Selective acetolysis of 6-deoxy-sugar oligosaccharide building blocks governed by the armed-disarmed effect

Article abstract of DOI:10.1016/j.tetlet.2008.02.090

The effect of the arming-disarming protection in the acetolysis of 6-deoxy-sugar oligosaccharides has been for the first time systematically investigated. Starting from the newly synthesized methyl glycosides, the acetolysis conditions employed here afforded 1-O-Ac oligosaccharides selectively without cleavage of the interglycosidic bonds, if a suitable protecting group pattern was used. Actually, the behavior of armed-disarmed, armed-armed, and disarmed-disarmed 6-deoxy-sugar disaccharides in acetolysis reactions was investigated: the results fit well with the prediction made on the basis of the armed-disarmed effect.

Full text of DOI:10.1016/j.tetlet.2008.02.090

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2546–2551
Selective acetolysis of 6-deoxy-sugar oligosaccharide building
blocks governed by the armed–disarmed effect
Emiliano Bedini *, Daniela Comegna , Annalida Di Nola, Michelangelo Parrilli
`
Dipartimento di Chimica Organica e Biochimica, Universita di Napoli ‘Federico II’, Complesso Universitario Monte Santangelo,
Via Cintia 4, 80126 Napoli, Italy
Received 24 January 2008; revised 15 February 2008; accepted 18 February 2008
Available online 21 February 2008
Abstract
The effect of the arming–disarming protection in the acetolysis of 6-deoxy-sugar oligosaccharides has been for the first time system-
atically investigated. Starting from the newly synthesized methyl glycosides, the acetolysis conditions employed here afforded 1-O-Ac
oligosaccharides selectively without cleavage of the interglycosidic bonds, if a suitable protecting group pattern was used. Actually,
the behavior of armed–disarmed, armed-armed, and disarmed–disarmed 6-deoxy-sugar disaccharides in acetolysis reactions was investi-
gated: the results fit well with the prediction made on the basis of the armed–disarmed effect.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Acetolysis; 6-Deoxy-sugar; Armed–disarmed; Oligosaccharide
The armed–disarmed concept refers to the relative ease
or difficulty of activating a sugar as a glycosyl donor in
glycosylation reactions.1 Disarmed glycosyl donors have
highly electron withdrawing protecting groups (e.g., esters,
amides) that destabilize the formation of the oxycarbenium
ion/ion pair2 during the course of the glycosylation,
whereas less electron withdrawing protecting groups (e.g.,
ethers) are less destabilizing and therefore arm the glycosyl
donor. The armed–disarmed concept had tremendous
importance in the study and development of glycosylation
reactions,3 and its re-examinations and extensions to other
reactions involving the anomeric position are still the
object of several works of great importance in the field.4
Acetolysis of carbohydrates is a widely used reaction
consisting in the cleavage of the glycosidic bond and the
contemporary acetylation of hydroxyl groups thus formed
and/or present before the solvolysis. Acetolysis finds exten-
sive application as selective degradation method used for
the structural elucidation of polysaccharides, especially
when they contain (1?6) glycosidic linkages, which are
extremely labile to acetolysis.5 Similarly, the conversion
of alkyl and aryl glycosides into 1-O-acetylated derivatives
is commonly accomplished by acetolysis on monosaccha-
rides6 as well as oligosaccharides:7 this reaction is often
of key importance in an oligosaccharide synthesis, since
1-O-Ac derivatives could be easily converted into both
glycosyl donors and glycosyl acceptors. Nevertheless, to
the best of our knowledge, there is only one systematic
report on the synthetic aspects of acetolysis of oligosaccha-
rides; it concerns the comparison of reaction rate in
peracetylated methyl glucobiosides.8
In this work, the effect of the arming–disarming protec-
tion in the acetolysis of 6-deoxy-sugar oligosaccharides is
systematically investigated.9 In principle, the armed–
disarmed strategy could help to activate or stabilize the
anomeric positions of an oligosaccharide and therefore to
foresee its behavior during acetolysis, as already demon-
strated in an analogue case regarding the solvolysis of
caged 1,6-anhydro-pyranoses.10 If the armed–disarmed
concept would be joined with reaction conditions that are
mild enough to discriminate between armed and disarmed
*
Corresponding author. Tel.: +39 81 674153; fax: +39 81 674393.
