55%). The H- and 13C-NMR spectra of the desilylation
product (HÀC(1E) at d ˆ 5.29, J(1E,2E) ˆ 3.6 Hz; C(1E) at d 92.22) indicated the
presence of only the a-d-anomer. Treatment of 6c with Cl3CCN and Cs2CO3 furnished
the disaccharide donor 6d (88%) which was coupled with the ring-F acceptor building
block 7, which is more reactive than previously employed ring-F acceptor units [1].
When the reaction was performed in ClCH2CH2Cl solution with Me3SiOTf as
promotor, trisaccharide 8a was obtained in 55% yield. Performing the reaction in
other solvents (MeCN, CH2Cl2, THF, and Et2O) resulted in lower yields [13].
Conversion of the TrocNH groups in 8a to AcNH functions was achieved on
reaction with activated Zn dust [7] or with ZnÀCu complex [15] in Ac2O and furnished
compound 8b in 63% yield. Treatment of 8b with saturated NH3 in THF/MeOH 9:1
opened the lactone ring to give uronamide 9a (81%). The carbamoyl group was then
introduced on reaction of the free OH group with trichloroacetyl isocyanate and
subsequent reductive removal of the trichloroacetyl group from the trichloroacetyl
urethane to give compound 9b [16]. By means of the Nakayama method [17], the two
allyl groups of 9b were removed with [Pd(PPh3)4] in degassed AcOH to furnish
1
compound 10a (94%). The H- and 13C-NMR spectra of 10a (HÀC(1F) at d 6.05,
J(1F,2F) ˆ 2.9Hz; C(1 F) at d 93.77) indicated that the anomeric equilibrium was

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 2
a) 1. BuOH, H2N(CH2)2NH2, 9 80; 2. TrocCl, MeOH/H2O, 208; 3. Ac2O, pyridine, 208; 77%. b)
[PdCl2(MeCN)2], Me2CO, 208; 55%. c) Cl3CCN, 4-ä molecular sieves, CH2Cl2, Cs2CO3, 208, 88%. d) 6d ‡
7, 4-ä molecular sieves, (ClCH2)2, Me3SiOTf, À308; 55%. e) Zn, Ac2O, 208; 63%. f) 8b, NH3, THF/MeOH, 08;
81% of 9a. g) 1. Cl3CONCO, CH2Cl2, 208; 2. Zn, Me3OH, 208; 96% of 9b. h) 9b, [Pd(PPh3)4], AcOH, 208; 9 4%
of 10a. i) Ac2O, pyridine, 208; 93% of 10b. j) H2NNH2 ¥ AcOH, DMF, 208; 67% of 10c. k) 9b, Bu4NF, THF, 208;
15% of 11a; or 9a, Bu4NF, THF, 208; 64% of 11d. l) TsCl, pyridine, DMAP, 208; 15% of 11b. m) TsCl, CH2Cl2/
pyridine, DMAP, 208; 40% of 11e. n) Conditions g; 48% of 11b. o) NaN3, DMF, 858; 34% of 11c. p) 8b,
conditions k; 43% of 12a. q) Conditions l; 52% of 12b. r) Conditions o; 14% of 12c.

Helvetica Chimica Acta Vol. 87 (2004)
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practically exclusively in favor of the a-d isomer. For the construction of the phosphoric
acid diester, the 4F-OH group had to be protected. Thus, acetylation of 10a yielded 10b
(HÀC(1F) at d 6.35, J(1F,2F) ˆ 3.0 Hz; C(1F) at d 90.46). Finally, selective removal of
the anomeric acetyl group from 10b with hydrazinium acetate in DMF [18] yielded
compound 10c. Again, only the a-d isomer was present (HÀC(1F) at d 6.01, J(1F,2F) ˆ
3.1 Hz; C(1F) at d 92.90).
Synthesis of a Moenomycin-Type Trisaccharide with a 6-Azido-6-deoxy Unit E.
Desilylation of 9b with Bu4NF [14] yielded compound 11a (Scheme 2). It turned out to
be difficult to remove Bu4NF chromatographically (FC (silica gel) or ion exchange
‡
(Dowex 50 W X2, H form)) or by extraction of 11a from the saturated NaCl solution
with AcOEt/BuOH 4 :1 [20]. In the latter case, the amount of isolated 11a was low.
Tosylation of 11a with TsCl and N,N-dimethylpyridin-4-amine (DMAP) in pyridine
furnished compound 11b in low yield because the carbamoyl group was unstable under
the reaction conditions. All of the problems mentioned could be avoided by
unproblematic desilylation of 9a with Bu4NF to give 11d; Bu4NF could be removed
by column chromatography. Selective tosylation of 11d with TsCl and pyridine
furnished compound 11e in 40% yield. The carbamoyl group was then introduced as
described above to give compound 11b (48%). Nucleophilic substitution with NaN3 in
DMF [21] converted 11b into 11c. The progress of the reaction had to be controlled
carefully by TLC since, at longer reaction times, the carbamoyl group was also
removed. Similarly, lactone 8b was converted into the 6E-azido-6E-deoxytrisaccharide
12c: Desilylation of 8b to give 12a had also to be controlled carefully by TLC since the
lactone did not withstand long reaction times. Tosylation of 12a with TsCl and pyridine
furnished compound 12b. The reaction of 12b with NaN3 in DMF gave 12c. At long
reaction times, also opening of the lactone was observed [13]. Trisaccharides 10c and
12c should be very useful intermediates for moenomycin analogues, provided that the
yields can be improved. From the azido group, an amino function can be released, i.e.,
an anchor for conjugation reactions. Likewise, the azido group should allow the
conjugation of reporter groups via a CuI-mediated 1,3-dipolar cycloaddition with
suitable alkyne-containing reagents [22] or by a Staudinger ligation [23].
Synthesis of a Moenomycin A Disaccharide Analogue. For the construction of the
phosphoric acid diester grouping, we used the phosphite methodology [24] as adapted
to the synthesis of moenomycin analogues [25]. Thus, the 2,2,2-trichloro-1,1-dimethyl-
ethyl phosphorodichloridite [26] was converted to the corresponding bis[triazolide],
which in turn was treated with disaccharide 13 [2] (Scheme 3). The reaction product
was allowed to react with methyl 2-O-dodecylglycerate [5] (added in three portions
within 2 h) to furnish the corresponding phosphorous acid triester, which, in turn, was
oxidized with bis(trimethylsilyl) peroxide [27 29] to give 14 in 59% yield from which
33% could be isolated as a single P-diastereoisomer. Removal of the P-protecting
group was achieved under the Imai conditions with freshly prepared ZnÀCu couple in
pyridine [30]; pentane-2,4-dione was added to chelate the produced zinc cations and
maintain the surface of the metal in a clean state. The ratio of the two products, 15 with
five acetyl groups (66%) and a second product (22%) with four acetyl groups, was
determined by 1H-NMR. The ester-protecting groups of 15 were removed by hydrolysis
with 0.3m aqueous LiOH in MeOH/H2O 2 :1, the solution of 15 in MeOH/H2O and the
aqueous LiOH solution being carefully degassed by sonication under Ar. The product

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 3
a) 1. 1H-1,2,4-triazole, Cl3CC(Me)2OPCl2, CH2Cl2/pyridine, 08; 2. 13, 08; 3. (R)-MeO2CCH(C12H25O)CH2OH,
08; 4. (Me3SiO)2, 08 ! 208; 59 % of14. b) ZnÀCu, pyridine, pentane-2,4-dione, 208; 66% of 15. c) LiOH,
MeOH/H2O, 208; 30% of 15b.
mixture consisted of the uronamide 16b (the target compound of the synthesis, 30%),
1
the less-polar 16a (8%), and the more polar uronic acid 16c (8%). The H-NMR and
the mass spectra of the hydrolysis product 16b were in accord with the shown structure.
Synthesis of a Moenomycin A Trisaccharide Analogue. By means of the methods
described above, the two triesters 17a and 17b were prepared each as a mixture of two
P-diastereoisomers from 10c and the 2-O-hexadecyl [31] and 2-O-([1,1'-biphenyl]-3-
ylmethyl) [5] derivatives of methyl glycerate (Scheme 4). In the case of 17a, we
succeeded to separate the P-stereoisomers. Removal of the trichloroethyl-1,1-dimethyl
protecting group from 17a under the Imai conditions [30] gave a mixture of two
compounds (87%) from which the desired compound 18a was isolated and charac-
terized by 1H-NMR and MS; the second compound, most likely, again arose from the
loss of an acetyl group. For the next step, the mixture was used without separation.

Helvetica Chimica Acta Vol. 87 (2004)
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Under identical conditions, 17b was converted to 18b, which was used for the next step
without purification. The final deprotection steps turned out to be unexpectedly
t
unreliable. From 18a and 18b, the BuPh2Si group had to be removed under carefully
controlled conditions with Bu4NF in THF. Too long reaction times or an excess of
Bu4NF caused loss of the carbamoyl group. Finally, the ester groups were hydrolyzed
with 0.3m aqueous LiOH in MeOH/H2O 2 :1. Again, all solutions were carefully
degassed under Ar. From 18a, only a mixture of two products was obtained, the target
compound 20a and the slightly less polar by-product 19 [13]. When 18b was submitted
to the same conditions, 20b was formed. Here the formation of a by-product could be
avoided.
Scheme 4
a) 1. 1H-1,2,4-Triazole, Cl3CC(Me)2OPCl2, CH2Cl2/pyridine, 08; 2. 12c, 08; 3. (R)-MeO2CCH(3-PhC6H4CH2O)-
CH2OH or (R)-MeO2CCH(C16H33O)CH2OH, 08; 4. (Me3SiO)2, 08 ! 208; 68% of 17a or 17% of 17b, resp. b)
ZnÀCu, pyridine, pentane-2,4-dione, 208; 87% of 18a. c) LiOH, MeOH/H2O, 208; 67% of 20a/19 [13] or 49% of
20b (over steps b and c, resp.).
The structural assignment of 20b is based on NMR and MS evidence. In the 1H-NMR spectra, the signals of
HÀC(1F) (br. s at d 5.92), HÀC(3F) (t at d 5.07), HÀC(5F) (d at d 4.32), HÀC(4F) (t at d 3.71), and HÀC(2F)
1
(hidden in a m at d 3.66 3.56) were unequivocally identified by H,1H-COSY. In addition, ESI-MS displayed

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Helvetica Chimica Acta Vol. 87 (2004)
the correct molecular ion at 1033.44931 ([M À H]À; calc. 1033.44869). Unfortunately, we could not find the
13C-NMR signal of the carbamoyl group at ca. d 156, probably due to the lack of an Overhauser effect.
In conclusion, methods are now at hand for the synthesis of moenomycin analogues
with modified units E (at position 6) and with modified lipid parts. They should be
useful for i) studying the transglycosylation reaction and the mode of action of the
moenomycins in more detail and ii) to prepare moenomycin-type transglycosylase
inhibitors with improved (pharmacokinetic) properties.
Financial support by the Deutsche Forschungsgemeinschaft, Sandoz Industrial Products GmbH (formerly
BC Biochemie GmbH), and the Fonds der Chemischen Industrie is gratefully acknowledged.
Experimental Part
General. See [6].
Disaccharide Formation from 3b and 4. a) In CH2Cl2. A mixture of 3b (100.0 mg, 0.16 mmol), 4 (100.0 mg,
0.14 mmol), 4-ä molecular sieves (200.8 mg), and dry CH2Cl2 (5.0 ml) was stirred for 1 h at 208 and then cooled
to 08. Me3SiOTf (6.0 ml) was then injected, and the mixture was stirred at 08 for 1 h. After quenching with Et3N
(20 ml), the mixture was filtered and the filter cake washed with CH2Cl2. The combined filtrate and washings
were washed with sat. NaHCO3 soln. and H2O. The org. phase was dried and evaporated. Purification by FC
(petroleum ether/AcOEt 2 :1) furnished 5a (125.1 mg, 76%) and 5b (18.0 mg, 8%) besides 12.2 mg of recovered
4.
b) In Et2O. As described above, with 3b (100.0 mg, 0.16 mmol), 4 (100.0 mg, 0.14 mmol), 4-ä molecular
sieves (200.7 mg), and dry Et2O (5.0 ml) instead of CH2Cl2: 5a (76.2 mg, 46%) and 5b (66.0 mg, 29%).
