Total synthesis of sialylgalactosylgloboside: Stage-specific embryonic antigen 4

Article abstract of DOI:10.1021/jo9608073

A versatile total synthesis of sialylgalactosylgloboside (SGG, 1), carrying the stage-specific embryonic antigen 4 (SSEA-4) is reported, illustrating a more general strategy for the synthesis of complex globo-series glycosphingolipids. Starting from readily available building blocks 7, 8, and 10, two different approaches to the synthesis of the key tetrasaccharide 6 have been developed in a highly convergent manner. Further glycosylations with galactosyl trichloroacetimidate (5) and sialyl phosphite (2) donors successively afforded the penta- and hexasaccharides 3 and 11. The latter was finally converted into the target molecule (SGG, 1) with the help of a azidosphingosine glycosylation procedure, favored in this case by the stereocontrolling properties of the 2a-O-pivaloyl protecting group. Valuable intermediates 6 and 3, having the oligosaccharidic skeletons of Gb₄ and Gb₅ (SSEA-3), respectively, were obtained in the course of the synthesis.

Full text of DOI:10.1021/jo9608073

J . Org. Chem. 1996, 61, 6873-6880
6873
Tota l Syn th esis of Sia lylga la ctosylglobosid e: Sta ge-Sp ecific
Em br yon ic An tigen 4
J ose´ M. Lassaletta,*,† Karin Carlsson,† Per J . Garegg,‡ and Richard R. Schmidt†
Fakulta¨t fu¨r Chemie, Universita¨t Konstanz, Postfach 5560 M 725, D-78434 Konstanz, Germany
Received May 2, 1996X
A versatile total synthesis of sialylgalactosylgloboside (SGG, 1), carrying the stage-specific embryonic
antigen 4 (SSEA-4) is reported, illustrating a more general strategy for the synthesis of complex
globo-series glycosphingolipids. Starting from readily available building blocks 7, 8, and 10, two
different approaches to the synthesis of the key tetrasaccharide 6 have been developed in a highly
convergent manner. Further glycosylations with galactosyl trichloroacetimidate (5) and sialyl
phosphite (2) donors successively afforded the penta- and hexasaccharides 3 and 11. The latter
was finally converted into the target molecule (SGG, 1) with the help of a azidosphingosine
glycosylation procedure, favored in this case by the stereocontrolling properties of the 2a-O-pivaloyl
protecting group. Valuable intermediates 6 and 3, having the oligosaccharidic skeletons of Gb4
and Gb5 (SSEA-3), respectively, were obtained in the course of the synthesis.
Glycosphingolipids (GLS’s) of the globo series are
membrane-associated antigens possessing as structural
feature a GalR1f4Gal (galabiose-like) linkage which is
responsible for their specific roles in recognition and cell
differentiation. They are recognized by proteins of
pathogenic Escherichia coli in human epithelial cells of
the urinary tract.1 They are also receptors for Shiga
toxin2 and verotoxin (Shiga-like toxin)3 and constitute the
basis of the P-blood group system.4 Many of them have
been described as tumor-associated antigens.5 Sialylga-
lactosylgloboside (SGG, 1), a ganglioside belonging to this
series, was first isolated in 1983 from chicken pectoral
muscles.6 In the same year, Solter et al.7 identified SGG
with a developmentally regulated antigen, the stage-
specific embryonic antigen 4 (SSEA-4), and found SSEA-3
(previously found to be expressed as Gb5)8 and SSEA-4
to be epitopes of this unique globo-series ganglioside
isolated from human teratocarcinoma cells. More recent
studies have shown that globo-series antigens SEEA-3
and SSEA-4 are expressed in different forms on human
and murine teratocarcinoma cells9 and are a hallmark
of the former.10 SSEA-4 has also been reported to bind
human parvovirus B19 capsids.11
The great interest in this family of GLS’s and the
difficulties for their isolation in sufficient quantities from
natural sources has stimulated interest in their chemical
synthesis. Table 1 summarizes the most significant
contributions that have appeared up to now in this field.
We describe herein a general strategy for the synthesis
of complex globo-series glycosphingolipids, as illustrated
for the detailed synthesis of SGG, carrying the SSEA-4
antigen, and including the Gb4 and Gb5 oligosaccharidic
skeletons as valuable intermediates. A preliminary
account of this work17 and a different approach to the
synthesis of SGG have recently appeared.18
Resu lts a n d Discu ssion
The retrosynthetic view of the target compound 1
outlined in Scheme 1 suggests six convenient disconnec-
tions designed in such a way that useful intermediates
would be obtained within the course of the synthesis.
Thus, the access to the target molecule is visualized from
compound 3, having the oligosaccharidic skeleton of
galactosylgloboside (Gb5, SSEA-3) and known building
blocks 219 and 420 (disconnections 1-3). Likewise, com-
* Author to whom correspondence should be addressed. Current
address: Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica,
Universidad de Sevilla, Apartado de Correos No. 553, E-41071, Seville,
Spain. FAX: 34-5-4624952. E-mail: ffernan@obelix.cica.es.
† Universita¨t Konstanz.
‡ Department of Organic Chemistry, Arrhenius Laboratory, Stock-
holm University, S-106 91 Stockholm, Sweden.
(10) Wenk, J .; Andrews, P. W., Casper, J .; Hata, J . I.; Pera, M. F.;
Vonkeitz, A., Damjanov, I.; Fenderson, B. A. Int. J . Cancer 1994, 58,
108.
(11) Cooling, L. L. V.; Koerner, T. A. W.; Naides, S. J . J . Infect. Dis.
1995, 172, 1198.
X Abstract published in Advance ACS Abstracts, August 15, 1996.
(1) Lanne, B.; Olsson, B.-M.; J ovalp, P.-A° .; A° ngstro¨m, J .; Linder,
H.; Marklund, B.-I.; Bergstro¨m, J .; Karlsson K.-A. J . Biol. Chem. 1995,
270, 9017, and references cited therein. Our synthetic SGG is currently
being used in this laboratory for further investigations on this topic.
(2) Lindberg, A. A.; Brown, J . E.; Stro¨mbreg, N.; Westling-Ryd, M.;
Schultz, J . E.; Karlsson, K. A. J . Biol. Chem. 1987, 262, 1779.
(3) Linwood, C. A.; Law, H.; Richardson, S.; Petric, M.; Brunton, J .
L.; De Grandis, S.; Karmali, M. J . Biol. Chem. 1987, 262, 8834.
(4) (a) Naiki, M.; Marcus, D. M. Biochem. Biophys. Res. Commun.
1974, 60, 1105. (b) Id. Biochemistry 1975, 14, 4837. (c) Marcus, D. M.;
Naiki, M.; Kundu, S. K. Proc. Natl. Acad. Sci. U.S.A. 1976, 73, 3263.
(5) Kalisiak, A.; Minniti, J . G.; Oosterwijk, E.; Old, L. J .; Scheinberg,
D. A. Int. J . Cancer 1991, 49, 837.
(12) (a) Shapiro, D.; Acher, A. J .; Chem. Phys. Lipids 1978, 22, 197.
(b) Koike, K.; Sugimoto, M.; Sato, S.; Ito, Y.; Nakahara, Y.; Ogawa, T.
Carbohydr. Res. 1987, 163, 189. (c) Nicolaou, K. C.; Caulfield, T.;
Kataoka, H.; Kumazawa, T. J . Am. Chem. Soc. 1988, 110, 7910. (d)
Qiu, D.; Schmidt, R. R. Liebigs Ann. Chem. 1992, 217.
(13) Leontein, K.; Nilsson, M.; Norberg, T. Carbohydr. Res. 1985,
144, 231.
(14) Magnusson, G.; Nilsson, U.; Ray, A. K.; Taylor, K. G. ACS
Symp. Ser. 1993, 519, 92, and references therein.
(15) Nunomura, S.; Ogawa, T. Tetrahedron Lett. 1988, 29, 5681.
(16) (a) Bilodeau, M. T.; Park, T. K.; Hu, S.; Randolph, J . T.;
Danishefsky, S. J .; Livingston, P. O.; Zhang, S. J . Am. Chem. Soc. 1995,
117, 7840. (b) Lassaletta, J . M.; Schmidt, R. R. Liebigs Ann. Chem.,
submitted.
(6) Chien, J .-L.; Hogan, E. L. J . Biol. Chem. 1983, 258, 10727.
(7) Kannagi, R.; Cochran, N. A.; Ishigami, F.; Hakomori, S.-i.;
Andrews, P. W.; Knowles, B. B.; Solter, D. EMBO J . 1983, 2, 2355.
(8) (a) Kannagi, R.; Levery, S. B.; Ishigami, F.; Hakomori, S.-i.,
Shevinski, L. H.; Knowles, B. B.; Solter, D. J . Biol. Chem. 1983, 258,
8934. (b) Shevinski, L. H.; Knowles, B. B., Damjanov, I.; Solter, D.
Cell 1982, 30, 697.
(17) Lassaletta, J . M.; Schmidt, R. R. Tetrahedron Lett. 1995, 36,
4209.
(18) Ishida, H.; Miyawaki, R.; Kiso, M.; Hasegawa, A. J . Carbohydr.
Chem 1996, 15, 163.
(9) Krupnick, J . G.; Damjanov, I.; Damjanov, A.; Zhu, Z. M.:
Fenderson, B. A. Int. J . Cancer 1994, 59, 692.
(19) Martin, T. J .; Brescello, R.; Toepfer, A.; Schmidt, R. R. Glyco-
conjugate J . 1993, 16, and references cited therein.
