Regioselective strategies mediated by lanthanide triflates for efficient assembly of oligomannans

Article abstract of DOI:10.1021/jo070018t

(Chemical Equation Presented) Readily prepared mannosyl n-pentenylorthoesters (NPOEs) serve as donors in themselves and as convenient intermediates for other glycosyl donors, such as n-pentenyl glycosides (NPGs), thioglycosides, and trichloroacetimidates.

Full text of DOI:10.1021/jo070018t

Regioselective Strategies Mediated by Lanthanide Triflates for
Efficient Assembly of Oligomannans†
K. N. Jayaprakash, Siddhartha Ray Chaudhuri, Changalvala V. S. R. Murty, and
Bert Fraser-Reid*
Natural Products and Glycotechnology Research Institute, Inc.,# 595 F Weathersfield Road,
Pittsboro, North Carolina 27312
dglucose@aol.com
ReceiVed January 4, 2007
Readily prepared mannosyl n-pentenylorthoesters (NPOEs) serve as donors in themselves and as convenient
intermediates for other glycosyl donors, such as n-pentenyl glycosides (NPGs), thioglycosides, and
trichloroacetimidates. These various donors are activated by different reagents, and are therefore amenable
to versatile, discriminate use. Scandium and ytterbium triflates respond very differently to these donors,
with the result that chemoselective discrimination between NPOEs, NPGs, trichloroacetimidates as well
as ethyl and phenyl thioglycosides can be achieved. Appropriate NPOEs are also able to provide 2,6 and
3,6 diol acceptors via rearrangement or glycoside formation, and these can be used for one-pot, sequential
glycosidations based on orthogonal donors, and in situ double differential glycosidations. Thus NPOEs
activated by iodonium ion, specifically generated from ytterbium triflate/N-iodosuccinimide, can be used
to monoglycosidate the diols rapidly, with exquisite regio, and sometimes chemo, selectivity. The residual
NPOE is converted into disarmed NPG, which is refractory to the reaction conditions, and so poses no
threat to the free-OH of the monoglycosidation product. Further glycosidation of the latter can then
achieved by direct addition of a trichloroacetimidate or ethyl thioglycoside. This basic strategy has been
used to prepare a branched chain pentadecamannan. The success is an example of the efficiency of donor/
acceptor MATCH concept for regioselective glycosylation.
Introduction
of the then fledgling area of oligosaccharide synthesis2 remains
a seminal document, because by summarizing (some of) the
early successes and failures, he inadvertently suggested areas
that were (are!) in need of future attention. Most activity has
focused on the development of novel donors from which the
aglycon, LVG, can be removed by mild, unique or specific
coaxing.3
The fundamental step in oligosaccharide assembly, as il-
lustrated in Scheme 1a, is the coupling of an incipient electro-
phile, the donor 1, with an acceptor, 2.1 Paulsen’s 1982 review
† Portions of this work have been reported in preliminary communications
cited in refs 5, 22, 28, and 29.
# An independent nonprofit research facility with laboratories at Centennial
Campus (North Carolina State University), Raleigh, NC.
(2) Paulsen, H. Angew. Chem., Int. Ed. 1982, 21, 155-177.
(3) See for example: Demchenko, A. V. Lett. Org. Chem. 2005, 2, 580-
589. Osborn, H. M. I.; Khan, T. H. Oligosaccharides: Their synthesis and
biological roles; Oxford University Press: Oxford, UK, 2000. Schmidt, R.
R.; Jung, K. H. In Carbohydrates in Chemistry and Biology; Ernst, B., Heat,
G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1, p
5. Oscarson, S. In Carbohydrates in Chemistry and Biology; Ernst, B., Hart,
G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1, p
93.
(1) Goodman, L. AdV. Carbohydr. Chem. Biochem. 1967, 22, 109.
Toshina, K.; Tatsuta, K. Chem. ReV. 1993, 93, 1503. Lindhorst, T. K.
Essentials of carbohydrate chemistry and biochemistry; Wiley-VCH: New
York, 2000. Nitz, M.; Bundle, D. K. In Glycoscience: Chemistry and
Chemical Biology, Fraser-Reid, B., Tatsuta, K., Thiem, J., Eds.; Springer:
Berlin, Germany, 2001; Vol. 2, p 1497. Boons, G.-J. In Carbohydrate
Chemistry; Boons, G.-J., Ed.; Blackie Academic Professional: London, UK,
1998, Chapter 5. Sinay, P. Pure Appl. Chem. 1978, 50, 1437.
10.1021/jo070018t CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/27/2007
5534
J. Org. Chem. 2007, 72, 5534-5545

Efficient Assembly of Oligomannans
SCHEME 1
With regard to the other partner, the traditional practice is to
ensure, as in 2, that only the targeted OH is free for presentation
to the donor during the coupling event. However, Scheme 1b
summarizes recent observations in our4,5 and Lopez’6 labora-
tories, in which a diol acceptor, 4, upon in situ presentation to
two donors, 5 and 6, produced only one double glycosidation
product, 8, of four possibilities.
The MATCH required to produce 7 and thence 8 dispenses
with the traditional procedure of extensive protection, as with
2 in Scheme 1a, to ensure that only one free-OH is presented
for the coupling event.
of their implication with HIV therapy.8 The latter occurs in
Candida albicans NIH A-204 (serotype A) strain as acid-stable
side chains9 to the â-(1f2) mannan backbone that has attracted
so much recent attention.10
Results and Discussion
MATCH and Regioselectivity. Our efforts to rationalize the
selectivities implicit in Scheme 1b have led us to invoke the
phenomenon of MATCHsbut because there are (at least) three
concepts associated with the word, some clarification is neces-
sary.
In this paper, we further explore the concept of MATCH in
context of the R-(3f6) and R-(2f6) mannan arrays 9 and 10.
Masamune’s usage of MATCH11 exemplified by Scheme 2a
reflects the principle of double diastereoselectivity in which one
set of chiral reactants, e.g., a (+) and (+) pair, generates more
(4) Anilkumar, G.; Nair, L. G.; Fraser-Reid, B. O. Org. Lett. 2000, 2,
2587-2589. Fraser-Reid, B.; Lopez, J. C.; Radhakrishnan, K. V.; Mach,
M.; Schlueter, U.; Gomez, A.; Uriel, C. J. Am. Chem. Soc. 2002, 124, 3198-
3199. Fraser-Reid, B.; Anilkumar, G. N.; Nair, L. G.; Radhakrishnan, K.
V.; Lopez, J. C.; Gomez, A.; Uriel, C. Aust. J. Chem. 2002, 55, 123-130.
(5) Jayaprakash, K. N.; Fraser-Reid, B. Org. Lett. 2004, 6, 4211-4214.
(6) Lo´pez, J. C.; Agocs, A.; Uriel, C.; Go´mez, A. M.; Fraser-Reid, B.
Chem. Commun. 2005, 5088-5090. Uriel, C.; Gomez, A. M.; Lo´pez, J.
C.; Fraser-Reid, B. J. Carbohydr. Chem. 2005, 24, 665-675.
(7) Trombetta, E. S. Glycobiology 2003, 13, 77R-91R. Burda, P.; Aebi,
M. Biochim. Biophys. Acta 1999, 1426, 239-257. Petrescu, A. J.; Butters,
T. D.; Reinkensmeier, G.; Petrescu, S.; Platt, F. M.; Dwek, R. A.; Wormald,
M. R. EMBO J. 1997, 16, 4302-4310. Scanlan, C. N.; Pantophlet, R.;
Wormald, M. R.; Ollmann Saphire, E.; Stanfield, R.; Wilson, I. A.; Katinger,
H.; Dwek, R. A.; Rudd, P. M.; Burton, D. R. J. Virol. 2002, 76, 7306-
7321.
(8) For leading references see: Geng, X.; Dudkin, V. Y.; Mandal, M.;
Danishefsky Angew. Chem., Int. Ed. 2004, 43, 2563-2565. Lam, S. N.;
Gervay-Hague, J. J. Org. Chem. 2005, 70, 8773-8779. Matsuo, I. M.;
Kashiwagi, T.; Totani, K.; Ito, Y. Tetrahedron Lett. 2005, 46, 4197-4200.
(9) Kobayashi, H.; Takaku, M.; Nishidate, Y.; Takahaski, S.; Takikawa,
M.; Shibata, N.; Suzuki, S. Carbohydr. Res. 1992, 231, 105-116. Masuoka,
J.; Hazen, K. C. Infect. Immun. 2004, 72, 6230-6236. Kobayashi, H.;
Shibata, N.; Osaka, T. Miyagawa, Y.; Ohkubo, Y.; Suzuki, S. Phytochem-
istry 1992, 31, 1147-1153.
(10) Crich, D.; Li, W.; Li, H. J. Am. Chem. Soc. 2004, 126, 15081-
15086. Crich, D.; Banerjee, A.; Yao, Q. J. Am. Chem. Soc. 2004, 126,
14930-14934. Wu, X.; Bundle, D. R. J. Org. Chem. 2005, 70, 7381-
7388. Nitz, M.; Bundle, D. R J. Org. Chem. 2001, 66, 8411-8423.
(11) Masamune, S.; Choy, W.; Petersen, J. S.; Sita, L. R. Angew. Chem.,
Int. Ed. Engl. 1985, 24, 1-30.
The former is an essential component of high-mannose oli-
gosaccharides7 that currently attracts special attention in view
J. Org. Chem, Vol. 72, No. 15, 2007 5535

Jayaprakash et al.
SCHEME 2
SCHEME 3
of the newly created chiral center than does another set, e.g., a
(+) and (-) pair. The (+)/(+) pair are therefore a MATCH,
and the (+)/(-) pair, a misMATCH.
Paulsen used the term to describe the extensive body of
observations in his and other laboratories, which showed that
one donor usually reacted more successfully than another, with
a given acceptor, success being measured by yield (Scheme 2b).
