Synthesis of α- and β-D-(1→6)-C-Disaccharides by Wittig Olefination of Formyl C-Glycosides with Glycopyranose 6-Phosphoranes

Article abstract of DOI:10.1021/jo971177n

The synthesis of (1→6)-C-disaccharides by Wittig condensation of formyl C-glycofuranosides and pyranosides with galacto- and glucopyranose 6-phosphoranes is described herein. The method involves the coupling of the sugar aldehydes with the ylides and the reduction of the double bond of the resulting sugar alkenes, in most of the cases by catalytic hydrogenation. The reduction with nickel boride or diimide is employed in some special cases. O-Benzyl protective groups are removed by catalytic hydrogenation either in the course of the reduction of the double bond or in a subsequent step, while O-isopropylidene groups are cleaved by treatment with Amberlite IR-120. In this way, eight free β-D-(1→6)-C-disaccharides have been prepared in 26-61% overall yield starting from β-linked formyl C-glycosides. These include C-linked analogues of the biologically active disaccharides allolactose (Galβ1,6Glc), gentiobiose (Glcβ1,6Glc), and N-acetylamino disaccharides (GalNHAcβ1,6Gal and GalNHAcβ1,6Glc). Moreover, the synthesis of two α-D-(1→6)-C-disaccharides is described from formyl C-furanosides. The limiting condition of the synthesis of these stereoisomers is the configurational instability of the α-linked formyl C-glycosides under the basic conditions of the Wittig olefination.

Full text of DOI:10.1021/jo971177n

8114
J . Org. Chem. 1997, 62, 8114-8124
Syn th esis of r- a n d â-D-(1f6)-C-Disa cch a r id es by Wittig
Olefin a tion of F or m yl C-Glycosid es w ith Glycop yr a n ose
6-P h osp h or a n es
Alessandro Dondoni,* Helene M. Zuurmond, and Alessia Boscarato
Dipartimento di Chimica, Laboratorio di Chimica Organica, Universita`, 44100-Ferrara, Italy
Received J une 27, 1997X
The synthesis of (1f6)-C-disaccharides by Wittig condensation of formyl C-glycofuranosides and
pyranosides with galacto- and glucopyranose 6-phosphoranes is described herein. The method
involves the coupling of the sugar aldehydes with the ylides and the reduction of the double bond
of the resulting sugar alkenes, in most of the cases by catalytic hydrogenation. The reduction
with nickel boride or diimide is employed in some special cases. O-Benzyl protective groups are
removed by catalytic hydrogenation either in the course of the reduction of the double bond or in
a subsequent step, while O-isopropylidene groups are cleaved by treatment with Amberlite IR-
120. In this way, eight free â-D-(1f6)-C-disaccharides have been prepared in 26-61% overall yield
starting from â-linked formyl C-glycosides. These include C-linked analogues of the biologically
active disaccharides allolactose (Galâ1,6Glc), gentiobiose (Glcâ1,6Glc), and N-acetylamino disac-
charides (GalNHAcâ1,6Gal and GalNHAcâ1,6Glc). Moreover, the synthesis of two R-D-(1f6)-C-
disaccharides is described from formyl C-furanosides. The limiting condition of the synthesis of
these stereoisomers is the configurational instability of the R-linked formyl C-glycosides under the
basic conditions of the Wittig olefination.
In tr od u ction
with suitable glycosyl partners. In all cases, the main
problem consists in the control of the stereochemistry at
the anomeric center of the sugar moiety serving as
glycosyl donor. A remarkable improvement in this rather
difficult task has been recently achieved by Sinay¨5a and
Beau5h and their co-workers by an intramolecular deliv-
ery strategy through ketal- or silaketal-tethered monosac-
charides.9,10 The coupling through the reaction of a
carbon-linked anomeric functionality with the desired
stereochemistry already in place is an attractive ap-
proach to this chemistry. For instance, Martin and Lai
have followed this concept in their nitroaldol-based
synthesis of one (1f6)-C-disaccharide by the use of an
anomeric glycosylnitromethane derivative and a C-5
substituted sugar aldehyde.11 A conceptually similar
approach to C-disaccharides has been described more
recently by others5m who, however, employed anomeric
C-glycosyl aldehydes and nitro sugars for the nitroaldol
The coupling of two or more monosaccharides by the
stereoselective formation of O- or C-glycosidic linkage is
a fundamental process in carbohydrate chemistry1 and
a key operation in numerous totally synthetic routes to
biologically active natural products and their analogues.2
Owing to intense work over the years, several methods
are available that permit the synthesis of oxygen-linked
disaccharides and trisaccharides (O-glycosides) of either
aldoses and ketoses in good yield and high stereocontrol
at the anomeric center.1,3 Various approaches have been
also developed in more recent times toward the synthesis
of carbon-linked isosteres (C-glycosides) of naturally
occurring O-glycosides and structurally related ana-
logues.4,5 The main purpose is to create stable carbohy-
drate mimics that may serve as glycosidase and glyco-
syltransferase inhibitors6 and as models for the study of
carbohydrate recognition in biological systems.7 For the
same reasons, suitably tailored C-disaccharides and
C-trisaccharides have been synthesized and their con-
formational properties have been compared with their
O-glycosidic counterparts.8 The most straightforward
C-glycoside syntheses occur through the coupling of
anomeric carbocations, radicals, carbanions, and carbenes
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S0022-3263(97)01177-8 CCC: $14.00 © 1997 American Chemical Society

R and â-D-(1f6)-C-Disaccharides
J . Org. Chem., Vol. 62, No. 23, 1997 8115
condensation. At the same time, we reported5n the
synthesis of (1f6)-C-disaccharides via Wittig olefination
of two model formyl C-glycosides with a protected galac-
tose 6-phosphorane followed by reduction of the resulting
alkenes. We have now considered the use of various
aldehydes (I) in this sugar coupling toward ethylene
bridged disaccharides (II) (Scheme 1) and have obtained
results that confirm the efficiency of the method particu-
larly for the assembly through â-linkage. Herein the
results of earlier5n and recent work are presented in full.
Sch em e 1a
a
Key: (a) Wittig with sugar ylide; (b) reduction of the alkene.
Ch a r t 1
Resu lts a n d Discu ssion
The opportunity for a Wittig olefination approach
toward the synthesis of C-disaccharides was provided by
the ready access to various anomeric formyl C-glycopy-
ranosides and furanosides 1-7 (Chart 1) through the
thiazole-based formylation of sugars that has been
recently developed in our laboratory.12 The synthetic
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P. Tetrahedron Lett. 1994, 35, 7743. (f) Lay, L. Nicotra, F.; Pangrazio,
C.; Panza, L.; Russo, G. J . Chem. Soc., Perkin Trans. 1 1994, 333. (g)
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Am. Chem. Soc. 1997, 119, 1480. (r) Witczak, Z. J .; Chhabra, R.;
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M. Biochemie 1982, 64, 977. Truscheit, E.; Frommer, W.; J unge, B.;
Mu¨ller, L.; Schmid, D. D.; Wingender, W. Angew. Chem., Int. Ed. Engl.
1981, 20, 744. Sinnott, M. L. In Enzyme Mechanisms; Page, M. I.,
Williams, A., Eds.; The Royal Society of Chemistry: London, 1987; p
259. (b) For some applications, see: treatment of AIDS (Karpas, A.;
Fleet, G. W. J .; Dwek, R. A.; Fellows, L. E.; Tyms, A. S.; Petursson, S.;
Namgoong, S. K.; Ramsden, N. G.; J acob, G. S.; Rademacher, T. W.
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value of this one-carbon extension of carbohydrates13
stems from both the ease of installation of the thiazole
ring at the anomeric carbon by addition of 2-lithiothiazole
to sugar lactones and the conversion of the heterocycle
into the formyl group under mild and neutral conditions14
that are tolerant to various common hydroxyl protective
groups employed in carbohydrate chemistry. In addition,
the method is amenable for the gram-scale synthesis of
all formyl C-glycosides shown in Chart 115 and therefore
provides the material for the preparation of C-disaccha-
rides on a similar scale.
As the other partner of the Wittig condensation with
the aldehydes 1-7, we chose the ylides from the galac-
topyranose and glucopyranose phosphonium iodides 8
and 9. The preparation of 8 from the corresponding
iodogalactose and the conditions for the generation of the
ylide and the reaction with nonanomeric aldehyde sugars
were originally described by Secrist and Wu.16 It has
been reported that this ylide is generated without
epimerization at C-5, a rather common process for
carbohydrate phosphoranes as a consequence of ring
opening and reclosure.17 In a similar fashion to 8, we
have prepared the hitherto unreported phosphonium salt
9 from the known methyl 2,3,4-tri-O-benzyl-6-deoxy-6-
iodo-R-D-glucopyranoside.18
(7) Rademacher, T. W.; Parekh, R. B.; Dwek, R. A. Annu. Rev.
Biochem. 1988, 57, 785. Hindsgaul, O.; Kare, D. P.; Bach, M.; Lemieux,
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Recognition in Cellular Function; Ciba-Geigy Symposium 145; Wiley:
Chichester, 1989; p 62. Kornfeld, R.; Kornfeld, S. Annu. Rev. Biochem.
1985, 54, 651 and references therein. Morenem, K. W.; Trimble, R.
B.; Herscovics, A. Glycobiology 1994, 4, 113.
(8) O’Leary, D. J .; Kishi, Y. J . Org. Chem. 1994, 59, 6629. Wei, A.;
Haudrechy, A.; Audin, C.; J un, H.-S.; Haudrechy-Bretel, N.; Kishi, Y.
J . Org. Chem. 1995, 60, 2160. Wei, A.; Boy, K. M.; Kishi, Y. J . Am.
Chem. Soc. 1995, 117, 9432 and previous papers. Espinosa, J .-F.;
Can˜ada, F. J .; Asensio, J . L.; Dietrich, H.; Mart´ın-Lomas, M.; Schmidt,
R. R.; J ime´nez-Barbero, J . Angew. Chem., Int. Ed. Engl. 1996, 35, 303.
(9) The “stereocontrolled synthesis of disaccharides via the tempo-
rary silicon connection” was originally described by Stork, G.; Suh, H.
S.; Kim, G. J . Am. Chem. Soc. 1991, 113, 7054.
Syn th esis of â-D-(1f6)-C-Disa cch a r id es. Among
the C-glycosyl aldehydes shown in Chart 1, the â-linked
(10) For a review of silicon-based methods for tethering, see: Bols,
M.; Skrydstrup, T. Chem. Rev. (Washington, D.C.) 1995, 95, 1253.
(11) (a) Martin, O. R.; Lai, W. J . Org. Chem. 1990, 55, 5188. (b)
Martin, O. R.; Lai, W. J . Org. Chem. 1993, 58, 176.
(13) For an account of this and other methods, see: Dondoni, A.;
Marra, A. In ref 1b, p 173.
(14) Dondoni, A.; Marra, A.; Perrone, D. J . Org. Chem. 1993, 58,
275.
(12) Dondoni, A.; Scherrmann, M.-C. J . Org. Chem. 1994, 59, 6404.

8116 J . Org. Chem., Vol. 62, No. 23, 1997
Dondoni et al.
Ta ble 1. Con d en sa tion of Ald eh yd es 1-5 w ith th e Ylid es fr om th e P h osp h on iu m Sa lts 8 a n d 9 a n d Red u ction of th e
Olefin s 10-17 to C-Disa cch a r id es 18-23, 25, a n d 27
a
Method A: (1) H2, Pd(OH)2, 3 bar; (2) Amberlite IR-120, H2O, 70 °C. Method B: (1) NiCl2‚6H2O + NaBH4 then Ac2O, pyridine; H2,
Pd(OH)2, 3 bar; (2) Amberlite IR-120, H2O, 70 °C. Method C: NiCl2‚6H2O + NaBH4 then Ac2O, pyridine; H2, Pd(OH)2, 3 bar.
galactopyranosyl and mannofuranosyl derivatives 1 and
2 were considered as model substrates for the Wittig
coupling with the galactose 6-phosphorane from 8. Fol-
lowing the procedure of Secrist and Wu,16 the red-colored
ylide was generated by the addition of 1 equiv of n-BuLi
to the salt dissolved in 2:1 THF-HMPA in the presence
of activated molecular sieves at -30 °C under nitrogen.
A THF solution of the freshly purified aldehyde (1.0-
1.5 equiv)19 was then added, and the reaction mixture
was allowed to warm slowly to 0 °C and then to room
temperature before workup. Under these conditions, the
alkenes 10 and 11 (Table 1) were isolated by chroma-
tography in 76 and 67% yields, respectively. Along with
10 was also obtained the C-formyl glycal 30 in 5% yield
(Chart 2). The formation of the byproduct 30 may be
ascribed to the base-induced â-elimination of the benzy-
loxy group at C-2 of the aldehyde 1.12 On the other hand,
reactions carried out in the absence of molecular sieves
and at a lower temperature (-60 °C) afforded the alkenes
10 and 11 in much lower yield (ca. 20%). In these cases,
the hydrolysis of the unreacted phosphorane20 produced
the sugar diphenylphosphine oxide 29 as the main
product (Chart 2). Compound 10 was obtained as a
(15) For instance, the aldehyde 1 is currently prepared in our
laboratory in stocks of 5.5-6.0 g (ca. 65% yield) starting from 9.0 g of
the tetrabenzyl galactonolactone.