E-mail address: ebedini@unina.it (E. Bedini).
`
Present address: Dipartimento di Chimica, Universita di Salerno, Via
Ponte don Melillo, 84084 Fisciano/Salerno, Italy.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.090

E. Bedini et al. / Tetrahedron Letters 49 (2008) 2546–2551
2547
positions, the selective acetolysis of oligosaccharide
building blocks could be accomplished in an easily foresee-
able manner. For this purpose, a set of 6-deoxy-sugar
disaccharide methyl glycosides with differently protected
2-O-positions was chosen as suitable model compounds.
The synthesis of these disaccharides is presented in Scheme
1. Compounds 3–5 and 7–9 were obtained from the known
disaccharide 1.11 De-O-benzensulfonylation with sodium
OSO2Bn
O
OR
i. DMSO, Ac2O, 50 °C
O
O
BnO
BnO
AllO
BnO
B
NaNH2, DMF, 70 °C
64%
ii. NaBH4, 9:1 THF/MeOH, 0 °C
OBn
O
OBn
O
OBn
O
AllO
AllO
HO
BnO
O
BnO
BnO
73%
A
O
O
1
2: R=H
6: R=H
OMe
OMe
OMe
Ac2O, py
99%
Ac2O, py
92%
3: R=Ac
7: R=Ac
BzCl, py
83%
BzCl, py
91%
4: R=Bz
8: R=Bz
9: R=Bn
BnBr, NaH
DMF, 0 °C
BnBr, NaH
C
DMF, 0 °
5: R=Bn
93%
74%
NH
O
CCl3
OBn
O
OBn
O
BnO
1% TMSOTf , -20°C
A
BnO
HO
O
+
+
O
BnO
AW-300 4Å MS, CH2Cl2
BnO
OMe
O
B
OMe
OMe
98%
OBz
O
BnO
12
10
11
BnO
OBz
NH
CCl3
OMe
A
O
1% TMSOTf , -20 °C
BnO
O
BnO
O
AW-300 4Å MS, CH2Cl2
BnO
BnO
O
OAc
HO
99%
OBz
OAc
13
O
11
B
14
BnO
BnO
OBz
Scheme 1. Synthesis of a set of 6-deoxy-sugar disaccharide methyl glycosides.
Table 1
Screening of acetolysis conditions on model compound 4
Entry
1
Protocol
Time
30 h
Productsa (% Yield)
A
OBz
O
OBz
O
BnO
B
BnO
AllO
AllO
OAc
O
O
OBn
OBn
O
A
O
AcO
AcO
OAc
15 (50%)
16 (25%)
OBz
O
BnO
AllO
B
OBn
O
BnO
A
O
17 (15%)
OAc
2
3
4
B
C
D
48 h
17 h
17 h
No reaction
17 (62%)
17 (46%)
Reaction conditions: (A) ZnCl2 (10 equiv). 2:1 v/v Ac2O/AcOH, 0 °C; (B) NalÁBF3ÁEt2O, 9:2 v/v CH3CN/AC2O, rt; (C) 10:10:1 v/v/v Ac2O/AcOH/TFA.
70 °C; (D) CSA, Ac2O, 70 °C.
a
Isolated yield.