The better yielding partners were therefore considered to
constitute a MATCH.12
Central to our approach to MATCH is the concept of
Reciprocal Donor Acceptor Selectivity (RDAS),17 which is
evinced in Scheme 1b. Thus, exclusive formation of 8 requires
that monoglycosidation product 7 be the ONLY intermediate.
Thus donor, 5, must select hydroxyl (A), and simultaneously
reject hydroxyl (B) of the acceptor diol 7. Conversely and
concomitantly, hydroxyl (A) must select donor 5 rather than
donor 6, whereas hydroxyl (B) must ignore donor 5. Thus, donor
5 and hydroxyl (A) constitute a MATCH whereas donor 5 and
hydroxyl (B) are a misMATCH.
We have examined the competitive double differential
glycosidation study depicted in Scheme 1b with three types of
donors, LVG ) OPentenyl, SEt, and trichloroacetimidate, and
found that in all cases, only one of four possible trisaccharides,
i.e., 8, was formed. However, there were substantial differences
in the yields, n-pentenylorthoesters (NPOEs) giving the best.
Some Aspects of Glycosyl Orthoesters. The functioning of
NPOEs as glycosyl donors is relevant to the discussion that
follows. Orthoester donors undergo ready acid-catalyzed rear-
rangement, 11 f 12 (Scheme 3), in which an oxolenium ion,
15, is the intermediate in transfer of the alkoxy moiety.18,19
Intermediate 15 could also glycosylate an in situ acceptor-OH
to give 17. However, the re-addition step, 15 f 12, obviously
offers competition. This problem had confronted Kotchetkov
and Bachinovsky, the primary exponents of acid-catalyzed
The usage of Fraser-Reid and Lopez13 shown in Scheme 2c
implies regioselectivity, an issue that was not considered by
Paulsen in 1982, nor could it have been, given the narrow range
of donors, reagents, and reaction conditions2,12,14 that were then
available for executing glycosidations. Notably, in commenting
on the recent synthesis of a dodecasaccharyl lipomannan
glycolipid of Mycobacterium tuberculosis reported by this
laboratory,15 Paulsen observed that “the study by Fraser-Reid
and co-workers demonstrates that this concept can be used to
simplify oligosaccharide synthesis using modern reagents...”.16
(12) Paulsen, H. In SelectiVity, a Goal for Synthetic Efficiency; Bartman,
W., Trost, B. M., Eds.; Verlag Chemie: Basel, Switzerland, 1984.
(13) Fraser-Reid, B.; Lopez, J. C.; Radhakrishnan, K. V.; Mach, M.;
Schlueter, U.; Gomez, A.; Uriel, C. Can. J. Chem. 2002, 80, 1075-1087.
(14) See for example: Igarashi, AdV. Carbohydr. Chem. Biochem. 1977,
34, 243. Helfrieh, B.; Wedemeyer, K. F. Ann. 1949, 563, 139. Lemieux, R.
U.; Hendriks, K. B.; Stick, R. V.; James, K. J. Am. Chem. Soc. 1975, 97,
4056. Pougny, J. R.; Nassr, M. A. N.; Naulet, N.; Sinay, P. NouV. J. Chim.
1978, 2, 389-395. Paulsen, H.; Lockhoff. Chem. Ber. 1981, 114, 3102-
3114.
(17) Fraser-Reid, B.; Lopez, J. C.; Gomez, A. M.; Uriel, C. Eur. J. Org.
Chem. 2004, 1387-1395.
(18) Bochkov, A. F.; Zaikov, G. E. Chemistry of the O-Glycosidic Bond;
Pergamon: Oxford, UK, 1979.
(15) Jayaprakash, K. N.; Lu, J.; Fraser-Reid, B. Angew. Chem., Int. Ed.
2005, 44, 5894.
(16) Borman, S. Key Oligosaccharide of Cell-Wall Prepared. In Chem.
Eng. News 2005, 83, 38.
(19) For a recent review see: Kong, F. Carbohydr. Res. 2007, 342, 345-
373.
5536 J. Org. Chem., Vol. 72, No. 15, 2007

Efficient Assembly of Oligomannans
SCHEME 4
glycosyl orthoester chemistry, and their efforts to overcome it
had led to seminal developments.20
19b to 24 followed by uneventful deprotections. Rearrangement
of tribenzoate 18 paved the way to tetrol 26b, which was then
converted into the 3,6-diol 27 as described previously.25 NPOE
19c was used to glycosylate allyl alcohol, and the resulting 2,6-
dibenzoate 28, upon saponification, gave diol 29.
In this context, the n-pentenyl analogues, 11b (Alk )
n-pentenyl), offered a way around the re-addition problem, e.g.,
15 f 12, since a halonium ion, e.g., Hal+, could sequester the
n-pentenyl moiety as the halomethyltetrahydrofuran, 14.
The mechanism in Scheme 3 also suggested facile procedures
leading to some other types of donors, as well as acceptors,
and this versatility prompted us to test for various selectivities
in donor/acceptor combinations.
Synthesis of Donors. n-Pentenyl orthoesters (NPOEs) can
be produced in three easy steps from the corresponding hexose,21
as exemplified for the case of the mannose derivative 18
(Scheme 4). The three hydroxyls can be readily differentiated
as in 19a, 19b, or 19c, thereby providing convenient entry to
the NPG family. Thus, an NPOE, e.g., 19a, can be quantitatively
rearranged into disarmed NPG 20a. The armed counterpart, 20b,
can then be routinely obtained.
MATCH Mediated by Donor/M(OTf)3 Selectivities. Iodo-
nium ion needed to activate n-pentenyl donors is usually
generated by the action of protic26 or Lewis27 acids on
N-iodosuccinimide (NIS). However, we have recently been
investigating the use of lanthanide salts for this purpose,28 and
have found dramatic differences between scandium and ytter-
bium triflates. When the salt and NIS are mixed in dichlo-
romethane, the formation of I+ is indicated by an immediately
generated purple color. Nevertheless, a substantial amount of
acid-catalyzed rearrangement still occurred. Since the latter is
an NPG (i.e., 12, Alk ) n-pentenyl), it is a potential donor via
the oxocarbenium ion 16 raising the possibility of double
glycosylation.
Acidic or oxidative hydrolysis converts the NPOE into the
corresponding 2-O-acylated glycoses22 (e.g., 19 f 21), from
which trichloroacetimidates 22a/b or the ethyl and phenyl
thioglycosides 23a-d can be obtained by standard proce-
dures.23,24
Compounds 18/19, 20, 22, and 23 represent a range of donors
of different capabilities, each activated by different reagent(s)
so that they can be used discriminatingly.
Synthesis of Acceptors. The acceptor diols used in the studies
below were obtained from NPOE 18 as the ultimate source,
via the differentially protected counterparts 19b and 19c as
shown in Scheme 5. Diol 25 was obtained by rearrangement of
However, our experiments have indicated that this potential
hazard can be avoided.28 Thus, as shown in Table 1, entry (i),
both salts, in the presence of NIS, promote glycosidation of an
alcohol, ROH, with NPOEs. However, entries (ii) and (iii) show
that glycosidation by armed or disarmed NPGs is not effected
by Yb(OTf)3/NIS.
Entries (i), (ii) ,and (iii) therefore show that lanthanide triflates
can be used to discriminate between various n-pentenyl donors.
Thus, when Sc(OTf)3/NIS is used, all n-pentenyl donors can
be activated.5 However, and most significantly, chemospecific
(25) Merritt, J. R.; Naisang, E.; Fraser-Reid, B. J. Org. Chem. 1994, 59,
4443-4449.
(20) Kochetkov, N. K. Tetrahedron 1987, 43, 2389.
(21) Mach, M.; Schlueter, U.; Mathew, F.; Fraser-Reid, B.; Hazen, K.
C. Tetrahedron 2002, 58, 7345-7354. Fraser-Reid, B.; Grimme, S.;
Piacenza, M.; Mach, M.; Schlueter, U. Chem. Eur. J 2003, 9, 4687-4692.
(22) Jayaprakash, K. N.; Lu, J.; Fraser-Reid, B. Bioorg. Med. Chem.
Lett. 2004, 14, 3815-3819.
(26) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H. Tetrahedron
Lett. 1990, 31, 1331-1334. Konradsson, P.; Udodong, U. E.; Fraser-Reid,
Tetrahedon Lett. 1990, 31, 4313. Konradsson, P.; Mootoo, D. R.; McDevitt,
R. E.; Fraser-Reid, B. J. Chem. Soc., Chem. Commun. 1990, 270-272.
(27) See for example: Madsen, R.; Udodong, U. E.; Roberts, C.; Mootoo,
D. R.; Konradsson, P.; Fraser-Reid, B. J. Am. Chem. Soc. 1995, 117, 1554-
1565. Debenham, J. S.; Debenham, S. D.; Fraser-Reid. B. Bioorg. Med.
Chem. 1996, 4, 1909-1918.
(23) Garegg, P. J. AdV. Carbohydr. Chem. Biochem. 1997, 52, 179-
205.
(24) Schmidt, R. R.; Kinzy, W. AdV. Carbohydr. Chem. Biochem. 1994,
50, 21-123.
(28) Jayaprakash, K. N.; Radhakrishnan, K. V.; Fraser-Reid, B. Tetra-
hedron Lett. 2002, 43, 6953-6955.
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Jayaprakash et al.