(tert-Butyl)dimethylsilyl
6-O-[(tert-Butyl)diphenylsilyl]-2-deoxy-3-O-{3,4,6-tri-O-acetyl-2-deoxy-2-
{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-d-glucopyranosyl}-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-
d-glucopyranoside (5a): Rf (petroleum ether/AcOEt 1:1): 0.68. 1H-NMR (300 MHz, CDCl3; signals that could
be assigned): 7.75 7.70, 7.42 7.36 (2m, 10 arom. H); 2.06, 2.06, 2.01 (3s, 3 MeCO); 1.08 (s, Me3C (tBuPh2Si));
0.94 (s, Me3C (tBuMe2Si)); 0.20, 0.16 (2 s, 2 Me).
(tert-Butyl)dimethylsilyl 6-O-[(tert-Butyl)diphenylsilyl]-2-deoxy-3,4-bis-O-{3,4,6-tri-O-acetyl-2-deoxy-2-
{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-d-glucopyranosyl}-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-
d-glucopyranoside (5b): Rf (petroleum ether/AcOEt 1 :1): 0.61. 1H-NMR (300 MHz, CDCl3; signals that could
be assigned): 7.82 7.43 (m, 10 arom. H); 2.19, 2.13, 2.07, 2.05, 2.01, 1.99 (6s, 6 MeCO); 1.17 (s, Me3C (tBuPh2Si));
0.96 (s, Me3C (tBuMe2Si)); 0.19, 0.15 (2s, 2 Me). ESI-MS (C61H82Cl9N3O25Si2 (1632.58, 1627.20)): 1628.22709
‡
([M ‡ H] ; calc. 1628.20425).
(tert-Butyl)dimethylsilyl 4-O-Acetyl-6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-3-O-{3,4,6-tri-O-acetyl-2-de-
oxy-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-d-glucopyranosyl}-2-{[(2,2,2-trichloroethoxy)carbonyl]ami-
no}-b-d-glucopyranoside (5c). To a soln. of 5a (100.0 mg, 0.086 mmol) in pyridine (0.50 ml), Ac2O (0.20 ml) and
DMAP (8.0 mg, 0.066 mmol) were added. After stirring for 2 h at 208, the mixture was evaporated. Purification
by FC (petroleum ether/AcOEt 2 :1) furnished 5c (90.1 mg, 87%). Rf (petroleum ether/AcOEt 1:1): 0.70.
1H-NMR (1H,1H-COSY; 600 MHz, CDCl3): 7.71 7.36 (m, 10 arom. H), 5.67 (br. s, NHTroc); 5.25 5.11 (m,
HÀC(1C), HÀC(3C), NHTroc); 5.01 (t, HÀC(4C)); 4.97 (t, HÀC(4E)); 4.83 4.65 (m, HÀC(1E), 2 CCl3CH2);
4.53 4.45 (m, HÀC(3E)); 4.22 (dd, HaÀC(6C)); 4.14 (d, HbÀC(6C)); 3.70 3.57 (m, HÀC(2C), HÀC(5E),
HÀC(5C), CH2(6E)); 3.07 3.00 (m, HÀC(2E)); 2.09, 2.01, 2.00, 1.86 (4s, 4 MeCO); 1.04 (s, Me3C (tBuPH2Si));
0.91 (s, Me3 (tBuMe2Si)); 0.15, 0.12 (2s, 2 Me); J(2E,3E) ˆ 9.6, J(3E,4E) ˆ 9.6, J(4E,5E) ˆ 9.6, J(3C,4C) ˆ 9.6,
J(4C,5C) ˆ 9.6, J(5C,6aC) ˆ 3.9, J(6C,6bC) ˆ 12.6. 13C-NMR (13C,1H-COSY, 75.5 MHz, CDCl3): 170.78, 170.50,
170.03, 169.53 (4 MeCO); 153.91 (2 CCl3CH2OCO); 135.76, 135.67, 133.21, 133.19, 129.84, 129.81, 127.84, 127.79
(arom. C); 100.10 (C(1E)); 95.52 (2 CCl3CH2OCO); 94.25 (C(1C)); 77.84 (C(3E)); 75.02 (C(3C)); 74.80, 74.62 (2
CCl3CH2O); 72.14 (C(5E)); 72.02 (C(5C)); 68.49(C (4E)); 68.47 (C(4C)); 63.16 (C(6C)); 61.94 (C(6E)); 60.72
(C(2E)); 56.49(C (2C)); 26.84 (Me3C (tBuPh2Si)); 25.77 (Me3C (tBuMe2Si)); 20.86, 20.73, 20.70, 20.68 (4 MeCO);
19.26 (Me3C (tBuPh2Si)); 18.06 (Me3C (tBuMe2Si)); À4.11, À5.18 (2 Me). ESI-MS (C48H66Cl6N2O17Si2 (1211.94,
‡
1208.20)): 1231.19438 ([M ‡ Na] ; calc. 1231.19210).
(tert-Butyl)dimethylsilyl 3-O-Acetyl-6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-4-O-{3,4,6-tri-O-acetyl-2-de-
oxy-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-d-glucopyranosyl}-2-{[(2,2,2-trichloroethoxy)carbonyl]ami-

Helvetica Chimica Acta Vol. 87 (2004)
1815
no}-b-d-glucopyranoside (6b). To a soln. of 6a (1.09g, 0.89mmol) in BuOH (32 ml) ethane-1,2-diamine
(8.0 ml) was added. The soln. was stirred at 908 for 12 h. After evaporation, the residue was dissolved in MeOH/
H2O 5 :1 (12 ml), then NaHCO3 (600.0 mg) was added. TrocCl (2.0 ml, 13.9mmol) was added dropwise at 20 8,
and the mixture was stirred for 1 h. The soln. was neutralized with 1m HCl (2.0 ml) and evaporated. The residue
was dissolved in pyridine (5.0 ml), Ac2O (3.0 ml) was added, then the mixture was stirred at 208 overnight. The
solvents were removed by azeotropic evaporation with toluene. Purification by FC (petroleum ether/AcOEt
2 :1) afforded 6b (830.2 mg, 77%). Rf (petroleum ether/AcOEt 1:1): 0.65. [a]2D6 ˆ À6 (c ˆ 1.0, CHCl3). 1H-NMR
(1H,1H-COSY; 600 MHz, CDCl3): 7.78 7.28 (m, 10 arom. H); 5.66 (d, NHTroc); 5.06 (t, HÀC(3E)); 4.84 (t,
HÀC(4C)); 4.78, 4.62 (AB, CCl3CH2OCO); 4.68 (d, HÀC(1E)); 4.67 (t, HÀC(3C)); 4.36 (dd, HaÀC(6C)); 4.64,
4.37 (AB, CCl3CH2OCO); 4.18 (d, HÀC(1C)); 4.06 (t, HÀC(4E)); 4.00 (br. d, HbÀC(6C)); 3.99 (br. d,
HaÀC(6E)); 3.75 3.71 (m, HÀC(2E)); 3.60 (br. d, HbÀC(6E)); 3.54 3.47 (m, HÀC(2C)); 3.43À3.40 (m,
HÀC(5C)); 3.34 (br. d, HÀC(5E)); 2.07, 2.05, 2.04, 1.95, (4s, 4 MeCO); 1.16 (s, Me3C (tBuPh2Si)); 0.93 (s, Me3C
(tBuMe2Si)); 0.20, À0.14 (2s,
2
Me); J(1E,2E) ˆ 8.0, J(2E,3E) ˆ 9.7, J(3E,4E) ˆ 9.7, J(4E,5E) ˆ 9.7,
J(5E,6bE) ˆ J(5E,6bE) ˆ small, J(6aE,6bE) ˆ 10.3, J(1C,2C) ˆ 7.2, J(2C,3C) ˆ 9.5, J(3C,4C) ˆ 9.5,
J(4C,5C) ˆ 9.5, J(5C,6aC) ˆ 4.8, J(6aC,6bC) ˆ 12.3, 2J(AB) ˆ 12.3, J(H,NHTroc) ˆ 7.8. 13C-NMR (13C,1H-COSY,
75.5 MHz, CDCl3): 171.46, 170.73, 170.34, 169.74 (4 MeCO), 154.82, 153.87 (2 CCl3CH2OCO), 136.17, 135.98,
133.53, 132.17, 131.00, 130.41, 128.99, 128.16 (arom. C); 100.26 (C(1C)); 97,00 (C(1E)); 95.81, 95.67 (2
CCl3CH2OCO); 75.01 (C(5E)); 74.86, 74.50 (2 CCl3CH2OCO); 73.95 (C(4E)); 72.73 (C(3E)); 72.61 (C(3C));
71.51 (C(5C)); 68.75 (C(4C)); 62.03 (C(6C)); 61.48 (C(6E)); 58.16 (C(2E)); 56.16 (C(2C)); 27.18 (Me3C
(tBuPH2Si)); 25.89( Me3C (tBuMe2Si)); 21.04, 20.92, 20.92, 20.79 (4 MeCO); 19.35 (Me3C (tBuPH2Si)); 18.29
(Me3C (tBuMe2Si)); À4.07, À4.79(2 Me). ESI-MS (C 48H66Cl6N2O17Si2 (1211.94, 1208.20)): 1209.20683 ([M ‡
‡
H] ; calc. 1209.21016).
3-O-Acetyl-6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-4-O-{3,4,6-tri-O-acetyl-2-deoxy-2-{[(2,2,2-trichloro-
ethoxy)carbonyl]amino}-b-d-glucopyranosyl}-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-a-d-glucopyranose
(6c). Bis(acetonitrile)dichloropalladium (130.0 mg, 0.50 mmol) was added to a foil-covered flask containing 6b
(1.20 g, 0.99 mmol) in acetone (20 ml). After stirring for 4 d at 208, the mixture was evaporated and the residue
purified by FC (petroleum ether/AcOEt 2 :1): 6c (600.2 mg, 55%). Rf (petroleum ether/AcOEt 1:1): 0.54.
1
[a]2D6 ˆ À33 (c ˆ 1.0, CHCl3). H-NMR (1H,1H-COSY; 300 MHz, CDCl3): 7.78 7.21 (m, 10 arom. H); 5.71 (t,
HÀC(3E)); 5.29( dd, HÀC(1E)); 5.05, 4.54 (AB, CCl3CH2OCO); 4.91 (t, HÀC(4C)); 4.79( d, OHÀC(1)); 4.59( t,
HÀC(3C)); 4.61, 4.37 (AB, CCl3CH2OCO); 4.41 (dd, HaÀC(6C)); 4.10 (d, HÀC(1C)); 4.09 3.96 ( m, HÀC(4E),
HÀC(2E), HbÀC(6C)); 3.84 3.58 (m, CH2(6E), HÀC(2C), HÀC(5E)); 3.78 3.41 (m, HÀC(5C)); 2.06, 2.05,
2.04, 2.01 (4s, 4 MeCO); 1.14 (s, Me3C); J(1E,2E) ˆ 3.6, J(2E,3E) ˆ 9.6, J(3E,4E) ˆ 9.6, J(1C,2C) ˆ 7.9,
J(2C,3C) ˆ 9.6, J(3C,4C) ˆ 9.6, J(4C,5C) ˆ 9.6, J(5C,6aC) ˆ 4.1, J(6aC,6bC) ˆ 12.6, J(H,OH) ˆ 4.6, 2JTroc
ˆ
12.1. 13C-NMR (13C,1H-COSY; 75.5 MHz, CDCl3): 170.82, 170.74, 170.72, 169.63 (4 Me3CO); 155.77, 155.47 (2
CCl3CH2OCO); 136.12, 136.06, 133.60, 132.53, 130.88, 130.33, 128.96, 128.13 (arom. C)); 101.06 (C(1C)); 96.31,
95.06 (2 CCl3CH2OCO); 92.22 (C(1E)); 74.90, 74.77 (2 CCl3CH2OCO); 74.77 (C(4E)); 72.24 (C(3C)); 71.41
(C(5C)); 70.89(C(3 E)); 70.39(C(5 E)); 68.38 (C(4C)); 61.81 (C(6E)); 61.74 (C(6C)); 56.16 (C(2E)); 54.89(C(2 C));
27.23 (Me3C); 21.10, 20.93, 20.93, 20.90 (4 MeCO); 19.44 (Me3C). ESI-MS (acetone/H2O/NH4CO3 ;
‡
C42H52Cl6N2O17Si (1097.68, 1094.12)): 1112.15218 ([M ‡ NH4] ; calc. 1112.15094).