2548
E. Bedini et al. / Tetrahedron Letters 49 (2008) 2546–2551
Table 2
Acetolysis of 6-deoxy-sugar oligosaccharide methyl glycosides
Entry
Oligosaccharide
Productsa (% yields)
Reaction condition
Time
19 h
OSO2Bn
O
BnO
AllO
OBn
1
1
A
O
BnO
O
18 (51%)
OAc
OAc
OAc
O
BnO
AllO
OBn
O
2
3
A
17 h
BnO
O
(71%)
19
OBn
OBn
O
O
BnO
AllO
BnO
AcO
3
5
A
30 h
OAc
OAc
(42%)
20
21 (57%)
(13%)
5
(15%)
21
20 (60%)
OBn
O
OBn
BnO
AllO
O
OBn
O
BnO
AcO
4
5
5
A
A
11 h
BnO
O
OMe
22 (15%)
23 (45%)
OAc
O
BnO
AllO
B
OBn
O
AcO
7
17 h
BnO
O
A
24 (69%)
OAc
OAc
O
BnO
AllO
OBn
O
BzO
BnO
O
6
8
A
16 h
(66%)
25
(22%)
21
(9%)
7
O
O
BnO
AllO
OBn
BnO
AllO
O
BnO
BnO
7
9
A
14 h
BnO
O
OAc
b
OAc
26 (30%)
(38%; / =3:1)
α β
27
OBn
O
BnO
O
OAc
8
12
A
20 h
O
BnO
BnO
OBz
28 (54%)

E. Bedini et al. / Tetrahedron Letters 49 (2008) 2546–2551
2549
Table 2 (continued)
Entry
9
Oligosaccharide
14
Productsa (% yields)
Reaction condition
A
Time
30 h
14 (64%)
OAc
OMe
Me
Me
O
O
MeO
O
MeO
O
107j
B
30 h
MeOOC
MeOOC
MeO
MeO
O
O
MeO
MeO
OMe
OMe
AcO
AcO
29
30 (67%)
OBz
O
BzO
AllO
OBz
O
BzO
O
OAc
11
31 (95%)
A
25 h
O
BzO
AcO
O
O
BzO
O
OMe
31
OBz
O
BzO
AllO
D
OBz
O
BzO
C
O
OAc
12
31
C
80 min
O
BzO
AcO
B
O
O
BzO
A
O
32 (76%)
OAc
Reaction conditions: (A) 10:10:1 v/v/v/ Ac2O/AcOH/TFA, 70 °C; (B) 10:10:0.5 v/v/v Ac2O/AcOH/TFA, 60 °C; (C) 50:20:0.5 v/v/v Ac2O/AcOH/H2SO4,
0 °C.
a
Isolated yield.
b
Anomeric ratio measured by 1H NMR.
amide12 gave alcohol 2 that was protected with an acetyl,
benzoyl, or benzyl group to give compounds 3, 4, and 5,
respectively. In addition, alcohol 2 was epimerized via oxi-
dation/reduction to give D-quinovose-D-rhamnose disac-
charide 6, which was acetylated, benzoylated, or
benzylated to afford compounds 7, 8, and 9, respectively.
Disaccharides 12 and 14 were obtained by glycosylation
of trichloroacetimidate donor 1113 with glycosyl acceptors
1014 and 13,15 respectively.
The next step of this work was the screening of acetol-
ysis conditions that would be mild enough to point out
the armed–disarmed effect.16 A slight modification17 of
the known procedure using freshly fused ZnCl2 in Ac2O18
(10 instead of 20 equiv of ZnCl2; 0 °C instead of rt) was
firstly tested on model compound 4 (Table 1, entry 1).
MALDI-MS analysis of the crude reaction mixture
revealed the absence of monosaccharide species obtained
by the acetolytic cleavage of the interglycosidic bond, but
the desired compound 17 was obtained in only 15% yield,
whereas the furanose 1,5-di-O-Ac-derivatives 1519 and 16
were isolated as the main products (50% and 25% yields,
respectively). The BF3ÁOEt2/NaI/Ac2O reagent system
was recently reported to convert selectively primary benzyl
and anomeric methyl groups into acetyls,20 but 4 was
recovered unaltered after 48 h. Finally, a slight modifica-
tion of a recently reported selective acetolysis7j (10:10:1
v/v/v Ac2O/AcOH/TFA at 70 °C; entry 3) was found to
give the conversion of the methyl glycoside into the 1-O-
acetyl derivative 17 in good yield (62%) with neither cleav-
age of the interglycosidic bond nor significant production
of furanose species. Similar results were obtained with
CSA/Ac2O at 70 °C21 but in slightly lower yield (entry 4).
The previously synthesized disaccharides were therefore
subjected to acetolysis with 10:10:1 v/v/v Ac2O/AcOH/
TFA at 70 °C.22 The results are summarized in Table 2.
They demonstrate that the acetolysis was strictly dependent
on the arming–disarming protection of the 2-O-positions.
Actually, when the monose unit A was protected with an
arming benzyl group at position O-2 and the B one carried
a 2-O-disarming ester or sulfonate protecting group
(compounds 1, 3, 7, 8, 12, entries 1, 2, 5, 6, 8), the acetolysis
proceeded selectively at the armed anomeric position,

2550
E. Bedini et al. / Tetrahedron Letters 49 (2008) 2546–2551
whatever the configuration of the C-2B was.19 Indeed, TLC
and MALDI-MS analysis of the crude reaction mixtures
demonstrated in all cases that only traces of the monosac-
charide compounds as well as disaccharide furanose species
could be detected. A very similar literature case7j is also
reported (entry 10): still in accordance with the armed–dis-
armed concept, the 1-O-Ac disaccharide 30 was obtained.