SCHEME 5
SCHEME 6
TABLE 1. Glycosidation of an Acceptor with Various Donors
Triggered by Scandium and Ytterbium Triflates
The effectiveness of lanthanide salts with thioglycosides and
trichloroacetimidates was also tested. The results in Table 1,
entry (iv), show positive responses for ethyl thioglycosides with
both salts; however, phenyl thioglycosides are activated with
Sc(OTf)3 but not by Yb(OTf)3, entry (v). Such differences in
reactivity between phenyl and ethyl thioglycosides have been
noted previously by Garegg and co-workers.23
Entry (vi) shows that trichloroacetimidates are activated by
both salts. It should be noted that Adinolfi and co-workers have
reported the action of lanthanide triflates on trifluoroacetimidate
donors.30
The data in Table 1 provide a basis for the one-pot use of
orthogonal donors31 suggested in Scheme 7a. Diol 4 can be
treated with an NPOE, used in excess, triggered by Yb(OTf)3/
NIS, in order to optimize regioselective monoglycosidation
leading to 33. Under the reaction conditions, the excess of the
NPOE will undergo acid-catalyzed rearrangement to the dis-
armed NPG 34, which being refractory to Yb(OTf)3/NIS, should
not glycosidate the free-OH of 33. However, since this reaction
mixture triggers trichloroacetimidates and ethyl thioglycosides,
subsequent addition of one of these donors should result in
further glycosidation to give 35.
Sc(OTf)3
Yb(OTf)3
(i)
NPOE + (NIS)
+
+
+
+
+
+
+
-
-
+
-
+
(ii)
(iii)
(iv)
(v)
NPGdis + (NIS)
NPGarm + (NIS)
ethyl thioglycoside + NIS
phenyl thioglycoside + NIS
trichloroacetimidate
(vi)
glycosidation with NPOE can be achieved by use of Yb(OTf)3
as the activator for NIS. This possibility is precluded for armed
and disarmed NPGs, since these require the use of Sc(OTf)3/
NIS, a nondiscriminating medium.
The advantage of the observations in entries (i), (ii), and (iii)
is that NPOEs can be used in excess with Yb(OTf)3/NIS to
optimize regioselective glycosidation, since any disarmed NPG
formed by rearrangement is refractory to these conditions.
However, the NPG is activated under Sc(OTf)3/NIS conditions,
so double glycosidation would occur. The contrast in using both
triflates is exemplified in Scheme 6. Thus, treatment of glucoside
30 with 2 equiv of NPOE 19a, under the influence of Yb(OTf)3/
NIS, afforded the O2 regioisomer 31 exquisitely. Switching to
Sc(OTf)3/NIS led to a near equal mixture of 31 and 32.
Interestingly we did not see the O3 regioisomer.5
The regioselective glycosidation offered by an NPOE, but-
tressed by chemoselective activation with Yb(OTf)3/NIS, means
that an excess of the donor could be used to optimize MATCH,
such as 4 f 7 (Scheme 1b) and 30 f 31 (Scheme 6). One
could therefore dispense with the traditional procedure of
extensive protection, as with 2 in Scheme 1a, to ensure that
only one free-OH is presented for the coupling event.
This hypothesis was reduced to practice in a preliminary
experiment involving the 3,6-mannosidyl diol 36, which upon
treatment with NPOE 19a (2 equiv), Yb(OTf)3 (0.3 equiv), and
NIS (2.5 equiv) led to rapid formation of disaccharide 37a
(29) Jayaprakash, K. N.; Fraser-Reid, B. Synlett 2004, 301-305.
(30) Adinolfi, M.; Barone, G.; Iadonisi, A.; Schiattarella, M. Tetrahedron
Lett. 2002, 43, 5573-5577.
(31) Yamada, H.; Kato, Y.; Takahashi, T. Tetrahedron Lett. 1999, 40,
4581-4584. Takahashi, T.; Adachi, M.; Matsuda, A.; Doi, T. Tetrahedron
Lett. 2000, 41, 2599-2603.
5538 J. Org. Chem., Vol. 72, No. 15, 2007

Efficient Assembly of Oligomannans
SCHEME 7
SCHEME 8
(Scheme 7b). This material could be isolated in 76% yield and
characterized in the usual way4,5 by acetylation of 37b and
analysis of the down-shifted proton (5.38 ppm, dd, J ) 1.8 and
7.2 Hz). However, in a subsequent experiment, trichloro-
acetimidate 22b (1.5 equiv) was added after 10 min had elapsed,
and stirring was continued for a further 10 min. Trisaccharide
38 was then isolated in 64% overall yield. Alternatively, the
ethyl thioglycoside 23b could be used in the second step to
obtain 38; however, in this case, the amount of NIS used in the
first step was increased to 4.0 equiv.
In the experiment in Scheme 7b the NPOE and trichloro-
acetimidate or ethyl thioglycoside functioned as sequential
donors to acceptor 36. Replacing the latter with the pentenyl
glycoside acceptor 25 allowed us to add chemoselectivity to
J. Org. Chem, Vol. 72, No. 15, 2007 5539

Jayaprakash et al.
SCHEME 9
the reaction possibilities (Scheme 7c). Indeed, use of the same
sequential methodology as in Scheme 7b led to the n-
pentenylated disaccharide 39, which was authenticated by
isolation in 71% yield. In the one-pot application, addition of
22b or 23b after 10 min afforded the trisaccharide 40 in 60-
62% overall yield.
Synthesis of Pentamannan 9. Sequential glycosidations of
the 3,6-diol 27 with NPOE 19a and trichloroacetimidate 22b
(Scheme 8), carried out as in the preliminary tests in Scheme
7, afforded the trisaccharide 41a in 61% yield. Debenzoylation
then afforded diol 41b. Glycosidation of both hydroxyls of the
latter was effected by using the trichloroacetimidate 22a (4
equiv) with ytterbium triflate as catalyst, to obtain the n-pentenyl
pentasaccharide 42 in 85% yield. Debenzoylation to the corre-
sponding NPG pentasaccharide diol 9 was routinely carried out
in 94% yield.
Synthesis of Pentadecamannan 48. A different approach
was taken to pentadecamannan 48 (Scheme 9), which is seen
5540 J. Org. Chem., Vol. 72, No. 15, 2007

Efficient Assembly of Oligomannans
reaction was monitored by TLC, and when complete, the reaction
was quenched with 10% aqueous sodium thiosulfate and saturated
sodium bicarbonate solution, extracted with DCM, and purified by
chromatography (gradient elution: hexane/ethyl acetate).
to have an R-1,6-backbone subtended with R-1,2-branches. The
6-O-benzoylated n-pentenyl orthoester 19c was used extensively
to provide all units of 48, the starting allyl glycoside acceptor
29 being most conveniently prepared as indicated in Scheme
5c. Treatment of 29 with 2 equiv of NPOE 19c in the presence
of NIS/Yb(OTf)3 afforded a 72% yield of the disaccharide,
which was directly debenzoylated to provide triol 43. Iteration
of the last two steps led to the trisaccharide tetraol 44 in 68%
and 91% yields, respectively.
All four hydroxyls of 44 were simultaneously glycosidated
by treatment with trichloroacetimidate 22a (8 equiv) in the
presence of Yb(OTf)3 to provide heptasaccharide in 90% yield,
which upon debenzoylation led to the heptasaccharyl tetraol 45
in 86% yield. Iteration of exhaustive glycosidation with trichlo-
roacetimidate 22a (8 equiv) added another four R-mannosidyl
residues with extremely high efficiency (92% yield), and after
debenzoylation, the corresponding undecasaccharide tetraol 46
was obtained in 96% yield.
2,3-Di-O-benzyl-6-O-benzoyl-â-D-mannopyranose 1,2-(Pent-
4-enyl orthobenzoate) (19c). The known NPOE20 19b (6 g, 8.07
mmol) was dissolved in THF (30 mL), TBAF (12 mL, 1.00M
solution in THF) was added, and the solution was stirred overnight.
Solvents were removed and the residue was extracted with DCM,
washed with water and brine, and dried under vacuum, and the
residue was dissolved in anhydrous pyridine. The mixture was
cooled to 0 °C and treated with DMAP (catalytic) and benzoyl
chloride (1.20 mL, 1.25 equiv) and stirred overnight. Pyridine was
removed by evaporation, and the residue was extracted with DCM,
washed with water and NaHCO3 solution, and then evaporated to
give a residue that was purified by chromatography (gradient elution
10-30 EtOAc/hexane) to give the desired product, 19c (4.16 g,
1
80%). H NMR (CDCl3, 300 MHz,) δ 7.91(d, J ) 8.4 Hz, 2H),
7.69-7.72 (m, 2H), 7.56 (t, J ) 8.4 Hz, 1H), 7.28-7.47 (m, 15H),
5.80 (m, 1H), 5.52 (d, J ) 2.7 Hz, 1H), 3.46-5.08 (m, 14H), 2.16-
2.19 (m, 2H), 1.72-1.77 (m, 2H). MS calcd for C39H40O8 636.27,
found 659.2 (M + Na).
Another iteration of exhaustive mannosylation with trichlo-
roacetimidate 22a was again highly efficient, affording the
pentadecasaccharide 47 in 95% yield and its debenzoylated
product 10 in 92%.
Exhaustive debenzylation with concomitant saturation of the
allylic double bond was achieved by treatment with hydrogen
and 5% palladium on carbon for 12 h to give compound 48.
Pent-4-enyl 2-O-Benzoyl-3,4-di-O-benzyl-6-O-tert-butyldiphen-
ylsilyl 3,4-Di-O-benzyl-R-D-mannopyranoside (24). Orthoester
19b (3.00 g, 4.03 mmol) was dissolved in DCM and cooled to 0
°C. TBDMSOTf (0.05 mL) was added and the solution was stirred
for 5 min. TLC was checked and the reaction was quenched by
adding triethylamine. Solvents were removed and the residue was
purified by chromatography to give the desired product (2.6 g,
87%). 1H NMR (CDCl3, 300 MHz,) δ 8.19 (d, 8.5 Hz, 2H), 7.79-
7.86 (m, 4H), 7.60 (t, J ) 8.00 Hz, 1H), 7.23-7.47 (m, 18H), 5.91-
5.99 (m, 1H), 5.77 (d, J ) 1.8 Hz, 1H), 3.87-5.37 (m, 14H), 1.20
(s, 9H).