3-O-Acetyl-6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-4-O-{3,4,6-tri-O-acetyl-2-deoxy-2-{[(2,2,2-trichloro-
ethoxy)carbonyl]amino}-b-d-glucopyranosyl}-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-1-O-(2,2,2-trichloro-
1-iminoethyl)-a-d-glucopyranose (6d). Trichloroacetonitrile (0.4 ml) and 4-ä molecular sieves (100 mg) were
added to a soln. of 6c (500 mg, 0.46 mmol) in dry CH2Cl2 (4.0 ml). The mixture was stirred for 1 h at 208. Dry
cesium carbonate (40.0 mg, 0.12 mmol) was then added and stirring continued for an additional 4.5 h. Et3N
(2.0 ml) was added and the mixture filtered through a short plug of silica gel. Evaporation and FC (petroleum
ether/AcOEt 2 :1) afforded 6d (500 mg, 88%). Rf (petroleum ether/AcOEt 1 :1): 0.58. [a]2D6 ˆ ‡14 (c ˆ 1.0,
CHCl3). 1H-NMR (1H,1H-COSY; 300 MHz, CDCl3): 8.71 (s, CˆNH); 7.77 7.43 (m, 10 arom. H); 6.47 (d,
HÀC(1E)); 5.24 (d, NH); 5.23 (dd, HÀC(3E)); 4.90 (t, HÀC(4C)); 4.79( t, HÀC(3C)); 4.72 (s, CCl3CH2OCO);
4.62, 4.48 (AB, CCl3CH2OCO); 4.37 (dd, HaÀC(6C)); 4.36 (d, HÀC(1C)); 4.23 4.14 (m, HÀC(2E); HÀC(4E));
3.99 (dd, HbÀC(6C)); 3.95 (br. d, HaÀC(6E)); 3.79 3.68 ( m, HbÀC(6E), HÀC(5E)); 3.55 3.40 (m, HÀC(2C),
HÀC(5C)); 2.06, 2.06, 2.03, 1.98, (4s, 4 MeCO); 1.14 (s, Me3C); J(1E,2E) ˆ 3.6, J(2E,3E) ˆ 10.2, J(3E,4E) ˆ 9.3,
J(5E,6aE) ˆ small, J(6aE,6bE) ˆ 12.9, J(1C,2C) ˆ 8.1, J(2C,3C) ˆ 9.6, J(3C,4C) ˆ 9.6, J(4C,5C) ˆ 9.6,
2
J(5C,6aC) ˆ 4.8, J(5C,6bC) ˆ 1.3, J(6aC,6bC) ˆ 12.6, J(H,NH) ˆ 9.0, JTroc ˆ 12.3. 13C-NMR (13C,1H-COSY;
75.5 MHz, CDCl3): 171.37, 170.70, 170.45, 169.77 (4 MeCO); 160.91 (CˆNH); 154.60, 153.87 (2 CCl3CH2OCO);
136.15, 135.95, 133.43, 132.24, 130.92, 130.45, 128.85, 128.26 (arom. C); 100.27 (C(1C)); 95.59, 95.19 (2
CCl3CH2OCO); 95.19 (C(1E)); 74.83 (C(NH)CCl3); 74.56 (2 CCl3CH2OCO); 73.67 (C(4E)); 73.21 (C(5C));

1816
Helvetica Chimica Acta Vol. 87 (2004)
72.44 (C(3C)); 71.66 (C(5E)); 70.33 (C(3E)); 68.63 (C(4C)); 61.95 (C(6C)); 61.14 (C(6E)); 56.22 (C(2E)); 54.52
(C(2C)); 27.22 (Me3C), 20.92 20.86 (4 MeCO); 19.53 (Me3C). ESI-MS (C44H52Cl9N3O17Si (1242.07, 1237.03)),
‡
1260.01042 ([M ‡ Na] ; calc. 1260.01533).
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-deoxy-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-d-glucopyranosyl-
(1 ! 4)-O-3-O-acetyl-6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-2-{[(2,2,2-trichloroethoxy)carbonyl]amino}-b-d-
glucopyranosyl-(1 ! 2)-5-O-prop-2-enyl-b-d-glucofuranosidurono-6,3-lactone (8a). A mixture of 6d (200.0 mg,
0.16 mmol), 7 [1] (80.0 mg, 0.31 mmol), 4-ä molecular sieves (200.0 mg), and dry 1,2-dichloroethane (5.0 ml)
was stirred for 1 h at 208 under Ar and then cooled to À308. Me3SiOTf (6 ml) was injected, and the mixture was
stirred at À308 for 45 min (TLC (petroleum ether/AcOEt 2 :1) monitoring). After quenching with Et3N (20 ml),
the mixture was filtered and the filter cake washed with CH2Cl2. The combined filtrate and washings were
washed with sat. NaHCO3 soln. and H2O. The org. phase was dried (Na2SO4) and evaporated. Purification by FC
(petroleum ether/AcOEt 2 :1) furnished 8a (118.0 mg, 55%). Rf (petroleum ether/AcOEt 1:1.5): 0.64. [a]D26
ˆ
À4 (c ˆ 1.0, CHCl3). 1H-NMR (1H,1H-COSY; 400 MHz, CDCl3): 7.74 7.41 (m, 10 arom. H); 6.07 (br. s, NH);
6.04 5.94, 5.86 5.76 (2 m, 2 CH2ˆCHCH2); 5.41 5.09( m, 2 CH2ˆCHCH2); 5.30 (s, HÀC(1F)); 5.07 (t,
HÀC(3E)); 4.93 (t, HÀC(4F)); 4.86 (t, HÀC(4C)); 4.84 (d, HÀC(3F)); 4.70 (d, HÀC(1E)); 4.81 4.48 (m, 2
CCl3CH2OCO, HÀC(3C)); 4.46 (s, HÀC(2F)); 4.33 (d, HÀC(1C)); 4.33 4.27 (m, HaÀC(6C)); CH2ˆCHCH2,
1 H of CH2ˆCHCH2); 4.14 (d, HÀC(5F)); 4.09( t, HÀC(4E)); 3.99 (dd, HbÀC(6C)); 3.94 (br. d, HaÀC(6E));
3.87 3.82 (m, 1 H, CH2ˆCHCH2); 3.78 3.73 (m, HÀC(2E)); 3.68 (br. d, HbÀC(6E)); 3.45 3.38 (m, HÀC(2C),
HÀC(5C)); 3.28 (br. d, HÀC(5E)); 2.05, 2.04, 2.02, 1.99 (4s, 4 MeCO); 1.12 (s, Me3C); J(3F,4F) ˆ 4.6, J(4F,5F) ˆ
6.7, J(1E,2E) ˆ 7.8, J(2E,3E) ˆ 9.2, J(3E,4E) ˆ 9.2, J(4E,5E) ˆ 9.2, J(6aE,6bE) ˆ 11.6, J(1C,2C) ˆ 7.8,
J(3C,4C) ˆ 9.5, J(4C,5C) ˆ 9.5, J(5C,6bC) ˆ 1.2, J(6aC,6bC) ˆ 11.2. 13C-NMR (13C,1H-COSY; 75.5 MHz,
CDCl3): 172.39, 171.32, 170.81, 170.52, 169.68 (4 MeCO, CO); 154.78, 153.87 (2 CCl3CH2OCO); 135.92,
135.74, 133.23, 132.07, 130.79, 130.35, 128.66, 128.15 (arom. C); 133.72, 133.69 (2 CH2ˆCHCH2); 119.07, 117.54
(CH2ˆCHCH2); 106.39(C(1 F)); 101.00 (C(1E)); 100.22 (C(1C)); 95.87, 95.41 (2 CCl3CH2OCO); 83.80 (C(2F));
81.71 (C(3F)); 76.20 (C(4F)); 75.09(C(5 E)); 74.63 (C(4C)); 74.45 (CCl3CH2OCO); 74.10 (C(5F)); 73.45 (C(4E));
72.36 (C(3E)); 72.05 (C(3C)); 71.78 (CCl3CH2OCO); 71.59(C(5 C)); 68.54 (2 CH2ˆCHCH2); 62.00 (C(6C));
61.37 (C(6E)); 56.43 (C(2C)); 55.76 (C(2E)); 27.15 (Me3C); 21.02, 20.82, 20.78, 20.73 (4 MeCO); 19.44 (Me3C).
‡
ESI-MS (C54H66Cl6N2O22Si (1335.92, 1332.20)): 1355.18850 ([M ‡ Na] ; calc. 1355.19057).
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-5-O-prop-2-enyl-b-d-gluco-
furanosidurono-6,3-lactone (8b). Activated Zn dust (4.5 g) was added to a soln. of 8a (300.0 mg, 0.23 mmol) in
Ac2O (4.5 ml). The mixture was stirred for 24 h at 208. The mixture was filtered through a plug of Celite, eluting
with AcOEt and MeOH. Evaporation and FC (AcOEt) furnished 8b (150.0 mg, 63%). Rf (CH2Cl2/MeOH
1
10 :1): 0.58. [a]2D6 ˆ À25 (c ˆ 1.0, CHCl3). H-NMR (1H,1H-COSY; 300 MHz, CDCl3): 7.74 7.41 (m, 10 arom.
H); 6.65 (br. s, NH); 6.01 5.92, 5.81 5.71 (2 m, 2 CH2ˆCHCH2); 5.39 5.25, 5.15 5.04 ( m, 2 CH2ˆCHCH2);
5.23 (s, HÀC(1F)); 4.97 (t, HÀC(3C)); 4.96 (t, HÀC(3E)); 4.94 (dd, HÀC(4F)); 4.90 (t, HÀC(4C)); 4.84 (d,
HÀC(3F)); 4.64 (d, HÀC(1C)); 4.48 (d, HÀC(1E)); 4.35 (s, HÀC(2F)); 4.34 4.23 (m, HaÀC(6C), CH2ˆCHCH2,
1 H of CH2ˆCHCH2); 4.17 (d, HÀC(5F)); 4.08 (t, HÀC(4E)); 4.04 3.97 (m, HÀC(2C)); 3.98 (br. d, HbÀC(6C));
3.91 (dd, HaÀC(6E)); 3.82 3.78 (m, 1 H, CH2ˆCHCH2); 3.75 3.66 (m, HÀC(2E)); 3.59( dd, HbÀC(6E));
3.46 3.42 (m, HÀC(5C)); 3.37 3.33 (m, HÀC(5E)); 2.03, 2.00, 1.98, 1.96, 1.95, 1.52 (6s, 6 MeCO); 1.09( s,
Me3C); J(3F,4F) ˆ 5.0, J(4F,5F) ˆ 6.7, J(1E,2E) ˆ 8.1, J(2E,3E) ˆ 9.2, J(3E,4E) ˆ 9.2, J(4E,5E) ˆ 9.2,
J(5E,6aE) ˆ 1.2, J(5E,6bE) ˆ 1.0, J(6aE,6bE) ˆ 12.3, J(1C,2C) ˆ 7.8, J(2C,3C) ˆ 9.5, J(3C,4C) ˆ 9.5,
J(4C,5C) ˆ 9.5, J(6aC,6bC) ˆ 12.3. 13C-NMR (13C,1H-COSY; 75.5 MHz, CDCl3): 172.97, 171.10, 170.96,
170.72, 170.72, 170.30, 169.74 (6 MeCO, CO); 136.07, 135.91, 133.78, 132.30, 130.66, 130.34, 128.55, 128.21
(arom. C); 133.78, 133.74 (2 CH2ˆCHCH2); 119.11, 117.65 (2 CH2ˆCHCH2); 106.30 (C(1F)); 101.06 (C(1C));
100.51 (C(1E)); 84.17 (C(2F)); 81.93 (C(3F)); 76.32 (C(4F)); 75.56 (C(5E)); 74.29(C(5 F)); 73.47 (C(4E)); 72.70
(C(3C)); 72.41 (C(3E)); 71.81 (CH2ˆCHCH2); 71.74 (C(5C)); 68.63 (CH2ˆCHCH2); 68.50 (C(4C)); 62.08
(C(6C)); 61.68 (C(6E)); 54.83 (C(2E)); 53.38 (C(2C)); 27.30 (Me3C); 23.46, 23.19, 20.89, 20.89, 20.89, 20.89 (6
‡
MeCO); 19.51 (Me3C). ESI-MS (C52H68N2O20Si (1069.20, 1068.41)): 1091.40550 ([M ‡ Na] ; calc. 1091.40327),
‡
1069.42372 ([M ‡ H] ; calc. 1069.42127).
