Sonication-assisted oligomannoside synthesis

Article abstract of DOI:10.1021/jo8019835

We have investigated the use of sonication for the synthesis of oligomannosides. A convenient sonication- mediated glycosylation protocol that is applicable to traditional glycosylation methods has been developed. This protocol can be applicable for activ

Full text of DOI:10.1021/jo8019835

Sonication-Assisted Oligomannoside Synthesis
Christabel T. Tanifum and Cheng-Wei T. Chang*
Department of Chemistry and Biochemistry, Utah State UniVersity, 0300 Old Main Hill,
Logan, Utah 84322-0300
tom.chang@usu.edu
ReceiVed September 9, 2008
We have investigated the use of sonication for the synthesis of oligomannosides. A convenient sonication-
mediated glycosylation protocol that is applicable to traditional glycosylation methods has been developed.
This protocol can be applicable for activating glycosyl donors that are known to have low reactivity
which enable the synthesis of oligomannosides of particular biological interest with the same efficiency.
Introduction
synthesis,12 one-pot programmable glycosylation,13,14 solid-
phase oligosaccharide synthesis,15,16 and iterative glycosyla-
tion,17 have been developed with the goal of alleviating the
challenges of oligosaccharide synthesis. Ironically, the diverse
and complicated methods documented in the literature often
bewilder researchers in selecting the appropriate mannose-based
donors and optimal activating agents for synthesizing the desired
oligomannosides, a common obstacle that could be both time-
and resource-consuming.
Oligomannosides often possess important biological implica-
tions and applications, albeit they are rare on the surface of
mammalian cells. For example, in addition to being utilized as
tumor-associated antigens,1 oligomannosides have been shown
to regulate immune response,2 mediate cellular interactions,3
and be involved in the infection of fungal,4 viral,5 and bacterial6
pathogens. Thus, the synthesis of structurally diverse natural
and non-natural oligomannosides has been pursued by research-
ers in various fields.7,8 Glycosylation is the essential step in
the synthesis of complex oligomannosides. Numerous methods
designed for activating various mannose-based donors have been
reported.9-11 Sophisticated methods, such as chemoenzymatic
Sonication has been employed to enhance the rate of many
traditional chemical reactions18 including carbohydrate synthe-
sis.19 Nevertheless, glycosylation using sonication has been
reported in only a few examples that employ glycosyl donors,
such as unprotected donors,20 glycosyl halides,21 and glycosyl
(1) Danishefsky, S. J.; Allen, J. R. Angew. Chem., Int. Ed. 2000, 39, 836–
863.
(2) Janeway, C. A., Jr.; Medzhitov, R. Annu. ReV. Immunol. 2002, 20, 197–
(11) Demchenko, A. V. Synlett 2003, 9, 1225–1240.
(12) Gijsen, H. J. M.; Qiao, L.; Fitz, W.; Wong, C.-H. Chem. ReV. 1996, 96,
443–474.
(13) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong,
C.-H. J. Am. Chem. Soc. 1999, 121, 734–753.
(14) Koeller, K. M.; Wong, C.-H. Chem. ReV. 2000, 100, 4465–4494.
(15) Seeberger, P. H.; Haase, W.-C. Chem. ReV. 2000, 100, 4349–4394.
(16) Plante, O. J.; Palmacci, E. R.; Seeberger, P. H. Science 2001, 291, 1523–
1527.
(17) Huang, X.; Huang, L.; Wang, H.; Ye, X.-S. Angew. Chem., Int. Ed.
2004, 43, 5221–5224.
(18) For example: (a) Lepore, S. D.; He, Y. J. Org. Chem. 2003, 68, 8261–
8263. (b) Gholap, A. R.; Venkatesan, K.; Daniel, T.; Lahoti, R. J.; Srinivasan,
K. V. Green Chem. 2003, 6, 693–696. (c) Chen, M.-Y.; Lu, K.-C.; Lee, A. S.-
Y.; Lin, C.-C. Tetrahedron Lett. 2002, 43, 2777–2780. (d) Adewuyi, Y. G. Ind.
Eng. Chem. Res. 2001, 40, 4681–4715.
(19) For review:Kardos, N.; Luche, J.-L. Carbohydr. Res. 2001, 332, 115–
131.
216.
(3) For example: Muramatsu, T. Science 2002, 295, 53–54.
(4) For example: (a) Santos, A. L. S.; Palmeira, V. F.; Rozental, S.; Kneipp,
L. F.; Nimrichter, L.; Alviano, D. S.; Rodrigues, M. L.; Alviano, C. S. FEMS
Microbiol. ReV 2007, 31, 570–591. (b) Ampel, N. M.; Nelson, D. K.; Li, L.;
Dionne, S. O.; Lake, D. F.; Simmons, K. A.; Pappagianis, D. Infect. Immun.
2005, 73, 2554–2555.
(5) For example: (a) Anders, E. M.; Hartley, C. A.; Jackson, D. C. Proc.
Natl. Acad. Sci. U.S.A. 1990, 87, 4485–4489. (b) Lifson, J.; Coutre, S.; Huang,
E.; Engleman, E. J. Exp. Med. 1986, 164, 2101–2106.
(6) For example:Malik, M.; Bayat, A.; Jury, F.; Kay, P.; Ollier, W. J.
Arthroplasty. 2007, 22, 265–270.
(7) Glycochemistry Principles, Synthesis, and Applications; Wang, P. G.,
Bertozzi, C. R., Eds.; Marcel Dekker, Inc.: New York, 2001.
(8) Carbohydrate-Based Drug DiscoVery; Wong, C.-H., Ed.; Wiley-VCH:
Weinheim, 2003.
(9) Toshima, K.; Tatsuta, K. Chem. ReV. 1993, 93, 1503–1531.
(10) Nicolaou, K. C.; Mitchell, H. J. Angew. Chem., Int. Ed. 2001, 40, 1576–
1624.
(20) Ferrie`res, V.; Bertho, J. N.; Plusquellec, D. Tetrahedron Lett. 1995, 36,
2749–2752.
634 J. Org. Chem. 2009, 74, 634–644
10.1021/jo8019835 CCC: $40.75 2009 American Chemical Society
Published on Web 12/08/2008

Sonication-Assisted Oligomannoside Synthesis
TABLE 1. Effects of Solvent and Protecting Groups on
Stereoselectivity
stereoselectivity in favoring the formation of an R-glycosidic
bond.25 Under our sonication-assisted protocol using the same
activating agents, the selectivity was only slightly improved
(Table 1, entry 9). Crich has proposed a general glycosylation
mechanism using phenylthiomannosides as the donors and
1-benzenesulfinyl piperidine (BSP) and Tf2O as the activating
agents.26 In this mechanism, a R-mannosyl triflate intermediate
converted from donor is in equilibrium with a ꢀ-selective contact
ion pair (CIP) and sequentially an R-selective solvent separated
ion pair (SSIP) (Figure 1). It is likely that sonication provides
energy that facilitates an SN2-like glycosylation via intermediate
A or CIP, respectively, leading to the formation of ꢀ-manno-
sides. Under the condition reported by Fraser-Reid, the glyco-
sylation is likely to occur via SSIP.
Despite the scramble in the stereoselectivity, it is evident that
sonication can certainly enhance the efficiency of glycosylation
(entries 5 -8, Table 1). For example, glycosylation under the
traditional method (-78 °C to rt or heating) in relatively less
polar solvents such as toluene and ether were unsuccessful,
probably because of the difficulty in forming oxycarbenium or
polar intermediates. In contrast, glycosylation can be ac-
complished in all of the examined solvents by using the same
protocol with modest to excellent yields.
Several mannose donors, compounds 3-8, were also exam-
ined including glycosyl acetate 3,27 which is known to have
low reactivity (Scheme 1). As compared to 1, glycosylation
using 3 yielded better R-selectivity. It is possible that, unlike
the phenylthio group, the acetate group is harder to activate by
Lewis acid and hampers an SN2-like glycosylation, leading to
the formation of more R-selective product via SSIP.
As expected, glycosylation using 5 and 7 with O-2 acetyl
participation offered only the R-anomer. Although the reason
is still unclear, it has been noted that mannose donors bearing
3-O-carboxylated esters, such as a benzoyl group, provide
predominantly R-mannosides.28 Neighboring group participation
via an intermediate in twist-boat conformation has been
proposed to provide explanation in the observed R-selectivity.29
Consistent with the reported observation, glycosylation using
4 and 6 both containing a 3-O-acetyl group gave only R-man-
nosides.
entry solvent
reagents and condition
yield (%)a R:ꢀ ratio
1
toluene NIS, TMSOTf, -78 °C to rt, no reaction
5 h to overnight
2
3
4
5
Et2Ob
no reaction
CH2Cl2
CH3CN
90
98
80
1:1
3:2
2:1
toluene NIS, TMSOTf, sonication,
ambient temp, 8 min
6
7
8
9
Et2O
CH2Cl2
CH3CN
40
92
65
80
1:1
3:2
3:2
3:1
CH2Cl2 NIS, BF3-OEt2, sonication,
ambient temp, 8 min
a Isolated yield. b No reaction was noted even after heating (30-40
°C) for 5 h.
sulfones.22 These glycosyl donors are either unsuitable or have
not been applied for the synthesis of oligosaccharides. We have
reported that sonication can also be applicable to glycosylation
using glycosyl donors that are known to be less reactive.23
Continuing from our prior work, we direct our effort on the
development of general protocols of glycosylation using mannose-
based donors including phenylthiomannosides and mannosyl
acetate. These two donors are relatively stable and can be prepared
in large quantity. However, their stability and low reactivity as
compared to the other glycosyl donors, such as glycosyl trichlo-
roacetimidate and glycosyl halide, especially with the acyl protect-
ing groups attached, often result in the difficulty or unsatisfactory
yields in glycosylation. As a result, diverse sulfur-philic reagents
or Lewis acids have been developed for activating phenylth-
ioglycosides and glycosyl acetate that have various degrees of
relative reactivity, which lead to the need for optimizing criteria
for achieving the desired synthetic goals.9-11 In light of the
significance and the synthetic deficiencies of oligomannosides,
we wish to investigate the possibility of generalizing the
glycosylation protocol by using sonication and NIS/TMSOTf
or BF3-OEt2 for activating phenylthiomannosides or mannosyl
acetate, respectively.
The presence of 4,6-O-benzylidene group has been utilized
to favor the formation of ꢀ-glycosydic bond.30 In contrast, the
4,6-O-benzylidene protected donors 8 provided R-anomers as
the dominant products. It is likely that sonication provides
enough energy to overcome the barrier in the conformation
constraint imposed by the presence of the benzylidene group.
In addition, the glycosylation method we used is different from
what has been reported by Crich, which involves a prior
activation of donor followed by addition of acceptor, whereas
in our protocol, the donor and acceptor are mixed together
followed by the addition of activating agent. The difference in
Results and Discussion
The initial study was to determine the effects of solvent and
protecting groups on the stereoselectivity of sonication-assisted
glycosylation. Despite numerous studies, the solvent effect is
still unclear. Both 2-O-acyl and 2-O-alkyl groups favor the
formation of a R-glycosydic bond via neighboring group
participation and anomeric effect, respectively. We chose 124
and 6-azidohexanol23 as the donor and acceptor, respectively.