Pent-4-enyl 3,4-Di-O-benzyl-R-D-mannopyranoside (25). Com-
pound 24 (2.5 g, 3.36 mmol) was dissolved in THF (20 mL) and
treated with 5 mL of TBAF solution in THF and the solution was
stirred overnight. Solvents were removed and the residue was
extracted with DCM and dried, then the residue was dissolved in
a mixture of DCM/MeOH (1:1). The mixture was treated with
NaOMe (10 mL, 1 M solution in MeOH) and stirred overnight.
Solvents were removed and the residue was extracted with DCM,
then washed with water and brine. Compound 25 was purified by
chromatography, using ethyl acetate/hexane (1.15 g, 79%). 1H NMR
(CDCl3, 300 MHz,) δ 7.32-7.37 (m, 10), 5.75-5.84 (m, 1H), 5.30
(d, 1.6 Hz, 1H), 3.80 (m, 14H), 2.62 (br s, 2H), 2.06-2.11 (m,
2H), 1.64-1.70 (m, 2H). MS calcd for C25H32O6 428.22, found
451.3 (M + Na).
Conclusion
Mannosyl n-pentenylorthoesters (NPOEs) serve as convenient
intermediates for other glycosyl donors, n-pentenyl glycosides
(NPGs), ethyl and phenyl thioglycosides, and trichloroacetimi-
dates, as shown in Scheme 4. These various donors are activated
by different reagents, and are therefore amenable to versatile,
discriminate use. Thus Sc(OTf)3 and Yb(OTf)3 respond very
differently to these donors, with the result that chemoselective
distinction between NPOEs and NPGs, as well as ethyl and
phenyl thioglycosides, is achieved, as shown in Table 1. The
versatility of NPOEs allows them to be used not only as donors,
but also as the progenitors to provide 2,6- and 3,6-diol acceptors
as shown in Scheme 5. Activation of the NPOEs, used in excess,
by iodonium ion, specifically generated from ytterbium triflate/
N-iodosuccinimide, monoglycosidates the diols rapidly, with
exquisite regio, and sometimes chemo, selectivity. The residual
NPOE is converted into disarmed NPG, which is refractory to
the reaction conditions, and so poses no threat to the free-OH
of the monoglycosylated product (Scheme 7). Glycosidation of
the latter can then be achieved by direct addition of a
trichloroacetimidate or ethyl thioglycoside.
Allyl 3,4-Di-O-benzyl-R-D-mannopyranoside (29). The ortho-
ester 19c (5 g, 7.85 mmol), allyl alcohol (0.682 g, 11.7 mmol),
and NIS (2.65 g, 11.77 mmol) were made to react under the agency
of Yb(OTf)3, using the standard glycosidation procedure, to give
the dibenzoylated derivative 28. The material was purified by
1
chromatography (4.10 g, 86%). H NMR (CDCl3, 300 MHz,) δ
The basic strategy has been used to prepare branched chain
mannans 9 and 10. Particularly in the case of the latter, which
is a pentadecasaccharide, glycosidations with both the NPOEs
and trichloroacetimidates maintain excellent selectivities and
yields, even as the molecule grows larger. The success is an
example of the efficiency of the donor/acceptor MATCH
concept.
8.03 (d, 7.5 Hz, 4H), 7.18-7.60 (m, 16H), 5.75-5.84 (m, 1H),
5.63 (d, 1.8 Hz, 1H), 3.44-5.06 (m, 14H). MS calcd for C37H36O8
608.24, found 631.2 (M + Na). This compound was dissolved in
a mixture of DCM/MeOH (1:1) and stirred with an excess of
NaOMe overnight. Solvents were removed and product was purified
by chromatography to give the desired product 29 (2.41 g, 92%).
1H NMR (CDCl3, 300 MHz,) δ 7.24-7.39 (m, 10H), 5.79-5.92
(m, 1H), 5.16-5.28 (m, 2H), 3.66-4.93 (m, 11H), 3.02 (br s, 1H),
2.60 (br s, 1H). MS calcd for C23H28O6 400.19, found 423.2 (M +
Na).
Experimental Section
General Glycosidation Conditions. The acceptor (1 equiv) and
NPOE (2.0 equiv) were dissolved together in a small quantity of
toluene, azeotroped to dryness, and kept overnight under vacuum.
The acceptor was dissolved in dry DCM (7 mL) cooled to 0 °C
under argon atmosphere, NIS (2.5 equiv) was added, and after
stirring for 5 min, the lanthanide salt (0.3 eq) was added. The
Methyl 2-O-(2-O-Benzoyl-3,4,6-tri-O-benzyl-R-D-mannopy-
ranosyl)-4,6-O-benzylidene-R-D-glucopyranoside (31). The ac-
ceptor 30 (24 mg, 0.085 mmol) and the donor 19a (106 mg, 0.170
mmol) were coupled with use of NIS (49 mg, 2.5 equiv) and Yb-
(OTf)3 (16 mg, 0.3 equiv) in ∼6 mL of CH2Cl2, using the general
1
glycosidation procedure to give 31 (44 mg, yield 62%). H NMR
J. Org. Chem, Vol. 72, No. 15, 2007 5541

Jayaprakash et al.
(CDCl3, 300 MHz) δ 8.05 (d, J ) 7.5 Hz, 2H), 7.00-7.6 (m, 23H),
5.78 (dd, J ) 1.8, 3.00 Hz, 1H), 5.60 (s, 1H), 5.32 (d, J ) 1.8 Hz,
1H), 3.15-4.90 (m, 18H), 2.6 (br s, 1H). 13C NMR (CDCl3, 75
MHz) δ 165.6, 138.6, 138.4, 138.2, 137.2, 133.3, 133.2, 130.1,
128.9, 128.5, 128.4, 128.3, 128.1, 128.1, 127.77, 127.74, 127.6,
126.1, 101.1, 100.4, 98.9, 81.5, 78.5, 75.6, 75.3, 74.8, 74.5, 73.7,
71.8, 71.8, 71.7, 69.7, 69.5, 69.3, 69.1, 62.7, 55.7. MS calcd for
C48H50O12 818.33, found 841.6 (M + Na).
MHz) δ 8.07 (d, J ) 7.5 Hz, 2H), 7.55 (t, J ) 7.5 Hz, 1H), 7.13-
7.39 (m, 22H), 5.79 (m, 1H), 5.70 (dd, J ) 1.8, 3.00 Hz), 5.12 (d,
J ) 1.8 Hz, 1H), 3.64-5.04 (m, 24H), 3.35-3.45 (m, 2H), 2.60
(d, J ) 2.4 Hz, 1H), 2.06-2.13 (m, 2H), 1.60-1.70 (m, 2H). 13C
NMR (CDCl3, 75 MHz) δ 165.7, 138.7, 138.6, 138.4, 138.1, 138.1,
133.2, 130.2, 130.1, 128.7, 128.57, 128.5, 128.48, 128.4, 128.2,
128.19, 128.1, 128.0, 127.94, 127.9, 127.8, 127.7, 127.68, 127.6,
115.1, 99.3, 98.3, 80.6, 78.0, 75.4, 75.3, 74.8, 74.5, 74.3, 73.6, 72.1,
71.9, 71.8, 71.5, 71.0, 69.6, 69.2, 68.6, 67.3, 66.8, 30.6, 28.9. MS
calcd for C59H64O12 964.44, found 987.8 (M + Na).
Pent-4-enyl 3,4-Di-O-benzyl-3-O-(2-O-benzoyl-3,4-di-O-ben-
zyl-6-O-tert-butyldiphenylsilyl)-6-O-(2-O-benzoyl-3,4-6-tri-O-
benzyl)-R-D-mannopyranoside (40): (a) The acceptor diol 25 (27
mg, 0.063 mmol), donor 19a (78 mg, 0.126 mmol), and donor 22b
(72 mg, 1.5 equiv) were coupled with NIS (36 mg, 2.5 equiv) and
Methyl 2,3-Di-O-(2-O-Benzoyl-3,4,6-tri-O-benzyl-R-D-man-
nopyranosyl)-4,6-O-benzylidene-R-D-glucopyranoside (32). The
acceptor 30 (28 mg, 0.100 mmol) and the donor 19a (124 mg, 0.200
mmol) were coupled with use of NIS (56 mg, 2.5 equiv) and Sc-
(OTf)3 (15 mg, 0.3 equiv ) in ∼8 mL of CH2Cl2, using the general
glycosidation procedure to give 32 (43 mg) and 31 (49 mg, yield
1
70%). H NMR (CDCl3, 300 MHz) δ 8.04 (d, J ) 7.5 Hz, 2H),
7.93 (d, J ) 7.5 Hz, 1H), 7.10-7.53 (m, 41H), 5.80 (dd, J ) 1.8,
3.00 Hz, 1H), 5.71 (dd, J ) 1.8, 3.00 Hz, 1H), 5.60 (s, 1H), 5.42
(d, J ) 1.8 Hz, 1H), 3.53-4.92 (m, 30H), 3.25 (s, 3H). MS calcd
for C82H82O18 1354.55, found 1377.7 (M + Na).
Yb(OTf) (12 mg, 0.3 equiv) in ∼7 mL of DCM, using the
3
procedure described above for 38, to give 40 (62 mg, yield 60%).