On the contrary, the acetolysis of the disarmed–disarmed
disaccharide 14 was expected to proceed noticeably more
slowly. Indeed, after 30 h at 70 °C the desired 1-O-Ac
disaccharide was detected in very low quantities (65%)
whereas the starting compound was recovered in 64% yield
(entry 9). Finally, the acetolysis of the armed-armed disac-
charides 5 and 9 gave contemporary cleavage of both
glycosidic linkages as expected, affording 1-O-acetyl-
ated monosaccharide derivatives as main products
(entries 3, 4, 7). The hypothesis that the cleavage of the
interglycosidic bond started only after the complete acetol-
ysis of the methyl aglycone was ruled out by quenching the
acetolysis before the complete disappearance of the starting
material: a high amount of monosaccharide compounds
was obtained anyway (entry 4). It is also worth noting that
D-quinovose-D-rhamnose 1-O-Ac disaccharide 26 was
recovered in double yield with respect to the D-rhamnose-
D-rhamnose analogue 22 (entries 4 and 7), as expected from
the greater acetolysis rate of manno-configured sugars with
respect to the gluco-configured ones.23
The last two entries regard the acetolysis of the tetrasac-
charide methyl glycoside 31,24 which carries disarming acyl
groups at positions O-2B, O-2C, and O-2D and is glycosyl-
ated at position O-2A. Acetolysis with 10:10:1 v/v/v Ac2O/
AcOH/TFA at 70 °C did not affect 31 (entry 11), as
expected because of the less arming effect of the carbohy-
drate moiety on O-2A with respect to a benzyl group.25
Nevertheless, stronger conditions (50:20:0.5 v/v/v Ac2O/
AcOH/H2SO4 at 0 °C) were proven to be effective for the
conversion of 31 into 3219 in good yield (76%) without
affecting the interglycosidic bonds, still in agreement with
the armed–disarmed concept (entry 12).
References and notes
1. (a) Mootoo, D. R.; Konradsson, P.; Udodong, U. E.; Fraser-Reid, B.
J. Am. Chem. Soc. 1988, 110, 5583–5584; (b) Fraser-Reid, B.; Wu, Z.
F.; Udodong, U. E.; Ottosson, H. J. Org. Chem. 1990, 55, 6068–6070;
(c) Fraser-Reid, B.; Wu, Z.; Andrews, C. W.; Skowronski, E. J. Am.
Chem. Soc. 1991, 113, 1434–1435.
2. Crich, D.; Hutton, T. K.; Banerjee, A.; Jayalath, P.; Picione, J.
Tetrahedron: Asymmetry 2005, 16, 105–119.
3. Garegg, P. J. Adv. Carbohydr. Chem. Biochem. 2004, 59, 69–134.
4. Some recent examples: (a) Li, Z.; Gildersleeve, J. C. J. Am. Chem.
Soc. 2006, 128, 11612–11619; (b) Li, Z.; Gildersleeve, J. C. Tetrahe-
dron Lett. 2007, 48, 559–562; (c) Crich, D.; Li, M. Org. Lett. 2007, 9,
4115–4118; (d) Pedersen, C. M.; Nordstrøm, L. U.; Bols, M. J. Am.
Chem. Soc. 2007, 129, 9222–9235; (e) Jensen, H. H.; Pedersen, C. M.;
Bols, M. Chem. Eur. J. 2007, 13, 7576–7582.
5. The Polysaccharides; Aspinall, G. O., Ed.; Academic Press: London,
United Kingdom, 1982; Vol. 1, pp 64–66.
6. Guthrie, R. D.; McCarthy, J. F. Adv. Carbohydr. Chem. Biochem.
1967, 22, 11–23.
7. Some examples: (a) Bebault, G. M.; Dutton, G. S. Can. J. Chem.
1972, 50, 3373–3378; (b) Bebault, G. M.; Dutton, G. S. Can. J. Chem.
1974, 52, 678–683; (c) Bebault, G. M.; Dutton, G. S.; Funnell, N. A.