S0022-3263(96)00807-9 CCC: $12.00 © 1996 American Chemical Society

6874 J . Org. Chem., Vol. 61, No. 20, 1996
Lassaletta et al.
ref
Ta ble 1. Ch em ica lly Syn th esized Globo-Ser ies Glycosp h in golip id s
globoside antigen
Pk
GalR1f4Galâ1f4Glcâ1f1Cer (Gb3)
12
13
14
15
16
GalNAcâ1f3GalR1f4Galâ1f4Glcâ1f1Cer (Gb4)
P
GalNAcR1f3GalNAcâ1f3GalR1f4Galâ1f4Glcâ1f1Cer (Forssman)
Galâ1f3GalNAcâ1f3GalR1f4Galâ1f4Glcâ1f1Cer (Gb5)
FucR1f2Galâ1f3GalNAcâ1f3GalR1f4Galâ1f4Glcâ1f1Cer (H-Gb4)
NeuNAcR2f3Galâ1f3GalNAcâ1f3GalR1f4Galâ1f4Glcâ1f1Cer (SGG)
Forssman
SSEA-3
MBr1
SSEA-4
17, 18, this work
Sch em e 1
pound 3 should be accessible starting from tetrasaccha-
ride 6 (Gb4) and the readily available galactosyl donor
521 (disconnection 4). A convergent retrosynthetic view
for the former leads to compound 10 as lactose building
block and disaccharide donor 9 (disconnection 5); evident
disconnection (6) of the latter is proposed from galactose
acceptor 8 and azidogalactose donor 7.
Two different approaches for the synthesis of the
globotetraose skeleton 6 have been tested (Scheme 2).
The choice of an appropriate AB (lactose) building block
was made considering the following requirements: (i) the
low nucleophilicity of 4b-OH should be enhanced by
benzyl-like protecting groups around this position; (b) a
sterically demanding â-stereocontrolling group should be
placed at the 2a-position, granting the formation of
â-anomers only and avoiding the formation of orthoesters
at the azidosphingosine glycosylation step.22 Compound
10,23 fulfilling these requisites, was chosen for both
approaches. For the first synthesis of the CD building
block 9, the known 3-O-monochloroacetyl-protected azi-
dogalactosyl donor 7a 24 was reacted with acceptor 8d .
The latter was synthesized starting from allyl galactoside
8a 25 in three steps: selective O-benzoylation (BzCN,
Et3N), benzylation under neutral conditions (BnOTf),26
and saponification of the 3-O-benzoyl group. The stereo-
chemistry of the glycosylation reaction was â-directed by
(22) (a) Schmidt, R. R.; Zimmermann, P. Angew. Chem. Int. Ed.
Engl. 1986, 25, 725, and references therein. (b) Kunz, H.; Harreus, A.
Liebigs Ann. Chem. 1982, 41.
(23) This compound was first synthesized by Ogawa’s group: Sato,
S.; Nunomura, S.; Nakano, T.; Ito, Y.; Ogawa, T. Tetrahedron Lett.
1988, 29, 4097. The low overall yield and length (14 steps) of the
synthesis, however, prompted us to develop a shorter, more efficient
synthesis of this compound: Lassaletta, J . M.; Schmidt, R. R. Synlett
1995, 925.
(20) (a) Schmidt, R. R.; Zimmermann, P.; Tetrahedron Lett. 1986,
27, 481. (b) Zimmermann, P.; Bommer, R.; Ba¨r, T.; Schmidt, R. R. J .
Carbohydr. Chem. 1988, 7, 435.
(21) Greilich. U.; Zimmermann, P.; J ung, K.-H.; Schmidt, R. R.
Liebigs Ann. Chem. 1993, 859.
(24) (a) Grundler, G.; Schmidt, R. R. Liebigs Ann. Chem. 1984, 1826.
(b) Rademann, J . Diplomarbeit, University of Konstanz, 1994.
(25) This compound was obtained in good yield by direct anomeric
O-alkylation of 4,6-O-benzylidenegalactopyranose (see Experimental
Section).

Total Synthesis of SGG
J . Org. Chem., Vol. 61, No. 20, 1996 6875
Sch em e 2a
however, afforded directly the 1-O-deprotected disaccha-
ride 9c in good yield, conditions being mild enough to
keep the acid-labile benzylidene protecting groups. The
transformation of 9c into the corresponding trichloro-
acetimidate donor again presented problems due to the
lability of the MCA group, which did not survive the basic
conditions required. To overcome this problem, 9c was
first quantitatively deprotected to diol 9d and subse-
quently transformed into the bis-trichloroacetimidate 9e.
Reaction of the latter with acceptor 10 furnished, with
the help of the inverse procedure (IP),29 the desired
tetrasaccharide 6a in a yield of 62%, acceptable for this
system. HCl-mediated hydrolysis of the 3d-O-trichloro-
acetimidoyl group afforded acceptor 6b in moderate (51%)
yield.
The general importance of the ABCD tetrasaccharide,
having the core structure of globoside Gb4 and being the
key for all higher globosides, merits an improved syn-
thesis. Therefore, a second approach was designed to
overcome the limitations referred to above. In this case,
the known tert-butyldimethylsilyl 2-azido-4,6-O-ben-
zylidene-â-D-galactopyranoside 7b24a was converted into
donor 7c by treatment with (i) TBAF and (ii) Cl3CCN/
DBU, without isolation of the intermediate hemiacetal.
Reaction of 7c with diol 8a proceeded regio- and stereo-
selectively, again taking advantage of the “nitrile effect”27
and the much higher reactivity of 3-OH than 2-OH in
the latter. Thus, the desired disaccharide 9f was ob-
tained as a single isomer and then transformed into
trichloroacetimidate CD donor 9i by benzylation (Ag2O/
BnBr, f9g), allyl cleavage (PdCl2/AcOH/NaOAc, f9h )
and imidate formation under established conditions.
Reaction of this compound with acceptor 10, again
applying the inverse procedure,29 afforded tetrasaccha-
ride 6c (63%, R:â ) 4:1). Selective removal of the 3d-O-
acetyl group to obtain 6b was then accomplished quan-
titatively by means of methanolic ammonia, keeping the
2a-O-pivaloyl group untouched. This material proved to
be identical with product 6b obtained from 6a . The
second approach, however, proved to be more efficient,
since the synthesis required fewer steps, and the overall
yield was higher.
For the transformation of this ABCD fragment 6b into
the target 1 (Scheme 3), â-galactosylation was first
achieved by using trichloroacetimidate donor 5 under
established conditions, yielding the globopentaose deriva-
tive 3a in almost quantitative yield. This material was
converted into the ABCDE acceptor 3b again using NH3/
MeOH for selective de-O-acylation. It is known19 that
sterically demanding sialyl donors can be attached in
good yields to the 3 position of 2,3,4- or 2,3-O-unprotected
galactose residues. Therefore, compound 3b reacted with
phosphite donor 2,14 affording an easily separable mix-
ture 11a r/11a â in good yield (62%, R:â ) 4:1).30 The
stereochemistry of both R and â sialylglycosides was
assigned on the basis of empirical rules.31 Compound 11a
was then converted into trichloroacetimidate 11d in three
convenient and high-yielding steps: (i) simultaneous
hydrogenolytic cleavage of benzyl and benzylidene pro-
tecting groups and reduction of the 2d-azido group, best
a
Reagents: (a) BzCN, Et3N (75%); (b) BnOTf (81%); (c) K2CO3,
MeOH/H2O (85%); (d) TMSOTf, CH3CN; (e) PdCl2, NaOAc, AcOH/
H2O (71%); (f) NaOMe, MeOH (quant); (g) Cl3CCN, DBU (76%);
(h) TMSOTf, Et2O, IP (62%); (i) HCl, MeOH/H2O (51%); (j) (i)
TBAF, AcOH (92%); (ii) CCl3CN, DBU (88%); (k) TMSOTf, CH3CN
(84%, â); (l) BnBr, Ag2O, DMF, 4 Å (81%); (m) PdCl2, NaOAc,
AcOH/H2O (86%); (n) CCl3CN, DBU (93%); (o) TMSOTf, IP (63%,
R:â ) 4:1); (p) NH3/MeOH (quant).
using conditions (-40 °C, CH3CN) in which the “nitrile
effect” operates;27 9a was isolated in 88% yield and no
R-product could be detected. The allyloxy group of 9a
could not be isomerized under standard conditions (i.e.,
Wilkinson’s catalyst in a protic solvent in the presence
of a DBU-like base) because partial cleavage of the labile
monochloroacetyl (MCA) group occurred (f9b). Use of
the buffered Ogawa’s reagent28 (PdCl2/AcOH/NaOAc),
(29) Schmidt, R. R.; Toepfer, A. Tetrahedron Lett. 1991, 32, 3353.
(30) Though the phosphite methodology (see ref 19) usually yields
virtually complete R-selectivities, other rather unpredictable results
have been observed for related systems. This result, however, can be
considered as acceptable due to the high yield obtained.
(31) a) δ 3-Heq(R) > δ 3-Heq(â): Dabrowski, U.; Friebolin, H.;
Brossmer, R.; Supp, M. Tetrahedron Lett. 1979, 4637. (b) δ 4-H(R) < δ
4-H(â): Paulsen, H.; Tietz, H. Carbohydr. Res. 1984, 125, 47.
(26) Lemieux, R. U.; Kondo, T. Carbohydr. Res. 1974, 35, C4. Other
standard conditions (NaH/BnBr or Ag2O/BnBr) led to benzoyl migra-
tion.
(27) Schmidt, R. R.; Behrendt, M.; Toepfer, A. Synlett 1990, 694.
(28) Ogawa, T.; Nakabayashi, S. Carbohydr. Res. 1981, 93, C1.

6876 J . Org. Chem., Vol. 61, No. 20, 1996
Lassaletta et al.