(16) Secrist, J . A., III; Wu, S.-R. J . Org. Chem. 1979, 44, 1434.
(17) (a) Secrist, J . A., III; Wu, S.-R. J . Org. Chem. 1977, 42, 4084.
(b) For an authorative review on the stereochemistry, mechanism, and
synthetic applications of the Wittig olefination, see: Maryanoff, B. E.;
Reitz, A. B. Chem. Rev. (Washington, D.C.) 1989, 89, 863.
(18) Sakairi, N.; Kuzuhara, H. Tetrahedron Lett. 1982, 23, 5327.
(19) These aldehydes were isolated in the form of hydrates as shown
by the complexity of their 1H NMR spectra in CDCl3 at room
temperature. However, a filtration over a short column of silica gel
just prior to use gave pure products showing simple NMR spectra.
(20) (a) Warren, S.; Clayden, J . Angew. Chem., Int. Ed. Engl. 1996,
35, 241. (b) Smith, D. J . H. In Comprehensive Organic Chemistry;
Barton, D., Ollis, W. D., Eds.; Pergamon Press Ltd: Oxford, 1979; p
1301.

R and â-D-(1f6)-C-Disaccharides
J . Org. Chem., Vol. 62, No. 23, 1997 8117
Ch a r t 2
and the coupling with the sugar aldehydes 1, 4, and 5
afforded the corresponding alkenes 15, 16, and 17 as
mixtures of E- and Z-isomers in 53-56% yields (Table
1). Unfortunately, the separation of these stereoisomers
by column chromatography turned out to be quite dif-
ficult, and therefore, the configuration at C-5 and C-8
was confirmed by 1H NMR analysis of the corresponding
alkanes (see below).
The second key operation required the reduction of the
double bond of the sugar alkenes 10-17. With the
exception of compounds 13 and 16 bearing the azido
group, all the other alkenes, either as a single isomer or
as a mixture of E- and Z-isomers, were readily reduced
by mild-pressure hydrogenation over Pd(OH)2 on carbon.
Also, the O-benzyl protective groups were removed in this
single step while the cleavage of the O-isopropylidene
groups required the treatment with Amberlite IR-120 at
70 °C.11b Under these conditions, the sugar rings re-
mained unaffected, while under different conditions, such
as in refluxing 80% acetic acid, the C-1 unprotected sugar
moieties equilibrate into furanose and pyranose forms.
In this way, the free â-D-(1f6)-C-disaccharides 18-20,
22, 23, and 27 were isolated in good to excellent yields
(Table 1). The conversion of the alkenes 13 and 16 to
the corresponding C-disaccharides required a different
procedure since the above catalytic hydrogenation did not
proceed in the presence of the azido group as shown by
the recovery of unreacted starting material even after
longer reaction time (24 h). Therefore, following an
earlier report by Paulsen and Ho¨lck24 and recent work
from this laboratory,25 we attempted the reduction of the
azido function and the alkene double bond in a single
step by the use of nickel boride generated in situ26 from
NiCl2 hexahydrate and NaBH4. This method appeared
to work quite well as shown by TLC analysis of the
reaction mixture. Then, after protection of the amino
group as N-acetyl derivative, the O-benzyl and O-isopro-
pylidene protective groups were removed by sequential
catalytic hydrogenation and treatment with Amberlite
IR-120 as described above to give the N-acetylamino
C-disaccharides 21 and 25 in satisfactory overall yields.
To confirm the assigned configuration at C-5 and C-8,
compounds 23, 25, and 27 were converted into the
corresponding peracetylated derivatives 24, 26, and 28,
single Z-isomer (J 6,7 ) 12 Hz),21 while 11 was a 2.3:1
mixture of (Z)- and (E)-alkenes. While the stereoselec-
tivity of the Wittig condensation17b was unimportant in
view of the subsequent reduction of the resulting olefin,
the preservation of the original configuration of the two
sugar moieties was a key issue in the context of the
planned synthesis. This was readily confirmed by 1H
NMR analysis. The spectrum of 10 showed a J 8,9 value
of 9.0 Hz, indicating the â-configuration at the anomeric
center of one sugar moiety and a J 4,5 value of 2.0 Hz
consistent with the R-D-galacto configuration in the other
moiety. The individual isomers (Z)-11 and (E)-11 were
separated, and in both cases the NMR spectra22 provided
evidence that the original â-D-manno configuration was
retained in the furanose ring and the R-D-galacto con-
figuration was retained in the pyranose ring. Encour-
aged by these results, the other â-linked C-glycopyranosyl
aldehydes 3-5 were subjected to the Wittig olefination
with the ylide from 8. The reaction of the mannopyra-
nosyl aldehyde 3 afforded the corresponding alkene 12,
although in much lower yield (42%) than 10 and 11, along
with compound 32 as a side product (Chart 2). In
agreement with the above isolation of the C-formyl glycal
30, the formation of the minor product 32 is likely to
occur via olefination of the corresponding glycal 31 that
in turn is easily produced by the aldehyde 3 under basic
conditions because of the favorable trans-diaxal disposi-
tion between the C-1 hydrogen and C-2 O-benzyl group.
On the other hand, the condensation of the 2-azidoga-
lactopyranosyl 4 and glucopyranosyl derivative 5 afforded
the corresponding alkenes 13 and 14 as Z-isomers (J 6,7
) 11.0 and 12.0 Hz, respectively)21 in good yields (Table
1). Also for these compounds, the integrity of the
1
which showed highly resolved H NMR spectra suitable
1
configuration at C-5 and C-823 was demonstrated by H
for structural assignment. In all cases, the J 8,9 and J 4,5
values were in the range of 9-11 Hz in agreement with
the â-linkage at the anomeric center of one sugar unit
and the R-D-gluco configuration in the other. These
examples also show that the glucose 6-phosphorane
generated from 9 reacted with sugar aledehydes without
apparent epimerization at C-5.
NMR analysis as described for compounds 10 and 11. In
the case of compound 12 bearing the mannopyranosyl
ring, the â-linkage was supported by the substantial NOE
between H-8 and H-12.
Next, we examined the condensation with the glucose
6-phosphorane from 9 to give a new set of (1f6)-C-
disaccharides bearing the glucopyranosyl moiety at one
side. Application of the above ylide generation procedure
A brief recapitulation and few comments may help to
better evaluate the above results. Eight â-D-(1f6)-C-
disaccharides have been prepared from C-formyl glyco-
sides by an olefination-reduction sequence. The overall
yield of isolated products ranged from 26 to 61%. The
method is compatible with O-benzyl and O-isopropylidene
protective groups and is tolerant to the presence of the
azido group as a substituent. Various â-linked C-formyl
glycosides with different structural arrays were ef-
ficiently employed, and in all cases there were no
(21) In this and in the other cases where only one isomer was
obtained, the Z configuration was assigned with enough confidence
since the observed J 6,7 values (11-12 Hz) were in the range of cis
ethylenic coupling constants. See: J ackman, L. M.; Sternhell, S. In
Applications of Nuclear Magnetic Resonance Spectroscopy in Organic
Chemistry; Barton, D., Ed.; Pergamon Press Ltd: Oxford, 1969; p 301.
Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. In Spectrometric
Identification of Organic Compounds; J ohn Wiley & Sons, Inc.: New
York, 1991; p 221.
(22) Both the (E)-11 and (Z)-11 (J 6,7 ) 15.0 and 12.0 Hz, respectively)
showed a substantial NOE between H-8 and H-11 and a J 4,5 value of
2.0 Hz.
(23) For all sugar olefins and the corresponding alkanes the same
conventional numbering system outlined for 10 and 18 was adopted;
i.e., counting starts from the reducing end of the disaccharide.
(24) Paulsen, H.; Ho¨lck, J .-P. Carbohydr. Res. 1982, 109, 89.
(25) Dondoni, A.; Perrone, D.; Semola, M. T. J . Org. Chem. 1995,
60, 7927.
(26) Brown, H. C.; Brown, C. A. J . Am. Chem. Soc. 1963, 85, 1003.

8118 J . Org. Chem., Vol. 62, No. 23, 1997
Dondoni et al.
Sch em e 2
indications that the configuration at the anomeric carbon
was changed. The same conclusion was drawn for the
configuration at C-5 of the two 6-phosphoranes employed.
This method appears to be more practical and to give
higher yields than the nitroaldol (Henry) condensation
wherein the removal of the hydroxyl and nitro groups in
the adduct is a troublesome operation requiring several
steps.5m,11b In contrast, in our Wittig olefination-based
method, the reduction of the ethylenic double bond is a
high-yield one-step process that in addition offers the
opportunity for the concomitant removal of the hydroxyl
protective groups. The higher efficiency of this method
is substantiated by the 46% overall yield of isolated
methyl â-C-allolactoside 23 (C-Galâ1,6Glc) from the
aldehyde 1 in comparison to the reported 5% yield
through the Henry route.5m It has been suggested5m that
this C-analogue of allolactose due to its resistance to
enzymatic hydrolysis by â-galactosidase could serve as
a potent inducer of the lac repressor protein and therefore
may exert control over the lactose operon. Also, the
isomer 22 (C-Glcâ1,6Gal) was isolated in good yield (50%
from the aldehyde 5), while a significantly lower value
(17%) was obtained from an earlier synthesis by conden-
sation of peracetylated glucosylnitromethane with a
galactose-derived aldehyde.11b A satisfactory yield (45%)
was also registered for the methyl â-C-gentiobioside 27
(C-Glcâ1,6Glc), the first example of a C-disaccharide
described in 1983 by Rouzaud and Sinay¨.27 Noteworthy
are the hitherto unreported amino C-disaccharides 21 (C-
GalNHAcâ1,6Gal) and 25 (C-GalNHAcâ1,6Glc), which
may bear significant relevance to biological systems
wherein 2-amino-2-deoxy sugars are involved such as
aminoglycosidic antibiotics28 and antigenic determinant
on cell surfaces.29 It is in this context that recent reports
have stressed the importance of the synthesis of alkyl
C-glycosides derived from D-glucosamine30 and D-galac-
tosamine.31
a
Key: (i) 8, n-BuLi, -30 °C, THF-HMPA; (ii) p-MeC6H4SO2-
NHNH2, AcONa, DME-H2O, then H2, Pd(OH)2, 3 atm, then
Amberlite IR-120, H2O, 70 °C.
compounds, in agreement with the original R-linkage at
C-1 of the furanose ring, no NOE was observed between
H-8 and H-11 by irradiation of the latter. The reduction
of the double bond of 33 by catalytic hydrogenation over
either Pd(OH)2 or Pd was hampered by the elimination
of the benzyloxy group from the furanose ring.33 Instead,
a clean reduction was carried out under mild conditions
by the use of diimide generated in situ from (p-toluene-
sulfonyl)hydrazine and sodium acetate.34 Then, the
O-benzyl and O-isopropylidene protective groups were
removed in the usual manner to give the final R-linked
C-disaccharide 34 in 56% isolated yield.
Since recent work from this laboratory has provided
access to the R-linked formyl C-mannofuranoside diac-
etonide 39 from the corresponding thiazolyl C-glycoside
3835 (Scheme 3), the condensation of this aldehyde with
the galactose 6-phosphorane from 8 was carried out as
well. The reaction afforded the alkene 40 exclusively as
Z-isomer (J 6,7 ) 11.5 Hz) in 62% yield after purification
by chromatography. The R-linkage at C-8 of 40 was
easily confirmed by the J 8,9 value of 1.0 Hz in comparison
to the 4.0 Hz of the â-linked isomer 11. Moreover, the
R-D-galacto configuration of the pyranose ring was proved
Syn t h esis of r-D-(1f6)-C-Disa cch a r id es. The
R-linked formyl C- glucopyranoside 6 and C-ribofurano-
side 7 (Chart 1) were at our disposal from previous
work.12 While the configurational stability at C-1 of 7
was supported by the well-known preference for a 1,2-
cis arrangement in ribofuranoses,32 the isomerization of
the sugar aldehyde 6 to the â-linked isomer 5 was likely
to occur under the basic conditions12 of the Wittig
olefination. Indeed, upon treatment of 6 with the galac-
tose 6-phosphorane from 8 under the above standard
conditions (n-BuLi, THF-HMPA, -30 °C), the main
isolated products were the alkenes 14 (Z-isomer) and 32
(Z/E, 2:1) in 43% overall yield. In contrast, the conden-
sation of the aldehyde 7 with the same ylide from 8
(Scheme 2) afforded the corresponding sugar alkene 33
(66%) as a 4:1 mixture of Z- and E-isomers. For these
(33) In addition to the expected debenzylated C-disaccharide 35, also
the deoxy derivative 36 (Gal ) galoctopyranoside diacetonide moiety
as in 33) was obtained in a 1:1 ratio (86% overall yield). Compound
36 showed the following data: [R]D ) -50 (c 0.3, CHCl3); 1H NMR
(CD3OD) δ 1.30, 1.32, 1.40, 1.50 (4 × s, 2 × C(CH3)2), 1.41-1.72 (m,
6H, H-6, H-6′, H-7, H-7′, H-9, H-9′), 3.43 (t, 1H, H-10, J 10,9 ≈ J 10,11
≈
6.0 Hz), 3.59 (t, 1H, H-12, J 12,11 ≈ J 12,12′ ≈ 4.5 Hz), 3.62-3.70 (m, 2H,
H-8, H-11), 3.74-3.80 (m, 2H, H-5, H-12′), 4.16 (dd, 1H, H-4, J 4,3
)
8.0 Hz, J 4,5 ) 2.0 Hz), 4.31 (dd, 1H, H-2, J 2,3 ) 2.5 Hz, J 2,1 ) 5.0 Hz),
4.59 (dd, 1H, H-3), 5.50 (d, 1H, H-1); 13C NMR (CD3OD) δ 22.8, 24.5,
25.1, 26.3, 31.3, 33.2, 64.6, 68.7, 71.9, 72.3, 73.9, 74.0, 74.4, 76.0, 98.0,
109.6, 110.0.