Can. J. Chem. 1974, 52, 3844–3846; (d) Bebault, G. M.; Dutton, G.
M.; Warfield, C. K. Carbohydr. Res. 1974, 34, 174–179; (e) Wessel,
H.-P.; Bundle, D. R. Carbohydr. Res. 1983, 124, 301–311; (f) Abbas,
S. A.; Matta, K. L. Carbohydr. Res. 1983, 124, 115–121; (g) Wang,
L.-X.; Lee, Y. C. J. Chem. Soc., Perkin Trans. 1 1996, 581–591; (h)
Bedini, E.; Parrilli, M.; Unverzagt, C. Tetrahedron Lett. 2002, 43,
8879–8882; (i) Nifantiev, N. E.; Sherman, A. A.; Yudina, O. N.;
Cheshev, P. E.; Tsvetkov, Y. E.; Khatuntseva, E. A.; Kornilov, A. V.;
Shashkov, A. S. Pure Appl. Chem. 2004, 76, 1705–1714; (j) Fekete, A.;
´
´
´
Gyergyoi, K.; Ko¨ver, K. E.; Bajza, I.; Liptak, A. Carbohydr. Res.
2006, 341, 1312–1321; (k) Meloncelli, P. J.; Williams, T. M.;
Hartmann, P. E.; Stick, R. V. Carbohydr. Res. 2007, 342, 1793–
1804; (l) Reiffarth, D.; Reimer, K. B. Carbohydr. Res. 2008, 343, 179–
188.
8. Rosenfeld, L.; Ballou, C. E. Carbohydr. Res. 1974, 32, 287–298.
9. The choice of 6-deoxy-sugars allowed us to focus the attention
exclusively on the acetolysis of the anomeric positions, avoiding the
acetolysis of ethereal protecting groups potentially present on primary
hydroxyl positions.6
10. Burgey, C.; Vollerthun, R.; Fraser-Reid, B. Tetrahedron Lett. 1994,
35, 2637–2640.
11. Bedini, E.; Carabellese, A.; Barone, G.; Parrilli, M. J. Org. Chem.
2005, 70, 8064–8070.
12. Awad, L. F.; El Ashry, E. S.; Schuerch, C. Bull. Chem. Soc. Jpn. 1986,
100, 411–417.
13. Lemanski, G.; Ziegler, T. Eur. J. Org. Chem. 2006, 2618–2630.
14. Zou, W.; Sen, A. K.; Szarek, W. A.; MacLean, D. B. Can. J. Chem.
1993, 71, 2194–2200.
15. Nifantiev, N. E.; Lipkind, G. M.; Shashkov, A. S.; Kochetkov, N. K.
Carbohydr. Res. 1992, 223, 109–128.
16. The typical acetolysis condition employed on non-deoxy-sugars (1%
H2SO4 in Ac2O at 0 °C) gave uncontrollable reactions on the 6-deoxy-
sugar oligosaccharides studied here, yielding only traces of the desired
1-O-Ac derivatives.
17. Lam, S. N.; Gervay-Hague, J. Carbohydr. Res. 2002, 337, 1953–1965.
18. Yang, G.; Ding, X.; Kong, F. Tetrahedron Lett. 1997, 38, 6725–6728.
19. Analytical and spectral data of selected compounds: Compound 15:
[a]D +5.9 (c 0.8, CH2Cl2); 1H NMR (500 MHz, CDCl3): d 8.07–7.26
(m, 15H, H-Ar), 6.22 (d, 1H, J1,2 = 3.0 Hz, H-1A), 5.87 (m, 1H,
OCH2CH@CH2), 5.38 (dd, 1H, J2,3 = 3.4 Hz, J2,1 = 2.0 Hz, H-2B),
5.28 (dd, 1H, Jvic = 18.0 Hz, Jgem = 1.5 Hz, trans OCH2CH@CHH),
5.18 (q, 1H, J5,6 = J5,4 = 6.0 Hz, H-5A), 5.12 (dd, 1H, Jvic = 10.0 Hz,
Jgem = 1.5 Hz, cis OCH2CH@CHH), 4.94 (d, 1H, Jgem = 11.0 Hz,
OCHHPh), 4.91 (d, 1H, J1,2 = 2.0 Hz, H-1B), 4.64 (m, 3H,
In our opinion, this selective acetolysis reaction based
on the armed–disarmed strategy could arise as a useful tool
for 6-deoxy-sugar chemistry. Actually, it was demonstrated
that the behavior of 6-deoxy-sugar oligosaccharide build-
ing blocks in this reaction can be easily predicted on the
basis of the arming–disarming protecting group pattern.