Sch em e 3a
a
Reagents: (a) TMSOTf (94%); (b) NH3/MeOH (quant); (c) TMSOTf, CH3CN (62%, R:â ) 3.5:1); (d) (i) Pd(OH)2/C, H2, MeOH, (ii)
Ac2O/Py (85%, R:â ) 1:1); (e) N2H4‚AcOH, DMF (94%); (f) CCl3CN, DBU (93%); (g) TMSOTf (72%); (h) (i) H2S, Py/H2O, (ii) C15H31COOH,
WSC (87%); (j) (i) NaOMe/MeOH, (ii) KOH/H2O, (iii) IRA 120 (H+) (quant).
achieved by using freshly prepared Pearlman catalyst,32
followed by peracetylation of the crude product (f11b,
85% of a 1:1 mixture of R- and â-acetates); (ii) regiose-
lective removal of the anomeric 1-O-acetyl group by
means of hydrazinium acetate33 in DMF (f11c, 94%);
and iii) imidate formation under established conditions
(f11d , 93%). The final stages of the synthesis, i.e., the
introduction of the ceramide aglycon, were accomplished
by application of the azidosphingosine glycosylation
procedure.20 The importance of the pivaloyl protecting
group chosen for the 2a position of 11d was here
demonstrated by the excellent yield (72%) observed for
the TMSOTf-promoted â-glycosylation of azidosphin-
gosine derivative 4, which yielded the corresponding
glycoside 12a ; no orthoester byproduct was detected in
the reaction mixture. This azido compound was then
reduced with H2S in pyridine/water without acyl migra-
tion, and the crude product was immediately treated with
palmitic acid in the presence of N-[3-(N,N-dimethylami-
no)propyl]-N′-ethylcarbodiimide hydrochloride (water
soluble carbodiimide, WSC) as condensing agent to
provide the protected glycosyl ceramide 12b in 87% yield.
Finally, the target 1 (SGG) was obtained quantitatively
from the latter by methanolysis (NaOMe/MeOH) of all
O-acyl protecting groups and subsequent hydrolysis
(aqueous KOH) of the methyl ester moiety. The 1H NMR
data of this compound are in full agreement with those
reported for the natural sample.8a,34
Con clu sion s
In summary, a versatile strategy has been described
for the synthesis of complex globo-series glycolipids,
based on powerful synthetic tools such as the trichloro-
acetimidate glycosylation procedure, the recently devel-
oped phosphite method for sialylation,19 the azidosphin-
gosine-based protocol for glycosphingolipid synthesis, and
the stereocontrolling properties of a neighbor pivaloyl
protecting group. An advantage of this strategy is the
construction of the difficult galabiose-type R(1f4) gly-
cosidic linkage in the first stages of the synthesis, thus
avoiding this connection later during the synthesis. It
should be also stressed that both 3b and 6b, bearing
appropriate protecting groups, are not only precursors
for the synthesis of Gb4 and Gb5 globosides but also for
further elongation to several higher globosides other than
the target SGG. Compound 6b, for instance, could be
alternatively glycosylated with an R-galactosamine donor
for the synthesis of the Forssman antigen. Likewise, the
considerable difference in reactivity between the 3d-OH
(32) Fieser, L. F.; Fieser, M. In Reagents for Organic Synthesis; J ohn
Wiley and Sons Inc.: New York, 1967; Vol. 1, p 782. The age of the
catalyst was found to be of importance; in our hands, the use of old
catalysts led to complex mixtures containing the desired product in
low yield.
(33) Excoffier, G.; Gagnaire, G.; Utille, J .-P. Carbohydr. Res. 1975,
39, 368.
(34) The molecular formula and the 1H NMR data reported for SGG
in ref 18 are erroneous.

Total Synthesis of SGG
J . Org. Chem., Vol. 61, No. 20, 1996 6877
allowed to rise up to -40 °C. After 16 h, pyridine (20 mL)
was added, and the mixture was warmed up to rt, washed with
H2O (3 × 100 mL), dried (MgSO4), and concentrated in vacuo.
The 2,6-di-tert-butylpyridine was finally removed by distilla-
tion (34 °C/0.4 mbar) and the residue purified by flash
chromatography (18:1 toluene-EA) to give unreacted material
and 2d-OH of 3b can be used for the synthesis of Globo-
H16 and Globo-A structures. Additionally, the lysogly-
cosphingolipid obtained after reduction of 12a is another
interesting intermediate, since it may have different
biological properties to that of the corresponding ceram-
ide derivative.35
(1.9 g) and crystalline 8c (8.64 g, 73%): mp 51 °C; [R]rt
D
1
+143.8° (c 1, CHCl3); TLC (3:1 toluene-acetone) Rf 0.47; H-
NMR δ 7.1-8.1 (m, 15H), 6.06-5.90 (m, 1H), 5.51 (s, 1H),
5.41-5.22 (m, 2H), 5.20 (dd, J ) 3.6, 10.2 Hz, 1H), 4.92 (d, J
) 10.1 Hz, 1H), 4.72 (d, J ) 10.1 Hz, 1H), 4.61 (d, J ) 7.8 Hz,
1H), 4-55-4-03 (m, 6H), 3.56 (br s, 1H). Anal. Calcd for
C30H30O7‚1/4H2O: C, 71.06; H, 5.96. Found: C, 70.90; H, 5.99.
Allyl 2-O-Ben zyl-4,6-O-ben zylid en e-â-D-ga la ctop yr a n o-
sid e (8d ). To a solution of 8c (11.22 g, 22.3 mmol) in 8:1
MeOH-H2O was added K2CO3 (1M, 2 mL) and the mixture
stirred for 7 h at rt. The solvent was then evaporated in vacuo
and the residue extracted with acetone and purified by flash
chromatography (7:1 toluene-acetone) to give 8d (7.53 g,
Exp er im en ta l Section
Melting points were measured in a metal block and are
uncorrected. Thin layer chromatography (TLC) was performed
on silica gel precoated plates. Purifications of the products
were carried out by flash chromatography. The light petro-
leum ether used had boiling range 35-65 °C. 1H NMR spectra
were recorded at 250 MHz, using chloroform-d as solvent and
tetramethylsilane as internal standard, unless noted other-
wise.
Sta r tin g Ma ter ia ls. 4,6-O-Benzylidene-R,â-D-galactopyr-
anose,36 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-1-(meth-
oxycarbonyl)-D-glycero-R-D-galacto-2-nonulopyranosyl diethyl
phosphite19 (2), (2S,3R,4E)-2-azido-3-(benzoyloxy)-4-octa-
decen-1-ol20 (4), 2,3-di-O-acetyl-4,6-O-benzylidene-R-D-galac-
topyranosyl trichloroacetimidate21 (5), 2-azido-4,6-O-benzylidene-
3-O-chloroacetyl-2-deoxy-R-D-galactopyranosyl trichloroacet-
imidate24 (7a), tert-butyldimethylsilyl 2-azido-4,6-O-benzylidene-
â-D-galactopyranoside24a (7b ), and benzyl 3,6-di-O-benzyl-4-
O-(2,3,6-tri-O-benzyl-â-D-galactopyranosyl)-2-O-pivaloyl-â-D-
glucopyranoside23 (10) were prepared according to literature
procedures.
85%): mp 69 °C; [R]rt +9.3° (c 1, CHCl3); TLC (7:1 toluene-
D
1
acetone) Rf 0.19; H-NMR δ 7.6-7.2 (m, 10H), 6.05-5.89 (m,
1H), 5.56 (s, 1H), 5.39-5.18 (m, 2H), 5.00 (d, J ) 10.1 Hz,
1H), 4.73 (d, J ) 10.1 Hz, 1H), 4.6-3.6 (m, 8H), 3.43-3.42
(m, 1H), 2.51 (d, J ) 8.0 Hz, 1H). Anal. Calcd for C23H26O6‚
H2O: C, 66.33; H, 6.77. Found: C, 66.36; H, 6.51.
Allyl 3-O-(2-Azido-4,6-O-ben zyliden e-3-O-(ch lor oacetyl)-
2-d eoxy-â-D-ga la ctop yr a n osyl)-2-O-ben zyl-4,6-O-ben zyl-
id en e-â-D-ga la ctop yr a n osid e (9a ). To a cooled (-40 °C)
solution of 8d (5.33 g, 13.38 mmol) and 7a (10.46 g, 20.07
mmol) in dry CH3CN (100 mL) was added TMSOTf (2.6 mL,
0.1M in CH3CN) under an argon atmosphere. After 1 h,
NaHCO3 (s, 0.1 g) and Et2O (400 mL) were added, and the
mixture was washed with saturated NaHCO3 solution (100
mL) and H2O (100 mL). The organic layer was dried (MgSO4)
and concentrated in vacuo, and the residue was purified by
flash chromatography (7:1 toluene-EA) to afford 9a (8.85 g,
88%): mp 112 °C; [R]rtD +25.4° (c 1, CHCl3); TLC (7:1 toluene-
Allyl 4,6-O-Ben zylid en e-â-D-ga la ctop yr a n osid e (8a ).