1H NMR (CDCl3, 300 MHz) δ 8.04-8.08 (m, 4H), 7.71-7.85 (m,
4H) 7.50-7.58 (m, 2H), 7.16-7.40 (m, 45H), 5.81 (dd, J ) 1.8,
3.00 Hz, 1H), 5.75 (m, 1H), 5.67 (dd, J ) 1.8, 3.00 Hz, 1H), 5.33
(d, J ) 1.8 Hz, 1H), 5.06 (d, J ) 1.8 Hz, 1H), 3.59-5.01 (m,
37H), 3.25-3.34 (m, 2H), 2.02-2.10 (m, 2H), 1.67-1.65 (m, 2H),
1.14 (s, 9H). 13C NMR (CDCl3, 75 MHz) δ 165.6, 165.5, 138.8,
138.7, 138.6, 138.5, 138.47, 138.4, 138.3, 138.2, 138.18, 138.1,
137.9, 133.3, 133.1, 130.2, 130.1, 129.9, 128.55, 128.5, 128.4,
128.3, 128.29, 128.26, 128.2, 128.09, 128.03, 127.9, 127.79, 127.7,
127.6, 127.6, 115.1, 99.89, 98.8, 97.7, 80.2, 78.4, 75.7, 75.4, 75.2,
75.0, 74.6, 74.4, 74.3, 73.7, 73.6, 72.8, 72.5, 72.3, 72.0, 71.97, 71.9,
71.6, 70.9, 69.5, 69.3, 69.2, 69.1, 69.0, 67.2, 67.0, 30.6, 28.9, 26.9,
19.8. MS calcd for C102H108O18Si 1648.73, found 1671.9 (M + Na).
(b) The acceptor diol 25 (25 mg, 0.058 mmol), donor 19a (72
mg, 0.116 mmol), and donor 23b (64 mg, 1.5 equiv) were coupled
Methyl 2,4-Di-O-benzyl-6-O-(2-O-benzoyl-3,4-6-tri-O-benzyl)-
R-D-mannopyranoside (37). Diol 36 (0.031 g, 0.084 mmol) was
treated with NPOE 19a (0.105 g, 2 equiv) under glycosidation
conditions, using Yb(OTf)3 (0.015 g, 0.3 equiv), to give the title
compound 37 (0.056 g, 76%). 1H NMR (CDCl3, 300 MHz,) δ 8.09
(d, J ) 7.5 Hz, 2H), 7.55 (t, J ) 7.5 Hz, 1H), 7.16-7.38 (m, 27H),
5.72 (dd, J ) 1.6, 3.2 Hz, 1H), 5.11 (d, J ) 1.6 Hz, 1H), 3.57-
4.92 (m, 22H), 3.28 (s, 3H), 2.40 (d, J ) 10 Hz, 1H). 13C NMR
(CDCl3, 75 MHz) δ 165.7, 138.7, 138.6, 138.1, 137.8, 133.3, 130.2,
129.1, 128.8, 128.58, 128.56, 128.3, 128.2, 128.1, 127.85, 127.80,
127.7, 127.6, 98.2, 97.9, 78.8, 77.8, 75.5, 75.0, 74.5, 73.2, 72.2,
71.9, 71.4, 70.6, 69.7, 69.0, 66.8, 55.1. MS calcd for C55H58O12
910.39, found 933.4 (M + Na).
Methyl 2,4-Di-O-benzyl-3-O-(2-O-benzoyl-3,4-di-O-benzyl-6-
O-tert-butyldiphenylsilyl)-6-O-(2-O-benzoyl-3,4-6-tri-O-benzyl)-
R-D-mannopyranoside (38): (a) Methyl 2,4-di-O-benzyl-R-D-
mannopyranoside (36) (0.043 g, 0.115 mmol) and NPOE 19a (0.143
g, 2 equiv) were dissolved together in a small amount of toluene,
evaporated to dryness, and kept under vacuum overnight. The
mixture was then dissolved in ∼10 mL of DCM and cooled to 0
°C. NIS (0.064 g, 2.5 equiv) was added and the solution was stirred
for a few minutes, followed by addition of Yb(OTf)3 (0.021 g, 0.3
equiv). The reaction mixture was stirred for 10 min and monitored
by TLC to ensure formation of 37. After 10 min, trichloroacetimi-
date donor 22b (0.142 g, 1.5 equiv) was added and the solution
was stirred for another 10 min. The reaction mixture was quenched
with saturated sodium bicarbonate and 10% sodium thiosulfate
solutions, extracted with DCM, and dried over Na2SO4. Solvents
were removed under reduced pressure and the residue was purified
by chromatography to give the desired compound 38 (0.117 g,
with NIS (52 mg, 4 equiv) and Yb(OTf) (11 mg, 0.3 equiv) in
3
∼7 mL of DCM, using the above-described procedure, to give 40
(60 mg, yield 62%).
Pent-4-enyl 2,4-Di-O-benzyl-3-O-(3,4-di-O-benzyl-6-O-tert-bu-
tyldiphenylsilyl)-6-O-(3,4,6-tri-O-benzyl)-R-D-mannopyrano-
side (41b). Diol 27 (0.143 g, 0.334 mmol) and the donor 19a (0.415
g, 2 equiv) were dissolved together in a small amount of toluene,
evaporated to dryness, and kept under vacuum overnight. The
mixture was then dissolved in ∼20 mL of DCM and cooled to 0
°C. NIS (0.225 g, 3 equiv) was added and the solution was stirred
for a few minutes, followed by the addition of Yb(OTf)3 (0.062 g,
0.3 equiv). The reaction mixture was stirred for 10 min and
monitored by TLC to check for completion of the first glycosidation.
To the above reaction mixture donor 22b (0.426 g, 1.5 equiv) was
added and the solution was stirred for another 10 min. The reaction
mixture was quenched with saturated sodium bicarbonate and 10%
sodium thiosulfate solutions, extracted with DCM, and dried over
Na2SO4. Solvents were removed under reduced pressure and the
residue was purified by chromatography to give compound 41a
(0.335 g, 61%). 1H NMR (CDCl3, 300 MHz,) δ 8.12 (d, J ) 8.00
Hz, 2H), 8.05 (d, J ) 8.10 Hz, 2H), 7.61-7.77 (m, 4H), 7.03-
7.45 (m, 47H), 5.86 (dd, J ) 1.5, 3.0 Hz, 1H), 5.79 (s, 1H), 5.56-
5.68 (m, 1H), 5.37 (d, J ) 1.5 Hz, 1H), 5.14 (d, J ) 1.5 Hz, 1H),
3.57-5.01 (m, 39H), 3.22-3.32 (m, 1H), 1.97-2.05 (m, 2H),
1.53-1.60 (m, 2H), 1.11 (s, 9H). 13C NMR (CDCl3, 75 MHz) δ
165.9, 165.7, 139.1, 138.88, 138.8, 138.3, 138.28, 138.2, 136.3,
136.2, 136.1, 135.96, 133.9, 133.4, 133.3, 130.3, 130.2, 129.9,
128.8, 128.78, 128.7, 128.66, 128.6, 128.3, 128.28, 128.2, 128.1,
128.0, 127.97, 127.9, 127.89, 127.8, 115.3, 100.2, 98.6, 97.3, 79.3,
78.8, 78.6, 78.5, 78.1, 77.6, 77.1, 76.0, 75.6, 75.3, 74.6, 74.5, 74.2,
73.8, 73.6, 72.8, 72.6, 72.4, 72.2, 72.1, 72.0, 71.6, 71.5, 70.1, 69.9,
69.4, 69.1, 68.2, 67.5, 67.0, 63.1, 30.8, 29.0, 27.4, 19.9. MS calcd
for C102H108O18Si 1648.73, found 1671.8 (M + Na). Trisaccharide
41a (0.50 g, 0.302 mmol) was dissolved in a DCM/CH3OH mixture
and treated with an excess of NaOMe (0.5 M solution in MeOH).
The mixture was stirred for a day at room temperature to complete
the debenzoylation. Solvents were removed and the residue was
1
64%). H NMR (CDCl3, 300 MHz,) δ 8.08-8.12 (m, 4H), 7.77
(d, J ) 7.7 Hz, 2H), 7.70 (d, J ) 7.7 Hz, 2H), 7.53-7.58 (m, 2H),
7.08-7.42 (m, 45H), 5.84 (dd, J ) 1.6, 3.00 Hz, 1H), 5.76 (dd, J
) 1.5, 3.00 Hz, 1H), 5.37 (d, J ) 1.5 Hz, 1H), 5.14 (d, J ) 1.6
Hz, 1H), 3.71-5.00 (m, 31H), 3.24 (s, 3H), 1.12 (s, 9H). 13C NMR
(CDCl3, 75 MHz) δ 165.7, 165.6, 138.9, 138.7, 138.6, 138.1, 138.0,
136.1, 135.8, 133.7, 133.2, 133.10, 129.7, 128.65, 128.60, 128.53,
128.52, 128.49, 128.47, 128.42, 128.2, 128.1, 128.0, 127.9, 127.89,
127.8, 127.7, 127.6, 99.9, 98.4, 78.6, 77.7, 75.4, 79.4, 73.6, 73.5,
72.6, 71.9, 71.3, 69.9, 69.7, 69.2, 69.0, 66.8, 63.2, 55.0, 27.0, 19.1.
MS calcd for C98H102O18Si 1594.68, found 1617.7 (M + Na).
(b) The above reaction was repeated with ethyl thioglycoside
donor 23b (instead of 22b). In this experiment 4 equiv of NIS was
used instead of 2.5 equiv. The yield of 38 was also 64%.