(34) van Tamelen, E. E.; Dewey, R. S. J . Am. Chem. Soc. 1961, 83,
3729.
(27) Rouzaud, D.; Sinay¨, P. J . Chem. Soc., Chem. Commun. 1983,
1353.
(28) Umezawa, S. In Advances In Carbohydrate Chemistry and
Biochemistry; Tipson, R. S., Horton, D., Eds.; Academic Press: London,
1974.
(29) Kabut, E. A. In Blood and Tissue Antigens, Aminoff, D., Ed.;
Academic Press: New York, 1970.
(30) Hoffmann, M.; Kessler, H. Tetrahedron Lett. 1994, 35, 6067.
(31) Ayadi, E.; Czernecki, S.; Xie, J . Chem. Commun. 1996, 347. The
key reaction in this paper is the addition of alkyllithium reagents to
2-azido-3,4,6-tri-O-benzyl-2-deoxy-D-galactonolactone. It is worth point-
ing out that the original synthesis of the azido sugar lactone and its
reaction with a C-nucleophile (2-lithiothiazole) described by one of us
in a much earlier report (ref 12) were not acknowledged.
(32) Ohrui, H.; J ones, G. H.; Moffatt, J . G.; Maddox, M. L.;
Christensen, A. T.; Byram, S. K. J . Am. Chem. Soc. 1975, 97, 4602.
(35) The thiazolyl C-glycoside 38 (oil, [R]D ) +22 (c 0.9, CHCl3), 1H
NMR (300 MHz, CDCl3) δ 5.31 (s, 1H, H-1)) was obtained in 83%
isolated yield by reduction of the ketol acetate 37 (see ref 12) using
SmI2 (A. Marra, A. Dondoni, to be published) as described for the
anomeric deoxygenation of O-acetylated 2-ulosonates (Hanessian, S.;
Girard, C. Synlett 1994, 863). It is noteworthy that the deoxygenation
of 37 under these conditions occurs with opposite stereoselectivity to
that obtained by the use of Et3SiH-TMSOTf (ref 12).

R and â-D-(1f6)-C-Disaccharides
J . Org. Chem., Vol. 62, No. 23, 1997 8119
and 13C NMR (75 MHz) were recorded at room temperature
for CDCl3 solutions, unless otherwise specified. Assignments
were aided by homo- and heteronuclear two-dimensional
experiments. Stocks of crude sugar aldehydes 1-7 were
prepared as described12 and stored at -20 °C without any
apparent decomposition for several days. The required amount
of aldehyde for immediate reaction was purified by elution
through a short column of silica gel with 1:2 ethyl acetate-
cyclohexane. The phosphonium iodide 8 was prepared on a
multigram scale (10 g) as described16 and stored at -20 °C.
Meth yl 2,3,4-Tr i-O-ben zyl-6-d eoxy-6-(tr ip h en ylp h os-
p h on io)-r-D-glu cop yr a n osid e iod id e (9). A degassed solu-
tion of methyl 2,3,4-tri-O-benzyl-6-deoxy-6-iodo-R-D-glucopy-
ranoside18 (1.9 g, 3.3 mmol) and triphenylphosphine (914 mg;
3.5 mmol) in tetramethylenesulfolane (2.5 mL) was heated
under nitrogen at 120 °C for 3 days. The mixture was diluted
with CH2Cl2 (20 mL), refluxed with activated carbon (1 g) for
10 min, and filtered over Celite. The resulting yellow solution
was dropped slowly into diethyl ether (1.2 L) to give a slightly
yellow precipitate, which was filtered, immediately washed
with diethyl ether (3 × 50 mL), and dried in vacuo to give 2.5
g (90%) of the phosphonium iodide 9 as a slightly yellow
solid: mp 178-179 °C (from chloroform-diethyl ether); [R]D
) +62 (c 0.8, CH3OH); 1H NMR δ 2.62 (s, 3H, OCH3), 3.47 (m,
1H, H-5), 3.61 (dd, H-2, J 2,1 ) 3.5 Hz, J 2,3 ) 9.5 Hz), 3.80-
3.91 (m, 3H, H-3, H-4, H-6), 4.40 (d, 1H, H-1), 4.51-4.63 (m,
1H, H-6), 4.62 and 4.76 (2d, 2H, J ) 12.0 Hz), 4.79 and 4.95
(2d, 2H, J ) 12.0 Hz), 5.05 and 5.10 (2d, 2H, J ) 12.0 Hz),
7.20-7.40 (m, 15H, Harom), 7.55-7.80 (m, 15H, Harom). Anal.
Calcd for C46H46IO5P: C, 66.03, H, 5.54. Found: C, 66.00, H,
5.70.
(Z)-8,12-An h ydr o-9,10,11,13-tetr a-O-ben zyl-6,7-dideoxy-
1,2:3,4-di-O-isopr opyliden e-r-D-glycer o-L-ma n n o-D-ga la cto-
tr id ec-6-en o-1,5-p yr a n ose (10). A mixture of the phospho-
nium salt 8 (350 mg; 0.55 mmol), activated 4-Å powdered
molecular sieves (480 mg), anhydrous THF (2 mL), and HMPA
(1 mL) was cooled to -30 °C. To this suspension was added
n-BuLi (346 µL, 0.55 mmol of 1.6 M solution in hexane),
followed by the aldehyde 1 (0.55 mmol; 150 mg) in anhydrous
THF (1.2 mL). The suspension was allowed to slowly warm
to room temperature (about 2.5 h), maintained for an ad-
ditional 30 min at the same temperature, and then filtered
through Celite. The filtrate was diluted with diethyl ether
(20 mL), and the organic layer was washed with water (10
mL), 5% sodium thiosulfate solution (10 mL) and water (10
mL), dried (Na2SO4), and concentrated. Flash chromatography
(4:1 cyclohexane-ethyl acetate) of the residue gave 325 mg
(76%) of the oily olefin 10 (only Z-isomer): [R]D ) -5 (c 0.4);
1H NMR δ 1.07, 1.25, 1.36, 1.43 (4 × s, 12H, 2 × C(CH3)2),
3.62 (m, 4H, H-10, H-12, H-13, H-13′), 3.66 (dd, 1H, H-4, J 4,3
) 8.0 Hz, J 4,5 ) 2.0 Hz), 3.70 (t, 1H, H-9, J 9,8 ≈ J 9,10 ≈ 9.0 Hz),
3.97 (d, 1H, H-11, J 11,10 ) 3.0 Hz), 4.00 (dd, 1H, H-8, J 8,7 ) 7.5
Hz), 4.16 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.2 Hz), 4.21 (dd,
1H, H-3, J 3,2 ) 2.2 Hz, J 3,4 ) 8.0 Hz), 4.34 and 4.42 (2d, 2H,
J ) 11.0 Hz, OCH2Ph), 4.56 and 4.85 (2d, 2H, J ) 11.0 Hz,
OCH2Ph), 4.57 and 4.87 (2d, 2H, J ) 11.0 Hz, OCH2Ph), 4.59
(dd, 1H, H-5, J 5,4 ) 2.0 Hz, J 5,6 ) 8.0 Hz), 4.60 and 4.68 (2d,
2H, J ) 11.0 Hz, OCH2Ph), 5.44 (d, 1H, H-1), 5.66 (dd, 1H,
H-7, J 7,6 ) 11.0 Hz), 5.74 (dd, 1H, H-6), 7.15-7.30 (m, 20H,
Harom); 13C NMR δ 24.5, 25.2, 26.4, 26.5, 66.7, 70.9, 71.1, 72.0,
73.6, 74.8, 75.2, 75.3, 75.6, 76.7, 77.7, 79.8, 85.0, 97.1, 108.5,
109.2, 127.2, 128.7, 127.7-128.7, 138.8, 139.1, 139.2, 139.4.
Anal. Calcd for C47H54O10: C, 72.47, H, 6.99. Found: C, 72.23,
H, 7.18.
Sch em e 3
a
Key: (i) MeOTf, MeCN, then NaBH4, MeOH, then HgCl2,
MeCN-H2O; (ii) 8, n-BuLi, -30 °C, THF-HMPA; (iii) H2, Pd(OH)2,
3 atm; (iv) Amberlite IR-120, H2O, 70 °C.
by the J 4,5 value of 2.0 Hz. The reduction of the double
bond of 40 was carried out by catalytic hydrogenation
over Pd(OH)2 without any appreciable side reaction to
give 41 (82%), which upon treatment with Amberlite IR-
120 afforded the free R-D-(1f6) C-disaccharide 42 in 89%
yield.
Con clu sion
Collectively, these examples show that â-linked formyl
C-glycosides can be effectively employed in a Wittig
olefination route to â-D-(1f6)-C-disaccharides. This suc-
cessful approach relies on the fact that the stereochem-
istry of the formyl group already in place in â-linked
sugar aldehydes is unaffected by the reaction conditions.
Since pyranose 6-phosphoranes may be prepared from
other sugars, this expeditious method should constitute
a general entry to various (1f6)-C-disaccharide linkages.
Of course, the availability of furanose 5-phosphoranes17a
may extend the scope of the synthesis to â-(1f5)-C-
disaccharides. On the other hand, the configurational
instability of R-linked formyl C-glycosides does not permit
the same wide scope synthesis of R-D-(1f6)-C-disaccha-
rides. Nevertheless, once stable sugar aldehydes are
available such as the R-linked formyl C-ribofuranoside
7 and mannofuranoside 39, the corresponding C-disac-
charide linkage can be effectively constructed.
Exp er im en ta l Section
All moisture-sensitive reactions were performed under a
nitrogen atmosphere using oven-dried glassware. All solvents
were dried over standard drying agents36 and freshly distilled
prior to use. Commercially available powdered 4-Å molecular
sieves (50 µm average particle size) were used without further
activation. Flash chromatography37 was performed on silica
gel 60 (230-400 mesh). Reactions were monitored by TLC
on silica gel 60 F254 with detection by charring with sulfuric
acid. Melting points were determined with a capillary ap-
paratus and are uncorrected. Optical rotations were measured
at 20 ( 2 °C in CHCl3 unless stated otherwise. 1H (300 MHz)
(Z/E)-8,11-An h yd r o-1,2:3,4:9,10:12,13-tetr a -O-isop r op y-
liden e-6,7-dideoxy-r-D-glycer o-D-ga la cto-D-ga la cto-tr idec-
6-en o-1,5-p yr a n ose (11). The phosphonium salt 8 (350 mg;
0.55 mmol) was reacted with the aldehyde 2 (150 mg; 0.55
mmol) as described for the preparation of 10 to afford, after
chromatography (5:2 cyclohexane-ethyl acetate), the olefin 11
(184 mg; 67%) as a mixture of E and Z isomers in a 3:7 ratio.
Pure samples of these compounds were obtained by flash
chromatography (4:1 cyclohexane-ethyl acetate). Eluted first
was (Z)-11 as an oil: [R]D ) -32 (c 0.2); 1H NMR (C6D6) δ
1.06, 1.14, 1.18, 1.32, 1.40, 1.47, 1.48, 1.50 (8 × s, 24H, 4 ×
C(CH3)2), 3.38 (dd, 1H, H-11, J 11,10 ) 3.5 Hz, J 11,12 ) 8.0 Hz),
(36) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: Oxford, 1988.
(37) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

8120 J . Org. Chem., Vol. 62, No. 23, 1997
Dondoni et al.
4.09 (dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5 ) 2.0 Hz), 4.11-4.12 (m,
2H, H-13, H-13′), 4.17 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.0
Hz), 4.37 (ddd, 1H, H-8, J 8,6 ) 1.0 Hz, J 8,7 ) 6.5 Hz, J 8,9 ) 4.0
Hz), 4.40 (dd, 1H, H-9, J 9,10 ) 6.0 Hz), 4.48 (dd, 1H, H-10),
4.53 (dd, 1H, H-3), 4.63 (dt, H-12, J 12,13 ≈ J 12,13′ ≈ 6.0 Hz),
4.82 (dd, 1H, H-5, J 5,6 ) 6.4 Hz), 5.56 (d, 1H, H-1), 5.98 (ddd,
1H, H-7, J 7,5 ) 1.0 Hz, J 7,6 ) 12.0 Hz), 6.06 (ddd, 1H, H-6);
13C NMR δ 24.3, 24.7, 24.9, 25.2, 25.8, 25.9, 26.3, 27.0, 65.1,
67.2, 70.2, 70.8, 72.9, 73.4, 78.8, 80.8, 81.9, 82.7, 96.4, 108.4,
75.3, 75.6, 76.7, 77.7, 79.8, 85.0, 97.1, 108.5, 109.0, 127.2, 128.7,
127.7-128.7, 138.8, 139.1, 139.2, 139.4. Anal. Calcd for
C47H54O10: C, 72.47, H, 6.99. Found: C, 71.73, H, 7.20.