To a stirred solution of 4,6-O-benzylidene-R,â-D-galactopyra-
nose (33.8 g, 126 mmol) and AllBr (17 mL, 200 mmol) in 1:1
dry THF/DMF (300 mL) was added NaH (3.56 g, 141 mmol)
in small portions. After 24 h MeOH (10 mL) was added and
the mixture stirred for another 30 min. The solvent was then
removed in vacuo and the residue extracted with acetone and
purified by flash chromatography (3:1 toluene-acetone). Allyl
4,6-O-benzylidene-R-D-galactopyranoside (7.3 g, 13%) eluted
1
acetone) Rf 0.50; H-NMR δ 7.6-7.2 (m, 15H), 6.04-5.88 (m,
1H), 5.59 (s, 1H), 5.48 (s, 1H), 5.37-5.17 (m, 2H), 5.02 (d, J )
10.6 Hz, 1H), 4.97 (d, J ) 7.2 Hz, 1H), 4.70 (d, J ) 10.6 Hz,
1H), 4.65 (dd, J ) 3.6, 10.9 Hz, 1H), 4.53-3.90 (m, 14H), 3.39
(br s, 1H), 3.31 (br s, 1H). Anal. Calcd for C38H40ClN3O11: C,
60.84; H, 5.37; N, 5.60. Found: C, 60.84; H, 5.55; N, 5.39.
Allyl 3-O-(2-Azid o-4,6-O-b en zylid en e-2-d eoxy-â-D-ga -
la ctop yr a n osyl)-2-O-ben zyl-4,6-O-ben zylid en e-â-D-ga la c-
top yr a n osid e (9b). (a) To a solution of compound 9a (50 mg,
67 µmol) in MeOH (1 mL) was added Et3N (1 drop), the
mixture was stirred for 1 h at rt and concentrated, and the
residue purified by flash chromatography (2:1 EA-toluene) to
first: mp 118-120 °C (lit.37 mp 115-117 °C); [R]rt +73.6° (c
D
1, CHCl3) [lit.37 [R]rtD +121 ° (c 1.9, CHCl3)]. 8a eluted second
(22.8 g, 59%): mp 174 °C; [R]rtD -36.4° (c 1, CHCl3); TLC (12:1
CH2Cl2-MeOH) Rf 0.57; 1H-NMR δ 7.3-7.5 (m, 5H), 6.02-
5.86 (m, 1H), 5.52 (s, 1H), 5.35-5.17 (m, 2H), 4.46-4.38 (m,
1H), 4.35-3.60 (m, 7H), 3.44 (br s, 1H), 2.65 (br s, 2H). Anal.
Calcd for C16H20O6‚1/4H2O: C, 61.43; H, 6.60. Found: C, 61.44;
H, 6.49.
Allyl 3-O-Ben zoyl-4,6-O-ben zylid en e-â-D-ga la ctop yr a -
n osid e (8b). To a stirred suspension of 8a (18 g, 58 mmol)
and BzCN (8.0 g, 1.03 eq) in dry CH3CN (150 mL) was added
Et3N (10 drops). After 30 min MeOH (10 mL) was added and
the mixture stirred for another 15 min. The solvent was then
removed in vacuo and the residue dissolved in MeOH and
concentrated two times. Crystallization from MeOH and flash
chromatography [2:1 toluene-ethyl acetate (EA)] of the mother
liquors yielded unreacted material (3 g) and 8b (17.7 g, 75%):
give 9b (43 mg, 96%): mp 120 °C; [R]rt +3.9° (c 1, CHCl3);
D
TLC (2:1 EA-toluene) Rf 0.29; 1H-NMR δ 7.6-7.2 (m, 15H),
6.04-5.90 (m, 1H), 5.59 (s, 1H), 5.52 (s, 1H), 5.37-5.17 (m,
2H), 5.00 (d, J ) 10.1 Hz, 1H), 4.83 (d, J ) 8.0 Hz, 1H), 4.74
(d, J ) 10.1 Hz, 1H), 4.55-3.27 (m, 15H), 2.60 (d, J ) 9.6 Hz,
1H). Anal. Calcd for C36H39N3O10‚H2O: C, 62.51; H, 5.97; N,
6.07. Found: C, 62.58; H, 5.93; N, 6.00.
mp 177 °C; [R]rt +76.8° (c 1, CHCl3); TLC (4:1 toluene-
(b) A mixture of 9a (50 mg, 67 µmol), Rh(PPh3)3Cl (6 mg,
6.7 µmol), and 9:1 EtOH-DBU (10 µL) in 9:1 EtOH-H2O (1
mL) was stirred at rt for 2 h. The solvent was removed in
vacuo and the residue purified by flash chromatography (2:1
EA-toluene) to give 9b (30 mg, 64%), identical with the
product described above.
D
1
acetone) Rf 0.38; H-NMR δ 7.2-8.1 (m, 10H), 6.03-5.87 (m,
1H), 5.50 (s, 1H), 5.19-5.36 (m, 2H), 5.14 (dd, J ) 3.7, 10.3
Hz, 1H), 4.51-4.05 (m, 7H), 3.57 (br s, 1H), 2.0 (br s, 1H).
Anal. Calcd for C23H24O7: C, 66.96; H, 5.87. Found: C, 66.86;
H, 5.87.
3-O-(2-Azid o-4,6-O-b en zylid en e-3-O-(ch lor oa cet yl)-2-
d eoxy-â-D-ga la ct op yr a n osyl)-2-O-b en zyl-4,6-O-b en zyli-
d en e-r/â-D-ga la ctop yr a n ose (9c). Compound 9a (6.24 g, 8.3
mmol), PdCl2 (3.4 g, 19.2 mmol), and NaOAc (11.7 g, 125 mmol)
were suspended in 9:1 AcOH-H2O (200 mL) and stirred for
12 h at rt. The mixture was then filtered through Celite,
slowly poured on saturated NaHCO3 solution (1 L), and
extracted with CH2Cl2 (3 × 300 mL). The organic layer was
then dried (MgSO4) and concentrated in vacuo, and the residue
was purified by flash chromatography (2:1 toluene-EA) to
yield 9c (4.21 g, 71%); [R]rtD +43.4° (c 1, CHCl3); TLC (2:1 EA-
toluene) Rf 0.55; 1H-NMR δ 7.6-7.2 (m, 15H), 5.59 (s, 1H),
5.50 and 5.48 (2 s, 1H), 5.36 (d, J ) 2.0 Hz, 0.5H), 5.07 (d, J
Allyl 3-O-Ben zoyl-2-O-b en zyl-4,6-O-b en zylid en e-â-D-
ga la ctop yr a n osid e (8c). To a solution of Tf2O (14.26 mL,
85.6 mmol) in dry CH2Cl2 (40 mL) was added dropwise at -75
°C a solution of benzyl alcohol (9.0 mL, 85.6 mmol) and 2,6-
di-tert-butylpyridine (18.8 mL, 85.6 mmol) in dry CH2Cl2 (70
mL) for over 30 min under an argon atmosphere. After stirring
for 20 min, a solution of compound 8b (11.6 g, 28.2 mmol) and
2,6-di-tert-butylpyridine (12.54 mL, 57 mmol) in CH2Cl2 (70
mL) was added dropwise (20 min) and the temperature was
(35) (a) Hannun, Y. A.; Bell, R. M. Science 1989, 243, 500. (b)
Hakomori, S.-i. J . Biol. Chem. 1990, 265, 18713.
(36) Gros, E. G.; Deulofeu, V. J . Org. Chem 1964, 29, 3647.
(37) Gigg, R.; Warren, C. D. J . Chem. Soc. (C) 1968, 1903.
) 8.0 Hz, 0.5H), 5.0-3.3 (m, 18H). Anal. Calcd for C35H36
-

6878 J . Org. Chem., Vol. 61, No. 20, 1996
Lassaletta et al.
ClN3O11‚1/4H2O: C, 58.45; H, 5.19; N, 5.84. Found: C, 58.68;
H, 5.24; N, 5.37.
1H), 5.48 (s, 1H), 5.35-5.15 (m, 2H), 4.96 (d, J ) 8.0 Hz, 1H),
4.71 (dd, J ) 3.5, 8.9 Hz, 1H), 4.5-3.99 (m, 11H), 3.85 (dd, J
) 3.5, 9.9 Hz, 1H), 3.46 (br s, 1H), 3.41 (br s, 1H), 2.12 (s, 3H).
Anal. Calcd for C31H35N3O11‚1/2H2O: C, 58.67; H, 5.71; N, 6.62.
Found: C, 58.67; H, 5.68; N, 6.15.
3-O-(2-Azid o-4,6-O-ben zylid en e-2-d eoxy-â-D-ga la ctop y-
r a n osyl)-2-O-ben zyl-4,6-O-b en zylid en e-r/â-D-ga la ct op y-
r a n ose (9d ). To a solution of 9c (0.8 g, 1.1 mmol) in MeOH
(10 mL) was added NaOMe (0.2 M in MeOH, few drops). After
5 min, ion exchange resin Amberlite IR 120 (H+) (0.1 g) was
added and the mixture was stirred for another 10 min, filtered,
Allyl 3-O-(3-O-Acetyl-2-azido-4,6-O-ben zyliden e-2-deoxy-
â-D-ga la ctop yr a n osyl)-2-O-ben zyl-4,6-O-ben zylid en e-â-D-
ga la ctop yr a n osid e (9g). To a suspension of 9f (6.51 g, 10.4
mmol), freshly prepared Ag2O (1.8 g), and 4 Å molecular sieves
in dry DMF (50 mL) was added BnBr (1.8 mL, 15.6 mmol),
and the mixture was stirred for 12 h at rt, filtered through
Celite, and concentrated. The resulting residue was purified
by column chromatography (7:1 toluene-acetone) to yield 9g
and concentrated in vacuo to give pure 9d (0.68 g, quant); [R]rt
D
1
+47.2° (c 1, CHCl3); TLC (5:2 toluene-acetone) Rf 0.26; H-
NMR δ 7.6-7.2 (m, 15H), 5.59 and 5.52 (2 s, 1H), 5.57 and
5.53 (2 s, 1H), 5.37 (d, J ) 1.9 Hz, 0.7H), 4.96 (d, J ) 7.9 Hz,
0.3H), 4.86-3.30 (m, 17H). Anal. Calcd for C33H35N3O10‚1/4-
H2O: C, 62.11; H, 5.61; N, 6.58. Found: C, 62.16; H, 5.64; N,
6.39.