Pent-4-enyl 3,4-Di-O-benzyl-6-O-(2-O-benzoyl-3,4-6-tri-O-
benzyl)-R-D-mannopyranoside (39). The diol acceptor 25 (39 mg,
0.091 mmol) and the donor 19a (113 mg, 0.182 mmol) were
coupled, using NIS (50 mg, 2.5 equiv) and Yb(OTf)3 (17 mg, 0.3
equiv), in ∼6 mL of DCM, using the general glycosidation
1
procedure, to give 39 (63 mg, yield 71%). H NMR (CDCl3, 300
5542 J. Org. Chem., Vol. 72, No. 15, 2007

Efficient Assembly of Oligomannans
extracted with CH2Cl2 and saturated ammonium chloride solution
and dried over Na2SO4. Dichloromethane was removed under
reduced pressure and residue was purified by chromatography to
minutes, and then a DCM solution of donor 19c was added dropwise
to the reaction mixture over a period of 10 min. TLC was checked
to ensure complete glycosidation. The reaction was quenched with
saturated sodium bicarbonate and 10% sodium thiosulfate solutions,
and the extract with DCM, and dried over Na2SO4. Solvents were
removed under reduced pressure and the residue was purified by
chromatography to give the desired disaccharide (0.710 g, 72%s
1
give the title product 41b (0.395 g, 90%). H NMR (CDCl3, 300
MHz,) δ 7.86 (d, J ) 7.5 Hz, 2H), 7.76 (d, J ) 7.5 Hz, 2H), 7.23-
7.49 (m, 41H), 5.78-5.89 (m, 1H), 5.35 (d, J ) 1.5 Hz, 1H), 5.21
(d, J ) 1.5 Hz, 1H), 3.65-5.11 (m, 36H), 3.34-3.41 (m, 1H),
2.52 (br s, 2H), 2.08-2.14 (m, 2H), 1.63-1.75 (m, 2H), 1.18 (s,
9H). 13C NMR (CDCl3, 75 MHz) δ 138.8, 138.7, 138.5, 138.1,
138.4, 138.3, 138.21, 136.2, 135.93, 133.9, 133.4, 129.85, 128.8,
128.78, 128.7, 128.5, 128.24, 128.21, 128.1, 128.0, 127.96, 127.9,
127.88, 127.84, 127.8, 127.6, 115.2, 101.8, 100.0, 97.2, 80.5, 80.0,
78.3, 75.4, 75.3, 75.1, 74.6, 74.5, 73.7, 73.4, 72.5, 72.4, 71.8, 71.5,
69.2, 69.1, 68.3, 67.5, 66.5, 63.6, 30.7, 28.9, 27.3, 19.8. MS calcd
for C88H100O16Si 1440.68, found 1463.7 (M + Na).
1
rest of the acceptor was recovered). H NMR (CDCl3, 300 MHz,)
δ 8.06 (d, J ) 7.5 Hz, 4H), 7.55-7.62 (m, 2H), 7.17-7.44 (m,
24H), 5.82-5.95 (m, 1H), 5.76 (dd, J ) 2.1,4.8 Hz, 1H), 5.17-
5.30 (m, 2H), 5.12 (d, J ) 2.1 Hz, 1H), 3.75-4.98 (m, 22H), 2.67
(br s, 1H). 13C NMR (CDCl3, 75 MHz) δ 166.1, 165.5, 138.1, 138.0,
137.8, 137.7, 133.5, 133.2, 133.0, 130.5, 129.9, 129.7, 128.6,
128.45, 128.4, 128.3, 128.28, 128.2, 128.1, 128.0, 127.9, 127.7,
127.7, 117.9, 98.2, 98.0, 80.4, 77.9, 75.3, 75.2, 74.2, 73.6, 72.0,
71.4, 70.9, 70.1, 68.9, 68.4, 68.1, 66.7, 63.4. MS calcd for C57H58O13
950.39, found 973.4 (M + Na). The disaccharide (0.700 g, 0.736
mmol) was dissolved in a DCM/CH3OH mixture and treated with
an excess of NaOMe (0.5 M solution in MeOH). The mixture was
stirred overnight at room temperature to complete the debenz-
oylation. Solvents were removed and the residue was extracted with
DCM and saturated ammonium chloride solution and dried over
Na2SO4. Dichloromethane was removed under reduced pressure and
residue was purified by chromatography to give the product 43
Pent-4-enyl 2,4-Di-O-benzyl-3-O-[(3,4-di-O-benzyl-6-O-tert-
butyldiphenylsilyl-R-D-mannopyranosyl)-2-O-(2-O-benzoyl-3,4-
6-tri-O-benzyl-R-D-mannopyranosyl)]-6-O-[(3,4,6-tri-O-benzyl)-
2-O-(2-O-benzoyl-3,4-6-tri-O-benzyl)-R-D-mannopyranosyl]-R-
D-mannopyranoside (42). Trisaccharide diol 41b (0.320 g, 0.222
mmol) and mannosyl trichloroacetimidate 22a (0.610 g, 4 equiv)
were dissolved in a small amount of toluene and evaporated to
dryness and the mixture was kept under vacuum for 4 h. The
reaction mixture was dissolved in ether (∼15 mL), a small amount
of molecular sieves was added, and the solution was cooled to 0
°C. Yb(OTf)3, (0.041 g, 0.3 equiv) was added and the solution was
stirred for 10 min, TLC was checked and the reaction was quenched
with triethylamine. Solvents were removed and the residue was
1
(0.460 g, 84%). H NMR (CDCl3, 300 MHz,) δ 7.19-7.40 (m,
20H), 5.78-5.91 (m, 1H), 5.14-5.28 (m, 2H), 5.07 (d, J ) 1.5
Hz, 1H), 3.60-4.93 (m, 23H), 2.8 (br s, 3H). 13C NMR (CDCl3,
75 MHz) δ 138.7, 138.4, 138.1, 138.0, 133.7, 132.1, 128.7, 128.68,
128.6, 128.5, 128.24, 128.2, 128.16, 128.1, 128.0, 127.9, 127.8,
127.6, 117.8, 99.9, 98.4, 80.4, 79.5, 75.4, 74.3, 74.1, 72.2, 72.0,
71.3, 68.4, 68.2, 66.1, 61.9. MS calcd for C43H50O11 742.34, found
765.4 (M + Na).
1
purified by chromatography to give 42 (0.468 g, 85%). H NMR
(CDCl3, 300 MHz,) δ 8.19 (d, J ) 7.5 Hz, 4H), 7.84 (d, J ) 7.5
Hz, 2H), 7.74 (d, J ) 7.5 Hz, 2H), 7.60 (m, 2H), 7.18-7.46 (m,
79H), 5.81-5.87 (m, 3H), 5.39 (d, J ) 1.5 Hz, 1H), 5.28 (d, J )
1.5 Hz, 1H), 5.25 (d, J ) 1.6 Hz, 1H), 3.35-5.08 (m, 66H), 2.13-
2.17 (m, 2H), 1.65-1.70 (m, 2H), 1.15 (s, 9H). 13C NMR (CDCl3,
75 MHz) δ 165.6, 163.6, 138.9, 138.8, 138.7, 138.6, 138.4, 138.3,
138.1, 136.1, 135.8, 133.7, 133.3, 130.2, 129.8, 128.7, 128.6,
128.57, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8,
127.5, 127.3, 115.2, 101.6, 99.9, 99.5, 97.0, 80.2, 79.4, 78.5, 75.9,
75.5, 75.4, 75.2, 74.9, 74.8, 74.6, 73.7, 73.6, 73.5, 72.7, 72.5, 72.4,
72.3, 72.1, 72.0, 71.8, 71.6, 69.4, 68.9, 67.5, 66.9, 63.8, 30.7, 28.9,
27.4, 19.7. MS calcd for C156H164O28Si 2513.12, found 2536.2 (M
+ Na).
Pent-4-enyl 2,4-Di-O-benzyl-3-O-[(3,4-di-O-benzyl-6-O-tert-
butyldiphenylsilyl-R-D-mannopyranosyl)-2-O-(3,4-6-tri-O-ben-
zyl-R-D-mannopyranosyl)]-6-O-[(3,4,6-tri-O-benzyl)-2-O-(3,4-6-
tri-O-benzyl)-R-D-mannopyranosyl]-R-D-mannopyranoside (9).
The pentasaccharide 42 (0.465 g, 0.185 mmol) was debenzoylated
with NaOMe to give the title compound 9 (0.401 g (94%). 1H NMR
(CDCl3, 300 MHz) δ 7.87 (d, J ) 7.5 Hz, 2H), 7.79 (d, J ) 7.5
Hz, 2H), 7.20-7.49 (m, 75H), 5.76-5.85 (m, 1H), 5.41 (d, J )
1.5 Hz, 1H), 5.32 (d, J ) 1.5 Hz, 1H), 5.23 (d, J ) 1.5 Hz, 1H),
5.14 (d, J ) 1.5 Hz, 1H), 3.40-5.03 (m, 66H), 2.60 (br s, 1H),
2.56 (br s, 1H), 2.09-2.14 (m, 2H), 1.65-1.70 (m, 2H), 1.21 (s,
9H). 13C NMR (CDCl3, 75 MHz) δ 139.0, 138.9, 138.9, 138.8,
138.76, 138.7, 138.5, 138.4, 138.37, 138.3, 138.2, 136.1, 135.8,
133.7, 133.3, 129.8, 128.8, 128.7, 128.69, 128.6, 128.57, 128.5,
128.2, 128.17, 128.1, 128.09, 128.0, 127.9, 127.8, 127.7, 127.6,
127.5, 127.4, 115.2, 101.6, 101.5, 99.6, 97.0, 80.4, 80.3, 79.57,
78.54, 75.5, 75.3, 75.2, 74.9, 74.8, 74.7, 79.6, 73.7, 73.5, 72.7, 72.5,
72.4, 72.2, 72.0, 71.9, 71.6, 69.9, 69.3, 69.0, 67.5, 67.0, 63.7, 30.7,
28.9, 27.4, 19.7. MS calcd for C142H156O26Si 2305.07, found 2328.1
(M + Na).