Eluted second was (E)-12 as a syrup: [R]D ) -47 (c 0.4); 1H
NMR δ 1.26, 1.30, 1.35, 1.45 (4 × s, 12H, 2 × C(CH3)2), 3.42
(ddd, 1H, H-12, J 12,11 ) 10.0 Hz, J 12,13 ) 5.0 Hz, J 12,13′ ) 2.0
Hz), 3.63 (dd, 1H, H-10, J 10,9 ) 3.0 Hz, J 10,11 ) 10.0 Hz), 3.76
(m, 2H, H-13, H-13′), 3.83 (d, 1H, H-9), 3.94 (d, 1H, H-8, J 8,7
) 5.0 Hz), 3.95 (t, 1H, H-11), 4.22 (dd, 1H, H-4, J 4,3 ) 8.0 Hz,
J 4,5 ) 2.0 Hz), 4.32 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 3.0 Hz),
4.34 (d, 1H, H-5, J 5,6 ) 5.0 Hz), 4.56 and 4.89 (2 × d, 2H, J )
10.0 Hz, OCH2Ph), 4.57 and 4.66 (2 × d, 2H, J ) 12.0 Hz,
OCH2Ph), 4.61 (dd, 1H, H-3), 4.62 and 4.65 (2 × d, 2H, J )
12.0 Hz, OCH2Ph), 4.78 and 4.85 (2 × d, H, J ) 12.0 Hz, OCH2-
Ph), 5.59 (d, 1H, H-1), 5.91 (dd, 1H, H-6, J 6,7 ) 16.0 Hz), 6.00
(dd, 1H, H-7), 7.05-7.40 (m, 20H, Harom); 13C NMR (C6D6) δ
24.3, 24.9, 26.3, 69.0, 70.3, 71.0, 71.3, 71.9, 73.7, 73.8, 75.1,
75.2, 75.5, 77.6, 78.9, 80.2, 85.0, 97.0, 108.3, 109.1, 127.2, 131.7,
109.2, 109.3, 112.6, 127.5, 128.9. Anal. Calcd for C25H38O10
:
C, 60.23; H, 7.68. Found: C, 59.74, H, 7.67.
1
Eluted second was (E)-11 as an oil: [R]D ) -36 (c 0.2); H
NMR (C6D6) δ 1.13, 1.15, 1.16, 1.32, 1.40, 1.48, 1.50 (7 × s,
24H, 4 × C(CH3)2), 3.32 (dd, 1H, H-11, J 11,10 ) 3.5 Hz, J 11,12
)
7.0 Hz), 3.60 (dd, 1H, H-8, J 8,7 ) 6.0 Hz, J 8,9 ) 4.0 Hz), 3.91
(dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5 ) 2.0 Hz), 4.02 (dd, 1H, H-9,
J 9,10 ) 6.0 Hz), 4.05 (dd, 1H, H-13, J 13,12 ) 6.0 Hz, J 13,13′ ) 8.0
Hz), 4.14 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.0 Hz), 4.18 (dd,
H-13′, J 13′,12 ) 5.7 Hz, J 13′,13 ) 8.0 Hz), 4.26 (dd, 1H, H-10),
4.43 (dd, 1H, H-3), 4.52 (dd, 1H, H-5, J 5,6 ) 5.7 Hz), 4.56 (dt,
1H, H-12), 6.24 (2H, H-6, H-7, J 6,7 ) 15.3 Hz, J 8,7 ) 6.0 Hz);
13C NMR δ 24.3, 24.6, 24.9, 25.1, 25.8, 26.0, 26.1, 27.0, 67.1,
68.5, 70.3, 70.8, 73.1, 73.3, 76.0, 80.8, 81.8, 82.5, 96.4 108.5,
127.5-128.3, 139.3, 139.7. Anal. Calcd for C47H54O10
72.47, H, 6.99. Found: C, 72.07, H, 7.44.
: C,
(Z)-8,12-An h yd r o-9-a zid o-10,11,13-t r i-O-b en zyl-6,7,9-
tr ideoxy-1,2:3,4-di-O-isopr opyliden e-r-D-glycer o-L-ma n n o-
D-ga la cto-tr id ec-6-en o-1,5-p yr a n ose (13). The phosphoni-
um salt 8 (209 mg; 0.33 mmol) was reacted with the aldehyde
4 (161 mg; 0.33 mmol) as described for the preparation of 10
to afford, after flash chromatography (4:1 cyclohexane-ethyl
acetate), 192 mg (80%) of the olefin 13, exclusively in the form
of the Z-isomer, as a syrup: [R]D ) -20 (c 0.5); 1H NMR (C6D6)
δ 1.07, 1.15, 1.50, 1.55 (4 × s, 12H, 2 × C(CH3)2), 3.32 (dd,
1H, H-10, J 10,9 ) 10.0 Hz, J 10,11 ) 3.0 Hz), 3.49 (dd, 1H, H-13′,
109.2, 112.5, 127.6, 131.5. Anal. Calcd for C25H38O10
60.23; H, 7.68. Found: C, 60.49; H, 7.42.
: C,
(Z/E)-8,12-An h yd r o-9,10,11,13-t et r a -O-b en zyl-6,7-d i-
d eoxy-1,2:3,4-d i-O-isop r op ylid en e-r-D-glycer o-D-ga la cto-
D-ga la cto-tr id ec-6-en o-1,5-p yr a n ose (12). The phospho-
nium salt 8 (330 mg; 0.52 mmol) was reacted with the aldehyde
3 (287 mg; 0.52 mmol) as described for the preparation of 10.
Flash chromatography (5:1 cyclohexane-ethyl acetate) of the
residue gave first a 1:2 mixture of (E)-32 and (Z)-32 (70 mg,
20%). Flash chromatography (30:1 toluene-acetone) afforded
almost pure samples of these isomers. (Z)-32: 1H NMR (C6D6)
δ 1.10, 1.15, 1.50, 1.55 (4 × s, 12H, 2 × C(CH3)2), 3.65 (dd,
1H, H-13, J 13,12 ) 7.5 Hz, J 13,13′ ) 10.0 Hz), 3.77 (dd, 1H, H-11,
J 13′,12 ) 5.0 Hz, J 13′,13 ) 8.0 Hz), 3.58 (dd, 1H, H-12, J 12,13
)
8.0 Hz), 3.74 (t, 1H, H-13), 3.88 (t, 1H, H-9, J 9,8 ) 10.0 Hz),
3.92 (1H, H-11), 4.14-4.26 (m, 4H, H-8, H-2, OCH2Ph), 4.29
(dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5 ) 2.0 Hz), 4.32 and 4.38 (2d,
2H, J ) 12.0 Hz, OCH2Ph), 4.96 (dd, 1H, H-5, J 5,6 ) 8.0 Hz),
5.55 (d, 1H, H-1, J 2,1 ) 5.0 Hz), 5.64 (ddd, 1H, H-7, J 7,5 ) 1.0
J 11,12 ) 9.0 Hz, J 11,10 ) 6.5 Hz), 3.92 (dd, 1H, H-13′, J 13′,12
)
Hz, J 7,6 ) 11.0 Hz, J 7,8 ) 8.0 Hz), 6.18 (ddd, 1H, H-6, J 6,8
)
2.5 Hz), 4.15 (ddd, 1H, H-12), 4.21 (m, 2H, H-2, H-10), 4.25
and 4.50 (2 × d, 2H, J ) 12.0 Hz, OCH2Ph), 4.34 and 4.41 (2
× d, 2H, J ) 12.0 Hz, OCH2Ph), 4.40 (m, 1H, H-3); 4.41 and
4.77 (2 × d, 2H, J ) 12.0 Hz, OCH2Ph), 4.90 (m, 2H, H-4, H-9),
5.55 (d, 1H, H-5, J 5,6 ) 7.0 Hz), 5.64 (d, 1H, H-7, J 6,7 ) 12.0
Hz), 5.65 (d, 1H, H-1, J 1,2 ) 5.0 Hz), 5.97 (dd, 1H, H-6); 7.00-
7.35 (m, 15H, Harom); 13C NMR (C6D6) δ 24.6, 25.1, 26.5, 26.7,
67.0, 70.2, 70.8, 71.6, 73.3, 73.5, 74.7, 75.1, 77.7, 78.0, 97.1,
103.0, 108.2, 108.8, 123.1, 126.9-128.5, 138.9, 139.1, 153.1.
(E)-32: 1H NMR δ 1.34, 1.35, 1.45, 1.52 (4 × s, 12H, 2 ×
C(CH3)2), 3.82 (dd, 1H, H-13′, J 13,12 ) 3.0 Hz, J 13,13′ ) 11.0 Hz),
3.86 (dd, 1H, H-13, J 13,12 ) 5.5 Hz), 3.92 (dd, 1H, H-11, J 11,10
) 6.5 Hz, J 11,12 ) 9.0 Hz), 4.40 (ddd, 1H, H-12), 4.25 (dd, 1H,
2.0 Hz), 7.05-7.40 (m, 15H, Harom); 13C NMR (C6D6) δ 23.5,
24.0, 25.4, 25.5, 62.7, 63.7, 67.8, 70.5, 70.8, 71.9, 72.6, 72.8,
74.2, 75.3, 76.3, 82.2, 96.2, 107.3, 108.3, 126.2-127.7 129.5,
129.9, 137.3, 137.7, 138.2. Anal. Calcd for C40H47N3O10: C,
67.30, H, 6.64, N, 5.89. Found: C, 67.46, H, 6.84, N, 5.97.
(Z)-8,12-An h ydr o-9,10,11,13-tetr a-O-ben zyl-6,7-dideoxy-
1,2:3,4-d i-O-isop r op ylid en e-r-D-glycer o-D-gu lo-D-ga la cto-
tr id ec-6-en o-1,5-p yr a n ose (14). The phosphonium salt 8
(209 mg; 0.33 mmol) was reacted with aldehyde 5 (183 mg;
0.33 mmol) as described for the preparation of 10 to afford,
after flash chromatography (4:1 cyclohexane-ethyl acetate),
198 mg (77%) of the olefin 14 exclusively as Z-isomer, as a
H-4, J 4,3 ) 8.0 Hz, J 4,5 ) 2.0 Hz), 4.32 (dd, 1H, H-10, J 10,9
)
1
syrup: [R]D ) +5 (c 0.5); H NMR (C6D6) δ 1.06, 1.10, 1.50,
3.0 Hz), 4.33 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.0 Hz), 4.40
(d, 1H, H-5, J 5,6 ) 5.0 Hz), 4.56 and 4.63 (2 × d, 2H, J ) 12.0
Hz, OCH2Ph), 4.60 and 4.64 (2 × d, 2H, J ) 12.0 Hz, OCH2-
Ph), 4.65 (dd, 1H, H-3), 4.68 and 4.85 (2 × d, 2H, J ) 12.0 Hz,
OCH2Ph), 4.95 (d, 1H, H-9), 5.60 (d, 1H, H-1), 6.10 (d, 1H, H-7,
J 7,6 ) 15.0 Hz), 6.20 (dd, 1H, H-6), 7.20-7.40 (m, 15H, Harom);
13C NMR (CDCl3) δ 24.3, 24.9, 26.0, 26.1, 67.9, 68.5, 70.2, 70.6,
73.1, 73.4, 73.7, 74.4, 77.2, 96.5, 101.1, 108.4, 109.2, 126.6,
127.2-128.4, 151.3.
1.64 (4 × s, 12H, 2 × C(CH3)2), 3.33 (t, H, H-9, J 9,8 ≈ J 9,10
≈
10.0 Hz), 3.51 (ddd, 1H, H-12, J 12,11 ) 9.0 Hz, J 12,13 ) 1.0 Hz,
J 12,13′ ) 3.5 Hz), 3.56 (dd, 1H, H-13, J 13,13′ ) 11.0 Hz), 3.70
(dd, 1H, H-13′), 3.79 (t, 1H, H-10, J 10,11 ) 9.0 Hz), 3.92 (t, 1H,
H-11), 3.91 (dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5 ) 2.0 Hz, J 4,3 ) 8.0
Hz), 4.17 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.5 Hz), 4.34 and
4.47 (2 × d, 2H, J ) 12.0 Hz, OCH2Ph), 4.39 (dd, 1H, H-3, J 3,4
) 8.0 Hz), 4.40 (t, 1H, H-8, J 8,7 ) 9.0 Hz), 4.51 and 4.74 (2 ×
d, 2H, J ) 11.0 Hz, OCH2Ph), 4.72 and 4.92 (2 × d, 2H, J )
11.0 Hz, OCH2Ph), 4.91 (s, 2H, OCH2Ph), 4.98 (d, 1H, H-5,
J 5,6 ) 8.0 Hz), 5.54 (d, 1H, H-1), 5.76 (dd, 1H, H-7, J 7,6 ) 12.0
Hz), 6.21 (dd, 1H, H-6), 7.00-7.32 (m, 20H, Harom); 13C NMR
(C6D6) δ 24.4, 24.9, 26.3, 26.5, 64.5, 69.3, 70.7, 71.5, 73.5, 73.6,
75.1, 75.6, 76.7, 78.6, 79.7, 82.9, 87.4, 97.2, 108.3, 109.0, 127.2-
128.3, 130.1, 131.8, 139.1, 139.2, 139.3, 139.4. Anal. Calcd
for C47H54O10: C, 72.47, H, 6.99. Found: C, 72.17, H, 6.93.