(6.03 g, 81%): [R]rt +34.6° (c 1, CHCl3); TLC (4:1 toluene-
D
1
acetone) Rf 0.51, H NMR: δ 7.6-7.2 (m, 15H), 5.96 (m, 1H),
5.59 (s, 1H), 5.47 (s, 1H), 5.38-5.15 (m, 2H), 4.99 (d, J ) 9.8
Hz, 1H), 4.93 (d, J ) 8.0 Hz, 1H), 4.74 (d, J ) 9.8 Hz, 2H),
4.63 (dd, J ) 3.5, 10.9 Hz, 1H), 4.5-3.9 (m, 11H), 3.38 (br s,
1H), 3.32 (br s, 1H), 2.15 (s, 3H). Anal. Calcd for C38H41N3-
O11: C, 63.77; H, 5.77; N, 5.87. Found: C, 63.78; H, 5.84; N,
5.87.
3-O-(2-Azid o-4,6-O-ben zylid en e-2-d eoxy-3-O-(tr ich lor o-
acetim idoyl)-â-D-galactopyr an osyl)-2-O-ben zyl-4,6-O-ben -
zyliden e-r-D-galactopyr an osyl Tr ich lor oacetim idate (9e).
To a solution of 9d (120 mg, 0.19 mmol) and Cl3CCN (0.4 mL)
in dry CH2Cl2 was added DBU (1 drop) and the mixture was
stirred for 2 h under an argon atmosphere. The solvent was
then removed in vacuo and the residue purified by flash
chromatography (8:1 toluene-acetone) to yield 9e (130 mg,
76%) as a foam: TLC (8:1 toluene-acetone) Rf 0.31; 1H-NMR
δ 8.57 (s, 1H), 8.46 (s, 1H), 7.2-7.6 (m, 15H), 6.58 (d, J ) 2.4
Hz, 1H), 5.60 (s, 1H), 5.55 (s, 1H), 4.93 (d, J ) 8.0 Hz, 1H),
4.8-4.0 (m, 6H), 3.91 (br s, 1H), 3.46 (br s, 1H).
3-O-(3-O-Acetyl-2-a zid o-4,6-O-ben zylid en e-2-d eoxy-â-D-
ga la ct op yr a n osyl)-2-O-b en zyl-4,6-O-b en zylid en e-r,â-D-
ga la ctop yr a n ose (9h ). A mixture of compound 9g (5.00 g,
6.98 mmol), NaOAc (7.5 g, 83 mmol), and PdCl2 (2.48 g, 14.0
mmol) in 9:1 AcOH-H2O (100 mL) was stirred for 12h at 4 °C
and then filtered through Celite. The filtrate was poured on
ice-water (500 mL), extracted with CH2Cl2 (3 × 200 mL),
washed with saturated NaHCO3 solution (2 × 200 mL), and
dried (MgSO4). After removal of the solvent in vacuo, the
resulting residue was purified by flash chromatography (7:1
Ben zyl O-(2-Azid o-4,6-O-ben zylid en e-2-d eoxy-3-O-(tr i-
ch lor oa cetim id oyl)-â-D-ga la ctop yr a n osyl)-(1f3)-O-(2-O-
b en zyl-4,6-O-b en zylid en e-r-D-ga la ct op yr a n osyl)-(1f4)-
O-(2,3,6-tr i-O-ben zyl-â-D-ga la ctop yr a n osyl)-(1f4)-(3,6-d i-
O-ben zyl-2-O-p iva loyl-â-D-glu cop yr a n osid e (6a ). To a
cooled (-10 °C) suspension of 9e (100 mg, 0.11 mmol) and 10
(160 mg, 0.17 mmol) in dry Et2O (0.2 mL) was added TMSOTf
(0.01 M in Et2O, 11 µL) under an argon atmosphere. After
stirring for 1 h, NaHCO3 (s, 10 mg) and Et2O were added, and
the mixture was washed with saturated NaHCO3 solution (5
mL) and H2O (5 mL). The organic layer was dried (MgSO4),
filtered, concentrated in vacuo, and the residue was purified
by flash chromatography (9:1 toluene-EA) to afford 6a (119
toluene-acetone) to give 9h (4.08 g, 86%): [R]rt +63.2° (c 1,
D
CHCl3); TLC (4:1 toluene-acetone) Rf 0.27 and 0.18, 1H NMR:
δ 7.6-7.2 (m, 15H), 5.58 and 5.49 (2 s, 1H), 5.60 and 5.48 (2
s, 1H), 5.35 (d, J ) 3.3 Hz, 1H), 5.0-3.9 (m, 16H), 3.43 (br s,
1H), 2.15 (s, 3H). Anal. Calcd for C35H37N3O11‚1/2H2O: C,
61.39; H, 5.59; N, 6.14. Found: C, 61.57; H 5.69; N, 6.11.
3-O-(3-O-Acetyl-2-a zid o-4,6-O-ben zylid en e-2-d eoxy-â-D-
ga la ctop yr a n osyl)-2-O-ben zyl-4,6-O-ben zylid en e-r- a n d
â-D-ga la ctop yr a n osyl Tr ich lor oa cetim id a te (9ir a n d 9iâ).
To a solution of 9h (2.60 g, 3.85 mmol) in dry CH2Cl2 (50 mL)
was added Cl3CCN (2 mL) and DBU (1 drop). After stirring
for 1 h, the solvent was removed in vacuo and the residue was
purified by flash chromatography (5:2 PE-EA + 1% Et3N).
mg, 62%): mp 87 °C; [R]rt +36.7° (c 1, CHCl3); TLC (7:1
D
toluene-acetone) Rf 0.36; 1H-NMR δ 8.45 (s, 1H), 7.6-7.1 (m,
45H), 5.40 (s, 1H), 5.39 (s, 1H), 5.17 (d, J ) 2.9 Hz, 1H), 5.06
(dd, J ) 7.9, 9.5 Hz, 1H), 4.90-3.20 (m, 40H), 1.11 (s, 9H).
Anal. Calcd for C94H99N4O21Cl3: C, 65.37; H, 5.78; N, 3.24.
Found: C, 65.29; H, 5.82; N, 3.44.
9iR eluted first (2.71 g, 86%): [R]rt +92.4° (c 1, CHCl3); TLC
D
(5:2 PE-EA) Rf 0.42; 1H NMR: δ 8.58 (s, 1H), 7.6-7.2 (m, 15H),
6.64 (br s, 1H), 5.61 (s, 1H), 5.49 (s, 1H), 4.91 (d, J ) 8.0 Hz,
1H), 4.72 (d, J ) 10.9 Hz, 1H), 4.67 (d, J ) 10.9 Hz, 1H), 4.62
(dd, J ) 3.5, 10.8 Hz, 1H), 4.52 (br s, 1H), 4.4-3.9 (m, 9H),
3.39 (br s, 1H), 2.13 (s, 3H). Anal. Calcd for C37H37N4O11Cl3:
C, 54.19; H, 4.55; N, 6.83. Found: C, 54.02; H, 4.41; N, 6.87.
3-O-Acetyl-2-a zid o-4,6-O-ben zylid en e-2-d eoxy-r- a n d
-â-D-ga la ct op yr a n osyl Tr ich lor oa cet im id a t e (7c). To a
solution of 7b24a (9.3 g, 20.7 mmol) and AcOH (1.31 mL, 22.8
mmol) in dry THF (120 mL) at -20 °C was added dropwise
TBAF (20.7 mL of a 1.1 M solution in THF). The mixture was
then warmed up to 0 °C, diluted with Et2O (500 mL), washed
with saturated NaHCO3 solution (300 mL) and brine (2 × 200
mL), dried (MgSO4), and concentrated in vacuo. To a solution
of this residue in dry CH2Cl2 (200 mL) was added Cl3CCN (10
mL) and DBU (few drops). After stirring for 1 h, the solvent
was removed in vacuo and the residue was purified by flash
chromatography (8:1 toluene-acetone + 1% Et3N) to yield 7c
(8.0 g, 81%) as a 1:3.5 R/â mixture: TLC (5:1 toluene-acetone)
9iâ eluted second (0.22 g, 7%): [R]rt +40.8° (c 1, CHCl3);
D
1
TLC Rf (5:2 PE-EA) Rf 0.30, H NMR: δ 8.67 (s, 1H), 7.6-7.2
(m, 15H), 5.81 (d, J ) 8.1 Hz, 1H), 5.61 (s, 1H), 5.49 (s, 1H),
4.99 (d, J ) 9.9 Hz, 1H), 4.91 (d, J ) 8.0 Hz, 1H), 4.79 (d, J )
9.9 Hz, 1H), 4.63 (dd, J ) 3.5, 10.9 Hz, 1H), 4.4-3.2 (m, 40H),
2.15 (s, 3H). Anal. Calcd for C37H37N4O11Cl3: C, 54.19; H,
4.55; N, 6.83. Found: C, 54.23; H, 4.42; N, 6.92.