Allyl 3,4-Di-O-benzyl-6-O-bis(3,4-di-O-benzyl-R-D-mannopy-
ranosyl)-R-D-mannopyranoside (44). Triol 43 (0.360 g, 0.484
mmol), NPOE 19c (0.769 g, 2.5 equiv), NIS (0.327 g, 3 equiv),
and Yb(OTf)3 (0.090 g, 0.3 equiv) were reacted using the procedure
described earlier to give a trisaccharide (0.426 g, 68%sthe rest of
1
the triol was recovered). H NMR (CDCl3, 300 MHz,) δ 8.01 (d,
J ) 7.8 Hz, 4H), 7.49-7.56 (m, 2H), 7.13-7.36 (m, 34H), 5.76-
5.88 (m, 1H), 5.71 (s, 1H), 3.62-5.25 (m, 36H), 2.76 (br s, 1H),
2.64 (br s, 1H). 13C NMR (CDCl3, 75 MHz) δ 166.3, 165.7, 138.6,
138.4, 138.2, 138.0, 133.7, 133.3, 133.1, 130.3, 130.1, 129.9, 128.9,
128.7, 128.0, 128.6, 128.56, 128.5, 128.4, 128.3, 128.2, 128.16,
128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 118.0, 99.8, 98.4, 98.2,
80.6, 80.1, 78.1, 75.5, 75.4, 75.3, 74.4, 74.3, 73.7, 72.2, 72.1, 71.9,
71.6, 71.1, 70.2, 69.1, 68.5, 68.3, 68.2, 66.7, 66.5, 63.5. MS calcd
for C77H80O18 1292.53, found 1315.5 (M + Na). The trisaccharide
(0.420 g, 0.330 mmol) was debenzolylated with NaOMe to give
1
tetrol 44 (0.319 g, 91%). H NMR (CDCl3, 300 MHz,) δ 7.12-
7.37 (m, 30H), 5.71-5.89 (m, 1H), 5.03-5.22 (m, 2H), 3.56-
4.99 (m, 34H), 3.04 (br s, 1H), 2.95 (br s, 1H), 2.89 (br s, 1H),
2.64 (br s, 1H). 13C NMR (CDCl3, 75 MHz) δ 138.2, 138.1, 137.94,
137.9, 137.5, 133.1, 128.36, 128.3, 128.2, 128.13, 128.1, 127.8,
127.75, 127.7, 127.65, 127.6, 127.5, 127.5, 127.4, 127.4, 127.1,
117.9, 98.9, 98.8, 97.5, 80.0, 79.5, 79.3, 75.0, 74.8, 74.2, 74.0, 73.0,
73.9, 72.1, 72.0, 71.8, 71.7, 71.66, 71.6, 70.6, 71.0, 70.6, 69.9, 68.1,
67.9, 67.8, 67.6, 65.9, 65.3, 61.7. MS calcd for C63H72O16 1084.48,
found 1107.4 (M + Na).
Allyl 3,4-Di-O-benzyl-2-O-[(3,4,6-tri-O-benzyl-R-D-mannopy-
ranosyl)-6-O-{3,4-di-O-benzyl-2-O-(3,4,6-tri-O-benzyl-R-D-man-
nopyranosyl)}]-6-O-[{3,4-di-O-benzyl-2-O-(3,4,6-tri-O-benzyl-R-
D-mannopyranosyl)}-6O-3,4-di-O-benzyl-R-D-mannopyranosyl]-
R-D-mannopyranoside (45). Triisaccharide tetrol 44 (0.210 g, 0.194
mmol) and mannosyl trichloroacetimidate 22a (1.053 g, 8 equiv)
were dissolved in a small amount of toluene, evaporated to dryness,
and kept under vacuum for 4 h. The reaction mixture was dissolved
in ether (∼15 mL), a small amount of molecular sieves was added,
and the solution was cooled to 0 °C. Yb(OTf)3 (0.036 g, 0.3 equiv)
was added, the solution was stirred for 10 min, TLC was checked,
Allyl 3,4-Di-O-benzyl-6-O-(3,4-di-O-benzyl-R-D-mannopyra-
nosyl)-R-D-mannopyranoside (43). Diol 29 (0.415 g, 1.03 mmol)
and mannosyl donor 19c (1.30 g, 2 equiv) were dissolved separately
in a small amount of toluene and evaporated to dryness in two
different flasks. The acceptor diol was dissolved in ∼20 mL of
DCM and cooled to 0 °C. NIS (0.579 g, 2.5 equiv) and Yb(OTf)3
(0.191 g, 0.3 equiv) were added, the solution was stirred for few
J. Org. Chem, Vol. 72, No. 15, 2007 5543

Jayaprakash et al.
and the reaction was quenched with triethylamine. Solvents were
removed and the residue was purified by chromatography to give
the heptasaccharide.(0.560 g, 90%). H NMR (CDCl3, 300 MHz)
nopyranosyl)-3,4,6-tri-O-benzyl-R-D-mannopyranosyl]-(3,4,6-tri-
O-benzyl-R-D-mannopyranosyl)}-6-O-bis-3,4-di-O-benzyl-2-O-
{2-O-[2-O-(2-O-{2-O-benzoyl-3,4,6-tri-O-benzyl-R-D-manno-
pyranosyl}-3,4,6-tri-O-benzyl)-R-D-mannopyranosyl](3,4,6-tri-O-benzyl-
r-D-mannopyranosyl)]-3,4-di-O-benzyl-R-D-mannopyranosyl)}-
6-O-{2-O-[2-O-(2-O-benzoyl-3,4,6-tri-O-benzyl-R-D-mannopyra-
nosyl)-3,4,6-tri-O-benzyl-r-D-mannopyranosyl]}-3,4,6-tri-O-benzyl-
R-D-mannopyranosyl}-R-D-mannopyranoside (47). The undecaasac-
charide tetraol 46 (0.104 g, 0.023 mmol) and mannosyl trichloro-
acetimidate 22a (0.125 g, 8 equiv) were dissolved in a small amount
of toluene, evaporated to dryness, and kept under vacuum for 4 h.
The reaction mixture was dissolved in ether (∼5 mL), a small
amount of molecular sieves was added, and the solution was cooled
to 0 °C. Yb(OTf)3 (0.005 g, 0.3 equiv) was added, the solution
was stirred for 10 min, TLC was checked, and the reaction was
quenched with triethylamine. Solvents were removed and the
residue was purified by chromatography to give 47 (0.146 g, 95%).
1H NMR (CDCl3, 300 MHz,) δ 8.09-8.12 (m, 8H), 7.43-7.62
(m, 4H), 6.89-7.45 (m, 218H), 5.72-5.82 (m, 3H), 5.69 (dd, J )
1.8, 3.2 Hz, 1H), 5.39 (s, 1H), 3.50-5.29 (m, 188H). 13C NMR
(CDCl3, 75 MHz) δ 165.9, 165.56, 165.52, 165.5, 138.9, 138.9,
138.8, 138.7, 138.6, 138.5, 138.4, 138.3, 138.2, 138.1, 138.0, 137.8,
135.7, 133.9, 133.5, 133.3, 133.2, 130.3, 130.1, 129.8, 129.2, 128.6,
128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6,
127.5, 127.4, 127.3, 127.1, 127.0, 126.6, 117.7, 101.8, 101.4, 101.3,
100.9, 100.8, 100.3, 99.7, 99.3, 98.3, 98.1, 80.2, 79.7, 78.5, 78.0,
77.5, 75.8, 75.6, 75.4, 75.4, 75.1, 74.8, 74.6, 74.4, 74.1, 73.7, 73.8,
72.5, 72.5, 72.3, 72.1, 71.9, 71.8, 71.7, 71.4, 71.1, 70.8, 70.6, 70.3,
70.0, 69.8, 69.6, 69.3, 69.1, 68.4, 68.1, 67.6, 65.3. MS calcd for
1
δ 8.13-8.19 (m, 8H), 7.58-7.65 (m, 4H), 7.13-7.48 (m, 98H),
5.86-5.99 (m, 4H), 5.80 (dd, J ) 1.6, 3.00 Hz, 1H), 3.56-5.43
(m, 85H). 13C NMR (CDCl3, 75 MHz) δ 165.6, 165.5, 165.3, 139.0,
138.8, 138.6, 138.4, 138.4, 138.2, 138.1, 137.9, 133.8, 133.3, 130.2,
128.8, 128.7, 128.6, 128.0, 128.5, 128.45, 128.4, 128.3, 128.2,
128.07, 128.0, 127.97, 127.9, 127.83, 127.8, 127.77, 127.7, 127.69,
127.6, 127.5, 127.3, 118.0, 100.1, 99.9, 99.3, 99.0, 98.3, 98.1, 80.3,
79.9, 79.0, 78.8, 78.6, 78.3, 78.1, 75.6, 75.5, 75.4, 75.1, 72.0, 74.8,
74.7, 74.5, 74.3, 74.3, 73.8, 73.7, 73.6, 72.6, 72.5, 72.16, 72.1, 71.9,
71.7, 71.4, 72.2, 70.8, 69.7, 69.6, 69.4, 68.9, 68.1, 67.4, 67.2, 66.3.
MS calcd for C199H200O40 3229.36, found 3252.4 (M + Na). The
Hepta(OBz)4 (0.558 g, 0.172 mmol) was dissolved in CH2Cl2/
MeOH and treated with NaOMe for 24 h to give pentaol 45 (0.430
1
g, 86%). H NMR (CDCl3, 300 MHz,) δ 7.05-7.30 (m, 90H),
5.72-5.82 (m, 1H), 3.47-5.30 (m, 89H), 2.80 (br s, 1H), 2.60 (br
s, 3H). 13C NMR (CDCl3, 75 MHz) δ 138.3, 138.2, 138.1, 138.0,
137.9, 137.8, 137.6, 137.5, 137.47, 137.44, 137.4, 133.3, 128.1,
128.07, 128.0, 127.9, 127.85, 127.8, 127.78, 127.7, 127.6, 127.57,
127.5, 127.4, 127.36, 127.3, 127.2, 127.1, 126.9, 126.5, 117.3,
101.5, 101.2, 100.8, 99.7, 96.6, 98.2, 97.7, 80.2, 79.9, 79.6, 79.1,
78.6, 77.1, 75.0, 74.8, 74.6, 74.4, 74.3, 74.1, 73.6, 73.1, 73.05, 73.0,
72.9, 72.0, 71.74, 71.7, 71.4, 71.0, 70.8, 70.6, 70.4, 69.7, 68.6, 68.1,
67.5, 66.6, 66.2, 64.3. MS calcd for C171H184O36 2813.26, found
2836.3 (M + Na).