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-5-O-prop-2-enyl-b-d-gluco-
furanosiduronamide (9a). Compound 8b (100.0 mg, 0.94 mmol) was added to a sat. NH3 soln. in THF/MeOH
9:1 (10.0 ml) at 0 8, and the mixture was stirred at 08 for 3 h (TLC (CHCl3/MeOH 10 :1) monitoring).
Evaporation and FC (CHCl3/MeOH 20 :1) furnished 9a (82.2 mg, 81%). Rf (CH2Cl2/MeOH 10 :1): 0.40. [a]D26
ˆ
À30 (c ˆ 1.0, CHCl3). 1H-NMR (1H,1H-COSY; 400 MHz, CDCl3): 7.70 7.36 (m, 10 arom. H); 6.73, 5.99 (2 br. s,

Helvetica Chimica Acta Vol. 87 (2004)
1817
CONH2); 6.31 (br. d, NHAc); 5.90 5.75 (m, 2 CH2ˆCHCH2, NHAc); 5.27 5.04 (m, 2 CH2ˆCHCH2); 5.06 (s,
HÀC(1F)); 4.93 (t, HÀC(3E)); 4.90 (t, HÀC(4C)); 4.81 (t, HÀC(3C)); 4.69( d, NHAc); 4.50 (d, HÀC(1E)); 4.43
(dd, HÀC(4F)); 4.39( d, HÀC(1C)); 4.23 (dd, HaÀC(6C)); 4.18 (d, HÀC(5F)); 4.18 4.07 (m, HÀC(2F),
HÀC(3F), CH2ˆCHCH2, 1 H of CH2ˆCHCH2); 4.06 3.99 (m, HÀC(4E), HÀC(2E)); 3.94 (dd, HbÀC(6C));
3.89 3.84 ( m, HaÀC(6E), 1 H of CH2ˆCHCH2); 3.79( t, HÀC(2C)); 3.53 (dd, HbÀC(6E)); 3.40 3.34 (m,
HÀC(5C)); 3.33 3.28 (m, HÀC(5E)); 1.99, 1.96, 1.94, 1.93, 1.90, 1.46 (6s, 6 MeCO); 1.05 (s, Me3C); J(3F,4F) ˆ
4.2, J(4F,5F) ˆ 3.6, J(1E,2E) ˆ 8.0, J(2E,3E) ˆ 9.6, J(3E,4E) ˆ 9.6, J(5E,6bE) ˆ 1.9, J(6aE,6bE) ˆ 11.4,
J(1C,2C) ˆ 8.4, J(2C,3C) ˆ 9.6, J(3C,4C) ˆ 9.6, J(4C,5C) ˆ 9.6, J(5C,6aC) ˆ 4.9, J(5C,6bC) ˆ 1.9,
J(6aC,6bC) ˆ 12.4. 13C-NMR (13C,1H-COSY; 50 MHz, CDCl3): 173.68, 171.17, 170.95, 170.66, 169.93, 169.50 (6
Me3CO); 135.99, 135.72, 133.60, 132.05, 130.51, 130.12, 128.46, 128.05 (arom. C); 134.12, 133.70 (2
CH2ˆCHCH2); 118.60, 117.09(2 CH2ˆCHCH2); 106.00 (C(1F)); 100.57 (C(1C)); 100.51 (C(1E)); 86.37
(C(2F)); 82.46 (C(4F)); 78.82 (C(5F)); 75.17 (C(5E)); 74.61 (C(3F)); 73.76 (C(4E)); 73.32 (CH2ˆCHCH2); 72.92
(C(3E)); 72.69(C(3 C)); 71.68 (C(5C)); 68.88 (CH2ˆCHCH2); 68.24 (C(4C)); 61.92 (C(6C)); 61.49(C(6 E)); 54.23
(C(2C)); 53.40 (C(2E)); 27.17 (Me3C); 23.22, 22.95, 20.86, 20.73, 20.73, 20.73 (6 MeCO); 19.35 (Me3C). ESI-MS
‡
(C52H71N3O20Si (1086.23, 1085.44)): 1086.44615 ([M ‡ H] ; calc. 1086.44782).
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-3-O-(aminocarbornyl)-5-O-
prop-2-enyl-b-d-glucofuranosiduronamide (9b). To a soln. of 9a (100.0 mg, 0.092 mmol) in dry CH2Cl2 (0.5 ml),
trichloroacetyl isocyanate (25 ml, 0.20 mmol) was added, and the mixture was stirred at 208 for 1 h. Excess
reagent was destroyed by addition of MeOH (0.2 ml), and stirring was continued at 08 for 10 min. After
evaporation, the residue was redissolved in MeOH (5.0 ml), Zn dust (100.0 mg) was added, and the mixture was
stirred at 208 for 3 h. Filtration, washing the solid with MeOH, evaporation of the combined liquid phases, and
purification by FC (CHCl3/MeOH 15 :1) furnished 9b (100.2 mg, 96%). Rf (CH2Cl2/MeOH 10 :1): 0.37.
1H-NMR (1H,1H-COSY; 300 MHz; CDCl3): 7.71 7.36 (m, 10 arom. H); 6.87 (d, NHAc); 6.54, 6.33 (2 br. s,
CONH2); 5.91 5.74 (m, 2 CH2ˆCHCH2); 5.23 5.02 (m, HÀC(3F), 2 CH2ˆCHCH2); 5.02 (d, HÀC(1F)); 4.88
(t, HÀC(4C)); 4.87 (t, HÀC(3E)); 4.76 (t, HÀC(3C)); 4.54 4.48 (m, HÀC(4F)); 4.50 (d, HÀC(1E)); 4.38 (d,
HÀC(1C)); 4.33 (dd, HÀC(2F)); 4.26 (dd, HaÀC(6C)); 4.20 4.00 (m, HÀC(2E), HÀC(4E), 1 CH2ˆCHCH2,
1 H of CH2ˆCHCH); 4.01 (d, HÀC(5F)); 3.96 3.89 (m, HbÀC(6C); 1 H of CH2ˆCHCH2); 3.87 (br. d,
HaÀC(6E)); 3.83 3.76 (m, HÀC(2C)); 3.47 (br. d, HbÀC(6E)); 3.39 3.34 ( m, HÀC(5C)); 3.32 3.28 (m,
HÀC(5E)); 1.99, 1.96, 1.95, 1.91, 1.84, 1.41 (6s, 6 MeCO); 1.05 (s, Me3C); J(1F,2F) ˆ 2.8, J(2F,3F) ˆ 3.0,
J(4F,5F) ˆ 5.3, J(1E,2E) ˆ 8.4, J(2E,3E) ˆ 9.6, J(3E,4E) ˆ 9.6, J(5E,6aE), J(5E,6bE) ˆ small, J(6aE,6bE) ˆ
12.4, J(1C,2C) ˆ 8.4, J(2C,3C) ˆ 9.6, J(3C,4C) ˆ 9.6, J(4C,5C) ˆ 9.6, J(5C,6aC) ˆ 4.6, J(6aC,6bC) ˆ 11.0,
J(H,NH) ˆ 9.5. 13C-NMR (13C,1H-COSY; 75.5 MHz, CDCl3): 173.62, 171.51, 171.08, 171.06, 170.82, 170.25,
169.67 (6 MeCO, CONH2); 156.23 (OCONH2); 136.21, 135.90, 133.95, 132.05, 130.78, 130.32, 128.73, 128.29
(arom. C); 134.41, 134.28 (2 CH2ˆCHCH2); 118.61, 117.25 (2 CH2ˆCHCH2); 106.66 (C(1F)); 100.96 (C(1E));
100.52 (C(1C)); 85.37 (C(2F)); 79.80 (C(4F)); 79.11 (C(5F)); 76.00 (C(3F)); 75.09(C(5 E)); 74.14 (C(4E)); 73.67
(C(3E)); 73.54 (C(3C)); 72.97 (C(5C)); 71.80, 69.89 (2 CH2ˆCHCH2); 68.29(C(4 C)); 61.98 (C(6C)); 61.45
(C(6E)); 54.09(C(2 C)); 53.68 (C(2E)); 27.33 (Me3C); 23.35, 23.10, 21.02, 20.94, 20.90, 20.85 (6 MeCO); 19.49
‡
(Me3C). ESI-MS (C53H72N4O21Si (1129.25, 1128.45)): 1129.45364 ([M ‡ H] ; calc. 1129.45311).
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-3-O-(aminocarbonyl)-5-O-prop-2-enyl-b-d-glucofuranosi-
duronamide (11a). To a soln. of 9b (100 mg, 0.089mmol) in THF (2 ml), 1 m Bu4NF in THF (30 ml) was added,
and the mixture was stirred at 208 for 3 h. Evaporation and FC (CHCl3/MeOH 10 :1) furnished impure 11a
(70 mg). To remove Bu4NF from 11a, it was extracted with AcOEt/BuOH 4 :1 from a sat. NaCl soln.
Subsequently ammonium salts were removed by passing a MeOH soln. through an ion-exchange column
‡
(Dowex 50 W X2, H form): 11a (12 mg, 15%). Rf (CH2Cl2/MeOH 10 :1.5): 0.28. 1H-NMR (400 MHz, CDCl3;
signals that could be assigned): 5.87 5.78 (m, 2 CH2ˆCHCH2); 4.94 (s, HÀC(1F)); 4.59, 4.57 (2d, HÀC(1C),
HÀC(1E)); 2.00, 1.95, 1.93, 1.92, 1.85, 1.84 (6s, 6 MeCO); J(1C,2C) ˆ 8.4, J(1C,2C) ˆ 8.4. 13C-NMR (75.5 MHz,
CD3OD/CDCl3 1:1): 172.50, 172.24, 171.61, 171.45, 171.37, 170.47 (6 MeCO); 134.26, 133.95 (2 CH2ˆCHCH2);
118.57, 117.71 (2 CH2ˆCHCH2); 107.04 (C(1F)); 101.39, 100.77 (C(1E), C(1C)); 85.39, 80.21, 75.76, 75.54, 75.48,
73.77, 73.29, 72.50, 71.86, 69.72, 68.82, 62.30, 60.15, 54.64, 53.81 (C(2E), C(2C)); 22.77, 22.77, 20.85, 20.79, 20.74,
‡
20.67 (6 MeCO). ESI-MS (C37H54N4O21 (890.85, 890.33)): 913.31712 ([M ‡ Na] ; calc. 913.31728), 891.33680
‡
([M ‡ H] ; calc. 891.33533).
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-2-deoxy-6-O-tosyl-b-d-glucopyranosyl-(1 ! 2)-3-O-(aminocarbonyl)-5-O-prop-2-enyl-b-d-glu-
cofuranosiduronamide (11b). a) To a soln. of 11a (70 mg, 0.079mmol) in dry pyridine (2 ml), TsCl (30 mg,

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Helvetica Chimica Acta Vol. 87 (2004)
0.16 mmol) and DMAP (7 mg) were added. The mixture was stirred at 208 overnight. The solvent was
evaporated and the residue purified by FC (CHCl3/MeOH 15 :1): 11b (12 mg, 14.6%).
b) To a soln. of 11e (7 mg, 0.007 mmol) in dry CH2Cl2 (0.5 ml), trichloroacetyl isocyanate (1.5 ml,
12.5 mmol) was added, and the mixture was stirred at 208 for 1 h. Excess reagent was destroyed by addition of
MeOH (0.2 ml), and stirring was continued at 08 for 10 min. After evaporation, the residue was dissolved in
MeOH (5 ml), Zn dust (20 mg) was added, and the mixture was stirred at 208 for 3 h. Filtration, washing the
solid with MeOH, evaporation of the combined liquid phases, and purification by FC (CHCl3/MeOH 15 :1)
furnished 11b (3.5 mg, 48%). Rf (CH2Cl2/MeOH 10 :1.5): 0.65. 1H-NMR (300 MHz, CDCl3; signals that could
be assigned): 7.78, 7.38 (2d, 4 arom. H); 5.89 5.76 ( m, 2 CH2ˆCHCH2); 5.35 4.96 (m, 2 CH2ˆCHCH2,
HÀC(3E), HÀC(3C), HÀC(3F), HÀC(4C)); 5.01 (s, HÀC(1F)); 4.58, 4.56 (2d, HÀC(1C), HÀC(1E)); 2.45 (s,
Me); 2.05, 1.99, 1.99, 1.98, 1.93, 1.88 (6s, 6 MeCO); J(1C,2C) ˆ 8.4, J(1E,2E) ˆ 8.4.