Among the solvents examined, there was no preference in the
stereoselectivity under our sonication-assisted protocol (Table
1). Interestingly, as reported by Fraser-Reid, the similar donor
2,3,4,6-tetra-O-benzyl-1-thio-R-D-mannopyranoside activated
using NIS/BF3-OEt2 in ether at -30 °C manifests excellent
(25) Lo´pez, J. C.; Go´mez, A. M.; Uriel, C.; Fraser-Reid, B. Tetrahedron
Lett. 2003, 44, 1417–1420.
(26) Crich, D.; Xu, H. J. Org. Chem. 2007, 72, 5183–5192.
(27) Li, C.; Yu, B.; Zhang, G.-T.; Hui, Y.-Z. Chin. J. Chem. 1998, 16, 381–
384.
(28) (a) Crich, D.; Cai, W.; Dai, Z. J. Org. Chem. 2000, 65, 1291–1297. (b)
Crich, D.; Yao, Q. J. Am. Chem. Soc. 2004, 126, 8232–8236.
(29) Crich, D. In Glycochemistry Principles, Synthesis, and Applications;
Wang, P. G., Bertozzi, C. R., Ed.; Marcel Dekker, Inc.: New York, 2001; pp,
53-75.
(21) Polidori, A.; Pucci, B.; Maurizis, J. C.; Pavia, A. A. New J. Chem. 1994,
18, 839–848.
(22) Brown, D. S.; Ley, S. V.; Vile, S. Tetrahedron Lett. 1988, 29, 4873–
4876.
(23) Deng, S.; Gangadharmath, U.; Chang, C.-W. T. J. Org. Chem. 2006,
71, 5179–5185.
(30) (a) Crich, D.; Sun, S. J. Am. Chem. Soc. 1998, 120, 435–436. (b) Crich,
D.; Sun, S. J. Org. Chem. 1997, 62, 1198–1199. (c) Crich, D.; Sun, S. J. Org.
Chem. 1996, 61, 4506–4507.
(24) Lemanski, G.; Ziegler, T. Tetrahedron 2000, 56, 563–579.
(31) Jiang, L.; Chan, T.-H. J. Org. Chem. 1998, 63, 6035–6038.
J. Org. Chem. Vol. 74, No. 2, 2009 635

Tanifum and Chang
FIGURE 1. Proposed glycosylation mechanism.
SCHEME 1. Investigation of Sonication-Assisted Glycosylation
conducting glycosylation could lead to the decrease in ꢀ-selec-
tivity that has also been noted by Crich.30c However, prior
activation of donor 8 using sonication followed by addition of
6-azidohexanol did not generate any detectable product. Finally,
although it has been reported in the literature that sonication
may be used to cleave the glycosidic bond, the frequency for
sonication is typically 500-800 kHz with power of 20-60 W.19
The sonicator we used provides frequency of 40 kHz at 185
W. Under this condition, we did not observe any cleavage of
the glycosidic bond even in acidic condition as we employed
for glycosylation.
After the investigation of stereoselectivity, attempts of using
sonication for the synthesis of di- and trimannosides was
engaged. We were pleased to notice that sonication exert similar
efficacy in synthesizing the designed dimannosides (Scheme 2).
Both mannose donors 5 and 1435 contain a 2-O-acetyl group,
which will favor the formation of R-glycosidic bond, to
minimize the complexity in characterizing the product.
The synthesis of linear trimannosides with 1,2- and 1,6-
linkages can be accomplished in similar efficiency using
sonication (Schemes 3-6). The stereoselectivity was confirmed
1
by JCH using HECTOR. The synthesis of 1,6-linked triman-
noside can be accomplished by glycosylation of 2138 with donor
1 (Scheme 3). After deprotection of the O-6 acetyl group on 22
followed by another glycosylation, a trimannoside, 24, can be
obtained. The purity of desired trimannoside can be further
enriched by additional column chromatography after the depro-
tection of the O-6 acetyl group on 24. Global deprotection of
the resulting trimannoside 25 using hydrogenation generates the
designed trimannoside 26.
Another 1,6-linked trimannoside, 32, can be synthesized in
similar fashion (Scheme 4). A different glycosyl donor, 5, was
employed for the second glycosylation. Interestingly, we did
observe a small quantity of ꢀ-epimer from the second glyco-
sylation despite the presence of an O-2 acetyl group on the
employed glycosyl donor. Fortunately, the minor ꢀ-epimer epi-
636 J. Org. Chem. Vol. 74, No. 2, 2009

Sonication-Assisted Oligomannoside Synthesis
SCHEME 2. Synthesis of Dimannosides
SCHEME 3. Synthesis of 1,6-Linked Trimannosides
31 after deacetylation can be separated after column chroma-
tography, allowing the preparation of pure final product.
The syntheses of 1,2-linked trimannosides were accomplished
using compound 5 as the glycosyl donor in all glycosylations
(Schemes 5 and 6). The synthesis of glycosyl acceptor 3540 can
also be expedited by employing sonication using known
compound 3332 as the starting material.
The stereoselectivity observed in the trimannoside synthesis
is rather unique. Under our sonication protocol, the glycosyl
donor 1 in previous examples in Table 1 exerts no obvious
selectivity. However, when 1 was employed in the synthesis of
trimannosides, excellent stereoselectivity favoring the formation
(35) Mayer, T. G.; Schmidt, R. R. Eur. J. Org. Chem. 1999, 1153–1165.
(36) Stork, G.; Kim, G. J. Am. Chem. Soc. 1992, 114, 1087–1088.
(37) Liptak, A.; Czegeny, I.; Harangi, J.; Nanasi, P. Carbohydr. Res. 1979,
73, 327–331.
(38) Vidal, S.; Morere, A.; Montero, J.-S. Heteroat. Chem. 2003, 7, 2457–
2460.
(32) Nambiar, S.; Daeuble, J. F.; Doyle, R. J.; Taylor, K. G. Tetrahedron
Lett. 1989, 30, 2179–2182.
(33) Szurmai, Z.; Blatoni, L.; Liptak, A. Carbohydr. Res. 1994, 254, 301–
309.
(39) Boren, H. B.; Eklind, K.; Garegg, P. J.; Lindberg, B.; Pilotti, A. Acta
Chem. Scand. 1972, 26, 4143–4146.
(34) Crich, D.; Sun, S. Tetrahedron 1998, 54, 8321–8348.
J. Org. Chem. Vol. 74, No. 2, 2009 637

Tanifum and Chang
SCHEME 4. Synthesis of 1,6-Linked Trimannosides
SCHEME 5. Synthesis of 1,2-Linked Trimannosides
SCHEME 6. Synthesis of 1,2-Linked Trimannosides
CIP. When a smaller nucleophile such as 6-azidohexanol was
used for glycosylation, the steric factor was less significant,
which resulted in the lack of stereoselectivity. Interestingly, one
recent article by Huang reported an unusual stereoselectivity
of glycosylation: when dimannose-based donor and mannose
acceptor were used, a modest selectivity was observed in
favoring the formation of ꢀ-glycosidic bond.43 Considering all
results, we agree with Huang’s comment that “factors controlling
of an R-glycosidic bond was obtained. One of the possible
reasons is that the steric hindrance between the 2-O-benzyl group
and the mannose acceptors in the trimannoside synthesis may
prevent SN2-like glycosylation via R-mannosyl intermediate or
638 J. Org. Chem. Vol. 74, No. 2, 2009

Sonication-Assisted Oligomannoside Synthesis
SCHEME 7. Synthesis of Man6
stereochemistry of glycosylation especially in the absence of
neighboring group participation are still not well understood”.
Conclusion
We have reported a convenient sonication-mediated glyco-
sylation protocol that is applicable to traditional glycosylation
methods. This protocol can be applicable even for the glycosyl
donors that are known to have low reactivity. We have also
demonstrated that oligomannosides of particular biological
interest can be prepared with the same efficiency.
Following the synthesis of trimannosides, the focus was
directed to the synthesis of more complex Man6,44 which can
be considered as the prelude to the synthesis of Man9 with
potential of being used for HIV vaccine development (Scheme
7).45 The synthesis began with a glycosylation using compounds
16 and 5 as the glycosyl acceptor and donor, respectively. A
regioselective reductive ring opening of the 4,6-benzylidene
Experimental Section
46
group using Cu(OTf)2/BH3 yielded 47 with O-6 OH, which
Proton magnetic resonance spectra were recorded using 300 or
400 MHz spectrometers. Chemical shifts are reported as parts per
million (ppm) downfield from tetramethylsilane in δ units, and
coupling constants are given in cycles per second (Hz). Splitting
patterns are designated as s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet. 13C spectra were obtained using a Jeol 300 spectrom-
eter at 75 Hz or Bruker 400 spectrometer at 100 Hz. Routine 13C
NMR spectra were fully decoupled by broadband waltz decoupling.
All NMR spectra were recorded at ambient temperature unless
otherwise noted. Sonication was conducted using Bransonic
ultrasonic bath (model 5510) at 40 kHz with a power of 185 W.
6′-Azidohexyl 6-O-Acetyl-2,3,4-tri-O-benzyl-r-D-mannopy-
ranoside (2). Please refer to the general procedure for sonication-
assisted glycosylation using phenylthioglycosyl donor (Rf ) 0.5
eluted with hexane/EtOAc ) 3/1). 1H (CDCl3, 300 MHz) δ 7.3-7.6
(m, 30H), 5.0-4.9 (m, 3H), 4.88 (d, J ) 1.7 Hz, 1H), 4.80 (d, J )
12.4 Hz, 1H), 4.74 (d, J ) 12.4 Hz, 1H), 4.6-4.7 (m, 4H), 4.57
(d, J ) 11.7 Hz, 1H), 4.48 (d, J ) 11.7 Hz, 1H), 4.4 (m, 1H),
4.3-4.4 (m, 3H), 3.9-4.0 (m, 6H), 3.8-3.9 (m, 3H), 3.6 (m, 1H),
3.4-3.6 (m, 3H), 3.27 (t, J ) 6.9 Hz, 4H), 2.09 (s, 3H, CH3), 2.07
(s, 3H, CH3), 1.6 (m, 8H), 1.3 (m, 8H); 13C NMR (CDCl3, 75 MHz)
δ 171.05 (ꢀ), 171.0 (R), 138.8, 138.5 (2 carbons), 138.4 (2 carbons),
138.29 (2 carbons), 138.28, 137.16, 128.6 (3 carbons), 128.5 (4
carbons), 128.47 (3 carbons), 128.33 (2 carbons), 128.28, 128.23,
can be glycosylated using compound 4 as the donor. After the
deprotection of acetyl groups, the triol 49 can be glycosylated
using compound 5. Once again, sonication enabled smooth
glycosylation even for the last glycosylation step, which
involved the incorporation of three glycosyl donors simulta-
neously. In addition, we did not observe cleavage of a glycosidic
bond in any of the oligomannosides syntheses.
(40) Boger, D. L.; Honda, T. J. Am. Chem. Soc. 1994, 116, 5647–5656.
(41) Zhang, Y. M.; Mallet, J.-M.; Sinay, P. Carbohydr. Res. 1992, 236, 73–
88.
(42) Madsen, J.; Viuf, C.; Bols, M. Chem.-Eur. J. 2000, 6, 1140–1146.
(43) Teumelsan, N.; Huang, X. J. Org. Chem. 2007, 72, 8976–8979.
(44) The synthesis of Man6 with different anomeric groups has been reported
previously: (a) Ratner, D. M.; Plante, O. J.; Seeberger, P. H. Eur. J. Org. Chem.