Eluted second was a 1:2.5 mixture of (E)-12 and (Z)-12 (170
mg, 42%). Flash chromatography (30:1 toluene-acetone) gave
pure samples of these isomers. Eluted first was (Z)-12 as an
oil: [R]D ) -27 (c 0.4); 1H NMR δ 1.25, 1.30, 1.45, 1.46 (4 × s,
12H, 2 × C(CH3)2), 3.47 (ddd, 1H, H-12, J 12,11 ) 9.5 Hz, J 12,13
) 6.0 Hz, J 12,13′ ) 10.0 Hz), 3.59 (dd, 1H, H-10, J 10,9 ) 2.6 Hz,
J 10,11 ) 9.5 Hz), 3.68 (dd, 1H, H-13, J 13,13′ ) 11.0 Hz), 3.76 (dd,
1H, H-13′), 3.80 (d, 1H, H-9), 3.82 (t, 1H, H-11), 4.19 (d, 1H,
H-8, J 8,7 ) 5.8 Hz), 4.23 (dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5 ) 2.0
Hz), 4.28 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.5 Hz), 4.50 (dd,
1H, H-3), 4.53 and 4.89 (2 × d, 2H, J ) 10.5 Hz, OCH2Ph),
4.62 and 4.68 (2 × d, 2H, J ) 12.0 Hz, OCH2Ph), 4.75 (dd, 1H,
H-5, J 5,6 ) 6.8 Hz), 4.76 and 4.84 (2 × d, 2H, J ) 12.0 Hz,
OCH2Ph), 5.53 (d, 1H, H-1), 5.61 (dd, 1H, H-6, J 6,7 ) 12.0 Hz),
5.72 (dd, 1H, H-7), 7.10-7.42 (m, 20H, Harom); 13C NMR (C6D6)
δ 24.5, 25.2, 26.4, 26.5, 66.7, 70.9, 71.1, 72.0, 73.6, 74.8, 75.2,
(Z/E)-Met h yl 8,12-An h yd r o-2,3,4,9,10,11,13-h ep t a -O-
ben zyl-6,7-d id eoxy-r-D-glycer o-L-m a n n o-D-glu co-tr id ec-
6-en op yr a n osid e (15). A mixture of phosphonium salt 9 (226
mg; 0.27 mmol), activated 4-Å powdered molecular sieves (240
mg), anhydrous THF (1 mL), and HMPA (0.5 mL) was cooled
to -30 °C. To this suspension was added n-BuLi (169 µL, 0.27
mmol of 1.6 M solution in hexane), followed by the aldehyde 1
(210 mg; 0.38 mmol) in anhydrous THF (1.0 mL). The

R and â-D-(1f6)-C-Disaccharides
J . Org. Chem., Vol. 62, No. 23, 1997 8121
suspension was allowed to slowly warm to room temperature
over 2.5 h, maintained at this temperature for additional 30
min, and then filtered through Celite. The filtrate was diluted
with diethyl ether (15 mL), and the organic layer was washed
with water (5 mL), 5% aqueous sodium thiosulfate (5 mL), and
water (5 mL), dried (Na2SO4), and concentrated. Flash chro-
matography (6:1 cyclohexane-ethyl acetate) of the residue
afforded 149 mg (56%) of the olefin 15 as a 3:7 mixture of E-
and Z-isomer. (Z)-15: 1H NMR (selected data) δ 5.54 and 5.56
(2 × dd, 2H, H-6, H-7, J 6,7 ) 12.0 Hz). (E)-15: 1H NMR
(selected data) δ 5.95 (2 × dd, 2H, H-6, H-7, J 6,7 ) 16.0 Hz).
1.42, 1.43, 1.51 (6 × s, 24H, 4 × C(CH3)2), 1.74 (m, 2H, H-7,
H-7′), 1.90 (m, 2H, H-6, H-6′), 3.41 (dd, 1H, H-11, J 11,10 ) 3.5
Hz, J 11,12 ) 8.0 Hz), 3.44 (m, 1H, H-8), 3.71 (m, 1H, H-5), 4.06
(m, 2H, H-13, H-13′), 4.14 (dd, 1H, H-4, J 4,3 ) 7.5 Hz, J 4,5
)
1.5 Hz), 4.28 (dd, 1H, H-2, J 2,3 ) 2.5 Hz, J 2,1 ) 5.0 Hz), 4.38
(dt, 1H, H-12, J 12,13 ≈ J
≈ 6.5 Hz), 4.58 (dd, 1H, H-3),
12,13′
4.59 (dd, 1H, H-9, J 9,8 ) 4.0 Hz, J 9,10 ) 6.5 Hz), 4.72 (dd, 1H,
H-10); 5.52 (d, 1H, H-1); 13C NMR (CDCl3) δ 24.3, 24.6, 24.7,
25.0, 25.2, 25.7, 26.0, 26.1, 27.0, 27.3, 67.0, 67.7, 70.5, 70.9,
72.7, 73.1, 80.7, 81.3, 81.6, 82.4, 96.5, 108.3, 109.0, 109.1, 112.1.
Anal. Calcd for C25H40O10: C, 59.98, H, 8.05. Found: C, 59.46,
H, 7.59. This product (22 mg; 0.044 mmol) dissolved in 1:1
methanol-water (2 mL) was treated with Amberlite IR-120
(H+) ion-exchange resin as described for compound 18 to give
after 4 h 12 mg (87%) of the free C-disaccharide 19 as a white
foam: [R]D ) +18 (c 0.5, H2O); 1H NMR (D2O) (selected data)
(Z/E)-Meth yl 8,12-An h yd r o-9-a zid o-2,3,4,10,11,13-h exa -
O-b e n zyl-6,7,9-t r id e oxy-r-D-glycer o-L-m a n n o-D-glu co-
tr id ec-6-en op yr a n osid e (16). The phosphonium salt 9 (151
mg; 0.18 mmol) was reacted with the aldehyde 4 (117 mg; 0.24
mmol) as described for the preparation of 15 to afford, after
flash chromatography (6:1 cyclohexane-ethyl acetate), 91 mg
(55%) of the olefin 16 as a 1:1 mixture of E- and Z-isomers.
(Z)-16: 1H NMR (C6D6) (selected data) δ 5.74 and 5.83 (2 ×
dd, 2H, H-6, H-7, J 6,7 ) 11.0 Hz). (E)-16: 1H NMR (C6D6)
(selected data) δ 6.25 (2 × dd, 2H, H-6, H-7, J 6,7 ) 16.0 Hz).
δ 4.52 (d, 1H, H-1â, J 1,2 ) 7.6 Hz), 5.20 (d, 1H, H-1R, J
)
1,2
3.7 Hz), relative intensity â/R 2:1; 13C NMR (D2O, some signals
are overlapping) δ 25.2, 26.6, 62.9, 69.2, 69.9, 71.5, 71.7, 72.9,
74.6, 78.3, 80.4, 92.1, 96.2. Anal. Calcd for C13H24O10: C,
45.88, H, 7.11. Found: C, 45.97, H, 7.31.
8,12-An h ydr o-6,7-dideoxy-D-glycer o-D-ga la cto-D-ga la cto-
tr id ecose (20). The olefin 12 (mixture of E- and Z-isomers)
(50 mg; 0.06 mmol) was treated for 5 h as described for the
preparation of 18 to afford, after flash chromatography (9:1
ethyl acetate-methanol), 20 mg (76%) of oily 8,12-anhydro-
6,7-dideoxy-1,2:3,4-di-O-isopropylidene-R-D-glycero-L-galacto-
D-galacto-trideco-1,5-pyranose: [R]D ) -53 (c 0.8); 1H NMR
(CD3OD) δ 1.50, 1.55, 1.59 (3 × s, 12H, 2 × C(CH3)2), 1.66 (m,
4H, H-6, H-6′, H-7, H-7′), 3.18 (ddd, 1H, H-12, J 12,11 ) 10.0
Hz, J 12,13′ ) 5.5 Hz, J 12,13 ) 2.5 Hz), 3.42 (m, 1H, H-8), 3.44
(dd, 1H, H-10, J 10,9 ) 3.5 Hz, J 10,11 ) 9.5 Hz), 3.58 (t, 1H, H-11),
3.70 (dd, 1H, H-13′, J 13′,13 ) 12.0 Hz), 3.70-3.74 (m, 2H, H-9,
H-5), 3.85 (dd, 1H, H-13), 4.16 (dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5
) 2.0 Hz), 4.30 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.5 Hz), 4.58
(dd, 1H, H-3), 5.48 (d, 1H, H-1); 13C NMR (CD3OD) δ 24.5,
25.1, 26.3, 27.6, 28.5, 63.1, 68.9, 69.1, 71.9, 72.2, 72.5, 74.1,
76.7, 79.6, 82.0, 97.9, 109.6, 110.1. Anal. Calcd for
C19H32O10: C, 54.27, H, 7.67. Found: C, 54.39, H, 7.56. This
product (15 mg; 0.036 mmol) dissolved in water (1 mL) was
treated with Amberlite 120-IR (H+) ion-exchange resin as
described for compound 18 for 1.5 h to give 10 mg (82%) of
(Z/E)-Met h yl 8,12-An h yd r o-2,3,4,9,10,11,13-h ep t a -O-
b en zyl-6,7-d id eoxy-r-D-glycer o-D-gu lo-D-glu co-t r id ec-6-
en op yr a n osid e (17). The phosphonium salt 9 (142 mg; 0.17
mmol) was reacted with the aldehyde 5 (127 mg; 0.23 mmol)
as described for the preparation of 15 to afford, after flash
chromatography (6:1 cylohexane-ethyl acetate), 92 mg (55%)
of the olefin 17 as 1:4 mixture of E- and Z-isomer. (Z)-17: 1H
NMR (selected data) δ 5.70 (2 × dd, 2H, H-6, H-7, J 6,7 ) 12.0
Hz). (E)-17: 1H NMR (selected data) δ 6.00 (2 × dd, 2H, H-6,
H-7, J 6,7 ) 16.0 Hz).
8,12-An h ydr o-6,7-dideoxy-D-glycer o-L-ma n n o-D-ga la cto-
tr id ecose (18). To a solution of the alkene 10 (111 mg; 0.14
mmol) in 1:1 ethyl acetate-ethanol (5 mL) was added Pd(OH)2
(20%, 20 mg). The reaction mixture was stirred under an
atmosphere of hydrogen for 4 h at 3 atm. The catalyst was
removed by filtration and the filtrate concentrated. The
residue was purified by flash chromatography (9:1 ethyl
acetate-methanol) to afford 57 mg (95%) of oily 8,12-anhydro-
6,7-dideoxy-1,2:3,4-di-O-isopropylidene-R-D-glycero-L-manno-
D-galacto-trideco-1,5-pyranose, which showed the following
1
data: [R]D ) -38 (c 1.2); H NMR (CD3OD) δ 1.34, 1.43, 1.56
1
the C-disaccharide 20 as an oil: [R]D ) +27 (c 0.5, H2O); H
(3 × s, 12H, 2 × C(CH3)2), 1.57 (m, 1H, H-7′), 1.70 (m, 1H,
H-6′), 1.80 (m, 1H, H-6), 2.14 (m, 1H, H-7), 3.10 (dt, 1H, H-8,
J 8,7′ ) 2.0 Hz, J 8,7 ≈ J 8,9 ≈ 9.0 Hz), 3.45 (t, 1H, H-9, J 9,10 ) 9.0
Hz), 3.46 (dd, 1H, H-10, J 10,11 ) 3.5 Hz), 3.47 (m, 1H, H-12),
3.70 (dd, 1H, H-13, J 13,13′ ) 12.0 Hz, J 13,12 ) 5.5 Hz), 3.72 (dd,
1H, H-13′, J 13′,12 ) 7.0 Hz), 3.80 (ddd, H, H-5, J 5,4 ) 2.0 Hz,
J 5,6 ) 8.0 Hz, J 5,6′ ) 5.5 Hz), 3.92 (d, 1H, H-11), 4.20 (dd, 1H,
H-4, J 4,3 ) 8.0 Hz), 4.36 (dd, 1H, H-2, J 2,3 ) 2.5 Hz, J 2,1 ) 5.0
Hz), 4.62 (dd, 1H, H-3), 5.48 (d, 1H, H-1); 13C NMR (CD3OD)
δ 22.0, 22.7, 23.8, 23.9, 25.0, 27.0, 60.2, 66.8, 68.3, 69.4, 69.7,
70.3, 71.5, 73.9, 77.6, 79.0, 95.4, 107.1, 107.5. Anal. Calcd
for C19H32O10: C, 54.27, H, 7.67. Found: C, 54.41, H, 7.81.