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-6-azido-2,6-dideoxy-b-d-glucopyranosyl-(1 ! 2)-3-O-(aminocarbonyl)-5-O-b-d-glucofuranosi-
duronamide (11c). To a soln. of 11b (10 mg, 0.01 mmol) in dry DMF (0.5 ml), NaN3 (5 mg, 0.077 mmol) was
added. The mixture was stirred at 858 for 3 h. The mixture was filtered and washed with MeOH. The combined
filtrate and washings were evaporated. The residue was purified by FC (CHCl3/MeOH 15 :1): 11c (3 mg, 34%)
and recovered 11b (2 mg). Rf (CH2Cl2/MeOH 10 :1.5): 0.62. 1H-NMR (300 MHz, (D5)pyridine; signals that
could be assigned): 9.48, 9.24 (2d, 2 NHAc); 5.54 (s, HÀC(1F)); 2.24, 2.12, 2.08, 2.01, 1.99, 1.99 (6s, 6 MeCO);
J(H,NH) ˆ 8.7. 13C-NMR (75.5 MHz, (D5)pyridine): 169.49, 169.21, 169.13, 169.04, 168.39 (6 MeCO); 155.25
(NH2COO); 133.10, 131.80 (2 CH2ˆCHCH2); 117.62, 115.60 (2 CH2ˆCHCH2); 106.29(C(1 F)); 99.88, 99.68
(C(1C), C(1E)); 85.21 (C(2F)); 78.31, 75.50, 73.65, 73.34, 72.39, 71.30, 70.64, 70.58, 68.02, 67.89, 66.61, 60.75, 54.87,
53.36 (C(2C), C(2E)); 49.49 (C(6E)); 21.77, 21.77, 21.57, 19.50, 19.13, 19.06 (6 MeCO). ESI-MS (C37H53N7O20
(915.86, 915.33)): inconclusive.
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-5-O-prop-2-enyl-b-d-glucofuranosiduronamide (11d). To a
soln. of 9a (30 mg, 0.028 mmol) in THF (3 ml), 1m Bu4NF in THF (0.07 ml) was added dropwise. The mixture
was stirred at 208 for 40 min and then evaporated. The residue was purified by FC (CHCl3/MeOH 20 :1): 11d
1
(15 mg, 64%). Rf (CH2Cl2/MeOH 10 :1.7): 0.52. H-NMR (1H,1H-COSY; 400 MHz, CDCl3): 5.93 5.87, 5.78
5.72 (2m, 2 CH2ˆCHCH2), 5.32 5.08 (m, CH2ˆCHCH2); 5.20 (s, HÀC(1F)); 5.07 (t, HÀC(3C)); 4.93 (t,
HÀC(4C), HÀC(3E)); 4.84 (dd, HÀC(4F)); 4.77 (d, HÀC(3F)); 4.54, 4.53 (2d, HÀC(1C), HÀC(1E)); 4.30 (dd,
HaÀC(6C)); 4.25 4.23 (m, HÀC(2F), 1 H of CH2ˆCHCH2); 4.20 4.17 (m, 1 H, CH2ˆCHCH2); 4.14 (d,
HÀC(5F)); 3.94 (dd, HbÀC(6C)); 3.84 3.77 (m, HÀC(2C), HÀC(2E), HÀC(4E)); 3.72 (dd, HaÀC(6E)); 3.63
3.56 (m, HÀC(5C), HbÀC(6E), CH2ˆCHCH2); 3.33 3.28 (m, HÀC(5E)); 2.00, 1.95, 1.93, 1.92, 1.85, 1.85 (6s, 6
MeCO); J(3F,4F) ˆ 5.2, J(4F,5F) ˆ 6.8, J(1E,2E) ˆ 8.3, J(2E,3E) ˆ 9.9, J(3E,4E) ˆ 9.9, J(6aE,6bE) ˆ 12.0,
J(1C,2C) ˆ 8.3, J(2C,3C) ˆ 9.9, J(3C,4C) ˆ 9.9, J(4C,5C) ˆ 9.9, J(5C,6aC) ˆ 4.2, J(5C,6bC) ˆ 1.2, J(6aC,6bC) ˆ
12.0. ESI-MS (C36H53N3O20 (847.82, 847.32)): inconclusive.
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl)-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-2-deoxy-6-O-tosyl-b-d-glucopyranosyl-(1 ! 2)-5-O-prop-2-enyl-b-d-glucofuranosiduronamide
(11e). To a soln. of 11d (15 mg, 0.018 mmol) and DMAP (3 mg) in pyridine/CH2Cl2 1 :1 (1 ml), TsCl (45 mg,
0.24 mmol) was added in three portions within 4 h. Then the mixture was stirred at 208 overnight and
evaporated. The residue was purified by FC (CHCl3/MeOH 15 :1): 11e (7 mg, 40%). Rf (CH2Cl2/MeOH 10 :1.5):
1
0.76. H-NMR (300 MHz, CDCl3; signals that could be assigned): 7.80, 7.41 (2d, 4 arom. H); 6.03 5.89, 5.87
5.71 (2m, 2 CH2ˆCHCH2); 4.69, 4.61 (2d, HÀC(1C), HÀC(1E)); 2.47 (s, Me); 2.08, 2.03, 2.02, 2.02, 1.97, 1.96 (6s,
6 MeCO); J(1C,2C) ˆ 7.5, J(1C,2C) ˆ 7.5. ESI-MS (C43H59N3O22S (1002.01, 1001.33)): inconclusive.
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-5-O-prop-2-enyl-b-d-glucofuranosidurono-6,3-lactone
(12a). As described for 11d, with 8b (80 mg, 0.075 mmol), THF (3 ml), and 1m Bu4NF (0.4 ml) (1 h): 12a (28 mg,
1
43%). Rf (CH2Cl2/MeOH 10 :1): 0.30. H-NMR (200 MHz, CDCl3; signals that could be assigned): 6.08 5.63
(m, 2 CH2ˆCHCH2); 2.07, 2.05, 2.02, 2.01, 1.96, 1.96 (6s, 6 MeCO). ESI-MS (C36H50N2O20 (830.79, 830.30)):
‡
‡
853.28580 ([M ‡ Na] ; calc. 853.28549), 831.30374 ([M ‡ H] ; calc. 831.30291).
Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-2-deoxy-6-O-tosyl-b-d-glucopyranosyl-(1 ! 2)-5-O-prop-2-enyl-b-d-glucofuranosidurono-6,3-
lactone (12b). As described for 11b (a)), with 12a (28 mg, 0.032 mmol), pyridine (2 ml), TsCl (30 mg,
0.16 mmol), and DMAP (3 mg): 12b (17 mg, 52%). Rf (CH2Cl2/MeOH 10 :1): 0.34. 1H-NMR (300 MHz,
CDCl3; signals that could be assigned): 7.80, 7.41 (2d, 4 arom. H); 6.03 5.60 (m, 2 CH2ˆCHCH2); 2.47 (s, Me);
2.05, 1.99, 1.99, 1.98, 1.93, 1.88 (6s, 6 MeCO).

Helvetica Chimica Acta Vol. 87 (2004)
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Prop-2-enyl O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-
(acetylamino)-6-azido-2,6-dideoxy-b-d-glucopyranosyl-(1 ! 2)-5-O-prop-2-enyl-b-d-glucofuranosidurono-6,3-
lactone (12c). As described for 11c, with 12b (17 mg, 0.017 mmol), DMF (1 ml), and NaN3 (11 mg, 0.17 mmol):
12c (2 mg, 14%). Rf (CH2Cl2/MeOH 10 :1): 0.32. 1H-NMR (300 MHz, (D5)pyridine; signals that could be
assigned): 6.05 5.85 (m, 2 CH2ˆCHCH2); 2.12, 2.11, 2.08, 2.06, 1.99, 1.99 (6s, 6 MeCO). 13C-NMR (75.5 MHz,
(D5)pyridine; signals that could be assigned): 119.89, 118.37 (CH2ˆCHCH2), 105.93 (C(1F)); 85.51 (C(2F));
55.44, 55.40 (C(2E), C(2C)); 50.79(C(6 E)). ESI-MS (C36H49N5O19 (855.81, 855.30)): inconclusive.
O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-(acetylamino)-
6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-3-O-(aminocarbonyl)-a-d-glucopyranuro-
namide (10a). A mixture of 9b (78.0 mg, 0.069mmol) and [Pd(PPh 3)4] (90.0 mg, 0.078 mmol) in degassed
AcOH (1 ml) was stirred under Ar at 208 for 5 h. The solvent was removed by azeotropic evaporation with
toluene. The residue was taken up in H2O and washed repeatedly with CHCl3, then H2O was removed by
lyophilization. The product was further purified by washing it with toluene/CHCl3/MeOH 10 :10 :3: 10a
(68.1 mg, 94%). [a]2D6 ˆ ‡12 (c ˆ 1.0, CHCl3). Rf (CH2Cl2/MeOH 3 :1): 0.47. 1H-NMR (1H,1H-COSY; 600 MHz,
(D5)pyridine): 8.74 (overlapped by solvent, NHAc), 8.53, 8.32 (2 br. s, NH2); 8.04 (d, NHAc); 7.99 7.35 (m,
NH2, arom. H); 6.31 (t, HÀC(3F)); 6.10 (t, HÀC(4C)); 6.05 (d, HÀC(1F)); 5.86 (t, HÀC(3E)); 5.59( d,
HÀC(1C)); 5.41 (t, HÀC(3C)); 5.35 (d, HÀC(1E)); 5.23 (d, HÀC(5F)); 4.71 (dd, HaÀC(6C)); 4.55 4.49( m,
HÀC(2E), HÀC(4E), HÀC(4F)); 4.29( dd, HÀC(2F)); 4.26 (br. d, HbÀC(6C)); 4.21 (dd, HaÀC(6E)); 4.15 (br. d,
HbÀC(6E)); 4.00 3.94 (m, HÀC(2C), HÀC(5C)); 3.71 3.66 (m, HÀC(5E)); 2.22, 2.16, 2.03, 2.02, 2.00, 1.99 (6s,
6 MeCO); 1.12 (s, Me3C); J(1F,2F) ˆ 2.9, J(2F,3F) ˆ 9.8, J(3F,4F) ˆ 9.8, J(4F,5F) ˆ 9.8, J(1E,2E) ˆ 8.1,
J(2E,3E) ˆ 9.3, J(3E,4E) ˆ 9.3, J(5E,6aE) ˆ 4.2, J(6aE,6bE) ˆ 11.0, J(1C,2C) ˆ 8.2, J(2C,3C) ˆ 9.9,
J(3C,4C) ˆ 9.9, J(4C,5C) ˆ 9.9, J(5C,6aC) ˆ 4.2, J(6aC,6bC) ˆ 12.0, J(H,NH) ˆ 8.8. 13C-NMR (13C,1H-COSY;
75.5 MHz, (D5)pyridine): 174.13, 171.22, 170.77, 170.70, 170.62, 170.13 (6 MeCO); 158.89(OCONH 2); 136.50,
136.39, 134.58, 134.44, 130.92, 130.83, 128.67, 128.60 (arom. C); 103.04 (C(1E)); 99.49 (C(1C)); 93.77 (C(1F));
79.24 (C(2F)); 76.79(C(5 E)); 75.93 (C(3F)); 74.80 (C(3E)); 74.13 (C(4F)); 73.07 (C(4E)); 72.66 (C(4C)); 72.23
(C(5F)); 72.23 (C(5C)); 69.12 (C(3C)); 63.50 (C(6E)); 62.45 (C(6C)); 56.98 (C(2E)); 55.28 (C(2C)); 27.25 (Me3C);
23.65, 23.37, 21.27, 20.81, 20.81, 20.72 (6 MeCO); 19.81 (Me3C). ESI-MS (C47H64N4O21Si (1049.12, 1048.38)):
‡
1071.37479([ M ‡ Na] ; calc. 1071.37245).