Ben zyl O-(3-O-Acetyl-2-a zid o-4,6-O-ben zylid en e-2-d e-
oxy-â-D-galactopyr an osyl)-(1f3)-O-(2-O-ben zyl-4,6-O-ben -
zylid en e-r- a n d -â-D-ga la ctop yr a n osyl)-(1f4)-O-(2,3,6-tr i-
O-ben zyl-â-D-ga la ctop yr a n osyl)-(1f4)-2,6-d i-O-ben zyl-â-
D-glu cop yr a n osid e (6cr a n d 6câ). To a solution of 10 (2 g,
2.1 mmol) in dry Et2O (5 mL) was added TMSOTf (0.5 mL of
a 0.1 M solution in dry Et2O) under an argon atmosphere. A
solution of 9iR/â (2.5 g of a 12:1 R/â mixture, 3.1 mmol) in dry
Et2O (10 mL) was then added dropwise while the reaction
stirred. After 30 min the mixture was neutralized with
NaHCO3 (s, 1 g), filtered, and concentrated in vacuo. The
residue was purified by flash chromatography (4:1 PE-EA).
1
Rf , 0.60, H NMR: δ 8.74 and 8.72 (2 s, 1H), 7.6-7.3 (m, 5H),
6.58 (d, J ) 2.9 Hz, 0.22H), 5.67 (d, J ) 8.2 Hz, 0.78H), 5.52
and 5.51 (2 s, 1H), 5.31 (dd, J ) 3.5, 9.6 Hz, 0.22H), 4.81 (dd,
J ) 3.6, 9.6 Hz, 0.78H), 2.17 and 2.15 (2 s, 3H). Anal. Calcd
for C17H17N4O6Cl3: C, 42.56; H, 3.57; N, 11.68. Found: C,
42.30; H, 3.41; N, 11.76.
Allyl 3-O-(3-O-Acetyl-2-azido-4,6-O-ben zyliden e-2-deoxy-
â-D-ga la ctop yr a n osyl)-4,6-O-ben zylid en e-â-D-ga la ctop y-
r a n osid e (9f). To a suspension of 7c (7.50 g, 15.6 mmol) and
8a (5.78 g, 18.8 mmol) in dry CH3CN (mL) was added TMSOTf
(7.8 mL of a 0.1M solution in dry CH3CN) at -20 °C under an
argon atmosphere. After stirring for 2 h, the resulting clear
solution was neutralized with NaHCO3 (s, 1 g), filtered, and
concentrated in vacuo. The residue was purified by flash
chromatography (5:1 toluene-acetone) to give 9f (8.22 g,
6cR eluted first (1.71 g, 51%): [R]rt +31.4° (c 1, CHCl3); TLC
D
(3:1 PE-EA) Rf 0.47, 1H NMR: δ 7.5-7.0 (m, 45H), 5.43 (s,
1H), 5.35 (s, 1H), 5.20 (d, J ) 2.7 Hz, 1H), 5.06 (dd, J ) 8.0,
9.5 Hz, 1H), 4.9-3.2 (m, 40H), 2.11 (s, 3H), 1.11 (s, 9H). Anal.
Calcd for C94H101N3O22: C, 69.48; H, 6.27; N, 2.59. Found: C,
69.77; H, 6.27; N, 2.84.
84%): [R]rt +28.0° (c 1, CHCl3); TLC (3:1 toluene-acetone)
D
Rf 0.45, 1H NMR: δ 7.6-7.2 (m, 10H), 5.94 (m, 1H), 5.57 (s,

Total Synthesis of SGG
J . Org. Chem., Vol. 61, No. 20, 1996 6879
6câ eluted second (0.40 g, 12%): [R]rt +15.3° (c 1, CHCl3);
for another 30 min. After addition of NaHCO3 (s, 0.1 g), the
reaction mixture was filtered and concentrated in vacuo, and
the resulting residue was purified by flash chromatography
D
TLC (4:1 toluene-acetone) Rf 0.52, 1H NMR: δ 7.7-6.7 (m,
45H), 5.48 (s, 1H), 5.16 (s, 1H), 5.13 (d, J ) 10.2Hz, 1H), 5.06
(dd, J ) 8.1, 9.5 Hz, 1H), 4.95-3.35 (m, 40H), 2.13 (s, 3H),
1.13 (s, 9H). Anal. Calcd for C94H101N3O22: C, 69.48; H, 6.27;
N, 2.59. Found: C, 69.36; H, 6.35; N, 2.44.
(3:1 toluene-acetone). 11a â eluted first (49 mg, 13%): [R]rt
D
+23.1° (c 1, CHCl3); TLC (4:1 toluene-acetone) Rf 0.40, 1H
NMR: δ 7.0-7.7 (m, 35H), 5.72 (s, 1H), 5.44 (s, 1H), 5.42 (s,
1H), 5.41 (m, 1H), 5.35 (m, 1H), 5.30 (m, 1H), 5.26 (dd, J )
2.3, 12.2 Hz, 1H), 5.18 (d, J ) 3.0 Hz, 1H), 5.09 (dd, J ) 7.9,
9.4 Hz, 1H), 4.66 (d, J ) 7.7 Hz, 1H), 4.58 (d, J ) 8.8 Hz, 1H),
4.48 (d, J ) 8.6 Hz, 1H), 4.44 (d, J ) 8.1 Hz, 1H), 3.97 (m,
1H), 3.78 (s, 3H), 2.74 (br s, 1H), 2.67 (dd, J ) 4.4, 12.2 Hz,
1H), 2.14 (s, 3H), 2.08 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H), 1.90
(t, J ) 13.1 Hz, 1H), 1.67 (s, 3H), 1.13 (s, 9H). Anal. Calcd
for C125H140N4O38: C, 65.09; H, 6.12; N, 2.43. Found: C, 64.88;
H 6.28; N, 2.64.
Ben zyl O-(2-Azid o-4,6-O-ben zylid en e-2-d eoxy-â-D-ga -
la ctop yr a n osyl)-(1f3)-O-(2-O-ben zyl-4,6-O-ben zylid en e-
r-D-ga la ctop yr a n osyl)-(1f4)-O-(2,3,6-tr i-O-ben zyl-â-D-ga -
la ct op yr a n osyl)-(1f4)-3,6-d i-O-b en zyl-2-O-p iva loyl-â-D-
glu cop yr a n osid e (6b). (a) To a solution of 6a (100 mg, 57.9
µmol) in MeOH (5 mL) was added 1 N HCl (1 mL), and the
mixture was stirred for 24 h at rt. After neutralization
(saturated NaHCO3 solution), the solvent was removed in
vacuo and the residue extracted with acetone and purified by
flash chromatography (3:1 PE-EA) to give 6b (47 mg, 61%)
as an amorphous powder: [R]rtD +21.7° (c 1, CHCl3); TLC (2:1
PE-EA) Rf 0.35; 1H-NMR δ 7.0-7.5 (m, 45H), 5.44 (s, 1H),
5.39 (s, 1H), 5.2 (d, J ) 2.5 Hz, 1H), 5.08 (dd, J ) 7.9, 9.6 Hz,
1H), 4.90-3.00 (m, 40H), 2.42 (d, J ) 9.7 Hz, 1H), 1.12 (s,
9H). Anal. Calcd for C92H99N3O21: C, 69.81; H, 6.30; N, 2.65.
Found: C, 69.83; H, 6.20; N, 2.87.
11a R eluted second (180 mg, 48%): [R]rt +24.6° (c 1,
D
CHCl3), 1H NMR: δ 7.5-7.0 (m, 50H), 5.45 (s, 2H), 5.40 (s, 1H),
5.43 (m, 1H), 5.30 (dd, J ) 1.6, 9.2 Hz, 1H), 5.17 (d, J ) 3.2
Hz, 1H), 5.16 (d, J ) 8.7 Hz, 1H), 5.09 (dd, J ) 8.0, 9.4 Hz,
1H), 4.88 (m, 1H), 4.66 (d, J ) 7.7 Hz, 1H), 4.58 (d, J ) 8.8
Hz, 1H), 4.48 (d, J ) 8.6 Hz, 1H), 4.44 (d, J ) 8.1 Hz, 1H),
4.35 (m, 1H), 4.02 (m, 1H), 3.50 (s, 3H), 2.74 (dd, J ) 4.5, 12.7
Hz, 1H), 2.73 (br s, 1H), 2.21 (s, 3H), 2.16 (s, 3H), 2.01 (s, 3H),
1.99 (s, 3H), 2.03 (t, J ) 12.8 Hz, 1H), 1.88 (s, 3H), 1.13 (s,
9H). Anal. Calcd for C125H140N4O38: C, 65.09; H, 6.12; N, 2.43.
Found: C, 65.00; H 6.39; N, 3.05.
(b) To a solution of 6cR (1.65 g, 1.02 mmol) in dry MeOH (5
mL) was added saturated methanolic ammonia solution (10
mL), and the mixture was stirred for 6 h at rt. After removal
of the solvent, the residue was purified through a short silica
gel column (2:1 PE-EA) to yield 6b (1.61 g, quant), identical
with the product described above.