This product (57 mg; 0.136 mmol) was dissolved in water (3
mL), and then Amberlite IR-120 (H+) ion-exchange resin,
previously washed with hot water (70 °C), was added, and the
mixture was heated at 70 °C for 2 h. After the misture was
cooled to room temperature, the resin was removed by filtra-
tion and the filtrate was concentrated to give 39 mg (85%) of
the free C-disaccharide 18 as an oil: [R]D ) +39 (c 0.9, CH3-
OH); 1H NMR (CD3OD) (selected data) δ 4.52 (d, 1H, H-1â,
J 1,2 ) 7.6 Hz), 5.20 (d, 1H, H-1R, J 1,2 ) 3.7 Hz), relative
intensity â/R 2:1; 13C NMR (CD3OD, some signals are overlap-
ping) δ 28.0, 29.2, 62.8, 70.5, 70.9, 71.1, 71.3, 72.0, 72.6, 72.7,
73.8, 75.2, 76.4, 80.0, 81.6, 81.6, 81.7, 94.1, 98.6. Anal. Calcd
for C13H24O10: C, 45.88, H, 7.11. Found: C, 45.73, H, 7.09.
NMR (D2O) (selected data) δ 4.50 (d, 1H, H-1â, J 1,2 ) 7.5 Hz),
5.20 (d, 1H, H-1R, J 1,2 ) 3.7 Hz), relative intensity â/R 2:1;
13C NMR (D2O, some signals are overlapping) δ 26.2, 26.5, 61.3,
67.3, 68.3, 69.3, 70.2, 70.5, 71.8, 73.0 74.2, 74.7, 78.0, 80.0,
92.2, 96.3. Anal. Calcd for C13H24O10
Found: C, 45.69, H, 7.37.
: C, 45.88, H, 7.11.
9-Acet a m id o-8,12-a n h yd r o-6,7,9-t r id eoxy-D-glycer o-L-
m a n n o-D-ga la cto-tr id ecose (21). The alkene 13 (52 mg,
0.074 mmol) was dissolved in ethanol (2 mL) together with
nickel(II) chloride (6 mg) and H3BO3 (3 mg). To this solution
was added dropwise a suspension of sodium borohydride (1.5
mg) in ethanol (0.5 mL). The mixture was concentrated,
dissolved in anhydrous pyridine (2 mL), and treated with acetic
anhydride (1 mL). The mixture was stirred at room temper-
ature for 2 h and then was concentrated. Flash chromatog-
raphy (2:1 ethyl acetate-cyclohexane) of the residue gave the
alkane, which was hydrogenated for 3 h as described for the
preparation of 18. Flash chromatography (9:1 ethyl acetate-
methanol) gave 17 mg (50%) of 9-acetamido-8,12-anhydro-
6,7,9-trideoxy-1,2:3,4-di-O-isopropylidene-R-D-glycero-L-manno-
D-galacto-trideco-1,5-pyranose as an oil: [R]D ) -61 (c 0.4),
1H NMR (CD3OD) δ 1.32, 1.33, 1.40, 1.43 (4 × s, 12H, 2 ×
C(CH3)2), 1.50 (m, 1H, H-7′), 1.61 (m, 1H, H-6′), 1.82 m, 2H,
H-6, H-7), 2.98 (s, 3H, CH3CONH), 3.20 (dt, 1H, H-8, J 8,7′ 2.0
Hz, J 8,9 ≈ J 8,7 ≈ 9.0 Hz), 3.40 (dt, 1H, H-12, J 12,11 ) 1.0 Hz,
J 12,13 ≈ J 12,13′ ≈ 6.0 Hz), 3.48 (dd, 1H, H-10, J 10,9 ) 10.0 Hz,
8,11-An h y d r o -6,7-d i d e o x y -D -g l yc er o-D -g a l a c t o-D -
ga la cto-tr id ecose (19). The alkene 11 (mixture of E- and
Z-isomers) (50 mg; 0.10 mmol) was reduced for 1.5 h as
described for the preparation of 18 to afford, after flash
chromatography (4:1 cyclohexane-ethyl acetate), 42 mg (83%)
of 8,11-anhydro-6,7-dideoxy-1,2:3,4:9,10;12,13-tetra-O-isopro-
pylidene-R-D-glycero-D-galacto-D-galacto-trideco-1,5-pyranose
as a syrup: [R]D ) -43 (c 0.6); 1H NMR δ 1.31, 1.32, 1.34,
J 10,11 ) 3.5 Hz), 3.66 (dd, 1H, H-13, J 13,12 ) 6.0 Hz, J 13,13′
)
12.0 Hz), 3.72 (m, 1H, H-5), 3.73 (dd, 1H, H-13′), 3.82 (d, 1H,
H-11), 3.87 (t, 1H, H-9), 4.14 (dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5
) 1.5 Hz), 4.29 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.0 Hz), 4.58
(dd, 1H, H-3), 5.46 (d, 1H, H-1); 13C NMR (CD3OD) δ 19.3,
24.5, 25.1, 26.2, 26.3, 27.5, 29.7, 53.6, 62.8, 69.4, 70.1, 71.9,

8122 J . Org. Chem., Vol. 62, No. 23, 1997
Dondoni et al.
3.84 (ddd, 1H, H-12, J 12,11 ) 1.0 Hz, J 12,13 ) 6.5 Hz, J 12,13′
72.2, 74.6, 80.2, 80.3, 97.9, 109.6, 110.0. Anal. Calcd for
)
C
21H35NO10: C, 54.65, H, 7.64, N, 3.03. Found: C, 54.85, H,
7.0 Hz), 4.04 (dd, 1H, H-13, J 13,13′ ) 11.0 Hz), 4.12 (dd, 1H,
H-13′), 4.83 (dd, 1H, H-4, J 4,3 ) 9.5 Hz), 4.84 (dd, 1H, H-2,
J 2,1 ) 4.0 Hz, J 2,3 ) 10.0 Hz), 4.88 (d, 1H, H-1), 5.00 (dd, 1H,
H-10, J 10,9 ) 10.0 Hz, J 10,11 ) 3.0 Hz), 5.07 (dd, 1H, H-9), 5.41
(dd, 1H, H-11), 5.42 (dd, 1H, H-3); 13C NMR δ 20.7, 26.9, 27.2,
55.2, 61.6, 67.7, 68.4, 69.3, 70.1, 71.1, 72.1, 72.2, 74.2, 78.3,
96.4, 169.9-170.5. Anal. Calcd for C28H40O17: C, 51.80, H,
6.17. Found: C, 51.53, H, 6.21.
Meth yl 9-Aceta m id o-8,12-a n h yd r o-6,7,9-tr id eoxy-r-D-
glycer o-L-ma n n o-D-glu co-tr idecop yr a n osid e (25). The ole-
fin 16 (mixture of E- and Z-isomers) was dissolved in ethanol
(2 mL) together with nickel(II) chloride (6 mg) and H3BO3 (3
mg). To this solution was added dropwise a suspension of
sodium borohydride (1.5 mg) in ethanol (0.5 mL). The mixture
was concentrated, dissolved in anhydrous pyridine (2 mL), and
treated with acetic anhydride (1 mL). The mixture was stirred
at room temperature for 2 h and then was concentrated. Flash
chromatography (2:1 ethyl acetate-cyclohexane) of the residue
gave the alkane, which was hydrogenated for 3 h as described
for the preparation of 23 to afford 10 mg (60%) of methyl
C-disaccharide 25 as a white foam: [R]D ) +63 (c 0.4, CH3-
OH); 1H NMR (CD3OD) δ 1.40 (m, 2H, H-6′, H-7′), 1.88 (m,
1H, H-6), 1.96 (s, 3H, CH3CONH), 2.18 (m, 1H, H-7), 3.01 (dd,
7.51, N, 2.65. This product (17 mg: 0.037 mmol) dissolved in
water (1 mL) was treated with Amberlite IR-120 (H+) ion-
exchange resin for 1 h as described for the preparation of 18
to afford 11 mg (80%) of the C-disaccharide 21 as an oil: [R]D
1
) +14 (c 0.7, CH3OH); H NMR (D2O) (selected data) δ 4.50
(d, 1H, H-1â, J 1,2 ) 7.6 Hz), 5.17 (d, 1H, H-1R, J 1,2 ) 3.7 Hz),
relative intensity â/R 2:1; 13C NMR (D2O, some signals are
overlapping) δ 21.2, 25.3, 26.7, 51.1, 60.5, 67.3, 68.4, 69.2, 69.7,
70.9, 71.3, 72.0, 73.9, 77.5, 77.8, 91.2, 95.4. Anal. Calcd for
C
15H27NO10: C, 47.24, H, 7.14. Found: 47.52, H, 7.16.
8,12-An h yd r o-6,7-d id eoxy-D-glycer o-D-gu lo-D-ga la cto-
tr id ecose (22). The olefin 14 (59 mg; 0.076 mmol) was
reduced for 5 h as described for the preparation of 18 to afford,
after flash chromatography (9:1 ethyl acetate-methanol), 24
mg (75%) of 8,12-anhydro-6,7-dideoxy-1,2:3,4-di-O-isopropyl-
idene-R-D-glycero-D-gulo-D-galacto-trideco-1,5-pyranose as a
syrup: [R]D ) -53 (c 1.1); 1H NMR (CD3OD) δ 1.30, 1.31, 1.40,
1.43 (4 × s, 12H, 2 × C(CH3)2), 1.43 (m, 1H, H-7), 1.65 (m,
1H, H-6), 1.85 (m, 1H, H-6′), 2.08 (m, 1H, H-7′), 3.05 (t, 1H,
H-9, J 9,8 ≈ J 9,10 ≈ 9.0 Hz), 3.12 (m, 1H, H-8), 3.18 (dt, 1H,
H-12, J 12,11 ) 9.0 Hz, J 12,13 ) 2.0 Hz, J 12,13′ ) 5.0 Hz), 3.24 (t,
1H, H-11, J 11,10 ) 9.0 Hz), 3.31 (t, 1H, H-10), 3.62 (dd, 1H,
H-13′, J 13′,13 ) 12.0 Hz), 3.75 (ddd, 1H, H-5, J 5,4 ) 2.0 Hz, J 5,6
) 5.0 Hz, J 5,6′ ) 9.0 Hz), 4.18 (dd, 1H, H-4, J 4,3 ) 7.5 Hz), 4.31
(dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.5 Hz), 4.59 (dd, 1H, H-3),
5.45 (d, 1H, H-1); 13C NMR (CD3OD) δ 24.5, 25.2, 26.3, 26.4,
27.3, 29.5, 63.2, 69.3, 71.9, 72.0, 72.2, 74.0, 75.5, 79.8, 80.8,
81.7, 97.9, 109.6, 110.0. Anal. Calcd for C19H32O10: C, 54.27,
H, 7.67. Found: C, 54.52, H, 7.61. This product (17 mg; 0.04
mmol) dissolved in water (1 mL) was treated with Amberlite
IR-120 (H+) ion-exchange resin as described for compound 18
for 1.5 h to give 12 mg (86%) of the C-disaccharide 22 as an
oil: [R]D ) +18 (c 0.7, CH3OH) (lit.11b [R]D ) +12 (c 1, H2O));
1H NMR (D2O) (selected data) δ 4.52 (d, 1H, H-1â, J 1,2 ) 7.6
Hz), 5.17 (d, 1H, H-1R, J 1,2 ) 3.5 Hz), relative intensity â/R
2:1; 13C NMR (D2O, some signals are overlapping) δ 24.9, 26.3,
60.1, 67.4, 68.4, 69.1, 69.1, 69.7, 70.9, 72.1, 72.5, 73.8, 76.4,
78.2, 78.5, 78.6, 91.2, 95.4. Anal. Calcd for C13H24O10: C,
45.88, H, 7.11. Found: C, 45.52, H, 7.56.
1H, H-4, J 4,3 ) 9.5 Hz, J
) 9.0 Hz), 3.14 (dd, 1H, H-8, J 8,7
4,5
) 9.0 Hz, J 8,7′ ) 1.5 Hz, J 8,9 ) 9.5 Hz), 3.34 (dd, 1H, H-2, J 2,1
) 1.0 Hz, J 2,3 ) 9.5 Hz), 3.35 (s, 3H, OCH3), 3.40 (m, 2H, H-5,
H-12), 3.48 (dd, 1H, H-10, J 10,9 ) 10.5 Hz, J 10,11 ) 3.0 Hz),
3.53 (dd, 1H, H-3), 3.66 (dd, 1H, H-13′, J 13′,12 ) 5.5 Hz, J 13,13′
) 11.5 Hz), 3.73 (dd, 1H, H-13, J 13,12 ) 6.5 Hz), 3.84 (dd, 1H,
H-11, J 11,12 ) 0.5 Hz), 3.87 (dd, 1H, H-9), 4.58 (d, 1H, H-1);
13C NMR (CD3OD) δ 20.2, 26.6, 27.0, 51.3, 52.7, 60.4, 67.5,
70.1, 71.1, 71.8, 72.4, 73.2, 77.6, 78.1, 78.4, 171.4. Anal. Calcd
for C16H29NO10: C, 48.60, H, 7.39, N, 3.54. Found: C, 48.83,
H, 7.37, N, 3.08.