2002, 826–833. (b) Zhang, J.; Kong, F. Tetrahedron: Asymmetry 2002, 13, 243–
252. (c) Geng, X.; Dudkin, V. Y.; Mandal, M.; Danishefsky, S. Angew. Chem.,
Int. Ed. 2004, 43, 2562–2565.
(45) For examples on the reported synthesis of Man9: (a) Calarese, D. A.;
Lee, H.-K.; Huang, C.-Y.; Best, M. D.; Astronomo, R. D.; Stanfield, R. L.;
Katinger, H.; Burton, D. R.; Wong, C.-H.; Wilson, I. A. Proc. Natl. Acad. Sci.
U.S.A. 2005, 102, 13372–13377. (b) Dudkin, V. Y.; Orlova, M.; Geng, X.;
Mandal, M.; Olson, W. C.; Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126,
9560–9562.
(46) Shie, C.; Tzeng, Z.; Kulkarni, S. S.; Uang, B.; Hsu, C.; Hung, S. Angew.
Chem., Int. Ed. 2005, 44, 1665–1668.
J. Org. Chem. Vol. 74, No. 2, 2009 639

Tanifum and Chang
127.9 (2 carbons), 127.89 (3 carbons), 127.79 (5 carbons), 127.78
(2 carbons), 127.6, 101.9 (ꢀ), 98.0 (R), 82.4, 80.3, 75.3, 74.8, 74.7,
74.68, 73.9, 73.8, 73.6, 72.7, 72.2, 71.5, 70.2, 69.9, 67.7, 63.9, 63.7,
51.4, 29.6, 29.4, 28.9, 28.87, 26.6, 25.9, 25.83, 21.06, 21.04; ESI/
APCI calcd for C35H43N3O7Na ([M + Na]+) m/e 640.2999;
measured m/e 640.2998.
4H); 13C NMR (CDCl3, 100 MHz) δ 170.4, 137.8, 137.5, 129.2,
128.7 (2 carbons), 128.4 (2 carbons), 128.2 (2 carbons), 126.4 (2
carbons), 101.9, 99.0, 77.4, 76.6, 76.5, 73.9, 70.8, 69.0, 68.0, 64.2,
51.6, 29.4, 28.9, 26.7, 25.9, 21.3; HRFAB calcd for C28H35N3O7Na
([M + Na]+) m/e 548.2373; measured m/e 548.2371.
6′-Azidohexyl 2,3-Di-O-acetyl-4,6-O-benzylidene-r-D-man-
nopyranoside (12). Please refer to the general procedure for
sonication-assisted glycosylation using phenylthioglycosyl donor
(Rf ) 0.5 eluted with hexane/EtOAc ) 3/1). 1H (CDCl3, 300 MHz)
δ 7.4-7.5 (m, 2H), 7.3-7.4 (m, 3H), 5.58 (s, 1H), 5.40 (dd, J )
3.6, 9.6 Hz, 1H, H-3), 5.33 (dd, J ) 1.7, 3.6 Hz, 1H, H-2), 4.75
(d, J ) 1.3 Hz, 1H, H-1), 4.27 (dd, J ) 4.1, 9.9 Hz, 1H), 4.03 (t,
J ) 9.3 Hz, 1H), 3.9 (m, 1H, H-5), 3.85 (t, J ) 9.9 Hz, 1H), 3.7
(m, 1H), 3.4 (m, 1H), 3.28 (t, J ) 6.9 Hz, 2H), 2.17 (s, 3H, CH3),
2.02 (s, 3H, CH3), 1.6 (m, 4H), 1.4 (m, 4H); 13C NMR (CDCl3, 75
MHz) δ 170.0, 169.9, 137.2, 129.2, 128.4 (2 carbons), 126.2 (2
carbons), 101.9, 98.7, 77.3, 76.3, 70.3, 68.8, 68.2, 63.9, 51.5, 29.3,
28.8, 26.6, 25.8, 21.0, 20.9; HRFAB calcd for C23H31N3O8Na ([M
+ Na]+) m/e 500.2009; measured m/e 500.2008.
6′-Azidohexyl 2,3-Di-O-benzyl-4,6-O-benzylidene-r-D-man-
nopyranoside (13). Please refer to the general procedure for
sonication-assisted glycosylation using phenylthioglycosyl donor
(Rf ) 0.7 eluted with hexane/EtOAc ) 3/1). 1H (CDCl3, 300 MHz)
δ 7.5-7.6 (m, 4H), 7.2-7.5 (m, 26H), 5.68 (s, 1H), 5.66 (s, 1H),
5.03 (d, J ) 12.4 Hz, 1H), 4.8-5.0 (m, 3H), 4.82 (d, J ) 1.4 Hz,
1H, H-1), 4.79 (s, 1H), 4.6-4.7 (m, 4H), 4.47 (s, 1H), 4.2-4.4
(m, 3H), 4.10 (t, J ) 6.9 Hz, 1H), 3.9-4.1 (m, 3H), 3.8-3.9 (m,
3H), 3.6 (m, 1H), 3.5 (m, 1H), 3.4 (m, 1H), 3.3 (m, 4H), 1.6 (m,
8H), 1.4 (m, 8H); 13C NMR (CDCl3, 75 MHz) δ 138.9, 138.6, 138.5,
138.3, 137.85, 137.83, 128.9, 128.8, 128.51 (3 carbons), 128.50 (3
carbons), 128.42 (4 carbons), 128.3, (5 carbons), 128.29 (2 carbons),
128.2 (3 carbons), 127.9 (2 carbons), 127.7, 127.6 (3 carbons), 127.2
(3 carbons), 126.2 (2 carbons), 102.4, 101.5, 99.5, 79.4, 78.8, 78.1,
76.7 (2 carbons), 75.9, 74.8, 73.7, 73.3, 72.5, 70.1, 69.0, 68.7, 67.7
(2 carbons), 64.3, 51.5 (2 carbons), 29.7, 29.3, 28.9 (2 carbons),
26.6 (2 carbons), 25.8; HRFAB calcd for C33H39N3O6Na ([M +
Na]+) m/e 596.2737; measured m/e 596.2731.
Phenyl 2,3-Di-O-acetyl-4,6-O-benzylidene-1-thio-r-D-man-
nopyranoside (7). To a solution of phenyl 4,6-O-benzylidene-1-
thio-R-D-mannopyranoside29 (2.50 g, 6.94 mmol), Et3N (3.41 mL,
24.3 mmol), and a catalytic amount of DMAP in anhydrous CH2Cl2
(20 mL) was slowly added acetic anhydride (1.64 mL, 17.3 mmol).
The reaction was stirred for 1 h and then quenched with saturated
NaHCO3(aq). The mixture was diluted with ethyl acetate, washed
with 1 N HCl(aq), water, saturated NaHCO3(aq), water, and brine,
and then dried over anhydrous Na2SO4(s). After removal of solvent
and purification with column chromatography, the product was
obtained as an oil (2.80 g, 6.31 mmol, 91%) (Rf ) 0.5 eluted with
hexane/EtOAc ) 3/1). 1H (CDCl3, 400 MHz) δ 7.3 -7.5 (m, 10H),
5.63 (dd, J ) 1.3, 3.4 Hz, H-2, 1H,), 5.61(s, 1H, H-1′), 5.45 (d, J
) 0.8 Hz, H-1, 1H,), 5.43 (dd, J ) 3.4, 10.5 Hz, H-3, 1H), 4.5 (m,
1H, H-5), 4.27 (dd, J ) 4.9 Hz, 10.4 Hz, H-6, 1H,), 4.15 (t, J )
9.7 Hz, H-4, 1H), 3.89 (t, J ) 10.3 Hz, H-6′, 1H), 2.18 (s, 3H,
CH3), 2.06 (s, 3H, CH3); 13C NMR (CDCl3, 75 MHz) δ 169.9,
169.8, 137.1, 132.2 (2 carbons), 129.3 (3 carbons), 128.4 (3
carbons), 128.2, 126.3 (2 carbons), 102.1, 86.9, 76.3, 71.6, 68.6,
68.5, 65.3, 21.0, 20.9; ESI/APCI calcd for C23H24O7SNa ([M +
Na]+) m/e 467.1140; measured m/e 467.1141.
6′-Azidohexyl 3,6-Di-O-acetyl-2,4-di-O-benzyl-r-D-mannopy-
ranoside (9). Please refer to the general procedure for sonication-
assisted glycosylation using phenylthioglycosyl donor (Rf ) 0.6
1
eluted with hexane/EtOAc ) 3/1). H (CDCl3, 400 MHz) δ 7.3
(m, 10H), 5.25 (dd, J ) 3.3, 9.1 Hz, 1H, H-3), 4.82 (s, 1H, H-1),
4.70 (d, J ) 11.2 Hz, 1H), 4.66 (d, J ) 12.3 Hz, 1H), 4.60 (s, 1H),
4.58 (d, J ) 11.1 Hz, 1H), 4.3 (m, 2H, H-6, H-6′), 3.9 (t, J ) 9.6
Hz, 1H, H-4), 3.9 (m, 2H, H-2, H-5), 3.7 (m, 1H), 3.4 (m, 1H),
3.27 (t, J ) 6.9 Hz, 2H), 2.08 (s, 3H, CH3), 2.00 (s, 3H, CH3), 1.6
(m, 4H), 1.4 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 171.0, 170.3,
138.1, 138.0, 128.7 (2 carbons), 128.6 (2 carbons), 128.1 (2
carbons), 128.0 (2 carbons), 127.9 (2 carbons), 97.9, 76.2, 75.0,
74.1, 73.6, 73.1, 69.9, 68.0, 63.6, 57.6, 29.4, 28.9, 26.7, 26.6, 21.3,
21.1; ESI/APCI calcd for C30H39N3O8Na ([M + Na]+) m/e
592.2635; measured m/e 592.2629.
6′-Azidohexyl 2-O-Benzyl-4,6-O-benzylidene-r-D-mannopy-
ranoside (17). To a solution of 6′-azidohexyl-4,6-O-benzylidene-
R-D-mannopyranoside (1.35 g, 3.43 mmol), tetrabutylammonium
hydrogen sulfate (0.35 g, 1.03 mmol), and BnBr (0.45 mL, 3.77
mmol) in CH2Cl2 (15 mL) was added aqueous NaOH (1 N, 6 mL).
The mixture was refluxed for 15 h and then diluted with CH2Cl2.
The organic layer was washed with water and brine and then dried
over anhydrous Na2SO4(s) After removal of solvent and purification
with column chromatography, the product was obtained as an oil
(0.71 g, 1.99 mmol, 58%) (Rf ) 0.7 eluted with hexane/EtOAc )
6′-Azidohexyl 2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-mannopy-
ranoside (10). Please refer to the general procedure for sonication-
assisted glycosylation using phenylthioglycosyl donor (Rf ) 0.6
eluted with hexane/EtOAc ) 3/1). 1H (CDCl3, 270 MHz) δ 7.1-7.5
(m, 15H), 5.37 (dd, J ) 3.0, 1.6 Hz, 1H), 4.87 (d, J ) 12.2 Hz,
1H), 4.84 (d, J ) 1.6 Hz, 1H), 4.72 (d, J ) 11.2 Hz, 1H), 4.69 (d,
J ) 12.2 Hz, 1H), 4.55 (d, J ) 10.7 Hz, 1H), 4.52 (d, J ) 11.2
Hz, 1H), 4.48 (d, J ) 10.7 Hz, 1H), 4.00 (dd, J ) 8.9, 3.0 Hz,
1H), 3.89 (dd, J ) 9.2, 9.2 Hz, 1H), 3.6-3.8 (m, 2H), 3.52 (dd, J
) 6.8, 6.8 Hz, 1H), 3.43 (dd, J ) 6.8, 6.3 Hz, 1H), 3.40 (dd, J )
6.8, 6.3 Hz, 1H), 3.25 (t, J ) 6.8 Hz, 2H), 2.16 (s, 3H), 1.5-1.6
(m, 4H), 1.3-1.4 (m, 4H); 13C NMR (CDCl3, 68 MHz) δ 170.6,
138.6, 138.49, 138.22, 128.7, 128.58 (2 carbons), 128.53 (3
carbons), 128.25 (2 carbons), 128.14 (2 carbons), 127.96 (2
carbons), 127.93, 127.85, 127.78, 97.9, 78.4, 75.3, 74.5, 73.5, 71.9,
71.5, 69.03, 68.97, 67.8, 51.5, 29.3, 28.8, 26.6, 25.8, 21.2; HRFAB
calcd for C35H43N3O7Na ([M + Na]+) m/e 640.2999; measured m/e
640.2987.