O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl)-(1 ! 4)-O-3-O-acetyl-2-(acetylamino)-
6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-1,4-di-O-acetyl-3-O-(aminocarbonyl)-a-d-
glucopyranuronamide (10b). Ac2O (1.3 ml) was added to a soln. of 10a (68.0 mg, 0.065 mmol) in pyridine
(2.0 ml), and the mixture was stirred at 208 for 2 h. The solvents were removed by azeotropic evaporation with
toluene. The crude product was purified by FC (CHCl3/MeOH 15 :1): 10b (68.2 mg, 93%). Rf (CH2Cl2/MeOH
8 :1): 0.36. [a]2D6 ˆ À15 (c ˆ 1.0, CHCl3). 1H-NMR (1H,1H-COSY; 600 MHz, CDCl3): 7.78 7.48 (m, 10 arom. H);
6.35 (d, HÀC(1F)); 6.33 (br. s, NHAc); 6.19(br. s, 1 H, NH2); 5.26 (t, HÀC(3F)); 5.14 (t, HÀC(4F)); 4.99 (t,
HÀC(3E)); 4.93 (t, HÀC(4C)); 4.79( t, HÀC(3C)); 4.60 (d, HÀC(1C)); 4.29 4.26 ( m, HÀC(1E), HaÀC(6C));
4.24 (d, HÀC(5F)); 4.10 4.07 (m, HÀC(4E), HÀC(2E)); 3.97 (br. d, HbÀC(6C)); 3.93 3.86 (m, HÀC(2F),
HaÀC(6E)); 3.83 3.78 (m, HÀC(2C)); 3.58 (br. d, HbÀC(6E)); 3.43 3.40 (m, HÀC(5E)); 3.36 3.34 (m,
HÀC(5C)); 2.16, 2.06, 2.06, 2.04, 2.01, 2.01, 1.98, 1.62 (8s, 8 MeCO); 1.14 (s, Me3C); J(1F,2F) ˆ 3.0, J(2F,3F) ˆ 9.7,
J(3F,4F) ˆ 9.7, J(4F,5F) ˆ 9.7, J(2E,3E) ˆ 9.3, J(3E,4E) ˆ 9.3, J(6aE,6bE) ˆ 10.2, J(1C,2C) ˆ 6.8, J(2C,3C) ˆ 9.7,
J(3C,4C) ˆ 9.7, J(4C,5C) ˆ 9.7, J(6aC,6bC) ˆ 11.0. 13C-NMR (13C,1H-COSY; 50 MHz, CDCl3): 170.96, 170.86,
170.59, 170.59, 170.44, 169.39, 169.21, 168.94 (8 MeCO); 156.14 (OCONH2); 135.95, 135.78, 133.50, 132.16,
130.66, 130.37, 128.53, 128.16 (arom. C); 102.64 (C(1E)); 100.48 (C(1C)); 90.46 (C(1F)); 75.88 (C(5E)); 75.70
(C(2F)); 73.37 (C(4E)); 73.12 (C(3E)); 72.52 (C(3C)); 72.05 (C(3F)); 71.62 (C(5C)); 70.22 (C(5F)); 69.95 (C(4F));
68.09(C(4 C)); 61.80 (C(6E); C(6C)); 54.09(C(2 C)); 53.09(C(2 E)); 27.16 (Me3C); 23.25, 23.06, 20.90, 20.85, 20.85,
20.85, 20.85, 20.85 (8 MeCO); 19.42 (Me3C). ESI-MS (C51H68N4O23Si (1133.20, 1132.40)): 1155.39492 ([M ‡
‡
‡
Na] ; calc. 1155.39358), 1133.41461 ([M ‡ H] ; calc. 1133.41164).
O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-(acetylamino)-
6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-4-O-acetyl-3-O-(aminocarbonyl)-a-d-glu-
copyranuronamide (10c). A mixture of 10b (68.0 mg, 0.060 mmol), hydrazinium acetate (11.0 mg, 0.12 mmol),
and DMF (0.8 ml) was stirred at 208 for 40 min. After addition of H2O, usual workup (CHCl3) and FC (CHCl3/
MeOH 15 :1) gave 10c (44.1 mg, 67%) besides recovered 10b (8.0 mg). Rf (CH2Cl2/MeOH 8 :1): 0.32. [a]2D6 ˆ À3
(c ˆ 1.0, CHCl3). 1H-NMR (1H,1H-COSY; 600 MHz, (D5)pyridine): 8.77 (d, NHAc); 8.38 (br. s, 1 H, NH2); 8.12
(d, NHAc); 8.00 (br. s, 1 H, NH2); 7.97 7.42 (m, 10 arom. H); 7.75 (br. s, NH2); 6.32 (t, HÀC(3F)); 6.09( t,
HÀC(4C)); 6.01 (d, HÀC(1F)); 5.94 (t, HÀC(4F)); 5.88 (t, HÀC(3E)); 5.57 (d, HÀC(1C)); 5.40 (t, HÀC(3C));
5.31 (d, HÀC(1E)); 5.23 (d, HÀC(5F)); 4.71 (dd, HaÀC(6C)); 4.50 (t, HÀC(4E)); 4.47 4.42 (m, HÀC(2E));

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Helvetica Chimica Acta Vol. 87 (2004)
4.27 4.25 (m, HÀC(2F), HbÀC(6C)); 4.21 (dd, HaÀC(6E)); 4.17 (dd, HbÀC(6E)); 3.98 3.91 (m, HÀC(5C),
HÀC(2C)); 3.72 3.70 (m, HÀC(5E)); 2.20, 2.15, 2.11, 2.02, 2.01, 2.01, 2.00 (7s, 7 MeCO); 1.11 (s, Me3C);
J(1F,2F) ˆ 3.1, J(2F,3F) ˆ 9.8, J(3F,4F) ˆ 9.8, J(4F,5F) ˆ 9.8, J(1E,2E) ˆ 8.3, J(2E,3E) ˆ 9.0, J(3E,4E) ˆ 9.0,
J(4E,5E) ˆ 9.0, J(5E,6aE) ˆ 4.4, J(5E,6bE) ˆ 1.0, J(6aE,6bE) ˆ 12.4, J(1C,2C) ˆ 8.2, J(2C,3C) ˆ 9.9,
J(3C,4C) ˆ 9.9, J(4C,5C) ˆ 9.9, J(5C,6aC) ˆ 4.7, J(5C,6bC) ˆ 2.1, J(6aC,6bC) ˆ 12.0, J(H,NH) ˆ 8.7. 13C-NMR
(13C,1H-COSY; 75.5 MHz, (D5)pyridine): 170.93, 170.57, 170.18, 170.13, 170.06, 170.02, 169.66, 169.47 (7 MeCO,
CONH2); 157.19(OCONH 2); 135.87, 135.43, 133.75, 133.03, 129.97, 128.06, 127.97 (arom. C); 102.15 (C(1E));
99.09 (C(1C)); 92.90 (C(1F)); 78.16 (C(2F)); 76.25 (C(5E)); 73.72 (C(4E)); 73.58 (C(3E)); 72.52 (C(3F)); 71.92
(C(4C)); 71.70 (C(5C)); 71.47 (C(4F)); 69.23 (C(3C)); 69.12 (C(5F)); 62.88 (C(6E)); 61.82 (C(6C)); 56.42 (C(2E));
54.95 (C(2C)); 26.63 (Me3C); 22.97, 22.74, 20.70, 20.65, 20.21, 20.15, 20.15 (7 MeCO); 19.23 (Me3C). ESI-MS
‡
(C49H66N4O22Si (1091.16, 1090.39)): (1091.40136 [M ‡ H] ; calc. 1091.40107).
4-O-Acetyl-3-O-(aminocarbonyl)-2-O-[3,4,6-tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl]-a-
d-glucopyranuronamide 1-[(2R)-2-(Dodecyloxy)-3-methoxy-3-oxopropyl 2,2,2-Trichloro-1,1-dimethylethyl
Phosphate] (14). To a soln. of 1H-1,2,4-triazole (45 mg, 0.67 mmol, 4.8 equiv.) in CH2Cl2/pyridine 4 :1
(1.5 ml), 2,2,2-trichloro-1,1-dimethylethyl phosphodichloridite (33 ml, 0.17 mmol, 1.2 equiv.) was added at 08.
This mixture was stirred at 08 under Ar for 30 min. A soln. of 13 (83 mg, 0.14 mmol) in 7:1 CH2Cl2/pyridine 7:1
(2.1 ml) was added, and the mixture was stirred for 3 h at 08. After addition of (2R)-methyl 2-O-
dodecylglycerate (48 mg, 0.21 mmol, 1.5 equiv.) in CH2Cl2/pyridine 7 :1 (2.1 ml) in three portions within 2 h,
the mixture was stirred for 1 h at 08. Bis(trimethylsilyl) peroxide (58 ml, 0.28 mmol, 2.0 equiv.) was injected, and
the mixture was stirred at 08 for 1 h, then at 208 for 15 h. The solvents were removed by azeotropic evaporation
with toluene (258, Ar stream). The residue was dissolved in CH2Cl2/MeOH and mixed with −Kieselguhr×
(500 mg), the mixture evaporated, the residue dried at 0.1 Torr, and the crude product transferred to the top of a
FC column (silica gel (20 g), CH2Cl2/MeOH 10 :1): pure P-diastereoisomer 14 (50 mg, 33%; containing some
triazole (1H-NMR)) and a mixture of two P-diastereoisomers (40 mg, 26%). 14: Rf (CHCl3/MeOH 9:1): 0.25.
IR (film): 3369(OH), 1747 (CO). 1H-NMR (1H,1H-COSY; 300 MHz, (D5)pyridine): 9.28 (d, NHAc); 8.69( s,
CONH2); 8.09( s, CONH2); 7.72 (s, H2NCOO); 6.52 (dd, HÀC(1F)); 6.12 (t, HÀC(3E)); 5.98 (t, HÀC(3F)); 5.96
(t, HÀC(4F)); 5.55 (d, HÀC(1E)); 5.47 (t, HÀC(4E)); 5.00 (m, HÀC(5F), partly overlapped by H2O); 4.80 4.39
(m, CH2(3H), CH2(6E), HÀC(2H)); 4.14 4.03 (m, HÀC(2F), HÀC(2E)); 4.10 4.00 (m, HÀC(5E)); 3.84 3.76
(m, HÀC(1I)); 3.76 (s, COOMe); 3.62 3.59( m, H'ÀC(1I)); 2.19, 2.16, 2.15, 2.07, 2.00 (5s, 7 Me); 1.70 1.62 (m,
HÀC(2I)); 1.21 (m, CH2(3I) to CH2 (11I)); 0.85 (t, Me(12I); J(1F,2F) ˆ 3.6, J(1F,P) ˆ 5.5, J(2F,3F) ˆ 9.5,
J(3F,4F) ˆ 9.5, J(4F,5F) ˆ 9.5, J(1E,2E) ˆ 8.8, J(NH,2E) ˆ 8.7, J(2E,3E) ˆ 10.0, J(3E,4E) ˆ 10.0, J(4E,5E) ˆ 9.3
.
13C-NMR (13C,1H-COSY; 75.5 MHz, (D5)pyridine): 170.41, 170.06, 169.51, 169.02 (CO); 156.73 (H2NCOO);
102.22 (C(1E)); 97.28 (d, C(1F)); 90.38 (d, Me2C); 78.18 (C(2F)); 77.97 (d, C(2H)); 72.32 (C(3E)); 71.59(C(5 E));
71.28 (C(5F)); 70.76 (C(3F)); 70.44 (C(4F)); 69.86 (C(1I)); 69.25 (C(4E)); 68.07 (C(3H)); 62.09(C(6 E)); 55.33
(C(2E)); 54.66 (no C,H correlation); 51.87 (COOMe); 31.73, 29.64, 29.52, 29.35, 29.21, 25.87 (C(2I) to C(11I));
23.34, 22.90, 22.55, 20.48, 20.40, 20.20, 20.11 (7s, 7 MeCO); 13.90 (C(12I)). 31P-NMR (121.5 MHz, (D5)pyridine):
‡
‡
À9.41. FAB-MS (C43H69Cl3N3O22P (1117.36, 1115.32)): 1138.3 ([M ‡ Na] ), 1116.3 ([M ‡ H] ).