O-(Meth yl 5-Aceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id e-
oxy-D-glycer o-r-D-ga la cto-2-n on u lopyr an osylon ate)-(2f3)-
O-(2,4,6-t r i-O-a cet yl-â-D-ga la ct op yr a n osyl)-(1f3)-O-(2-
acetam ido-4,6-di-O-acetyl-2-deoxy-â-D-galactopyr an osyl)-
(1f3)-O-(2,4,6-tr i-O-a cetyl-r-D-ga la ctop yr a n osyl)-(1f4)-
O-(2,3,6-t r i-O-a cet yl-â-D-ga la ct op yr a n osyl)-(1f4)-1,3,6-
tr i-O-a cetyl-2-O-p iva loyl-r/â-D-glu cop yr a n osid e (11b). A
mixture of 11a (145 mg, 62.8 mmol) and freshly prepared32
Pd(OH)2 (19% on carbon, 50 mg) in MeOH (50 mL) was stirred
under H2 (4 bar) at rt for 24 h. The mixture was filtered and
washed with MeOH (50 mL). The filtrate was concentrated,
and the resulting residue was coevaporated with toluene (2 ×
10 mL), dissolved in 1:1 Py-Ac2O (3 mL), and kept at rt for
24 h. The mixture was then poured on ice-water (50 mL) and
extracted with CH2Cl2 (3 × 25 mL). The organic layer was
washed with 1 M HCl (50 mL), saturated NaHCO3 solution
(50 mL), and brine (50 mL). After removal of the solvent in
vacuo, the resulting residue was purified by flash chromatog-
raphy (40:1 CHCl3-MeOH) to yield 11b (108 mg, 85%) as a
1:1 mixture of R and â anomers: TLC (30:1 CHCl3-MeOH)
Ben zyl O-(2,3-Di-O-Acetyl-4,6-O-ben zylid en e-â-D-ga la c-
topyr an osyl)-(1f3)-O-(2-azido-4,6-O-ben zyliden e-2-deoxy-
â-D-ga la ctop yr a n osyl)-(1f3)-O-(2-O-ben zyl-4,6-O-ben zyl-
id en e-r-D-ga la ctop yr a n osyl)-(1f4)-O-(2,3,6-tr i-O-ben zyl-
â-D-galactopyr an osyl)-(1f4)-3,6-di-O-ben zyl-2-O-pivaloyl-
â-D-glu cop yr a n osid e (3a ). To a stirred suspension of 6b (1.5
g, 0.95 mmol) and 5 (0.71 g, 1.42 mmol) in dry Et2O (5 mL)
was added TMSOTf (0.47 mL of a 0.1 M solution in dry Et2O)
under an argon atmosphere. The mixture was stirred for 30
min at rt, NaHCO3 (s, 1 g) was added, and the mixture was
filtered and concentrated in vacuo. The residue was purified
by flash chromatography (2:1 PE-EA) to yield 3a (1.82 g,
94%): [R]rt +44.8° (c 1, CHCl3); TLC (7:4 PE-EA) Rf 0.22,
D
1H NMR: δ 7.6-7.0 (m, 50H), 5.53 (s, 1H), 5.44 (s, 1H), 5.41
(s, 1H), 5.39 (dd, J ) 8.0, 10.4 Hz, 1H), 5.18 (d, J ) 2.9 Hz,
1H), 5.09 (dd, J ) 8.0, 9.5 Hz, 1H), 4.99 (dd, J ) 3.6, 10.4 Hz,
1H), 4.9-3.15 (m, 45H), 2.08 (s, 3H), 2.03 (s, 3H), 1.13 (s, 9H).
Anal. Calcd for C109H117N3O28: C, 68.29; H, 6.15; N, 2.19.
Found: C, 67.88; H, 6.27; N, 2.37.
1
Rf 0.29, H NMR: δ 6.30 (d, J ) 3.7 Hz), 4.05 (m, 1H), 3.85 (s,
3H), 2.58 (dd, J ) 4.6, 12.7 Hz, 1H), 2.25-1.80 (m, 60H), 1.68
(t, J ) 12.4 Hz, 1H), 1.13 and 1.14 (2 s, 9H); MS-FAB
(thioglycerol matrix, NaI) m/ z 2037 (MNa+). Anal. Calcd for
C85H118N2O53: C, 50.64; H, 5.90; N, 1.39. Found: C, 50.70; H
6.07; N, 1.01.
Ben zyl O-(4,6-O-Ben zylid en e-â-D-ga la ct op yr a n osyl)-
(1f3)-O-(2-a zid o-4,6-O-ben zylid en e-2-d eoxy-â-D-ga la cto-
p yr a n osyl)-(1f3)-O-(2-O-b en zyl-4,6-O-b en zylid en e-r-D-
ga la ct op yr a n osyl)-(1f4)-O-(2,3,6-t r i-O-b e n zyl-â-D-ga -
la ct op yr a n osyl)-(1f4)-3,6-d i-O-b en zyl-2-O-p iva loyl-â-D-
glu cop yr a n osid e (3b). To a solution of 3a (533 mg, 0.28
mmol) in dry MeOH (3 mL) was added saturated methanolic
ammonia solution (5 mL) and the mixture was stirred for 4 h
at rt. After removal of the solvent, the residue was purified
through a short silica gel column (4:1 toluene-acetone) to yield
O-(Meth yl 5-Aceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id e-
oxy-D-glycer o-r-D-ga la cto-2-n on u lopyr an osylon ate)-(2f3)-
O-(2,4,6-t r i-O-a cet yl-â-D-ga la ct op yr a n osyl)-(1f3)-O-(2-
acetam ido-4,6-di-O-acetyl-2-deoxy-â-D-galactopyr an osyl)-
(1f3)-O-(2,4,6-tr i-O-a cetyl-r-D-ga la ctop yr a n osyl)-(1f4)-
O-(2,3,6-tr i-O-a cetyl-â-D-ga la ctop yr a n osyl)-(1f4)-3,6-d i-
O-acetyl-2-O-pivaloyl-r,â-D-glu copyr an ose (11c). A solution
of 11b (100 mg, 49.7 µmol) in dry DMF (3 mL) was stirred
with NH2NH2‚AcOH (8 mg) at 40 °C for 1 h. The mixture was
then diluted with AcOEt (30 mL) and washed with brine (20
mL). The aqueous layer was washed (AcOEt, 2 × 15 mL) and
the combined organic layer was concentrated in vacuo and
purified by column chromatography (40:1 CH2Cl2-MeOH) to
3b (510 mg, quant): [R]rt + 48.0° (c 1, CHCl3); TLC (4:1
D
1
toluene-acetone) Rf 0.30, H NMR: δ 7.6-7.0 (m, 50H), 5.58
(s, 1H), 5.46 (s, 1H), 5.45 (s, 1H), 5.20 (d, J ) 3.0 Hz, 1H),
5.10 (dd, J ) 8.0, 9.6 Hz, 1H), 4.9-3.1 (m, 47H), 2.83 (br s,
1H), 2.52 (br s, 1H), 1.13 (s, 9H). Anal. Calcd for C105H113N3O26:
C, 68.80; H, 6.21; N, 2.29. Found: C, 68.56; H, 6.30; N, 2.40.
Ben zyl O-(Meth yl 5-Aceta m id o-4,7,8,9-tetr a -O-a cetyl-
3,5-d id eoxy-D-glycer o-r- a n d â-D-ga la cto-2-n on u lop yr a -
n osylon a te)-(2f3)-O-(4,6-O-ben zylid en e-â-D-ga la ctop yr -
a n osyl)-(1f3)-O-(2-a zid o-4,6-O-ben zylid en e-2-d eoxy-â-D-
galactopyr an osyl)-(1f3)-O-(2-O-ben zyl-4,6-O-ben zyliden e-
r-D-ga la ct op yr a n osyl)-(1f4)-O-(2,3,6-t r i-O-b en zyl-â-D-
ga la ctop yr a n osyl)-(1f4)-3,6-d i-O-ben zyl-2-O-p iva loyl-â-
D-glu cop yr a n osid e (11a a n d 11a â). To a solution of 3b (300
mg, 0.16 mmol of a 5:1 R/â mixture) and 2 (150 mg, 0.25 mmol)
in dry CH3CN (3 mL) was added TMSOTf (0.16 mL of a 0.1 M
solution in dry CH3CN) at -50 °C under an argon atmosphere.
After stirring for 30 min, more 2 (50 mg, 0.08 mmol, solution
in 0.5 mL of dry CH3CN) was added and the mixture stirred
yield 11c (92 mg, 94%): [R]rt +55.6° (c 1, CHCl3); TLC (20:1
D
CHCl3-MeOH) Rf 0.44, 1H NMR: 6.18 (d, J ) 8.0 Hz, 1H),
3.81 (s, 3H), 2.54 (dd, J ) 4.1, 12.2 Hz, 1H), 2.25-1.82 (m,
57H), 1.67 (t, J ) 12.3 Hz, 1H), 1.15 (s, 9H); MS-FAB
(thioglycerol matrix, NaI) m/ z 1995 (MNa+). Anal. Calcd for
C83H116N2O52: C, 50.50; H, 5.92; N, 1.42. Found: C, 50.22; H
6.11; N, 1.25.
O-(Meth yl 5-Aceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id e-
oxy-D-glycer o-r-D-ga la cto-2-n on u lopyr an osylon ate)-(2f3)-
O-(2,4,6-t r i-O-a cet yl-â-D-ga la ct op yr a n osyl)-(1f3)-O-(2-
acetam ido-4,6-di-O-acetyl-2-deoxy-â-D-galactopyr an osyl)-

6880 J . Org. Chem., Vol. 61, No. 20, 1996
Lassaletta et al.