6′-Azidohexyl 3-O-Acetyl-2-O-benzyl-4,6-O-benzylidene-r-D-
mannopyranoside (11). Please refer to the general procedure for
sonication-assisted glycosylation using phenylthioglycosyl donor
(Rf ) 0.7 eluted with hexane/EtOAc ) 3/1). 1H (CDCl3, 400 MHz)
δ 7.4-7.5 (m, 2H), 7.3-7.4 (m, 8H), 5.59 (s, 1H, H-1′), 5.31 (dd,
J ) 3.4, 10.4 Hz, 1H, H-3), 4.81 (s, 1H, H-1), 4.68 (d, J ) 11.9
Hz, 1H), 4.64 (d, J ) 11.9 Hz, 1H), 4.26 (d, J ) 5.6 Hz, 1H), 4.2
(m, 1H, H-5), 3.96 (s, 1H), 3.9 (m, 2H), 3.7 (m, 1H), 3.4 (m, 1H),
3.29 (t, J ) 6.8 Hz, 2H), 2.05 (s, 3H, CH3), 1.6 (m, 4H), 1.4 (m,
1
65/35). H (CDCl3, 300 MHz) δ 7.5-7.6 (m, 2H), 7.3-7.4 (m,
8H), 5.59 (s, 1H, H-1′), 4.84 (d, J ) 1.2 Hz, H-1, 1H,), 4.76 (d, J
) 11.8 Hz, 1H), 4.72 (d, J ) 11.8 Hz, 1H), 4.26 (dd, J ) 3.7, 9.1
Hz, H-6, 1H), 4.10 (m, 1H, H-5), 3.93 (t, J ) 9.0 Hz, H-4, 1H),
3.8-3.7 (m, 3H), 3.6 (m, 1H), 3.3 (m, 1H), 3.28 (t, J ) 6.9 Hz.
2H), 2.38 (d, 1H, OH), 1.61 (m, 4H), 1.39 (m, 4H); 13C NMR
(CDCl3, 100 MHz) δ 137.9, 137.5, 129.3, 128.8 (2 carbons), 128.5
(2 carbons), 128.3, 128.2 (2 carbons), 126.4 (2 carbons), 102.3,
98.5, 79.8, 78.9, 73.9, 69.0, 68.9, 67.9, 63.7, 51.6, 29.4, 28.9, 26.7,
25.9; ESI/APCI calcd for C26H33N3O6Na ([M + Na]+) m/e
506.2267; measured m/e 506.2281.
Phenyl 2-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-mannopyra-
nosyl)-3,4,6-tri-O-benzyl-1-thio-r-D-mannopyranoside (18).
Please refer to the general procedure for sonication-assisted
glycosylation using glycosyl acetate as the donor (Rf ) 0.5 eluted
with hexane/EtOAc ) 3/1). 1H (CDCl3, 400 MHz) δ 7.4 (m, 2H),
7.1-7.4 (m, 33H), 5.67 (d, J ) 1.6 Hz, 1H, H-1), 5.54 (dd, J )
1.8, 3.1 Hz, 1H, H-2′), 5.09 (d, J ) 1.5 Hz, 1H, H-1′), 4.91 (d, J
) 10.8 Hz, 1H), 4.84 (d, J ) 10.9 Hz, 1H), 4.75 (d, J ) 11.7 Hz,
1H), 4.71 (d, J ) 11.7 Hz, 1H), 4.68 (d, J ) 10.8 Hz, 1H), 4.62
(d, J ) 11.0 Hz, 1H), 4.56 (d, J ) 12.3 Hz, 1H), 4.49 (d, J ) 12.6
Hz, 2H), 4.4 (m, 2H), 4.3 (m, 1H), 4.25 (t, J ) 2.1 Hz, 1H), 3.9-4.0
640 J. Org. Chem. Vol. 74, No. 2, 2009

Sonication-Assisted Oligomannoside Synthesis
(m, 5H), 3.8-3.9 (m, 2H), 3.7-3.8 (m, 2H), 3.60 (dd, J ) 1.7,
10.6 Hz, 1H), 2.15 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ
170.4, 138.7, 138.6 (2 carbons), 138.4, 138.3, 138.2, 134.4, 131.9
(2 carbons), 129.2 (2 carbons), 128.7 (2 carbons), 128.6 (2 carbons),
128.55 (6 carbons), 128.50 (4 carbons), 128.4 (4 carbons), 128.3
(2 carbons), 128.2 (2 carbons), 128.0 (2 carbons), 127.9 (4 carbons),
127.8 (2 carbons), 127.7 (3 carbons), 127.6 (2 carbons), 99.9, 87.4,
80.2, 78.3, 77.0, 75.4, 75.3, 75.0, 74.6, 73.4 (2 carbons), 73.1, 72.4,
72.2, 72.1, 69.4, 69.0, 68.9, 21.3; ESI/APCI calcd for C62H64O11SNa
([M + Na]+) m/e 1039.4067; measured m/e 1039.4082.
matography, the product was obtained as an oil (0.55 g,, 0.57 mmol,
72%) (Rf ) 0.4 eluted with hexane/EtOAc ) 3/1). 1H (CDCl3, 300
MHz) δ 7.2-7.4 (m, 35H), 5.10 (d, J ) 1.4 Hz, 1H), 5.00 (d, J )
11.0 Hz, 1H), 4.92 (d, J ) 1.7 Hz, 1H, H-1), 4.6-4.8 (m, 9H),
4.61 (d, J ) 12.0 Hz, 1H), 4.55 (d, J ) 12.0 Hz, 1H), 4.53 (d, J )
14.0 Hz, 1H), 4.43 (d, J ) 11.7 Hz, 1H), 3.7-4.0 (m, 12H) 1.98
(s, 1H, OH); 13C NMR (CDCl3, 75 MHz) δ 138.72, 138.70, 138.5
(2 carbons), 138.4, 138.2, 137.2, 128.6, 128.5 (10 carbons), 128.4
(2 carbons), 128.1, 128.0 (5 carbons), 127.9 (2 carbons), 127.8 (2
carbons), 127.7 (3 carbons), 127.6 (2 carbons), 98.4, 97.1, 80.4,
79.5, 75.3, 75.1, 74.90, 74.86, 74.7, 72.9, 72.8, 72.3 (2 carbons),
71.9, 71.7, 69.0, 66.3, 62.4; ESI/APCI calcd for C61H64O11Na ([M
+ Na]+) m/e 995.4346; measured m/e 995.4340.
Methyl 3-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-mannopyra-
nosyl)-2-O-benzyl-4,6-O-benzylidene-r-D-mannopyranoside (19).
Please refer to the general procedure for sonication-assisted
glycosylation using phenylthioglycosyl donor (Rf ) 0.7 eluted with
Benzyl 6-O-(6-O-(6-O-Acetyl-2,3,4-tri-O-benzyl-r-D-mannopy-
ranosyl)-2,3,4-tri-O-benzyl-r-D-mannopyranosyl)-2,3,4-tri-O-
benzyl-r-D-mannopyranoside (24). Please refer to the general
procedure for sonication-assisted glycosylation using phenylth-
ioglycosyl donor (Rf ) 0.7 eluted with hexane/EtOAc ) 65/35).
1H (CDCl3, 400 MHz) δ 7.2-7.4 (m, 65H), 5.15 (s, 1H), 5.07 (s,
1H), 4.8-5.0 (m, 4H), 4.4-4.7 (m, 20H), 4.23 (m, 1H), 3.8-4.0
(m, 10H), 3.7 (m, 2H), 3.6 (m, 1H), 2.01 (s, 3H, CH3), 1.99 (s,
3H, CH3); 13C NMR (CDCl3, 75 MHz) δ 171.0 (2 carbons), 138.8
(2 carbons), 138.6 (2 carbons),, 138.5 (3 carbons),, 138.3, 138.2 (3
carbons), 137.2, 128.5 (2 carbons), 128.4 (8 carbons),, 128.31 (2
carbons), 128.30 (2 carbons), 128.1, 127.9 (8 carbons), 127.82 (2
carbons), 127.8 (2 carbons), 127.7 (3 carbons), 127.66 (3 carbons),
127.60, 102.4 (ꢀ), 98.3 (R), 98.1 (2 carbons, R/ꢀ), 97.0 (2 carbons,
R/ꢀ), 81.9, 80.4, 79.6 (2 carbons), 79.3, 77.9, 77.3 (4 carbons),
75.2 (5 carbons), 74.8 (2 carbons), 74.7 (3 carbons), 74.5, 74.3 (2
carbons), 72.9, 72.8, 72.3, 72.2, 71.9, 71.8, 71.6, 71.3, 71.2, 70.1,
68.9 (2 carbons), 66.2, 65.9, 63.3, 20.9; ESI/APCI calcd for
C90H98NO17 ([M + NH4]+) m/e 1464.6835; measured m/e 1464.6818.
Benzyl 2,3,4-Tri-O-benzyl-6-O-(6-O-(2,3,4-tri-O-benzyl-r-D-
mannopyranosyl)-2,3,4-tri-O-benzyl-r-D-mannopyranosyl)-r-D-
mannopyranoside (25). Please refer to the procedure for the
synthesis of compound 23 (Rf ) 0.5 eluted with hexane/EtOAc )
1
hexane/EtOAc ) 65/35). H (CDCl3, 400 MHz) δ 7.2-7.5 (m,
25H), 5.64 (s, 2H, H-1′, H-2), 5.33 (s, 1H, H-1), 4.90 (d, J ) 10.8
Hz, 2H), 4.74 (d, J ) 12.2 Hz), 4.72 (s, 1H, H-1), 4.6-4.7 (m,
5H), 4.4-4.5 (m, 4H), 4.2-4.3 (m, 4H), 4.00 (dd, J ) 3.2, 12.1
Hz, 2H), 3.6-3.9 (m, 9H), 3.31 (s, 3H, OMe). 2.11 (s, 3H, CH3);
13C NMR (CDCl3, 100 MHz) δ 170.2, 138.8, 138.6, 138.1, 138.0,
137.6, 128.9128.7, 128.5, 128.4 (3 carbons), 128.30 (2 carbons),
128.28 (2 carbons), 128.0 (4 carbons), 127.9 (4 carbons), 127.7 (2
carbons), 126.2 (2 carbons), 101.4, 100.5, 99.0, 79.3, 78.1, 77.4 (4
carbons), 75.2, 74.5, 73.8, 73.6, 73.4, 72.4, 71.7, 68.9, 68.4, 64.1,
60.6, 55.0, 21.2; ESI/APCI calcd for C50H54O12Na ([M + Na]+)
m/e 869.3513; measured m/e 869.3507.