Second P-diastereoisomer: Rf (CHCl3/MeOH 9:1): 0.20. 31P-NMR (121.5 MHz, (D5)pyridine): À7.84.
4-O-Acetyl-3-O-(aminocarbonyl)-2-O-[3,4,6-tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl]-a-
d-glucopyranuronamide 1-[(2R)-2-(Dodecyloxy)-3-methoxy-3-oxopropyl Hydrogen Phosphate] (15)/Partly
Deacetylated Derivative 3 :1. To a soln. of 14 (90 mg, 0.08 mmol) in dry pyridine (3.5 ml), ZnÀCu couple
(freshly prepared; 70 mg, 1.14 mmol) and pentane-2,4-dione (90 ml, 0.77 mmol) were added, and the mixture
was stirred under Ar at 208 for 8 h. Excess ZnÀCu was removed by filtration and the residue washed with
CH2Cl2 (3 Â 10 ml), EtOH (3 Â 10 ml), and MeOH (3 Â 10 ml). After evaporation, the residue was taken up in
‡
H2O/EtOH 8 :1 (18 ml). Dowex 50 W X2 /50-100 (H form, 1.0 g) was added, and the mixture was stirred for 1 h.
After filtration, the resin was washed with CH2Cl2 (3 Â 10 ml), EtOH (3 Â 10 ml), MeOH (3 Â 10 ml), and
MeOH/H2O 1 :1 (3 Â 10 ml). The org. solvents were evaporated and the remaining aq. soln. was lyophilized.
The crude product was dissolved in CH2Cl2/MeOH and mixed with −Kieselguhr×, the mixture evaporated, and
the crude product transferred to the top of a FC column (CHCl3/MeOH 4 :1): 15/compound with only 4 acetyl
groups, ratio 3 :1 (1H-NMR; 50 mg, 66%). Rf (CHCl3/MeOH 2 :1): 0.10. 1H-NMR (1H,1H-COSY; 300 MHz,
(D5)pyridine; 15/partly deacetylated derivative): 15: 9.23 (d, NHAc); 8.51 (s, CONH2); 8.37 (s, CONH2); 6.54
(m, HÀC(1F)); 5.96 (t, HÀC(3E)); 5.93 (t, HÀC(4F)); 5.43 (d, HÀC(1E)); 5.36 (t, HÀC(3F)); 5.25 (t, HÀC(4E));
5.07 (d, HÀC(5F)); 4.90 4.45 (m, HÀC(5E), CH2(6E), CH2(3H)); 4.37 4.25 (m, HÀC(2F)); 4.20 4.10 (m,
HÀC(2F)); 4.08 3.96 (m, HÀC(2H)); 3.79 3.60 ( m, overlapping COOMe, CH2(1I)); J(2F,3F) ˆ 9.9,
J(3F,4F) ˆ 9.9, J(4F,5F) ˆ 9.9, J(1E,2E) ˆ 9.0, J(NH,2E) ˆ 8.4, J(2E,3E) ˆ 9.9, J(3E,4E) ˆ 9.9, J(4E,5E) ˆ 9.9,
partly deacetylated derivative: 9.45 (d, NHAc); 8.31 (s, CONH2); 8.11 (s, CONH2); 6.83 (m, HÀC(1F)); 5.99 (t,

Helvetica Chimica Acta Vol. 87 (2004)
1821
HÀC(3F)); 5.96 (t, HÀC(4F)); 5.72 (t, HÀC(3E)); 5.29( d, HÀC(5F)); 5.17 (d, HÀC(1E)); 4.90 4.45 (m,
HÀC(5E), CH2(6E), CH2(3H)); 4.37 4.25 (m, HÀC(2E)); 4.08 3.96 (m, HÀC(2F), HÀC(2H)); 3.79 3.60 ( m,
overlapping COOMe, CH2(1I)); 15/partly deacetylated derivative: 7.32 (hidden by solvent peak, H2NCOO);
3.67, 3.60 (2s, 2 COOMe); 2.24 1.93 (Me of units E and F); 1.64 (m, HÀC(2I)); 1.19( m, CH2(3I) to CH2 (11I));
0.84 (t, Me(12I)); J(2F,3F) ˆ 9.9, J(3F,4F) ˆ 9.9, J(4F,5F) ˆ 9.9, J(1E,2E) ˆ 9.0, J(NH,2E) ˆ 8.7, J(2E,3E) ˆ 9.9,
J(3E,4E) ˆ 9.9, J(4E,5E) ˆ 9.9. 13C-NMR (75.5 MHz, (D5)pyridine; 15/partly deacetylated derivative): 171.17,
170.99, 170.49, 170.44, 170.32, 170.15, 170.10, 169.98, 169.44, 169.30 (CO); 157.02, 156.95 (H2NCOO); 102.68,
102.26 (C(1E)); 95.20, 95.12 (C(1F)); 79.11, 78.98 (C(2F), C(2H)); 75.68 (C(1I)); 73.80 (C(3E)); 73.14 (C(3F));
71.68, 71.61, 71.11, 70.69, 70.29, 69.51, 69.34 (C(5E), C(3E), C(5F), C(4F)); 66.55 66.18 (C(3F), C(1I), C(4E),
C(3H)); 62.30, 61.25 (C(6E)); 54.81, 54.45 (C(2E)); 51.69, 51.56 (COOMe); 49.33, 31.77, 29.85, 29.59, 29.46, 29.26,
25.97, 23.03, 22.93, 22.59 (NHCOMe, CHI2 ); 20.63, 20.50, 20.26, 20.16 (Me of units E and F); 13.94 (C(12I)). 31P-
NMR (81.0 MHz, CD3OD): À3.21. ESI-MS (15; C39H64N3O22P (957.91, 957.37)), 956.36551 ([M À H]À; calc.
956.36463). ESI-MS (partly deacetylated derivative; C37H62N3O21P (915.88, 915.36)): 914.35518 ([M À H]À;
calc. 914.35352).
Deprotection of 15. To a degassed soln. (Ar stream, sonication) of 15 (30 mg, 0.03 mmol) in MeOH/H2O
2 :1 (bidist.; 3.6 ml) at 08, a degassed 0.3m aq. LiOH soln. (700 ml, 7.0 equiv.) was added. The mixture was stirred
at 08 for 30 min, then at 208 for 2 h. The pH of the reaction was controlled with pH paper. The reaction was
‡
stopped by addition of Dowex 50 W X2 (H form, 0.5 g). Stirring at 208 was continued for 10 min. After
filtration, the resin was washed with MeOH/H2O 2 :1 then with H2O. The combined filtrates were evaporated,
and the remaining aq. soln. was lyophilized. The crude products TLC (CHCl3/MeOH/H2O 18 :13 :2.7) were
purified by FC (silica gel, CHCl3/MeOH/H2O 18 :13 :2.7): 16b (7.0 mg, 30%), 16c (2.0 mg, 8%), and a less-polar
product, probably methyl ester 16a (2.0 mg, 8%).
2-O-[2-(Acetylamino)-2-deoxy-b-d-glucopyranosyl]-3-O-(aminocarbonyl)-a-d-glucopyranuronamide 1-
[(2R)-2-(Dodecyloxy)-3-methoxy-3-oxopropyl Hydrogen Phosphate] (16a): Rf (CHCl3/MeOH/H2O
18 :13 :2.7): 0.38. 1H-NMR: uninformative. 31P-NMR (81.0 MHz, D2O): 14.50. ESI-MS (C31H56N3O18P
(789.76, 789.33)): 788.32411 ([M À H]À; calc. 788.32170).
2-O-[2-(Acetylamino)-2-deoxy-b-d-glucopyranosyl]-3-O-(aminocarbonyl)-a-d-glucopyranuronamide 1-
[(2R)-2-Carboxy-2-(dodecyloxy)ethyl Hydrogen Phosphate] (16b): Rf (CHCl3/MeOH/H2O 18 :13 :2.7): 0.3.
1H-NMR (300 MHz, D2O; signals that could be assigned): 5.72 (m, HÀC(1F)); 4.86 (t, HÀC(3F)); 4.54 (d,
HÀC(1E)); 4.20 (d, HÀC(5F)); 1.89( s, NHAc); 1.48 (m, HÀC(2I)); 1,13 (m, CH2(3I) to CH2(11I)); 0.71 (t,
Me(12I)), J(2F,3F) ˆ 9.6, J(3F,4F) ˆ 9.6, J(4F,5F) ˆ 10.2, J(1E,2E) ˆ 8.0. 31P-NMR (81.0 MHz, D2O): 14.50.
ESI-MS (C30H54N3O18P (775.74, 775.31)): 774.31001 ([M À H]À; calc. 774.30620), 796.29251 ([M ‡ Na À 2 H]À;
calc. 796.28812).
2-O-[2-(Acetylamino)-2-deoxy-b-d-glucopyranosyl]-3-O-(aminocarbonyl)-a-d-glucopyranuronic Acid 1-
[(2R)-2-Carboxy-2-(dodecyloxy)ethyl Hydrogen Phosphate] (16c): Rf (CHCl3/MeOH/H2O 18 :13 :2.7): 0.29.
1H-NMR: uninformative. 31P-NMR (81.0 MHz, D2O): 14.51. ESI-MS (C30H53N2O19P (776.72, 776.30)):
797.25975 ([M ‡ Na À 2 H]À; calc. 797.27190).
O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-2-(acetylamino)-
6-O-[(tert-butyl)diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-4-O-acetyl-3-O-(aminocarbonyl)-a-d-glu-
copyranuronamide 1-[(2R)-2-([1,1'-Biphenyl]-3-ylmethoxy)-3-methoxy-3-oxopropyl 2,2,2-Trichloro-1,1-dime-
thylethyl Phosphate] (17a). To a soln. of 1H-1,2,4-triazole (18.2 mg, 0.26 mmol) in CH2Cl2/pyridine 4 :1 (0.6 ml),
2,2,2-trichloro-1,1-dimethylethyl phosphorodichloridite (14 ml, 0.069mmol) was added at 0 8 under Ar. The
mixture was stirred at 08 for 30 min. A soln. of 10c (60.0 mg, 0.055 mmol), in CH2Cl2/pyridine 7:1 (2.0 ml) was
added and the mixture was stirred at 08 for 2 h. After addition of methyl 2-O-([1,1'-biphenyl]-3-
ylmethyl)glycerate (50.0 mg, 0.18 mmol) in CH2Cl2/pyridine 7:1 (0.6 ml) in three portions within 2 h at 08,
bis(trimethylsilyl) peroxide (22 ml, 0.10 mmol) was injected, and the mixture was stirred at 08 for 1 h, then at 208
for 17 h. The solvents were removed by azeotropic evaporation with toluene. The residue was purified by FC
(CHCl3/MeOH 20 :1): pure P-diastereoisomer 17a (20.0 mg, 27%) and mixture of the P-diastereoisomers
(30.1 mg, 41%). Rf (CH2Cl2/MeOH 8 :1): 0.58, 0.56. [a]2D6 ˆ À2 (c ˆ 1.0, CHCl3). 1H-NMR (1H,1H-COSY;
600 MHz, (D5)pyridine): 8.78 7.35 (m, 4 Ph, 2 NHAc, 2 NH2); 6.51 (dd, HÀC(1F)); 6.05 (t, HÀC(3F)); 6.00 (t,
HÀC(3C)); 5.99 (t, HÀC(4F)); 5.68 (t, HÀC(3E)); 5.49( d, HÀC(1C)); 5.41 (t, HÀC(4C)); 5.15 (d, HÀC(1E));
5.14 (d, HÀC(5F)); 5.05, 4.85 (AB, PhC6H4CH2); 4.88 4.84, 4.81 4.77 (2 m, CH2(3H)); 4.72 (dd, HaÀC(6C));
4.69 4.68 ( m, HÀC(2H)); 4.49 4.45 ( m, HÀC(2E)); 4.48 (t, HÀC(4E)); 4.31 (dd, HÀC(2F)); 4.28 (dd,
HbÀC(6C)); 4.23 4.18 (m, CH2(6E)); 4.08 4.03 (m, HÀC(2C)); 3.97 3.95 (m, HÀC(5C)); 3.73 (s, MeO);
3.66 3.64 (m, HÀC(5E)); 2.22, 2.20, 2.18, 2.16, 2.07, 2.02, 2.01, 2.00, 1.99 (9s, 7 MeCO, 2 Me); 1.20 (s, Me3C);
J(1F,2F) ˆ 3.7, J(1F,P) ˆ 5.2, J(2F,3F) ˆ 9.4, J(3F,4F) ˆ 9.4, J(4F,5F) ˆ 9.4, J(1E,2E) ˆ 8.4, J(2E,3E) ˆ 9.4,

1822
Helvetica Chimica Acta Vol. 87 (2004)
J(3E,4E) ˆ 9.4, J(4E,5E) ˆ 9.4, J(1C,2C) ˆ 7.9, J(2C,3C) ˆ 9.4, J(3C,4C) ˆ 9.4, J(4C,5C) ˆ 9.4, J(5C,6aC) ˆ 4.2,
2
J(5C,6bC) ˆ 1.5, J(6aC,6bC) ˆ 11.5, JAB ˆ 12.0. 31P-NMR (121.5 MHz, (D5)pyridine): À5.40. ESI-MS
‡
(C70H88Cl3N4O28PSi (1598.90, 1596.42)): 1597.42460 ([M ‡ H] ; calc. 1597.42303).