(1f3)-O-(2,4,6-tr i-O-a cetyl-r-D-ga la ctop yr a n osyl)-(1f4)-
O-(2,3,6-tr i-O-a cetyl-â-D-ga la ctop yr a n osyl)-(1f4)-3,6-d i-
(33 mg, 87%): [R]rt +32.9° (c 1, CHCl3); TLC (25:1 CH2Cl2-
D
1
MeOH) Rf 0.50, H NMR: δ 8.1-7.4 (m, 5‚ , Ph), 5.88 (dt, J )
O-a cet yl-2-O-p iva loyl-r-D-glu cop yr a n osyl
Tr ich lor o-
6.6, 14.7, 1H, H-5cer), 5.75 (d, J ) 8.2 Hz, 1H, NH-2d), 5.73
(d, J ) 9.8 Hz, 1H, NH-2cer), 5.6-5.4 (m, 5H, H-8f, H-3cer,
H-1c, H-4d, H-4cer), 5.37 (dd, J ) 2.5, 8.8 Hz, 1H, H-7f), 5.18
(d, J ) 8.7 Hz, 1H, H-1d), 4.69 (d, J ) 7.8 Hz, 1H, H-1e), 4.48
(m, H-2cer), 4.47 (d, J ) 8.3 Hz, 1H, H-1b), 4.44 (d, J ) 8.0
Hz, 1H, H-1a), 3.85 (s, 3H, CO2Me), 2.59 (dd, J ) 4.5, 12.5
Hz, 1H, H-3feq), 2.25-1.90 (m, 53H, 17 OAc, H-6cer, H-6′cer),
3.33 (m, 1H, H-2d), 1.85 (s, 3H, NAc), 1.73 (s, 3H, NAc), 1.63
(t, J ) 13.3 Hz, 1H, H-3fax), 1.4-1.2 (m, 48H, 24 CH2), 1.15
(s, 9H, OPiv), 0.88 (t, J ) 6.5 Hz, 6H, 2 CH3); MS-FAB
(thioglycerol matrix, NaI) m/ z 2620 (MNa+). Anal. Calcd for
C124H186N3O55: C, 57.33; H, 7.18; N, 1.62. Found: C, 56.98;
H 7.29; N, 1.45.
a cetim id a te (11d ). To a solution of 11c (80 mg, 40 µmol) in
dry CH2Cl2 (5 mL) was added Cl3CCN (40 µL) and DBU (1
drop). After stirring for 2 h, the solvent was removed in vacuo
and the residue was purified through a short silica gel column
(50:1 CH2Cl2-MeOH) to afford 11d (80 mg, 93%): [R]rtD +72.8°
(c 1, CHCl3); TLC (40:1 CH2Cl2-MeOH) Rf 0.28, 1H NMR: δ
8.66 (s, 1H), 6.51 (d, J ) 3.6 Hz, 1H), 3.84 (s, 3H), 2.58 (dd, J
) 4.6, 12.9 Hz, 1H), 2.25-1.94 (m, 54H), 1.85 (s, 3H), 1.73 (s,
3H), 1.68 (t, J ) 12.3 Hz, 1H), 1.14 (s, 9H). Anal. Calcd for
C85H116N4O52Cl3: C, 48.20; H, 5.52; N, 2.65. Found: C, 48.13;
H, 5.61; N, 2.43.
O-(Meth yl 5-Aceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id e-
oxy-D-glycer o-r-D-ga la cto-2-n on u lopyr an osylon ate)-(2f3)-
O-(2,4,6-t r i-O-a cet yl-â-D-ga la ct op yr a n osyl)-(1f3)-O-(2-
acetam ido-4,6-di-O-acetyl-2-deoxy-â-D-galactopyr an osyl)-
(1f3)-O-(2,4,6-tr i-O-a cetyl-r-D-ga la ctop yr a n osyl)-(1f4)-
O-(2,3,6-tr i-O-a cetyl-â-D-ga la ctop yr a n osyl)-(1f4)-3,6-d i-
O-a ce t yl-2-O-p iva loyl-â-D-glu cop yr a n osyl-(1f1)-(2S ,-
3R,4E)-2-a zid o-3-O-ben zoyl-4-octa d ecen e-1,3-d iol (12a ).
To a solution of 11d (70 mg, 30 µmol) and (2S,3R,4E)-2-azido-
3-(benzoyloxy)-4-octadecen-1-ol (4) (25 mg, 60 µmol) in dry CH2-
Cl2 (200 µL) was added TMSOTf (17 µL of a 0.01 M solution
in dry CH2Cl2) under an argon atmosphere and the mixture
was stirred at rt for 1 h. NaHCO3 (s, 10 mg) was then added
and the mixture was filtered, concentrated, and purified by
flash chromatography (40:1 CH2Cl2-MeOH) to yield 23 (57
O-(5-Acet a m id o-3,5-d id eoxy-D-glycer o-r-D-ga la cto-2-
n on u lop yr a n osylon ic Acid )-(2f3)-O-(â-D-ga la ctop yr a n o-
syl)-(1f3)-O-(2-acetam ido-2-deoxy-â-D-galactopyr an osyl)-
(1f3)-O-(r-D-ga la ct op yr a n osyl)-(1f4)-O-(â-D-ga la ct o-
p yr a n osyl)-(1f4)-â-D-glu cop yr a n osyl-(1f1)-(2S,3R,4E)-2-
h exa d eca n a m id o-4-octa d ecen e-1,3-d iol (1). To a solution
of 12b (22 mg, 8.5 µmol) in dry MeOH (1.5 mL) was added
NaOMe (0.2 M in MeOH, 0.35 mL) and the mixture was stirred
for 24 h at 40 °C. KOH (0.2 M in water, 0.4 mL) was added
and the mixture stirred at rt for another 24 h. The solution
was then neutralized with ion-exchange resin Amberlite IR
120 (H+), filtered, and concentrated in vacuo. The residue was
purified by column chromatography (1:1 CH2Cl2-EtOH) on
Sephadex LH-20 (15 mL) to yield 1 (14.2 mg, quantitative) as
mg, 72%): [R]rt +29.7° (c 1, CHCl3); TLC (25:1 CH2Cl2-
a white powder: [R]rt +8.5° (c 0.4, Py); TLC (8:4:3 n-BuOH-
D
D
MeOH) Rf 0.45, 1H NMR: δ 8.1-7.4 (m, 5‚ ), 5.91 (dt, J ) 6.5,
14.5, 1H), 5.75 (d, J ) 7.4 Hz, 1H), 4.70 (d, J ) 8.0 Hz, 1H),
3.85 (s, 3H), 3.34 (m, 1H), 2.59 (dd, J ) 4.3, 12.4 Hz, 1H), 2.25-
1.94 (m, 53H), 1.85 (s, 3H), 1.80 (s, 3H), 1.68 (t, J ) 12.5 Hz,
1H), 1.4-1.2 (m, 22H), 1.17 (s, 9H), 0.88 (t, J ) 6.6 Hz, 3H);
MS-FAB (thioglycerol matrix + NaI) m/ z 2406 (MNa+). Anal.
Calcd for C108H153N5O54: C, 54.38; H, 6.46; N, 2.94. Found:
C, 54.66; H 6.47; N, 2.77.
AcOH-H2O) Rf 0.37, 1H NMR (500 » Hz, 95:5 DMSO-d6/D2O,
40 °C): δ 5.51 (dt, J ) 6.8, 15.4, 1H, H-5cer), 5.33 (dd J ) 7.1,
15.4 Hz, 1H, H-4cer), 4.79 (d, J ) 4.0 Hz, 1H, H-1c), 4.56 (d,
J ) 7.3 Hz, 1H, H-1d), 4.24 (d, J ) 7.7 Hz, 1H, H-1b or e),
4.22 (d, J ) 7.9 Hz, 1H, H-1b or e), 4.16 (d, J ) 7.8 Hz, 1H,
H-1a), 3.86 (m, 1H, H-3cer), 3.53 (m, 1H, H-4f), 3.02 (dd J )
7.2, 8.2, 1H, H-2a), , 2.74 (dd J ) 4.6, 11.8, 1 H, H-3feq), 2.01
(t, J ) 7.1 Hz, 2H, COCH2), 1.91 (m, 2H, H-6cer, H-6′cer), 1.86
(s, 3H, NAc), 1.78 (s, 3H, NAc), 1.34 (t, J ) 11.6 Hz, 1H,
H-3fax), 0.83 (t, J ) 6.9 Hz, 6H, 2 CH3). MS-FAB (thioglycerol/
PNB matrix, NaI) m/ z 1725 (M + 2Na+); (thioglycerol/PNB
matrix, CsI) m/ z 1945 (M + 2Cs+).
O-(Meth yl 5-Aceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id e-
oxy-D-glycer o-r-D-ga la cto-2-n on u lopyr an osylon ate)-(2f3)-
O-(2,4,6-t r i-O-a cet yl-â-D-ga la ct op yr a n osyl)-(1f3)-O-(2-
acetam ido-4,6-di-O-acetyl-2-deoxy-â-D-galactopyr an osyl)-
(1f3)-O-(2,4,6-tr i-O-a cetyl-r-D-ga la ctop yr a n osyl)-(1f4)-
O-(2,3,6-tr i-O-a cetyl-â-D-ga la ctop yr a n osyl)-(1f4)-3,6-d i-
O-a cet yl-2-O-p iva loyl-r,â-D-glu cop yr a n osyl-(1f1)-(2S,-
3R,4E)-2-h exa d eca n a m id o-3-O-ben zoyl-4-octa d ecen e-1,3-
d iol (12b). H2S was slowly bubbled through a solution of 23
(35 mg, 14.7 µmol) in 8:2 Py-H2O (4 mL) for 2 h at rt. After
stirring for 48 h, the solvent was concentrated in vacuo, the
bath temperature being kept under 30 °C. To a solution of
the residue in dry CH2Cl2 (3 mL) were added palmitic acid (9
mg, 34 µmol) and N-(3-(N,N-dimethylamino)propyl)-N′-ethyl-
carbodiimide hydrochloride (WSC) (9 mg, 46 µmol), and the
mixture was stirred for 18 h at rt. The reaction mixture was
then diluted with more CH2Cl2 (15 mL), washed with H2O (2
× 5 mL), and concentrated in vacuo. The residue was purified
by flash chromatography (40:1 CH2Cl2-MeOH) to yield 12b
Ack n ow led gm en t. We thank the EC (Human Capi-
tal and Mobility program), the Deutsche Forschungs-
gemeinschaft, and the Fonds der Chemischen Industrie
for financial support. KC is grateful for a fellowship
within the Erasmus program (EC).
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectrum
for compound 1 (2 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
J O9608073