Moreover, the already scatterly reported examples of
methyl oligosaccharide acetolysis on 6-deoxy-sugar con-
taining compounds7a–d,l fit well with the behavior systemat-
ically reported here. Therefore, this study provides a new
valuable tool for protecting group manipulation strategies
in oligosaccharide total synthesis.
Acknowledgments
NMR and MS facilities of CIMCF (Centro di Metodol-
ogie Chimico-Fisiche) of University of Naples ‘Federico II’
are gratefully acknowledged.

E. Bedini et al. / Tetrahedron Letters 49 (2008) 2546–2551
2551
3OCHHPh), 4.43 (t, 1H, J3,4 = J3,2 = 5.4 Hz, H-3A), 4.20 (m, 2H,
H-4A, OCHHCH@CH2), 4.09 (m, 2H, H-5B, OCHHCH@CH2), 3.96
(m, 2H, H-2A, H-3B), 3.49 (t, 1H, J4,5 = J4,3 = 9.0 Hz, H-4B), 2.08 (s,
3H, CH3CO), 2.06 (s, 3H, CH3CO), 1.31 (d, 3H, J6,5 = 6.0 Hz, H-6A),
1.21 (d, 3H, J6,5 = 6.0 Hz, H-6B); 13C NMR (CDCl3, 50 MHz) d
169.9, 169.8, 165.5 (3CO), 138.6, 137.1 (2Cipso-Bn), 134.6
(OCH2CH@CH2), 133.1 (Cipso-Bz), 129.9–127.6 (C-Ar), 117.3
(OCH2CH@CH2), 99.5, 98.3 (C-1A, C-1B), 81.4, 80.8, 79.7, 77.4,
76.6, 75.0, 72.5, 70.6, 69.7, 68.6, 68.5 (C-2A, C-2B, C-3A, C-3B, C-4A,
C-4B, C-5A, C-5B, 2OCH2Ph, OCH2CH@CH2), 21.4, 21.2 (2CH3CO),
18.2, 16.4 (C-6A, C-6B). MALDI-MS for C40H46O12 (m/z): Mr (calcd)
718.30, Mr (found) 741.03 (M+Na)+. Anal. Calcd: C, 66.84; H, 6.45.
Found: C, 66.68; H, 6.32.
C-3B, C-4A, C-4B, C-5A, C-5B, 3OCH2Ph, OCH2CH@CH2), 21.1, 20.7
(2CH3CO), 18.0, 17.9 (C-6A, C-6B). MALDI-MS for C40H48O11
(m/z): Mr (calcd) 704.32, Mr (found) 727.03 (M+Na)+. Anal. Calcd:
C, 68.16; H, 6.86. Found: C, 68.30; H, 7.00.
Compound 32: [a]D À65.9 (c 1.6, CH2Cl2); 1H NMR (400 MHz,
CDCl3): d 8.13–7.24 (m, 30H, H-Ar), 6.26 (d, 1H, J1,2 = 1.8 Hz,
H-1A), 5.68 (dd, 1H, J2,3 = 3.4 Hz, J2,1 = 1.6 Hz, H-2C), 5.65 (t, 1H,
J4,5 = J4,3 = 9.8 Hz, H-4C), 5.51–5.38 (m, 3H, H-3B, H-4A,
OCH2CH@CH2), 5.33 (br s, 1H, H-1C), 5.30–5.22 (m, 4H, H-1D,
H-2D, H-4B, H-4D), 5.08 (dd, 1H, J2,3 = 3.3 Hz, J2,1 = 2.0 Hz, H-2B),
5.00 (d, 1H, J1,2 = 1.6 Hz, H-1B), 4.87 (dd, 1H, Jvic = 17.4 Hz,
Jgem = 1.6 Hz, trans OCH2CH@CHH), 4.77 (dd, 1H, Jvic = 10.2 Hz,
Jgem = 1.6 Hz, cis OCH2CH@CHH), 4.59 (dd, 1H, J3,4 = 9.8 Hz,
J3,2 = 3.2 Hz, H-3C), 4.31–4.20 (m, 3H, H-3A, H-5B, H-5C), 4.08 (dd,
1H, J2,3 = 3.3 Hz, J2,1 = 1.8 Hz, H-2A), 4.03 (dq, 2H, J5,4 = 9.7 Hz,