6′-Azidohexyl 3-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-man-
nopyranosyl)-2-O-benzyl-4,6-O-benzylidene-r-D-mannopyrano-
side (20). Please refer to the general procedure for sonication-
assisted glycosylation using phenylthioglycosyl donor (Rf ) 0.5
eluted with hexane/EtOAc ) 3/1). 1H (CDCl3, 400 MHz) δ 7.4-7.6
(m, 3H,), 7.1-7.3 (m, 22H), 5.65 (s, 1H), 5.63 (d, J ) 1.9 Hz,
1H), 5.34 (s, 1H), 4.90 (d, J ) 10.9 Hz, 2H), 4.77 (s, 2H), 4.73 (d,
J ) 5.4 Hz, 1H), 4.6 (m, 3H), 4.4-4.5 (m, 4H), 4.2 (m, 2H), 4.00
(dd, J ) 3.3 hz, 1H), 3.7-3.9 (m, 3H), 3,5-3.6 (m, 2H), 3.3 (m,
1H), 3.24 (t, J ) 6.9 Hz, 2H), 2.11 (s, 3H, CH3), 1.5 (m, 4H), 1.4
(m, 4H); 13C NMR (CDCl3, 100 MHz) δ 170.2, 138.8, 138.5, 138.1
(2 carbons), 137.6, 128.9, 128.7 (2 carbons), 128.6 (3 carbons),
128.5 (4 carbons), 128.4 (3 carbons), 128.3 (2 carbons), 128.3 (3
carbons), 128.0 (4 carbons), 127.9 (3 carbons), 127.7 (2 carbons),
126.2 (2 carbons), 101.4, 99.4, 99.1, 79.3, 78.1, 77.8 (2 carbons),
77.4 (2 carbons), 75.2, 74.4, 73.8, 73.7, 73.5 (2 carbons), 72.4,
71.7, 69.1, 68.9, 68.4, 67.8, 64.3, 51.6, 29.4, 28.9, 26.7, 25.9, 21.2;
ESI/APCI calcd for C55H67N4O12 ([M + NH4]+) m/e 975.4755;
measured m/e 975.4774.
Benzyl 6-O-(6-O-Acetyl-2,3,4-tri-O-benzyl-r-D-mannopyra-
nosyl)-2,3,4-tri-O-benzyl-r-D-mannopyranoside (22). Please refer
to the general procedure for sonication-assisted glycosylation using
phenylthioglycosyl donor (Rf ) 0.6 eluted with hexane/EtOAc )
3/1). 1H (CDCl3, 300 MHz) δ 7.2-7.4 (m, 35H), 5.13, (s, 1H, H-1),
4.97 (d, J ) 10.6 HZ, 1H), 4.94 (d, J ) 11.0 Hz, 1H), 4.90 (d, J )
1.7 Hz, 1H, H-1′), 4.4-4.7 (m, 11H), 4.41 (d, J ) 12.0 HZ, 1H),
4.2-4.4 (m, 2H), 3.8-3.9 (m, 6H), 3.84 (m, 2H), 3.7-3.8 (m, 2H)
2.03 (s, 3H, CH3); 13C NMR (CDCl3, 75 MHz) δ 171.1, 138.7,
138.5 (3 carbons), 138.29, 138.24, 137.2, 128.56, 128.53 (8
carbons), 128.3, 128.2, 128.0 (4 carbons), 127.9 (4 carbons), 127.85,
127.80 (3 carbons), 127.7, 127.65 (2 carbons), 127.6, 98.1, 97.0,
80.4, 79.5, 75.2 (2 carbons), 74.9, 74.7 (2 carbons), 74.4, 72.9,
72.5, 72.3, 72.0, 71.6, 70.2, 68.9, 66.3, 63.6, 21.0; ESI/APCI calcd
for C63H66O12Na ([M + Na]+) m/e 1037.4446; measured m/e
1037.4445.
1
65/35). H (CDCl3, 400 MHz) δ 7.2-7.4 (m, 50H), 5.10 (d, J )
1.0 Hz, 1H), 5.08 (s, 1H), 4.94 (d, J ) 11.0 Hz, 1H), 4.93 (d, J )
10.9 Hz, 1H), 4.90 (d, J ) 1.6 Hz, 1H), 4.6 (m, 11H), 4.6 (m, 2H),
4.5 (m, 4H), 4.42 (d, J ) 11.9 Hz, 1H), 3.9 (m, 10H), 3.8 (m, 2H),
3.6 (m, 7H); 13C NMR (CDCl3, 75 MHz) δ 138.8 (2 carbons), 138.7,
138.6, 138.5 (2 carbons), 138.4, 138.3, 138.2, 137.2, 128.5 (2
carbons), 128.45 (6 carbons), 128.40 (4 carbons), 128.3 (4 carbons),
128.1 (2 carbons), 127.95 (4 carbons), 127.92 (4 carbons), 127.82
(2 carbons), 127.78 (2 carbons), 127.71 (4 carbons), 127.64 (4
carbons), 127.58 (2 carbons), 127.54 (2 carbons), 98.4, 98.3, 97.1,
80.4, 79.6, 79.4, 77.3 (2 carbons), 75.2 (5 carbons), 75.1 (3 carbons),
74.8 (2 carbons), 74.7 (2 carbons), 74.67, 74.4, 72.9, 72.8, 72.7,
72.3 (4 carbons), 71.9, 71.7, 71.7, 71.6 (2 carbons), 71.5 (2 carbons);
ESI/APCI calcd for C88H92O16Na ([M + Na]+) m/e 1427.6283;
measured m/e 1427.6259.
6-O-(6-O-(r-D-Mannopyranosyl)-r-D-mannopyranosyl)-D-
mannopyranose (26). A solution of compound 25 (0.15 g, 0.11
mmol) and catalytic amount of Pd/C in degassed methanol was
stirred at room temperature under atmospheric hydrogen overnight.
The reaction mixture was filtered through Celite, and the residue
was washed with distilled water. After removal of solvents, the
product (0.060 g, 0.11 mmol, 99%) (Rf ) 0.1 eluted with EtOAc).
1H (D2O, 400 MHz) δ 5.06 (s, 1H), 4.8 (m, 3H), 4.71 (s, 1H), 3.8
(m, 11H), 3.5-3.7 (m, 16H); 13C NMR (D2O, 75 MHz) δ 102.2
(ꢀ), 102.1, 101.9, 96.8, 96.4 (ꢀ), 84.3, 76.7 (ꢀ), 75.8 (ꢀ), 75.3 (2
carbons), 73.7 (ꢀ), 73.3 (3 carbons), 73.1 (4 carbons), 72.5 (2
carbons), 72.4, 69.3 (2 carbons), 69.2 (2 carbons), 69.1 (2 carbons),
69.0 (ꢀ), 68.3 (ꢀ), 68.2 (2 carbons), 63.5; ESI/APCI calcd for
C18H32O16Na ([M + Na]+) m/e 527.1588; measured m/e 527.1581.
Methyl 6-O-(6-O-Acetyl-2,3,4-tri-O-benzyl-r-D-mannopyra-
nosyl)-2,3,4-tri-O-benzyl-r-D-mannopyranoside (28). Please refer
to the general procedure for sonication-assisted glycosylation using
phenylthioglycosyl donor (Rf ) 0.5 eluted with hexane/EtOAc )
Benzyl 2,3,4-Tri-O-benzyl-6-O-(2,3,4-tri-O-benzyl-r-D-man-
nopyranosyl)-r-D-mannopyranoside (23). To a solution of com-
pound 22 (0.80 g, 0.79 mmol) in anhydrous CH2Cl2 (1 mL) and
MeOH (8 mL) was added 5 drops of NaOMe solution (1 M in
methanol), and the reaction mixture was stirred at room temperature
for 1 h. After completion of the reaction, Amberlite IR-120 resin
(H+) was added, and the mixture was filtered through Celite. After
removal of solvents and purification with gradient column chro-
J. Org. Chem. Vol. 74, No. 2, 2009 641

Tanifum and Chang
1
65/35). H (CDCl3, 300 MHz) δ 7.2-7.4 (m, 30H), 5.10 (s, 1H),
4.6-4.7 (m, 4H) 4.68 (m, 4H), 4.4-4.6 (m, 13H), 4.1-4.2 (m,
3H), 3.9-3.7 (m, 14H), 3.7 (m, 1H), 3.6 (m, 2H), 3.5 (m, 1H), 3.3
(m, 1H), 3.2 (m, 3H, OMe); 13C NMR (CDCl3, 75 MHz) δ 138.9,
138.7, 138.6 (2 carbons), 138.5, 138.4, 138.2 (2 carbons), 138.0,
128.7 (2 carbons), 128.5 (2 carbons), 128.4 (8 carbons), 128.34 (2
carbons), 128.31 (2 carbons), 128.2 (2 carbons), 128.1 (2 carbons),
128.0 (2 carbons), 127.9 (2 carbons), 127.8 (4 carbons), 127.7 (4
carbons), 127.6 (4 carbons), 127.5, (2carbons), 102.2, 100.3, 98.9,
82.2, 80.4, 79.4, 77.9, 77.3 (2 carbons), 75.3, 75.1, 75.0 (3 carbons),
74.8, 74.4 (2 carbons), 74.3, 73.8, 73.4 (3 carbons), 72.7, 72.0,
71.4 2 (carbons) 71.3 (2 carbons), 69.0, 68.9, 67.8, 66.8, 54.7; ESI/
APCI calcd for C82H92O16N ([M + NH4]+) m/e 1346.6416;
measured m/e 1346.6401.
4.92 (d, J ) 10.9 Hz, 1H), 4.90 (d, J ) 10.9 Hz, 1H), 4.4-4.7 (m,
11H), 4.2 (m, 2H), 3.86 -3.94 (m, 6H), 3.8 (m, 2H), 3.7 (m, 2H),
3.24 (s, 3H, OMe), 1.99 (s, 3H, CH3); 13C NMR (CDCl3, 75 MHz)
δ 171.04, 138.6, 138.5 (2 carbons), 138.47, 138.3, 138.27, 128.5
(5 carbons), 128.4 (4 carbons), 128.3 (2 carbons), 128.1 (2 carbons),
127.9 (3 carbons), 127.8, 127.7 (4 carbons), 127.68 (2 carbons),
127.64 (2 carbons), 127.56, 99.02, 98.04, 80.4 (2 carbons), 79.3,
77.3, 75.1 (2 carbons), 74.8, 74.7, 74.6, 74.4, 72.9, 72.4, 72.2, 71.5
(4 carbons), 70.2, 66.2, 63.6, 54.8, 20.9; ESI/APCI calcd for
C57H62O12Na ([M + Na]+) m/e 961.4139; measured m/e 961.4135.