Meth yl 9-Aceta m id o-2,3,4,10,11,13-h exa -O-a cetyl-8,12-
an h ydr o-6,7,9-tr ideoxy-r-D-glycer o-L-ma n n o-D-glu co-tr ide-
cop yr a n osid e (26). Compound 25 (8 mg, 0.02 mmol) was
acetylated as described for 24. Flash chromatography (7:2
ethyl acetate-cyclohexane) of the residue gave 10 mg (77%)
of acetylated product 26 as a white foam: [R]D ) +63 (c 0.4);
1H NMR δ 1.25-1.40 (m, 1H, H-5), 1.60-1.45 (m, 1H, H-7),
1.80-2.00 (m, 2H, H-7′, H-6′), 1.94-2.16 (7 × s, 21H, 7 ×
OCOCH3), 3.18 (ddd, 1H, H-8, J 8,7 ) 10.0 Hz, J 8,7′ ) 1.0 Hz,
Meth yl 8,12-An h yd r o-6,7-d id eoxy-r-D-glycer o-L-ma n n o-
D-glu co-tr id ecop yr a n osid e (23). To a solution of the alkene
15 (mixture of E- and Z-isomers) (39 mg; 0.04 mmol) in 1:1
ethyl acetate-ethanol (2 mL) was added Pd(OH)2 (20%, 10
mg). The reaction mixture was stirred under an atmosphere
of hydrogen for 4 h at 3 atm. The catalyst was removed by
filtration and the filtrate concentrated to afford 12 mg (82%)
of methyl C-disaccharide 23 as a white foam: [R]D ) +83 (c
0.4, CH3OH); 1H NMR (CD3OD) δ 1.40 (m, 2H, H-6, H-7), 2.20
(m, 2H, H-6′, H-7′), 3.04 (dd, 1H, H-4, J 4,3 ≈ J 4,5 ≈ 9.0 Hz),
3.08 (ddd, 1H, H-8, J 8,7 ) 9.0 Hz, J 8,7′ ) 1.0 Hz, J 8,9 ) 10.0
Hz), 3.37 (dd, 1H, H-2, J 2,1 ) 4.0 Hz, J 2,3 ) 9.5 Hz), 3.38 (s,
3H, OCH3), 3.39 (m, 2H, H-9, H-10), 3.43 (ddd, 1H, H-12, J 12,11
) 1.0 Hz, J 12,13′ ) 7.0 Hz, J 12,13 ) 5.5 Hz), 3.44 (ddd, 1H, H-5,
J 5,6 ) 9.5 Hz, J 5,6′ ) 1.5 Hz), 3.55 (dd, 1H, H-3), 3.64 (dd, 1H,
H-13′, J 13′,13 ) 11.5 Hz), 3.71 (dd, 1H, H-13), 3.85 (dd, 1H, J 11,10
) 2.5 Hz), 4.60 (d, 1H, H-1); 13C NMR (CD3OD) δ 29.0, 29.2,
55.5, 62.9, 70.9, 72.8, 73.8, 75.1, 75.9, 76.5, 80.2, 81.9, 101.10.
Anal. Calcd for C14H26O10: C, 47.45, H, 7.40. Found: C, 47.40,
H, 7.64.
J 8,9 ) 11.0 Hz), 3.36 (s, 3H, OCH3), 3.73 (ddd, 1H, H-5, J 5,4
)
9.5 Hz, J 5,6 ) 9.0 Hz, J 5,6′ ) 2.0 Hz), 3.78 (ddd, 1H, J 12,11 ) 1.0
Hz, J 12,13 ) 6.0 Hz, J 12,13′ ) 7.0 Hz), 4.04 (dd, 1H, H-13, J 13,13′
) 11.0 Hz), 4.11 (dd, 1H, H-13′), 4.18 (ddd, 1H, J 9,NHAc ) 10.0
Hz, J 9,10 ) 11.0 Hz), 4.78-4.88 (m, 3H, H-2, H-4, H-1), 5.26
(d, 1H, CH3CONH), 5.34 (dd, 1H, H-11), 5.42 (dd, 1H, H-3,
J 3,2 ) 10.5 Hz, J 3,4 ) 9.0 Hz); 13C NMR δ 19.8, 22.4, 26.4,
42.2, 54.3, 60.9, 66.2, 67.4, 69.2, 70.2, 70.9, 71.2, 73.3, 79.3,
95.4, 169.2, 169.3, 169.4, 169.5, 170.2. Anal. Calcd for
C28H41NO16: C, 51.88, H, 6.33, N, 2.16. Found: C, 51.58, H,
6.26, N, 1.83.
Meth yl 8,12-An h yd r o-6,7-d id eoxy-r-D-glycer o-D-gu lo-D-
glu co-tr id ecop yr a n osid e (27). The olefin 17 (E/Z mixture)
(70 mg; 0.07 mmol) was hydrogenated as described for the
preparation of 23 to afford 21 mg (85%) of methyl C-disaccha-
ride 27 as a white foam: [R]D ) +61 (c 0.6, CH3OH) (lit.27 [R]D
1
) +88 (c 1, CH3OH)); H NMR (CD3OD) δ 1.38 (m, 2H, H-6,
H-7), 2.19 (m, 2H, H-6′, H-7′), 3.04 (dd, 1H, H-4, J 4,3 ) 9.0 Hz,
J 4,5 ) 9.5 Hz), 3.05 (dd, 1H, H-9, J 9,8 ) 9.5 Hz, J 9,10 ) 10 Hz),
3.12 (dd, 1H, H-8, J 8,7 ) 9.0 Hz, J 8,7′ ) 1.5 Hz), 3.18 (ddd, 1H,
H-12, J 12,11 ) 9.0 Hz, J 12,13′ ) 5.5 Hz, J 12,13 ) 2.0 Hz), 3.23 (dd,
1H, H-10, J 10,11 ) 9.5 Hz), 3.30 (dd, 1H, H-11), 3.37 (dd, 1H,
H-2, J 2,1 ) 4.0 Hz, J 2,3 ) 9.5 Hz), 3.38 (s, 3H, OCH3), 3.44 (ddd,
1H, H-5, J 5,4 ) 9.5 Hz, J 5,6 ) 9.0 Hz, J 5,6′ ) 1.0 Hz), 3.55 (dd,
1H, H-3), 3.62 (dd, 1H, H-13′, J 13,13′ ) 12.0 Hz), 3.83 (dd, 1H,
H-13), 4.61 (d, 1H, H-1); 13C NMR (CD3OD) δ 26.2, 26.8 52.9,
60.7, 69.5, 70.1, 71.1, 72.4, 72.9, 73.1, 77.2, 78.5, 78.9, 98.4.
Anal. Calcd for C14H26O10: C, 47.45, H, 7.40. Found: C, 47.65,
H, 7.59.
Meth yl 2,3,4,9,10,11,13-Hep ta -O-a cetyl-8,12-a n h yd r o-
6,7-d id eoxy-r-D-glycer o-L-m a n n o-D-glu co-tr id ecop yr a n o-
sid e (24). Compound 23 (20 mg; 0.056 mmol) was dissolved
in 2:1 pyridine-acetic anhydride (3 mL), and the solution was
allowed to stand overnight at room temperature. The mixture
was concentrated in vacuo, and the traces of acetic anhydride
were removed by evaporation with toluene (3 × 5 mL). The
residue was purified by flash chromatography (1:1 ethyl
acetate-cyclohexane) to afford 25 mg (70%) of the acetylated
1
compound 24 as a white foam: [R]D ) +69 (c 0.7); H NMR δ
1.36-1.54 (m, 2H, H-6, H-7), 1.76-1.84 (m, 2H, H-7′, H-6′),
1.97-2.14 (7 × s, 21H, 7 × OCOCH3), 3.38 (s, 3H, OCH3), 3.18
(ddd, 1H, H-8, J 8,7 ) 7.3 Hz, J 8,7′ ) 2.7 Hz, J 8,9 ) 9.0 Hz), 3.74
(ddd, 1H, H-5, J 5,4 ) 10.0 Hz, J 5,6 ) 8.5 Hz, J 5,6′ ) 1.5 Hz),
Meth yl 2,3,4,9,10,11,13-Hep ta -O-a cetyl-8,12-a n h yd r o-
6,7-d id eoxy-r-D-glycer o-D-gu lo-D-glu co-t r id ecop yr a n o-
sid e (28). Compound 27 (14 mg, 0.04 mmol) was acetylated

R and â-D-(1f6)-C-Disaccharides
J . Org. Chem., Vol. 62, No. 23, 1997 8123
as described for 24. Flash chromatography (4:5 ethyl acetate-
3.80 (m, 3H, H-5, H-8, H-11), 3.91 (t, 1H, H-10, J 10,11 ) 5.5
Hz), 4.16 (dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5 ) 2.0 Hz), 4.31 (dd,
1H, H-2, J 2,3 ) 2.5 Hz, J 2,1 ) 5.0 Hz), 4.59 (dd, 1H, H-3), 5.45
(d, 1H, H-1); 13C NMR (CD3OD) δ 26.4, 27.5, 27.8, 28.8, 31.0,
53.6, 63.6, 69.0, 71.9, 72.3, 72.8, 74.0, 76.3, 84.2, 85.6, 97.7,
109.6, 110.1. Anal. Calcd for C18H30O9: C, 55.37, H, 7.74.
Found: 54.81, H, 7.26. This product (21 mg; 0.051 mmol)
dissolved in water (1 mL) was treated with Amberlite IR-120
(H+) ion-exchange resin as described for compound 18 for 2 h
to give free C-disaccharide 34 as an oil: [R]D ) -16 (c 0.5,
cyclohexane) of the residue gave 17 mg (67%) of the acetylated
product 28 as a white foam: [R]D ) +63 (c 0.7) (lit.27 [R]D
)
+55 (c 1)); 1H NMR δ 1.46-1.38 (m, 2H, H-6, H-7), 1.84-1.74
(m, 2H, H-6′, H-7′), 1.99-2.10 (7 × s, 21H, 7 × OCOCH3), 3.35
(s, 3H, OCH3), 3.38 (ddd, 1H, H-8, J 8,7 ) 10.0 Hz, J 8,7′ ) 1.0
Hz, J 8,9 ) 9.0 Hz), 3.61 (ddd, 1H, H-12, J 12,11 ) 9.7 Hz, J 12,13
) 5.5 Hz, J 12,13′ ) 2.0 Hz), 3.73 (dd, 1H, H-5, J 5,4 ) 9.5 Hz, J 5,6
) 7.0 Hz, J 5,6′ ) 1.5 Hz), 4.07 (dd, 1H, H-13′, J 13′,13 ) 12.5 Hz),
4.23 (dd, 1H, H-13), 4.79-4.90 (m, 4H, H-1, H-2, H-9, H-4),
5.02 (dd, H-11, J 11,10 ) 9.5 Hz), 5.16 (dd, 1H, H-10, J 10,9 ) 9.5
Hz), 5.42 (t, 1H, H-3, J 3,2 ≈ J 3,4 ≈ 9.8 Hz); 13C NMR δ 20.6,
26.7, 26.9, 55.2, 62.2, 68.3, 68.6, 70.0, 71.1, 71.7, 72.1, 74.2,
75.6, 77.8, 96.4, 169.5, 169.2, 169.9, 170.0, 170.2, 170.3, 170.6.
Anal. Calcd for C28H40O17: C, 51.80, H, 6.17. Found: C, 51.71,
H, 6.12.
1
H2O); H NMR (D2O) (selected data) δ 4.50 (d, 1H, H-1â, J 1,2
) 7.6 Hz), 5.20 (d, 1H, H-1R, J 1,2 ) 3.7 Hz), relative intensity
â/R 2:1; 13C NMR (D2O, some signals are overlapping) δ 26.1,
28.9, 61.6, 68.3, 69.3, 69.9, 70.1, 70.5, 70.6, 71.0, 71.7, 71.8,
72.9, 74.3, 74.6, 82.6, 83.1, 92.1, 96.3. Anal. Calcd for
C12H22O9: C, 46.45, H, 7.15. Found: C, 46.01, H, 7.32.