O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-3-O-acetyl-6-O-[(tert-butyl)-
diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-4-O-acetyl-3-O-(aminocarbonyl)-a-d-glucopyranuronamide
1-[(2R)-2-([1,1'-Biphenyl]-3-ylmethoxy)-3-methoxy-3-oxopropyl Hydrogen Phosphate] (18a). To a soln. of 17a
(40.0 mg, 0.025 mmol) in dry pyridine (2.0 ml), ZnÀCu couple (freshly prepared; 120.0 mg, 1.82 mmol) and
pentane-2,4-dione (0.16 ml, 1.36 mmol) were added. The mixture was stirred under Ar overnight. Excess
ZnÀCu was removed by filtration, and the residue was washed with MeOH. After evaporation, the residue was
‡
dried at 10 Pa for 1 h, then taken up in H2O/EtOH 8 :1 (9.0 ml). Dowex 50 W X2 (H form, 2.0 g) was added,
and the mixture was stirred for 1 h. After filtration, the resin was washed with MeOH. The org. solvents were
evaporated and the remaining aq. soln. was lyophilized. The crude product was purified by FC (CHCl3/MeOH
5 :1): 7 mg of 18a (Rf (CH2Cl2/MeOH 4 :1): 0.48) and a fraction containing 18a and a second compound (Rf
0.46). Total yield: 29.0 mg, ca. 87%). 18a: [a]2D6 ˆ À2 (c ˆ 1.0, CHCl3). 1H-NMR (1H,1H-COSY; 600 MHz,
CDCl3/CD3OD 1:1): 7.69 7.30 ( m, 4 Ph, 2 NHAc, 2 NH2); 5.71 (br. s, HÀC(1F)); 5.17 (t, HÀC(3F)); 5.09( t,
HÀC(4F)); 5.06 (t, HÀC(3C)); 4.98 (t, HÀC(3E)); 4.93 (t, HÀC(4C)); 4.74, 4.58 (AB, PhC6H4CH2); 4.55 (d,
HÀC(1C)); 4.52 (d, HÀC(1E)); 4.40 (d, HÀC(5F)); 4.28 (dd, HaÀC(6C)); 4.26 4.21 (m, CH2(3H)); 4.15 4.12
(m, HÀC(2H)); 3.98 3.94 (m, HÀC(2E)); 3.91 (t, HÀC(4E)); 3.89( dd, HbÀC(6C)); 3.76 3.70 (m, HÀC(2F),
HÀC(2C), CH2(6E)); 3.60 3.57 (m, HÀC(5E)); 3.45 3.42 (m, HÀC(5C)); 3.31 (s, MeO); 2.00, 1.99, 1.98, 1.97,
1.96, 1.91, 1.68 (7s, 7 MeCO); 1.07 (s, Me3C); J(2F,3F) ˆ 9.9, J(3F,4F) ˆ 9.9, J(4F,5F) ˆ 9.9, J(1E,2E) ˆ 7.9,
J(2E,3E) ˆ 9.4, J(3E,4E) ˆ 9.4, J(4E,5E) ˆ 9.4, J(1C,2C) ˆ 7.9, J(2C,3C) ˆ 9.9, J(3C,4C) ˆ 9.9, J(4C,5C) ˆ 9.9,
2
J(5C,6aC) ˆ 4.2, J(5C,6bC) ˆ 1.6, J(6aC,6bC) ˆ 12.0, JAB ˆ 12.0. 31P-NMR (121.5 MHz, (D5)pyridine): À2.63.
ESI-MS (C66H83N4O28PSi (1439.45, 1438.47)): 1437.46137 ([M À H]À; calc. 1437.46279).
O-3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-3-O-acetyl-2-(acetylamino)-6-
O-[(tert-butyl)diphenylsilyl]-2-deoxy-b-d-glucopyranosyl-(1 ! 2)-4-O-acetyl-3-O-(aminocarbonyl)-a-d-gluco-
pyranuronamide 1-[(2R)-2-(Hexadecyloxy)-3-methoxy-3-oxopropyl 2,2,2-Trichloro-1,1-dimethylethyl Phos-
phate] (17b). As described for 17a, with 1H-1,2,4-triazole (15.2 mg, 0.22 mmol), CH2Cl2/pyridine 4 :1
(0.6 ml), 2,2,2-trichloro-1,1-dimethylethyl phosphorodichloridite (12 ml, 0.058 mmol), 10c (50.0 mg,
0.046 mmol), CH2Cl2/pyridine 7 :1 (2.0 ml), methyl 2-O-hexadecylglycerate [31] (36.0 mg, 0.10 mmol),
CH2Cl2/pyridine 7:1 (0.6 ml), bis(trimethylsilyl) peroxide (18 ml, 0.87 mmol): P-diastereoisomer mixture 17b
(2.5 :1; 13.1 mg, 17%). Rf (CH2Cl2/MeOH 8 :1): 0.50, 0.49. 1H-NMR (1H,1H-COSY; 600 MHz, (D5)pyridine;
major isomer in the mixture): 8.90 (d, NHAc); 8.78, 7.83 (2 br. s, NH2); 8.40 7.00 (m, NHAc, NH2); 6.50 (br. s,
HÀC(1F)); 6.06 6.00 (m, HÀC(3F), HÀC(3C), HÀC(4F)); 5.70 5.67 (overlapped by solvent, HÀC(3E)); 5.51
(d, HÀC(1C)); 5.41 (t, HÀC(4C)); 5.14 (d, HÀC(1E)); 5.07 5.04 (m, HÀC(5F)); 4.94 4.53 (m, HÀC(2H),
CH2(3H), CH2(1I), HaÀC(6C)); 4.49 4.44 ( m, HÀC(2E), HÀC(4E)); 4.31 4.26 (m, HÀC(2F), HbÀC(6C));
4.23 4.16 (m, CH2(6E)); 4.06 4.03 (m, HÀC(2C)); 3.99 3.96 (m, HÀC(5C)); 3.73 (s, MeO); 3.65 3.61 (m,
HÀC(5E)); 2.25, 2.22, 2.18, 2.16, 2.11, 2.02, 2.01, 2.00, 1.99 (9s, 7 MeCO, 2 Me); 1.28 1.24 (m, (CH2)14); 1.20 (s,
Me3C); 0.86 (t, Me of unit I); J(1E,2E) ˆ 8.3, J(1C,2C) ˆ 7.8, J(3C,4C) ˆ 9.9, J(4C,5C) ˆ 9.9, 2J(H,NH) ˆ 7.9.
31P-NMR (121.5 MHz, (D5)pyridine): À8.96 (major isomer), À8.41 (minor isomer).
O-2-(Acetylamino)-2-deoxy-b-d-glucopyranosyl-(1 ! 4)-O-2-(acetylamino)-2-deoxy-b-d-glucopyranosyl-
(1 ! 2)-3-O-(aminocarbonyl)-a-d-glucopyranuronamide 1-[(2R)-2-Carboxy-2-(hexadecyloxy)ethyl Hydrogen
Phosphate] (20b). As described for 18a, with 17b (13.0 mg, 8.0 mmol), pyridine (2.0 ml), ZnÀCu (40.0 mg,
‡
0.60 mmol), pentane-2,4-dione (55 ml, 47 mmol), and Dowex 50 W X2 (H form, 2.00 g). The crude 18b was
dissolved in dry THF (0.50 ml), 1m Bu4NF in THF (80 ml) was added, and the mixture stirred at 208 for 40 min
(TLC (CH2Cl2/MeOH 4 :1) monitoring). The mixture was evaporated, the residue dried and then dissolved in
degassed (Ar stream, sonication) MeOH (p.a)/H2O (bidist.) 2 :1 (0.50 ml), and the soln. cooled to 08. Then 0.3m
LiOH (degassed; 0.22 ml, 8 equiv.) was added, and the mixture was stirred at 08 for 30 min, then at 208 for 6 h.
‡
Excess base was neutralized by addition of Dowex 50 W X2 (H form). Stirring at 208 was continued for 5 min.
After filtration, the resin was washed with MeOH/H2O 1:1. The combined filtrate and washings were
evaporated, and the remaining aq. soln. was lyophilized. The crude product was purified by FC (CHCl3/MeOH/
H2O 18 :11:2.7) to yield three compounds which were shown by ESI-MS to be incompletely deprotected
products. The 1st compound (ESI-MS: 1047.46264 ([M À H]À)) contained the COOMe group, the 2nd (ESI-
MS: 1089.46987 ([M À H]À)) 1 Ac and the COOMe group, and the 3rd (ESI-MS: 1131.47812 ([M À H]À)) 2 Ac
and the COOMe group. The mixture was submitted to the deprotection conditions as described above (0.3m
LiOH (0.11 ml, 4 equiv., 3 h). FC (CHCl3/MeOH/H2O 18 :11:2.7), and filtration through Sephadex LH 20 with
MeOH/H2O 1:1 yielded 20b (4.0 mg, 49%). Rf (CHCl3/MeOH/H2O 18 :11:2.7): 0.20. 1H-NMR (1H,1H-COSY;

Helvetica Chimica Acta Vol. 87 (2004)
1823
600 MHz, CD3OD): 5.92 (br. s, HÀC(1F)); 5.07 (t, HÀC(3F)); 4.64 (d, HÀC(1E)); 4.45 (d, HÀC(1C)); 4.32 (d,
HÀC(5F)); 4.31 4.10 (m, CH2(3H), HÀC(2H); 3.90 (br. d, HaÀC(6E)); 3.79(br. d, HaÀC(6C)); 3.73 (dd,
HÀC(2C)); 3.71 (t, HÀC(4F)); 3.66 3.56 (m, HÀC(2E), HÀC(2F), HbÀC(6E), HbÀC(6C), OCH2I ); 3.51 (t,
HÀC(4E)); 3.42 (t, HÀC(3C)); 3.36 3.29( m, HÀC(3E), HÀC(4C), HÀC(5E), HÀC(5C)); 2.01, 1.99 (2s, 2
MeCO); 1.59 1.66, 1.28 1.39 (2 m, (CH2)I14); 0.90 (t, MeI); J(2F,3F) ˆ 9.4, J(3F,4F) ˆ 9.4, J(4F,5F) ˆ 9.4,
J(1E,2E) ˆ 8.0, J(3E,4E) ˆ 9.0, J(4E,5E) ˆ 9.0, J(6aE,6bE) ˆ 11.4, J(1C,2C) ˆ 8.4, J(2C,3C) ˆ 9.9, J(3C,4C) ˆ
9.9, J(6aC,6bC) ˆ 12.4. 13C-NMR (1H,13C-COSY; 100 MHz, CD3OD): 102.74, 102.44, 95.56 (C(1F)); 80.62, 78.91,
77.14, 75.31, 75.00, 73.69, 72.62, 71.32, 71.22, 70.92, 70.70, 70.43, 66.22, 61.55, 60.36, 57.17, 56.17, 32.06, 29.81-29.40,
26.12, 22.72, 20.04, 13.42. ESI-MS (C42H75N4O23P (1035.04, 1034.46)): 1033.44931 ([M À H]À; calc. 1033.44869).
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Received December 17, 2003