Methyl 2,3,4-Tri-O-benzyl-6-O-(2,3,4-tri-O-benzyl-r-D-man-
nopyranosyl)-r-D-mannopyranoside (29). Please refer to the
procedure for the synthesis of compound 23 (Rf ) 0.3 eluted with
Methyl 6-O-(6-O-(r-D-Mannopyranosyl)-r-D-mannopyrano-
1
hexane/EtOAc ) 65/35). H (CDCl3, 300 MHz) δ 7.2-7.4 (m,
syl)-r-D-mannopyranoside (32). Please refer to the procedure for
1
30H), 5.06 (d, J ) 1.3 Hz, 1H), 4.95 (d, J ) 10.7 Hz, 1H), 4.91
(d, J ) 10.7 Hz, 1H), 4.7 (m, 4H), 4.6-4.7 (m, 5H), 4.54 (d, J )
12.0 Hz, 1H), 4.49 (d, J ) 11.0 Hz, 1H), 3.8-4.0 (m, 7H), 3.8 (m,
1H), 3.8-3.6 (m, 4H), 3.25 (s, 3H, OMe), 1.92 (s, 1H, OH); 13C
NMR (CDCl3, 75 MHz) δ 138.7 (2 carbons), 138.6, 138.5, 138.4,
138.3, 128.5 (4 carbons), 128.4 (5 carbons), 128.4 (2 carbons), 128.1
(2 carbons), 127.9 (2 carbons), 127.9 (2 carbons), 127.84, 127.80
(3 carbons), 127.7 (4 carbons), 127.6 (2 carbons), 99.0, 98.3, 80.3,
79.4, 75.2, 75.1, 75.0, 74.8, 74.7, 74.6, 72.9, 72.8, 72.3, 72.2, 71.7,
71.4, 66.2 (2 carbons), 62.4 (2 carbons), 54.8; ESI/APCI calcd for
C55H60O11Na ([M + Na]+) m/e 919.4033; measured m/e 919.4027.
Methyl 6-O-(6-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-man-
nopyranosyl)-2,3,4-tri-O-benzyl-r-D-mannopyranosyl)-2,3,4-tri-
O-benzyl-r-D-mannopyranoside (30). Please refer to the general
procedure for sonication-assisted glycosylation using phenylth-
ioglycosyl donor (Rf ) 0.5 eluted with hexane/EtOAc ) 65/35).
1H (CDCl3, 400 MHz) δ 7.4-7.10 (m, 45H), 5.51 (dd, J ) 2.7,
4.8 Hz, 1H, H-2′′), 5.10 (s, 1H, H-1′′), 4.96 (s, 1H, H-1′), 4.95 (d,
J ) 10.9 Hz, 1H), 4.90 (d, J ) 10.6 Hz, 1H), 4.83 (d, J ) 10.9
Hz, 1H), 4.6-4.7 (m, 13H), 4.3-4.5 (m, 8H), 3.8-3.9 (m, 14H),
3.5-3.7 (m, 8H), 3.23 (s, 3H, OMe), 2.15 (s, 3H, CH3); 13C NMR
(CDCl3, 100 MHz) δ 170.3, 138.97, 138.91, 138.8, 138.7, 138.54,
138.50, 138.47, 138.1, 128.6 (6 carbons), 128.48 (5 carbons), 128.41
(4 carbons), 128.1 (2 carbons), 128.08 (2 carbons), 128.00 (3
carbons), 127.9 (4 carbons), 127.87 (4 carbons), 127.85 (4 carbons),
127.81 (4 carbons), 127.7 (2 carbons), 127.67 (4 carbons), 127.60,
127.5, 99.1, 98.3, 98.1, 80.5, 79.5, 77.9, 75.2 (2 carbons), 75.1,
75.02, 74.9, 74.7, 74.6, 74.3, 73.5, 73.04, 72.6, 72.3, 71.7, 71.6,
71.5 (2 carbons), 71.3, 68.9, 68.6, 66.7, 66.2, 21.4; ESI/APCI calcd
for C84H94NO17 ([M + NH4]+) m/e 1388.6522; measured m/e
1388.6500.
Methyl 2,3,4-Tri-O-benzyl-6-O-(6-O-(3,4,6-tri-O-benzyl-r-D-
mannopyranosyl)-2,3,4-tri-O-benzyl-r-D-mannopyranosyl)-r-D-
mannopyranoside (31). Please refer to the procedure for the
synthesis of compound 23 (Rf ) 0.5 eluted with hexane/EtOAc )
1/1). 1H (CDCl3, 400 MHz) δ 7.1-7.4 (m, 45H), 5.1 (m, 2H, H-1′,
H-1′′), 4.9 (m, 3H), 4.8 (m, 2H), 4.4-4.7 (m, 27H), 4.1 (m, 1H),
3.8-3.9 (m, 17H), 3.6-3.7 (m, 11H), 3.3 (m, 3H, OMe); 13C NMR
(CDCl3, 100 MHz) δ 138.93, 138.88, 138.78, 138.71, 138.6, 138.56,
138.51, 138.4, 138.1, 128.66 (3 carbons), 128.60 (5 carbons), 128.54
(4 carbons), 128.50 (5 carbons), 128.45 (3 carbons), 128.15 (2
carbons), 128.11 (5 carbons), 128.08 (5 carbons), 127.9 (2 carbons),
127.86 (3 carbons), 127.81 (5 carbons), 127.7 (2 carbons), 127.6,
99.9, 99.2, 98.1, 80.5, 79.8, 79.4, 77.4, 75.2 (3 carbons), 74.9, 74.7,
74.6, 74.4, 73.6, 73.1, 72.7, 72.3, 71.7 (2 carbons), 71.6 (2 carbons),
71.3, 69.0, 68.1, 66.3, 66.1, 54.9; ESI/APCI calcd for C82H92O16N
([M + NH4]+) m/e 1346.6416; measured m/e 1346.6383.
the synthesis of compound 26 (Rf ) 0.1 eluted EtOAc). H (D2O,
400 MHz) δ 4.80 (s, 1H), 4.78 (s, 1H), 4.70 (s, 2H), 4.64 (s, 1H),
3.8 (m, 7H), 3.7 (m, 6H), 3.6 (m, 10H), 3.29 (s, 3H, OMe), 3.23
(d, J ) 2.2 Hz, 1H), 2.90 (s, 1H), 2.74 (s, 1H); 13C NMR (D2O,
100 MHz) δ 101.2, 99.6, 99.4, 72.9, 70.9 (2 carbons), 70.8, 70.7
(2 carbons), 70.1 (3 carbons), 66.9, 66.7, 66.6, 65.7, 65.6, 61.1,
54.9; ESI/APCI calcd for C19H34O16Na ([M + Na]+) m/e 541.1745;
measured m/e 541.1736.
Benzyl 2-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-mannopyra-
nosyl)-3,4,6-tri-O-benzyl-r-D-mannopyranoside (36). Please refer
to the general procedure for sonication-assisted glycosylation using
phenylthioglycosyl donor (Rf ) 0.5 eluted with hexane/EtOAc )
3/1). 1H (CDCl3, 400 MHz) δ 7.1-7.4 (m, 35H), 5.59 (d, J ) 0.9
Hz, 1H, H-2), 5.11 (s, broad, 1H, H-1′), 5.00 (d, J ) 0.9 Hz, 1H,
H-1), 4.90 (d, J ) 10.7 Hz, 1H), 4.88 (d, J ) 10.8 Hz, 1H), 4.6-4.7
(m, 6H), 4.5-4.6 (m, 2H), 4.3 -4.5 (m, 4H), 4.08 (broad, 1H),
3.9-4.0 (m, 2H), 3.7-3.9 (m, 7H), 3.59 (d, J ) 10.1 Hz, 1H),
2.16 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ 170.4, 138.75,
138.71, 138.6 (2 carbons), 138.4, 138.2, 137.5, 128.6 (4 carbons),
128.55 (5 carbons), 128.5 (4 carbons), 128.41 (2 carbons), 128.3
(2 carbons), 128.1 (2 carbons), 128.06 (2 carbons), 128.02 (3
carbons), 127.9 (2 carbons), 127.8, 127.76 (4 carbons), 127.71 (2
carbons), 127.6, 99.9, 98.2, 79.9, 78.4, 75.4, 75.3, 75.1, 74.9, 74.5,
73.6, 73.5, 72.3, 72.2, 72.0, 69.4, 69.2, 69.0, 68.9 (2 carbons), 21.4;
ESI/APCI calcd for C63H70NO12 ([M + NH4]+) m/e 1032.4898;
measured m/e 1032.4892.
Benzyl 3,4,6-Tri-O-benzyl-2-O-(3,4,6-tri-O-benzyl-r-D-man-
nopyranosyl)-r-D-mannopyranoside (37). Please refer to the
procedure for the synthesis of compound 23 (Rf ) 0.2 eluted with
hexane/EtOAc ) 3/1). 1H (CDCl3, 300 MHz) δ 7.1-7.4 (m, 35H),
5.16 (s, 1H), 5.02 (s, 1H), 4.8-4.9 (m, 2H), 4.6-4.7 (m, 4H), 4.6
(m, 1H), 4.4-4.6 (m, 6H), 4.36 (d, J ) 12.0 Hz, 1H), 4.15 (s, 1H),
4.09 (s, 1H), 3.9 (m, 1H), 3.7-3.9 (m, 6H), 3.6-3.7 (m, 2H), 3.58
(d, J ) 10.7 Hz, 1H), 2.42 (d, J ) 2.1 Hz, 1H, OH); 13C NMR
(CDCl3, 75 MHz) δ 138.7, 138.5 (2 carbons), 138.3 (2 carbons),
138.1, 137.4, 128.7, 128.6 (3 carbons), 128.5 (5 carbons), 128.4 (5
carbons), 128.1, 128.09 (3 carbons), 127.9, 127.86 (3 carbons),
127.82 (3 carbons), 127.7 (4 carbons), 127.6 (2 carbons), 127.5,
101, 98.3, 80.1, 79.8, 75.3, 75.07, 75.0, 74.9, 74.4 (2 carbons),
73.5, 73.4, 72.4, 72.3, 72.2, 71.6, 69.4, 69.1 (2 carbons), 69.0, 68.6
(2 carbons); ESI/APCI calcd for C61H64O11Na ([M + NH4]+) m/e
995.4346; measured m/e 995.4354.
Benzyl 2-O-(2-O-(2-O-acetyl-3,4,6-tri-O-benzyl-r-D-mannopy-
ranosyl)-3,4,6-tri-O-benzyl-r-D-mannopyranosyl)-3,4,6-tri-O-
benzyl-r-D-mannopyranoside (38). Please refer to the general
procedure for sonication-assisted glycosylation using phenylth-
1
ioglycosyl donor (Rf ) 0.5 eluted with hexane/EtOAc ) 3/1). H
Methyl 2,3,4-Tri-O-benzyl-6-O-(6-O-(3,4,6-tri-O-benzyl-ꢀ-D-
mannopyranosyl)-2,3,4-tri-O-benzyl-r-D-mannopyranosyl)-r-D-
mannopyranoside (epi-31). Please refer to the procedure for the
synthesis of compound 23 (Rf ) 0.6 eluted with hexane/EtOAc )
1/1). 1H (CDCl3, 400 MHz) δ 7.5 (m, 2H), 7.2-7.4 (m, 41H), 7.1
(m, 2H), 5.31 (s, 1H), 5.07 (s, 1H), 4.99 (d, J ) 12.2 Hz, 1H), 4.9
(d, J ) 11.0 Hz, 1H), 4.89 (d, J ) 11.4 Hz, 1H), 4.8 (m, 2H),
(CDCl3, 400 MHz) δ 7.1-7.4 (m, 50H), 5.55 (dd, J ) 1.8, 3.2 Hz,
1H, H-2′′), 5.19 (d, J ) 1.6 Hz, 1H, H-1′′), 5.06 (d, J ) 1.6 Hz,
H-1′), 5.02 (d, J ) 1.7 Hz, 1H, H-1), 4.8-4.9 (m, 3H), 4.71 (d, J
) 11.6 Hz, 2H), 4.5-4.7 (m, 9H), 4.5 (m, 1H), 4.41 (d, J ) 10.9
Hz, 1H), 4.33 (d, J ) 11.7 Hz, 1H), 4.30 (d, J ) 12.0 Hz, 1H), 4.1
(m, 1H), 4.03 (m, 2H), 3.8-3.9 (m, 6H), 3.7-3.8 (m, 5H), 3.6-3.7
(m, 5H), 3.52 (d, J ) 10.5 Hz, 1H), 2.14 (s, 3H, CH3); 13C NMR
642 J. Org. Chem. Vol. 74, No. 2, 2009

Sonication-Assisted Oligomannoside Synthesis
(CDCl3, 100 MHz) δ 170.3, 138.8 (2 carbons), 138.7 (2 carbons),
138.6 (2 carbons), 138.5, 138.4, 138.2, 137.6, 128.6 (3 carbons),
128.5 (6 carbons), 128.4 (3 carbons), 128.4 (2 carbons), 128.2 (4
carbons), 128.0 (4 carbons), 127.9 (4 carbons), 127.8 (3 carbons),
127.7 (5 carbons), 127.7 (6 carbons), 100.9, 99.6, 98.4, 79.7 (2
carbons), 79.5, 78.4 (2 carbons), 77.5 (3 carbons), 75.3 (4 carbons),
75.2 (2 carbons), 75.1, 74.9, 74.4, 73.5, (5 carbons) 72.3, (2
carbons), 72.2, 72.1, (3 carbons), 69.5 (2 carbons), 69.3, 68.9 (3
carbons), 21.9; ESI/APCI calcd for C90H98NO17 ([M + NH4]+) m/e
1464.6835; measured m/e 1464.6838.