J5,6 = 6.2 Hz, H-5A, H-5D), 3.82 (dd, 1H, J3,4 = 9.8 Hz, J3,2 = 3.2 Hz,
H-3D), 3.75 (dd, 1H, Jgem = 12.0 Hz, Jvic = 5.4 Hz, OCHHCH@CH2),
3.57 (dd, 1H, Jgem = 12.0 Hz, Jvic = 5.4 Hz, OCHHCH@CH2), 2.18
(s, 3H, COCH3), 1.93 (s, 3H, COCH3), 1.60 (s, 3H, COCH3), 1.38 (d,
3H, J6,5 = 6.2 Hz, H-6A), 1.34 (d, 3H, J6,5 = 6.2 Hz, H-6C), 1.26 (d,
3H, J6,5 = 6.2 Hz, H-6D), 1.14 (d, 3H, J6,5 = 6.2 Hz, H-6B). 13C NMR
(100 MHz, CDCl3): d 169.3, 168.7, 168.6 (3C@O Ac), 166.1, 165.9,
165.5, 165.4, 165.2, 165.1 (6C@O Bz), 134.0 (OCH2CH@CH2), 133.5–
132.8 (6Cipso), 130.0–128.2 (C-Ar), 117.2 (OCH2CH@CH2), 100.3,
99.8, 99.3 (C-1B, C-1C, C-1D), 92.1 (C-1A), 77.7, 75.2, 73.9, 73.1, 73.0,
72.5, 72.2, 71.5, 70.2, 70.0, 69.6, 69.2, 68.4, 67.9, 67.8, 67.7,60.4 (C-2A,
C-2B, C-2C, C-2D, C-3A, C-3B, C-3C, C-3D, C-4A, C-4B, C-4C, C-4D,
C-5A, C-5B, C-5C, C-5D, OCH2CH@CH2), 21.0, 20.5, 20.2 (3
CH3C@O), 17.8, 17.7, 17.5, 17.4 (C-6A, C-6B, C-6C, C-6D).
MALDI-MS for C75H76O26 (m/z): Mr (calcd) 1392.46, Mr (found)
1415.06 (M+Na)+. Anal. Calcd: C, 64.65; H, 5.50. Found: C, 64.41;
H, 5.29.
Compound 17: [a]D À2.5 (c 1.2, CH2Cl2); 1H NMR (200 MHz,
CDCl3): d 8.07–7.16 (m, 20H, H-Ar), 6.14 (d, 1H, J1,2 = 2.0 Hz, H-
1A), 5.84 (m, 1H, OCH2CH@CH2), 5.68 (dd, 1H, J2,1 = 1.6 Hz,
J2,3 = 3.4 Hz,
H-2B),
5.25–5.21
(m,
2H,
H-1B,
trans
OCH2CH@CHH), 5.08 (dd, 1H, Jvic = 10.2 Hz, Jgem = 1.8 Hz, cis
OCH2CH@CHH), 4.95 (d, 1H, Jgem = 11.0 Hz, OCHHPh), 4.90 (d,
1H, Jgem = 11.0 Hz, OCHHPh), 4.79 (d, 1H, Jgem = 12.0 Hz,
OCHHPh), 4.72–4.62 (m, 3H, 3OCHHPh), 4.19 (dd, 1H,
Jgem = 12.0 Hz, Jvic = 5.0 Hz, OCHHCH@CH2), 4.12–4.05 (m, 2H,
H-3A, OCHHCH@CH2), 3.98 (dd, 1H, J3,2 = 3.2 Hz, J3,4 = 9.2 Hz,
H-3B), 3.91–3.65 (m, 4H, H-2A, H-4A, H-5A, H-5B), 3.51 (t, 1H,
J4,5 = J4,3 = 9.6 Hz, H-4B), 2.06 (s, 3H, CH3CO), 1.32 (d, 3H,
J6,5 = 6.2 Hz, H-6B), 1.29 (d, 3H, J6,5 = 6.2 Hz, H-6A); 13C NMR
(CDCl3, 50 MHz) d 169.2, 165.5 (2CO), 138.6, 137.8, 137.5 (3Cipso
-
Bn), 134.6 (OCH2CH@CH2), 133.1 (Cipso-Bz), 129.8–125.3 (C-Ar),
117.1 (OCH2CH@CH2), 99.5 (C-1B), 91.2 (C-1A), 80.1, 79.9, 77.6,
77.4, 76.7, 75.5, 75.2, 72.6, 72.5, 70.6, 69.6, 68.4 (C-2A, C-2B, C-3A, C-
3B, C-4A, C-4B, C-5A, C-5B, 3 OCH2Ph, OCH2CH@CH2), 21.0
(CH3CO), 18.2, 18.1 (C-6A, C-6B). MALDI-MS for C45H50O11 (m/z):
Mr (calcd) 766.34, Mr (found) 789.42 (M+Na)+. Anal. Calcd: C,
70.48; H, 6.57. Found: C, 70.28; H, 6.34.