2,5-An h yd r o-3,4:6,7-d i-O-isop r op ylid en e-a ld eh yd o-D-
glycer o-D-ta lo-h ep ta fu r a n ose (39). A mixture of 38 (128
mg; 0.39 mmol) and activated 4-Å powdered molecular sieves
(780 mg) in dry CH3CN (3.6 mL) was stirred at room temper-
ature for 10 min, and then methyl triflate (58 µL, 0.50 mmol)
was added. The suspension was stirred for 15 min and then
concentrated to dryness. The crude N-methylthiazolium salt
was suspended in MeOH (3.6 mL), cooled to 0 °C, and then
treated with NaBH4 (34 mg; 0.88 mmol). The mixture was
stirred at room temperature for an additional 10 min, diluted
with acetone (5.2 mL), filtered through Celite, and concen-
trated. To the solution of the crude thiazolidine in 10:1 CH3-
CN-H2O (3.6 mL) was added HgCl2 (107 mg, 0.39 mmol). The
mixture was stirred for 15 min and then filtered through
Celite. The solvent was evaporated and the residue suspended
in CH2Cl2 (10 mL) and washed with 20% aqueous KI (3 × 10
mL) and water (10 mL). The organic layer was dried (Na2-
SO4) and concentrated to give a syrup, which was diluted with
diethyl ether (10 mL) and filtered through a short pad of
Florisil (100-200 mesh) to afford a colorless solution. After a
further washing of the Florisil pad with AcOEt (3 mL), the
filtrate was concentrated to give 82 mg (77%) of almost pure
(NMR analysis) aldehyde 39 as an oil; 1H NMR (DMSO-d6,
120 °C) δ 1.30, 1.32, 1.33, 1.38 (4 × s, 12H, 2 × C(CH3)2, 3.84
(dd, 1H, H-5, J 5,4 ) 3.5 Hz, J 5,6 ) 6.3 Hz), 3.98 (dd, 1H, H-7,
J 7,6 ) 6.3 Hz, J 7,7′ ) 8.3 Hz), 4.05 (dd, 1H, H-7′, J 7′,6 ) 6.3 Hz),
(E/Z)-8,11-An h yd r o-9,10,12-t r i-O-b en zyl-6,7-d id eoxy-
1,2:3,4-d i-O-isop r op ylid en e-r-D-a ltr o-D-ga la cto-tr id ec-6-
en o-1,5-p yr a n ose (33). The phosphonium salt 8 (130 mg;
0.21 mmol) was reacted with the aldehyde 7 (91 mg; 0.21
mmol) as described for the preparation of 10 to afford, after
flash chromatography (4:1 cyclohexane-ethyl acetate), a 1:4
mixture of (E)-33 and (Z)-33 (91 mg; 66%). Pure samples of
these compounds were obtained by flash chromatography (30:1
toluene-acetone). Eluted first was (Z)-33 as an oil: [R]D ) -18
(c 1.1); 1H NMR δ 1.15, 1.32, 1.45, 1.54 (4 × s, 12H, 2 ×
C(CH3)2), 3.49 (dd, 1H, H-12, J 12,11 ) 5.0 Hz, J 12,12′ ) 11.0 Hz),
3.53 (dd, 1H, H-12′, J 12′,11 ) 4.0 Hz), 3.68 (dd, 1H, H-9, J 9,8
8.0 Hz, J 9,10 ) 5.0 Hz), 3.97 (dd, 1H, H-4, J 4,3 ) 8.0 Hz, J 4,5
)
)
2.0 Hz), 3.98 (dd, 1H, H-10, J 10,11 ) 2.0 Hz), 4.24 (m, 2H, H-2,
H-11), 4.32 (dd, 1H, H-3, J 3,2 ) 2.0 Hz), 4.43 and 4.59 (2 × d,
2H, J ) 12.0 Hz, OCH2Ph), 4.51 and 4.56 (2 × d, 2H, J ) 12.0
Hz, OCH2Ph), 4.56 and 4.61 (2 × d, 2H, J ) 12.0 Hz, OCH2-
Ph), 4.64 (dd, H-5, J 5,6 ) 8.5 Hz), 4.75 (t, 1H, H-8, J 8,7 ) 8.0
Hz), 5.51 (d, 1H, H-1, J 1,2 ) 5.0 Hz), 5.61 (dd, 1H, H-7, J 7,6
)
11.0 Hz), 5.75 (dd, 1H, H-6), 7.21-7.39 (m, 15H, Harom); 13C
NMR (C6D6) δ 24.4, 25.0, 25.8, 26.4, 64.7, 67.8, 70.6, 71.2, 71.6,
72.2, 73.6, 74.6, 77.2, 78.2, 82.8, 83.3, 97.1, 108.4, 108.9, 127.7-
128.6, 130.6, 132.0, 138.8. Anal. Calcd for C39H46O9: C, 71.10,
H, 7.04. Found: C, 70.93, 6.95.
1
Eluted second was (E)-33 as an oil: [R]D ) -32 (c 0.2); H
NMR δ 1.32, 1.37, 1.43, 1.54 (4 × s, 12H, 2 × C(CH3)2), 3.52
(dd, 1H, H-12, J 12,12′ ) 11.0 Hz, J 12,11 ) 5.0 Hz), 3.57 (dd, 1H,
H-12′, J 12′,11 ) 4.5 Hz), 3.75 (t, 1H, H-9, J 9,8 ≈ J 9,10 ≈ 5.5 Hz),
3.91 (t, 1H, H-10, J 10,11 ) 5.5 Hz), 4.16 (dd, 1H, H-4, J 4,3 ) 8.0
4.31 (q, 1H, H-6), 4.42 (d, 1H, H-2), 4.73 (dd, 1H, H-4, J 4,3
)
5.6 Hz), 5.01 (dd, 1H, H-3, J 3,2 ) 1.4 Hz), 9.62 (s, 1H, H-1).
(Z)-8,11-An h yd r o-1,2:3,4:9,10:12,13-t et r a -O-isop r op y-
lid en e-6,7-d id eoxy-r-D-glycer o-D-ta lo-D-ga la cto-tr id ec-6-
en o-1,5-p yr a n ose (40). The phosphonium salt 8 (189 mg;
0.30 mmol) was reacted with the aldehyde 39 (82 mg; 0.30
mmol) as described for the preparation of 10 to afford, after
flash chromatography (3:1 cyclohexane-ethyl acetate), 92 mg
(62%) of the (Z)-alkene 40 as an oil: [R]D ) -43 (c 1.3); 1H
NMR δ 1.32, 1.35, 1.39, 1.45, 1.50, 1.59 (6 × s, 24H, 4 ×
C(CH3)2), 3.79 (dd, 1H, H-11, J 11,10 ) 3.5 Hz, J 11,12 ) 7.5 Hz),
4.04 (dd, 1H, H-13, J 13,12 ) 4.5 Hz, J 13,13′ ) 9.0 Hz), 4.08 (dd,
1H, H-13′, J 13′,12 ) 6.0 Hz), 4.26 (dd, 1H, H-4, J 4,3 ) 8.0 Hz,
J 4,5 ) 2.0 Hz), 4.32 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.5 Hz),
4.40 (ddd, 1H, H-12), 4.62 (dd, 1H, H-3), 4.70 (d, 1H, H-9, J 9,10
) 6.0 Hz), 4.73-4.78 (m, 2H, H-5, H-10), 4.81 (dd, 1H, H-8,
J 8,6 ) 1.5 Hz, J 8,7 ) 6.0 Hz), 5.66 (d, 1H, H-1), 5.61 (ddd, 1H,
H-7, J 7,5 ) 1.0 Hz, J 7,6 ) 11.5 Hz), 5.77 (dd, 1H, H-6, J 6,5 ) 8.5
Hz); 13C NMR δ 24.4, 24.7, 24.9, 25.2, 26.1, 26.2, 26.3, 26.9,
66.4, 67.1, 70.4, 70.9, 72.8, 73.4, 80.0, 80.7, 83.6, 85.4, 96.5,
Hz, J 4,5 ) 2.0 Hz), 4.20 (q, 1H, H-11), 4.29 (dd, 1H, H-5, J 5,6
)
5.5 Hz), 4.31 (dd, 1H, H-2, J 2,1 ) 5.0 Hz, J 2,3 ) 2.1 Hz), 4.49
and 4.64 (2 × d, 2H, J ) 12.0 Hz, OCH2Ph), 4.52 and 4.62 (2
× d, 2H, J ) 12.0 Hz, OCH2Ph), 4.55 and 4.60 (2 × d, 2H, J
) 12.0 Hz, OCH2Ph), 4.54 (m, 1H, H-8), 4.59 (dd, 1H, H-3),
5.58 (d, 1H, H-1), 5.79 (ddd, 1H, H-7, J 7,5 ) 1.0 Hz, J 7,6 ) 16.0
Hz, J 7,8 ) 7.0 Hz), 5.95 (ddd, 1H, H-6, J 6,8 ) 1.0 Hz), 7.22-
7.40 (m, 15H, Harom); 13C NMR δ 24.3, 24.9, 25.9, 26.1, 68.0,
70.2, 70.4, 70.7, 72.0, 73.1, 73.4, 76.0, 77.7, 81.1, 81.7, 96.4,
108.4, 109.1, 127.7-128.3, 129.2, 131.4, 138.0. Anal. Calcd
for C39H46O9: C, 71.10, H, 7.04. Found: C, 71.23, H, 7.21.
8,11-An h y d r o -6,7-d id e o x y -D -a l t r o-D d -g a l a ct o-t r i-
d ecose (34). A solution of the alkene 33 (mixture of E- and
Z-isomers) (48 mg; 0.073 mmol) and (p-toluenesulfonyl)hydra-
zine (40 mg; 0.22 mmol) in dimethoxyethane (7.6 mL) was
heated to reflux. A solution of NaOAc (18.0 mg; 0.22 mmol)
in water (4 mL) was added dropwise over a 6 h period. The
reaction was stirred for an additional 12 h at reflux and then
cooled to room temperature. The solution was diluted with
diethyl ether, and the organic layer washed with water and
brine, dried (Na2SO4), and concentrated. Flash chromatogra-
phy (4:1 cyclohexane-ethyl acetate) of the residue gave the
reduced product, which was hydrogenated for 3 h as described
for the preparation of 18. Flash chromatography (9:1 ethyl
acetate-methanol) gave 21 mg (73%) of oily 8,11-anhydro-6,7-
dideoxy-1,2:3,4-di-O-isopropylidene-R-D-altro-D-galacto-trideco-
1,5-pyranose that showed: [R]D ) -47 (c 0.6); 1H NMR
(CD3OD) δ 1.32, 1.33, 1.40, 1.50 (4 × s, 12H, 2 × C(CH3)2),
1.52 (m, 2H, H-6, H-6′), 1.70 (m, 2H, H-7, H-7′), 3.54 (dd, 1H,
H-12, J 12,11 ) 5.0 Hz, J 12,12′ ) 12.0 Hz), 3.66 (dd, 1H, H-12′,
J 12′,11 ) 3.5 Hz), 3.67 (t, 1H, H-9, J 9,8 ≈ J 9,10 ≈ 5.5 Hz), 3.70-
108.3, 109.1, 109.2, 112.5. Anal. Calcd for C25H38O10
60.23, H, 7.68. Found: C, 60.10, H, 8.27.
: C,
8,11-An h yd r o-1,2:3,4:9,10:12,13-tetr a -O-isop r op ylid en e-
6,7-d id eoxy-r-D-glycer o-D-ta lo-D-ga la cto-tr id ec-1,5-p yr a -
n ose (41). The olefin 40 (34 mg; 0.068 mmol) was reduced
for 1.5 h as described for the preparation of 18 to afford, after
flash chromatography (3:1 cyclohexane-ethyl acetate), 28 mg
(82%) of the reduced product 41 as an oil: [R]D ) -34 (c 0.5);
1H NMR (CDCl3) δ 1.33, 1.34, 1.38, 1.45, 1.49, 1.52 (6 × s,
24H, 4 × C(CH3)2), 1.44 (m, 1H, H-7′), 1.54-1.68 (m, 2H, H-7,
H-6), 1.74-1.86 (m, 1H, H-6′), 3.72 (dd, 1H, H-11, J 11,10 ) 4.0
Hz, J 11,12 ) 8.0 Hz), 3.76 (ddd, 1H, H-5, J 5,4 ) 1.5 Hz, J 5,6
)
4.0 Hz, J 5,6′ ) 9.0 Hz), 4.02 (dd, 1H, H-13, J 13,12 ) 4.5 Hz, J 13,13′
) 8.5 Hz), 4.07 (m, 1H, H-8), 4.10 (dd, 1H, H-4, J 4,3 ) 8.0 Hz),

8124 J . Org. Chem., Vol. 62, No. 23, 1997
Dondoni et al.
4.13 (dd, 1H, H-13′, J 13′,12 ) 7.0 Hz), 4.30 (dd, 1H, H-2, J 2,1
)
74.3, 74.7, 77.2, 79.7, 80.8, 93.1, 97.7. This compound was
highly hygroscopic, thus preventing a satisfactory elemental
analysis.
5.0 Hz, J 2,3 ) 2.5 Hz), 4.38 (ddd, 1H, H-12), 4.52 (d, 1H, H-9,
J 9,10 ) 6.0 Hz), 4.59 (dd, 1H, H-3), 4.76 (dd, 1H, H-10), 5.51
(d, 1H, H-1). Anal. Calcd for C25H40H10: C, 59.98, H, 8.05.
Found: C, 60.32, H, 8.62.
Ack n ow led gm en t. Financial support was provided
by the Ministero dell′ Universita` e della Ricerca Scien-
tifica e Tecnologica (Italy). We are also grateful to the
EC (TMR program) for a postdoctoral fellowship to
H.M.Z. We thank Dr. A. Marra for the information on
the SmI2-based synthesis of the thiazolyl mannofura-
noside 38 and Mr. P. Formaglio for NMR measurements.
8,11-An h yd r o-6,7-d id eoxy-D-glycer o-D-ta lo-D-ga la cto-
tr id ecose (42). Compound 41 (20 mg; 0.04 mmol) dissolved
in 1:1 ethyl acetate-water (2 mL) was treated with Amberlite
IR-120 (H+) ion-exchange resin as described for compound 18
for 5 h to give 12 mg (89%) of the free C-disaccharide 42: [R]D
1
) +30 (c 0.2, CH3OH); H NMR (D2O) (selected data) δ 4.38
(d, 1H, H-1â, J 1,2 ) 7.6 Hz), 5.02 (d, 1H, H-1R, J 1,2 ) 3.7 Hz),
relative intensity â/R 2:1; 13C NMR (CD3OD, some signals are
overlapping) δ 27.1, 29.8, 64.0, 69.5, 70.7, 70.9, 71.6, 72.5, 72.8,
J O971177N