APCI calcd for C55H60O11Na ([M + Na]+) m/e 919.4033; measured
m/e 919.4030.
Methyl 2-O-(2-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-man-
nopyranosyl)-3,4,6-tri-O-benzyl-r-D-mannopyranosyl)-3,4,6-tri-
O-benzyl-r-D-mannopyranoside (44). Please refer to the general
procedure for sonication-assisted glycosylation using phenylth-
1
ioglycosyl donor (Rf ) 0.4 eluted with hexane/EtOAc ) 3/1). H
(CDCl3, 300 MHz) δ 7.1 -7.4 (m, 45H), 5.52 (d, J ) 2.1 Hz, 1H),
5.18 (s, 1H), 5.04 (d, J ) 1.7 Hz, 1H), 4.8 (m, 4H), 4.6-4.7 (m,
3H), 4.61 (m, 1H), 4.5 (m, 4H), 4.5 (m, 2H), 4.4-4.5 (m, 3H),
4.30 (d, J ) 12.0 Hz, 1H), 4.1 (m, 1H), 3.8-4.0 (m, 6H), 3.6-3.8
(m, 10H), 3.51 (d, J ) 10.3 Hz, 1H), 3.22 (s, 3H, OMe), 2.12 (s,
3H, CH3); 13C NMR (CDCl3, 100 MHz) δ 170.1, 138.65 (2
carbons), 137.54 (3 carbons), 138.4 (2 carbons), 138.25, 138.1,
128.5 (8 carbons), 128.4 (3 carbons), 128.36 (3 carbons), 128.2 (3
carbons),128.10 (3 carbons), 127.97 (3 carbons), 127.96 (3 carbons),
127.90 (3 carbons), 127.88 (3 carbons), 127.7 (5 carbons), 127.68
(4 carbons), 127.5 (3 carbons), 100.8, 99.9, 99.8, 79.9, 78.3 (2
carbons), 77.4 (4 carbons), 75.3 (2 carbons), 75.2, 74.95, 74.94,
73.56 (3 carbons), 72.3, 72.29, 72.25, 72.1 (2 carbons), 71.8, 69.5
(2 carbons), 68.9 (2 carbons), 54.8, 21.4; ESI/APCI calcd for
C84H94NO17 ([M + NH4]+) m/e 1388.6522; measured m/e 1388.6519.
Methyl 3,4,6-Tri-O-benzyl-2-O-(2-O-(3,4,6-tri-O-benzyl-r-D-
mannopyranosyl)-3,4,6-tri-O-benzyl-r-D-mannopyranosyl)-r-D-
mannopyranoside (45). Please refer to the procedure for the
synthesis of compound 23 (Rf ) 0.6 eluted with hexane/EtOAc )
Benzyl 3,4,6-Tri-O-benzyl-2-O-(2-O-(3,4,6-tri-O-benzyl-r-D-
mannopyranosyl)-3,4,6-tri-O-benzyl-r-D-mannopyranosyl)-r-D-
mannopyranoside (39). Please refer to the procedure for the
synthesis of compound 23 (Rf ) 0.7 eluted with hexane/EtOAc )
1
65/35). H (CDCl3, 300 MHz) δ 7.1-7.4 (m, 50H), 5.21 (d, J )
1.7 Hz, 1H, H-1′′), 5.13 (d, J ) 1.4 Hz, 1H, H-1′), 5.03 (d, J ) 1.7
Hz, 1H, H-1), 4.82 (d, J ) 11.0 Hz, 1H), 4.80 (d, J ) 10.7 Hz,
1H), 4.7-4.4 (m, 16H), 4.34 (d, J ) 11.7 Hz, 1H), 4.31 (d, J )
12.0 Hz, 1H), 4.12 (s, 2H), 4.02 (s, 1H), 3.8-3.9 (m, 7H), 3.5-3.8
(m, 8H), 2.36 (d, J ) 2.4 Hz, 1H, OH); 13C NMR (CDCl3, 75 MHz)
δ 138.7 (2 carbons), 138.6 (2 carbons), 138.5, 138.4 (2 carbons),
138.3, 138.1, 137.5, 128.55 (3 carbons), 128.5 (2 carbons), 128.4
(9 carbons), 128.1 (2 carbons), 127.9 (8 carbons), 127.86 (3
carbons), 127.79 (4 carbons), 127.72 (5 carbons), 127.6 (5 carbons),
127.5 (2 carbons), 101.1, 101.0, 98.3, 80.1, 79.5, 77.3 (2 carbons),
75.4, 75.2 (2 carbons), 75.1, 75.0, 74.9 (2 carbons), 74.4, 73.4 (2
carbons), 73.3 (3 carbons), 72.4 (2 carbons), 72.3, 72.2 (2 carbons),
72.1, 71.96, 71.67, 69.5, 69.4, 69.16 (2 carbons), 69.03, 68.63 (2
carbons); ESI/APCI calcd for C88H96NO16 ([M + NH4]+) m/e
1422.6729; measured m/e 1422.6729.
1
65/35). H (CDCl3, 400 MHz) δ 7.2-7.4 (m, 45H), 5.25 (d, J )
1.6 Hz, 1H), 5.15 (d, J ) 1.5 Hz, 1H), 4.8 (m, 4H), 4.70 (d, J )
12.1 Hz, 1H), 4.68 (d, J ) 12.3 Hz, 1H), 4.6 (m, 4H), 4.5 (m, 6H),
4.49 (d, J ) 10.7 Hz, 1H), 4.47 (d, J ) 11.6 Hz, 1H), 4.36 (d, J )
12.2 Hz, 1H), 4.14 (s, 2H), 4.00 (t, J ) 2.4 Hz, 1H), 3.9 (m, 5H),
3.8 (m, 2H), 3.8 (m, 4H), 3.7 (m, 2H), 3.6 (m, 1H), 3.6 (m, 1H),
3.25 (s, 3H, OMe), 2.46 (s, 1H, OH); 13C NMR (CDCl3, 100 MHz)
δ 138.8 (2 carbons), 138.7 (3 carbons), 138.6, 138.5, 138.4, 138.3,
128.7 (4 carbons), 128.6 (2 carbons), 128.5 (8 carbons), 128.1 (8
carbons), 128.0 (5 carbons), 127.9 (2 carbons), 127.81 (2 carbons),
127.8 (2 carbons), 127.7 (5 carbons), 127.6 (2 carbons), 101.2,
101.0, 99.9, 80.2, 79.6 (2 carbons), 77.46, 75.3, 75.2 (3 carbons),
75.2 (3 carbons), 74.9, 74.5, 73.55 (2 carbons), 73.50 (3 carbons),
72.54, 72.5, 72.3, 71.9, 71.8, 71.7, 69.8, 69.6, 69.1, 68.7, 54.7;
ESI/APCI calcd for C82H92NO16 ([M + NH4]+) m/e 1346.6391;
measured m/e 1346.6397.
2-O-(2-O-(r-D-Mannopyranosyl)-r-D-mannopyranosyl)-D-
mannopyranose (40). Please refer to the procedure for the synthesis
1
of compound 26 (Rf ) 0.2 eluted with EtOAc/MeOH ) 9/1). H
(D2O, 400 MHz) δ 5.26 (s, 1H), 5.19 (s, 1H), 4.93 (s, 2H), 3.5-4.0
(m, 28H); 13C NMR (D2O, 100 MHz) δ 102.4, 100.7, 92.6, 79.5,
78.7, 73.4 (2 carbons), 72.6, 70.5, 70.1 (3 carbons), 67.2 (2 carbons),
66.9, 61.2 (2 carbons), 61.1; ESI/APCI calcd for ESI/APCI calcd
for C18H32O16Na ([M + Na]+) m/e 527.1588; measured m/e
527.1577.
Methyl 2-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-mannopyra-
nosyl)-3,4,6-tri-O-benzyl-r-D-mannopyranoside (42). Please refer
to the general procedure for sonication-assisted glycosylation using
phenylthioglycosyl donor (Rf ) 0.7 eluted with hexane/EtOAc )
65/35). 1H (CDCl3, 300 MHz) δ 7.1-7.5 (m, 30H), 5.53 (dd, J )
3.1, 1.8 Hz, 1H), 5.07 (d, J ) 1.8 Hz, 1H), 4.84 (d, J ) 10.9 Hz,
1H), 4.83 (d, J ) 10.9 Hz, 1H), 4.76 (d, J ) 2.0 Hz, 1H), 4.6-4.7
(m, 4H), 4.4-4.6 (m, 5H), 4.39 (d, J ) 10.9 Hz, 1H), 3.7-4.0 (m,
11H), 3.24 (s, 3H), 2.10 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ
170.2, 138.61, 138.58, 138.55, 138.46, 138.29, 138.09, 128.48 (3
carbons), 128.40 (5 carbons), 128.28 (2 carbons), 128.15 (2
carbons), 127.97 (3 carbons0, 127.8, 127.68 (3 carbons), 127.61
(3 carbons), 127.5 (3 carbons), 99.8, 99.6, 79.8, 78.2, 77.3, 75.2 (2
carbons), 74.7 (3 carbons), 74.4, 73.5 (2 carbons), 73.4 (2 carbons),
72.1 (2 carbons), 72.0 (2 carbons), 71.9 (2 carbons), 71.7 (2
carbons), 54.8, 21.2; HRFAB calcd for C57H62O12Na ([M + Na]+)
m/e 961.4133; measured m/e 961.4148.