Allyl 3,4-Di-O-benzyl-2-O-{2-O-[2-O-(3,4,6-tri-O-benzyl-R-D-
mannopyranosyl)-3,4,6-tri-O-benzyl-R-D-mannopyranosyl] (3,4,6-
tri-O-benzyl-R-D-mannopyranosyl)}-6-O-bis-3,4-di-O-benzyl-
2-O-{2-O-[2-O-(3,4,6-tri-O-benzyl)-R-D-mannopyranosyl]-
[(3,4,6-tri-O-benzyl-R-D-mannopyranosyl)](3,4-di-O-benzyl-R-D-man-
nopyranosyl)}-6-O-{2-O-(3,4,6-tri-O-benzyl-R-D-mannopyranosyl)}-
3,4,6-tri-O-benzyl-R-D-mannopyranosyl}-R-D-mannopyrano-
side (46). The heptasaccharide tetraol 45(0.428 g, 0.152 mmol) and
mannosyl trichloroacetimidate 22a (0.835 g, 8 equiv) were dissolved
in a small amount of toluene and evaporated to dryness and mixture
was kept under vacuum for 4 h. The reaction mixture was dissolved
in ether (∼10 mL), a small amount of molecular sieves was added,
and the solution was cooled to 0 °C. Yb(OTf)3 (0.028 g, 0.3 equiv)
was added and the solution was stirred for 10 min, TLC was
checked, and the reaction was quenched with triethylamine. Solvents
were removed and the residue was purified by chromatography to
C
415H424O80 6686.91, found 6688.3 (M + H).
Allyl 3,4-Di-O-benzyl-2-O-{2-O-[2-O-(2-O-{3,4,6-tri-O-benzyl-
R-D-mannopyranosyl} 3,4,6-tri-O-benzyl-R-D-mannopyranosyl)-
3,4,6-tri-O-benzyl-R-D-mannopyranosyl]-3,4,6-tri-O-benzyl-R-D-
mannopyranosyl)}-6-O-bis-3,4-di-O-benzyl-2-O-{2-O-[2-O-(2-
O-{3,4,6-tri-O-benzyl-R-D-mannopyranosyl}-3,4,6-tri-O-benzyl)-
R-D-mannopyranosyl](3,4,6-tri-O-benzyl-R-D-mannopyranosyl)]-
3,4-di-O-benzyl-R-D-mannopyranosyl)}-6-O-{2-O-[2-O-(3,4,6-tri-
O-benzyl-R-D-mannopyranosyl)-3,4,6-tri-O-benzyl-R-D-
mannopyranosyl]}-3,4,6-tri-O-benzyl-R-D-mannopyranosyl}R-
D-mannopyranoside (10). The tetrabenzoate 47 (0.145 g, 0.021
mmol) was dissolved in DCM/MeOH and treated with NaOMe for
1
24 h to give tetraol 10 as a gummy oil (0.125 g, 92%). H NMR
(CDCl3, 300 MHz,) δ 7.01-7.37 (m, 210H), 5.70-5.84 (m, 1H),
5.25-3.20 (m, 193H), 2.30-2.45 (m, 2H). 13C NMR (CDCl3, 75
MHz) δ 141.1, 138.9, 138.8, 138.70, 138.6, 138.5, 138.4, 138.34,
138.3, 138.2, 138.0, 138.0, 137.8, 133.9, 128.65, 128.62, 128.6,
128.5, 128.4, 128.4, 128.3, 128.2, 128.15, 128.1, 128.0, 127.9,
127.8, 127.7, 127.6, 127.5, 127.3, 127.1, 127.0, 117.7, 101.8, 101.1,
100.9, 99.6, 99.2, 99.0, 98.3, 80.3, 79.8, 79.6, 77.5, 75.7, 75.6, 75.3,
75.1, 75.0, 74.8, 74.4, 74.0, 73.5, 73.4, 72.6, 72.3, 72.1, 72.0, 71.8,
71.6, 71.0, 70.8, 70.6, 69.5, 69.3, 68.7, 68.1, 67.6, 65.6, 64.7, 60.7.
MS calcd for C387H408O76 6270.81, found 6293.9 (M + Na).
1
give an undecasaccharide (0.700 g, 92%). H NMR (CDCl3, 300
MHz,) δ 8.19-8.26 (m, 8H), 7.51-7.67 (m, 4H), 7.10-7.44 (m,
158H), 5.91-5.95 (m, 5H), 3.51-5.46 (m, 137H). 13C NMR
(CDCl3, 75 MHz) δ 165.8, 165.6, 165.5, 138.9, 138.9, 138.6, 138.5,
138.4, 138.3, 138.1, 134.0, 133.3, 130.3, 128.8, 128.0, 128.6, 128.5,
128.4, 128.3, 128.2, 128.2, 128.0, 127.7, 127.0, 127.5, 117.9, 101.1,
100.9, 99.8, 99.4, 98.4, 80.3, 78.6, 78.2, 75.5, 74.9, 74.6, 73.8, 73.7,
73.5, 72.6, 72.0, 71.2, 69.8, 69.3, 68.2, 67.7, 64.1. MS calcd for
C
307H312O60 4958.14, found 4981.2 (M + Na). The above un-
decasaccharide (0.696 g, 0.140 mmol) was dissolved in DCM/
MeOH and treated with NaOMe for 24 h to give undecasaccharyl
title tetraol 46 (0.616 g, 96%). H NMR (CDCl3, 300 MHz,) δ
n-Propyl 2-O-{2-O-[2-O-(2-O-R-D-Mannopyranosyl)-R-D-manno-
pyranosyl)-R-D-mannopyranosyl]-R-D-mannopyranosyl}-6-O-
bis-2-O-{2-O-[2-O-(2-O-{R-D-mannopyranosyl}-R-D-mannopy-
ranosyl](R-D-mannopyranosyl)mannopyranosyl)}-6-O-{2-O-[2-
O-R-D-mannopyranosyl)R-D-mannopyranosyl]}-R-D-manno-
pyranosyl}-R-D-mannopyranoside (48). To a solution of penta-
decatetraol 10 (0.032 g, 0.005 mmol) in THF/MeOH/water (3:3:1)
was added Pd/C(30 mg, 5%) and the solution was hydrogenated
for 12 h. The reaction mixture was filtered through a short celite
plug with i-PrOH/H2O as eluent, concentrated, and lyophilized to
1
7.00-7.29 (m, 150H), 5.68-5.80 (m, 1H), 3.20-5.29 (m, 141H),
2.30-2.40 (m, 4H). 13C NMR (CDCl3, 75 MHz) δ 139.0, 138.9,
138.88, 138.8, 138.8, 138.76, 138.7, 138.6, 138.58, 138.5, 138.48,
138.4, 138.34, 138.3, 138.2, 138.1, 138.1, 138.0, 137.9, 133.9,
130.2, 128.77, 128.7, 128.6, 128.5, 128.46, 128.4, 128.39, 128.3,
128.29, 128.2, 128.17, 128.1, 128.09, 128.0, 127.9, 127.8, 127.7,
127.6, 127.5, 127.4, 127.3, 127.2, 127.1, 117.8, 101.5, 101.38,
101.30, 101.2, 101.1, 101.0, 100.9, 99.4, 99.2, 98.3, 80.3, 80.1,
80.0, 79.8, 79.3, 77.6, 75.4, 75.3, 75.1, 74.9, 74.6, 74.4, 73.6, 73.5,
73.4, 72.7, 72.5, 72.4, 72.3, 72.1, 74.9, 71.8, 71.6, 71.5, 71.2, 71.1,
70.7, 69.6, 69.5, 69.4, 69.3, 69.2, 69.0, 68.9, 68.8, 68.1, 67.8, 67.6,
66.8. MS calcd for C279H296O56 4542.03, found 4565.1 (M + Na).
Allyl 3,4-Di-O-benzyl-2-O-{2-O-[2-O-(2-O-{2-O-benzoyl-3,4,6-
tri-O-benzyl-R-D-mannopyranosyl}(3,4,6-tri-O-benzyl-R-D-man-
1
give 48 as a white solid (0.012 g, 95%). H NMR (CDCl3/CD3-
OD/D2O (1:1.5:0.5), 400 MHz) δ 5.32-5.26 (m, 5H), 5.15 (br s,
2H), 5.11-5.00 (br s, 4H), 4.88 (br s, 2H), 4.80 (br s, 2H), 4.40-
3.47 (m, 90H), 2.40-2.31 (m, 2H), 1.65-1.55 (m, 2H), 0.93 (t, J
) 6.9 Hz, 3H). MS calcd for C93H158O76 2490.85, found 2514.0
(M + Na).
5544 J. Org. Chem., Vol. 72, No. 15, 2007

Efficient Assembly of Oligomannans
Supporting Information Available: General experimental
Acknowledgment. We are grateful to the National Science
Foundation (CHE-0243436) for support. We thank Dr. George
Dubay, Director of Instrument Operations in the Department
of Chemistry, Duke University, for the mass spectroscopy and
MALDI measurements.
1
methods and H and 13C NMR spectra of all compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
JO070018T
J. Org. Chem, Vol. 72, No. 15, 2007 5545