20. Brar, A.; Vankar, Y. D. Tetrahedron Lett. 2006, 47, 5207–
5210.
Compound 24: [a]D +60.6 (c 1.4, CH2Cl2); 1H NMR (200 MHz,
CDCl3): d 7.41–7.26 (m, 15H, H-Ar), 6.16 (m, 1H, H-1A), 5.89 (m,
1H, OCH2CH@CH2), 5.23 (dd, 1H, Jvic = 17.4 Hz, Jgem = 1.6 Hz,
trans OCH2CH@CHH), 5.21 (br s, 1H, H-1B), 5.12 (dd, 1H,
Jvic = 10.2 Hz, Jgem = 1.6 Hz, cis OCH2CH@CHH), 4.99 (d, 1H,
Jgem = 11.6 Hz, OCHHPh), 4.87 (m, 2H, H-2B, OCHHPh), 4.77 (d,
1H, Jgem = 11.6 Hz, OCHHPh), 4.70–4.57 (m, 3H, 3OCHHPh), 4.24
(m, 2H, OCH2CH@CH2), 4.02–3.86 (m, 3H, H-3A, H-3B, H-5B), 3.78
(m, 2H, H-2A, H-5A), 3.63 (t, 1H, J4,3 = J4,5 = 9.4 Hz, H-4A), 3.17 (t,
1H, J4,3 = J4,5 = 10.0 Hz, H-4B), 2.10 (s, 3H, COCH3), 1.79 (s, 3H,
COCH3), 1.26 (d, 3H, J6,5 = 5.6 Hz, H-6A), 1.18 (d, 3H, J6,5 = 6.2 Hz,
H-6B); 13C NMR (CDCl3, 50 MHz) d 170.5, 169.3 (2CO), 138.3,
138.2, 137.7 (3Cipso-Bn), 134.9 (OCH2CH@CH2), 128.4–127.3 (C-Ar),
116.6 (OCH2CH@CH2), 98.0 (C-1B), 90.8 (C-1A), 83.7, 79.3, 79.1,
77.6, 77.1, 75.1, 74.8, 74.1, 73.3, 72.3, 70.5, 67.7 (C-2A, C-2B, C-3A,
21. Cao, Y.; Okada, Y.; Yamada, H. Carbohydr. Res. 2006, 341, 2219–
2223.
22. Typical procedure for acetolysis of methyl 6-deoxy-sugar oligosaccha-
rides: Methyl glycoside (66 lmol) was dissolved in a mixture of 1:1:0.1
v/v/v Ac2O/AcOH/TFA (2.1 mL). The solution was stirred at 70 °C,
then diluted with CH2Cl2, the organic layer was washed with brine
and 0.2 M NaHCO3, then collected, dried over anhydrous Na2SO4,
filtered and concentrated. The residue was subject to column
chromatography (ethyl acetate in toluene).
´
23. Kaczmarek, J.; Kaczynski, Z.; Trumpakaj, Z.; Szafranek, J.; Bogale-
cka, M.; Lo¨nnberg, H. Carbohydr. Res. 2000, 325, 16–29.
24. Bedini, E.; Carabellese, A.; Corsaro, M. M.; De Castro, C.; Parrilli,
M. Carbohydr. Res. 2004, 339, 1907–1915.
25. Zhang, Z.; Ollman, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong,
C.-H. J. Am. Chem. Soc. 1999, 121, 734–753.