Methyl 2-O-(2-O-(r-D-Mannopyranosyl)-r-D-mannopyrano-
syl)-r-D-mannopyranoside (46). Please refer to the procedure for
1
the synthesis of compound 26 (Rf ) 0.1 eluted EtOAc). H (D2O,
400 MHz) δ 5.15 (d, J ) 1.0 Hz, 1H), 4.90 (d, J ) 1.4 Hz, 1H),
4.85 (d, J ) 1.0 Hz, 1H), 4.68 (s, 2H), 3.93 (s, 1H), 3.92 (s, 1H),
3.4-3.8 (m, 22H), 3.26 (s, 3H, OMe); 13C NMR (D2O, 100 MHz)
δ 102.4, 100.8, 99.4, 78.9, 78.7, 73.4 (2 carbons), 72.7, 70.5, 70.3,
70.1 (2 carbons), 67.2, 67.1, 66.9, 61.3, 61.2, 61.1, 55.0; ESI/APCI
calcd for C19H34O16Na ([M + Na]+) m/e 541.1745; measured m/e
541.1733.
Methyl 3-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-mannopyra-
nosyl)-2,4-di-O-benzyl-r-D-mannopyranoside (47). To a solution
of compound 19 (0.27 g, 0.32 mmol) and Cu(OTf)2 (0.017 g, 0.048
mmol) in anhydrous CH2Cl2 (10 mL), borane complex (0.6 mL)
was added and the mixture was stirred for 2 h at room temperature.
After completion of the reaction, the reaction was quenched with
Methyl 3,4,6-Tri-O-benzyl-2-O-(3,4,6-tri-O-benzyl-r-D-man-
nopyranosyl)-r-D-mannopyranoside (43). Please refer to the
procedure for the synthesis of compound 23 (Rf ) 0.4 eluted with
MeOH, diluted with EtOAc, and washed with saturated NaHCO3(aq)
,
water, and brine. After removal of solvents and purification with
gradient column chromatography, the product was obtained as an
oil (0.27 g,, 0.31 mmol, 98%) (Rf ) 0.3 eluted with hexane/EtOAc
) 65/35). 1H (CDCl3, 400 MHz) δ 7.2-7.4 (m, 25H), 5.52 (d, J )
1.7 Hz, 1H, H-2), 5.23 (s, 1H, H-1), 4.90 (d, J ) 11.2 Hz, 1H),
4.81 (d, J ) 10.9 Hz, 1H), 4.6-4.7 (m, 8H), 4.4-4.5 (m, 4H),
4.1-4.2 (m, 3H), 3.6-4.0 (m); 3.28 (s, 3H, OMe), 2.11 (s, 3H,
CH3); 13C NMR (CDCl3, 100 MHz) δ 170.3, 138.8, 138.5, 138.3,
138.1, 138.0, 128.7 (5 carbons), 128.6 (2 carbons), 128.4 (5
carbons), 128.3 (2 carbons), 128.2 (3 carbons), 128.0, 127.9 (2
1
hexane/EtOAc ) 65/35). H (CDCl3, 300 MHz) δ 7.4 (m, 30H),
5.16 (s, 1H, H-1′), 4.8-4.9 (m, 3H), 4.7 (m, 1H), 4.6-4.7 (m, 4H),
4.5-4.6 (m, 5H), 4.1 (m, 1H), 4.0 (m, 1H), 3.7-4.0 (m, 11H),
3.25 (s, 3H, O Me), 2.44 (d, J ) 1.7 Hz, 1H, OH); 13C NMR
(CDCl3, 75 MHz) δ 138.7, 138.6, 138.5, 138.4, 138.3, 138.1, 128.6
(3 carbons), 128.4 (7 carbons), 127.99 (5 carbons), 127.96 (6
carbons), 127.8 (3 carbons), 127.7 (2 carbons), 127.6, 127.56 (2
carbons), 127.50, 101.2, 99.9, 80.1, 79.9, 75.2, 75.1, 74.9, 74.8,
74.5, 73.5, 73.4, 72.3, 72.2, 71.8, 71.7, 69.4, 69.3, 68.6, 54.8; ESI/
J. Org. Chem. Vol. 74, No. 2, 2009 643

Tanifum and Chang
carbons), 127.88 (4 carbons), 127.74 (2 carbons), 127.71, 99.8, 98.9,
78.26, 78.1, 77.4, 75.4, 75.2, 75.14, 74.6, 73.7, 72.7, 72.4, 72.3,
71.9, 69.4, 68.9, 62.3, 55.04, 21.2; ESI/APCI calcd for C50H56O12Na
([M + Na]+) m/e 871.3664; measured m/e 871.3650.
71.6, 69.5, 68.9, 66.2, 62.4, 55.0; ESI/APCI calcd for C68H76O16Na
([M + Na]+) m/e 1171.5031; measured m/e 1171.5005.
Methyl 3-O-(2-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-man-
nopyranosyl)-3,4,6-tri-O-benzyl-r-D-mannopyranosyl)-6-O-(3,6-
di-O-(2-O-acetyl-3,4,6-tri-O-benzyl-r-D-mannopyranosyl)-2,4-di-
O-benzyl-r-D-mannopyranosyl)-2,4-di-O-benzyl-r-D-
mannopyranoside (50). Please refer to the general procedure for
sonication-assisted glycosylation using phenylthioglycosyl donor
(Rf ) 0.5 eluted with hexane/EtOAc ) 1/1). 1H (CDCl3, 300 MHz)
δ 7.4-7.1 (m, 80H), 5.51 (s, broad, 3H), 5.21 (s, 2H), 5.01 (s,
1H), 4.98 (s, 1H), 4.96 (s, 1H), 4.7-4.9 (m, 5H), 4.72 (d, J ) 11.3
Hz, 2H), 4.3-4.7 (m, 28H), 4.30 (d, J ) 12.0 Hz, 2H), 4.25 (d, J
) 12.0 Hz, 1H), 4.0-4.2 (m, 3H), 3.4-4.0 (m, 28H), 3.35 (d, J )
10.3 Hz, 1H), 3.17 (s, 3H, OMe), 2.14 (s, 3H, CH3), 2.10 (s, 3H,
CH3), 2.06(s, 3H, CH3); 13C NMR (CDCl3, 75 MHz) δ 170.3, 170.2
(2 carbons), 138.8 (2 carbons), 138.7, 138.6 (2 carbons), 138.5 (2
carbons), 138.3 (4 carbons), 138.18 (2 carbons), 138.16, 137.96,
137.89, 128.6 (2 carbons), 128.47 (8 carbons), 128.40 (8 carbons),
128.3 (6 carbons), 128.29 (10 carbons), 128.16 (3 carbons), 127.89
(8 carbons), 127.86 (6 carbons), 127.78 (3 carbons), 127.67 (4
carbons), 127.56 (4 carbons), 127.55 (5 carbons), 127.48 (4
carbons), 127.29 (2 carbons), 101.2, 99.8, 99.5, 98.4, 98.1, 97.0,
79.8, 78.3 (2 carbons), 78.2 (2 carbons), 77.8 (2 carbons), 77.3 (3
carbons), 75.09 (2 carbons), 74.98 (3 carbons), 74.8 (2 carbons),
74.76, 74.74, 74.16 (4 carbons), 73.46 (2 carbons), 73.44 (3
carbons), 73.25 (2 carbons), 72.8, 72.25 (4 carbons), 72.12 (3
carbons), 71.92 (2 carbons), 72.90 (2 carbons), 71.63 (2carbons),
71.5, 71.3 (2 carbons), 71.0, 68.8 (3 carbons), 68.4 (2 carbons),
54.8, 21.26 (2 carbons), 21.2; ESI/APCI calcd for C155H170O34N
([M + NH4]+) m/e 2589.1599; measured m/e 2589.1604.
Methyl 3-O-(2-O-Acetyl-3,4,6-tri-O-benzyl-r-D-mannopyra-
nosyl)-6-O-(3,6-di-O-acetyl-2,4-di-O-benzyl-r-D-mannopyrano-
syl)-2,4-di-O-benzyl-r-D-mannopyranoside (48). Please refer to
the general procedure for sonication-assisted glycosylation using
phenylthioglycosyl donor (Rf ) 0.5 eluted with hexane/EtOAc )
1
65/35). H (CDCl3, 400 MHz) δ 7.1-7.3 (m, 35H), 5.51 (s, 1H,
H-2′′), 5.31 (s, 1H, H-1′′), 5.21 (s, 1H, H-3′′′), 5.11 (d, J ) 1.8
Hz, 1H, H-1′′), 4.88 (d, J ) 10.9 Hz, 1H), 4.83 (d, J ) 11.1 Hz,
1H), 4.5-4.7 (m, 9H), 4.4-4.5 (m, 3H), 4.39 (d, J ) 12.2 Hz,
1H), 4.1 (m, 1H), 3.6-4.0 (m, 15H), 3.25 (s, 3H, OMe), 2.08 (s,
3H, CH3), 2.05 (s, 3H, CH3), 1.98 (s, 3H, CH3); 13C NMR (CDCl3,
75 MHz) δ 170.9, 170.1 (2 carbons), 138.7, 138.4, 138.3, 138.2,
138.1, 138.07, 137.9, 128.5 (7 carbons), 128.4 (2 carbons), 128.3
(6 carbons), 127.9 (4 carbons), 127.8 (3 carbons), 127.7 (2 carbons),
127.65 (3 carbons), 127.6 (3 carbons), 99.8, 98.6, 97.7, 78.1 (2
carbons), 77.9, 77.3 (6 carbons), 76.3, 75.2 (2 carbons), 74.9, 74.8,
74.4, 73.8, 73.5, 73.3, 72.7, 72.6, 72.3, 71.9 (2 carbons), 69.8, 69.2,
68.8, 63.4, 54.8, 21.2, 21.1, 20.9; ESI/APCI calcd for C74H82O19Na
([M + Na]+) m/e 1297.5348; measured m/e 1297.5328.
Methyl 6-O-(2,4-Di-O-benzyl-r-D-mannopyranosyl)-3-O-(3,4,6-
tri-O-benzyl-r-D-mannopyranosyl)-2,4-di-O-benzyl-r-D-man-
nopyranoside (49). Please refer to the procedure for the synthesis
of compound 23 (Rf ) 0.1 eluted with hexane/EtOAc ) 65/35).
1H (CDCl3, 400 MHz) δ 7.2-7.4 (m, 35H), 5,26 (s, 1H), 5.15 (s,
1H), 4.94 (d, J ) 11.1 Hz, 1H), 4.86 (d, J ) 11.1 Hz, 1H), 4.77
(d, J ) 11.0 Hz, 1H), 4.5-4.7 (m, 11H), 4.42 (d, J ) 11.8 Hz,
1H), 4.1 (m, 1H), 3.6-4.0 (m, 18H), 3.27 (s, 3H, OMe), 2.39 (s,
1H, OH), 2.33 (d, J ) 9.4 Hz, 1H, OH); 13C NMR (CDCl3, 100
MHz) δ 138.7, 138.6, 138.5, 138.4, 138.2, 138.0 (2 carbons), 128.7
(5 carbons), 128. Six (4 carbons), 128.4 (4 carbons), 128.1 (2
carbons), 128.0 (2 carbons), 127.97 (3 carbons), 127.9 (4 carbons),
127.79 (4 carbons), 127.76 (3 carbons), 127.6 (2 carbons), 127.56,
101.5, 98.7, 97.5, 80.2, 78.9, 77.7, 76.7, 75.2 (4 carbons), 75.0,
74.6, 73.7 (2 carbons), 72.9, 72.7, 72.3, 72.2, 71.9 (2 carbons),
Acknowledgment. We acknowledge support from the De-
partment of Chemistry and Biochemistry, Utah State University.
1
Supporting Information Available: H and 13C spectra of
the synthesized compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO8019835
644 J. Org. Chem. Vol. 74, No. 2, 2009