Novel Bicylic Donors for the Synthesis of 2-Deoxy-β-Glycosides

Article abstract of DOI:10.1021/jo971934h

Novel bicyclic glycosyl donors have been prepared by the cycloaddition reaction of glycals with 3-thiono-2,4-pentanedione 17 followed by methylenation of the resulting ketone. Treatment of the heterocyclic donors with triflic acid in the presence of a variety of alcohol acceptors leads to the formation of β-glycosides in good yields and with excellent stereoselectivities. Desulfurization of the C-2 carbon-sulfur bonds gives the corresponding 2-deoxy-β-glycosides. This method has been extended to the synthesis of glycosidic linkages found in the aureolic acid antibiotics. Tetra-N-butylammonium triflate proved to be a useful additive in these glycosylation reactions, suggesting an important role for triflate anion in stabilizing intermediates which are formed.

Full text of DOI:10.1021/jo971934h

J . Org. Chem. 1998, 63, 2197-2208
2197
Novel Bicylic Don or s for th e Syn th esis of 2-Deoxy-â-Glycosid es†
Richard W. Franck* and Cecilia H. Marzabadi*
Department of Chemistry, Hunter College/ CUNY, 695 Park Avenue,
New York, New York 10021
Received October 20, 1997
Novel bicyclic glycosyl donors have been prepared by the cycloaddition reaction of glycals with
3-thiono-2,4-pentanedione 17 followed by methylenation of the resulting ketone. Treatment of the
heterocyclic donors with triflic acid in the presence of a variety of alcohol acceptors leads to the
formation of â-glycosides in good yields and with excellent stereoselectivities. Desulfurization of
the C-2 carbon-sulfur bonds gives the corresponding 2-deoxy-â-glycosides. This method has been
extended to the synthesis of glycosidic linkages found in the aureolic acid antibiotics. Tetra-N-
butylammonium triflate proved to be a useful additive in these glycosylation reactions, suggesting
an important role for triflate anion in stabilizing intermediates which are formed.
In tr od u ction
simplified triethylene glycol-aglycone fragment9 forms
2:1 complexes with Mg2+, and these complexes interact
with DNA. Because of their high toxicity, the aureolic
acids have found limited therapeutic application.1 How-
ever, because of their significant biological activity, efforts
to synthesize less toxic analogues and to understand the
nature of the interactions of these antibiotics with DNA
are important.
The 2-deoxy-â-glycosidic linkage is an important struc-
tural component in many natural products including: the
aureolic acids1 1, the calchiceamicins,2 the cardiac gly-
cosides,3 and the angucycline antibiotics.4 In the past
two decades, more than a dozen attractive methods for
the synthesis of the 2-deoxy-â-linkage have been re-
ported, and these methods have been the subject of
reviews.5 However, thus far, no single method has been
recognized as “first among equals”.
As part of our ongoing interest in the synthesis of the
aureolic acid antibiotics, we have previously confronted
the problems inherent in the construction of the 2-deoxy-
â-glycosidic linkage.10 The aureolic acids are particularly
challenging molecules, in that, 2-deoxy-â-glycosides are
found both in the saccharide chains, as well as between
the aglycone moiety and the saccharide chains. The A-B
disaccharides are linked to phenolic residues, and the
C-D-E trisaccharides to R-hydroxy ketones. A variety
of approaches to the synthesis of these molecules have
been reported. Most recently, in a series of papers, Roush
has reviewed these methods and has described his
successful approaches to forging these linkages en route
to a total synthesis of the aureolic acid antibiotic olivo-
mycin A.11 To date, no method has been described which
utilizes a common sugar donor to effect all of the glycoside
linkages in this family of antibiotics.
The aureolic acid antitumor antibiotics are inhibitors
of DNA-dependent RNA polymerase and are known to
bind as 2:1 antibiotic:Mg2+ complexes in the DNA minor
groove.6 Structure-activity studies have shown that the
two intact oligosaccharide chains are essential for bio-
logical activity.7 Kahne has shown that the complete
C-D-E trisaccharide-aglycone8 or, more recently, a
We describe herein the results of our studies on the
development of a highly selective glycosylation protocol
(6) Gao, X.; Patel, D. J . Biochemistry 1989, 28, 751. (b) Banville, D.
L.; Keniry, M. A.; Shafer, R. H. Biochemistry 1990, 29, 6521. (c) Ibid.
Biochemistry 1990, 29, 9204. (d) Gao, X.; Patel, D. J . Biochemistry
1990, 29, 10940. (e) Gao, X.; Mirau, P.; Patel, D. J . J . Mol. Biol. 1992,
223, 259. (f) Sastry, M.; Patel, D. J . Biochemistry 1993, 32, 6588.
(7) Koshel, K.; Hartmann, G.; Kersten, W.; Kersten, H. Biochem.
Z. 1966, 344, 76. (b) Behr, W.; Honikel, K.; Hartmann, G. Eur. J .
Biochem. 1969, 9, 82. (c) Hayaska, T.; Inoue, Y. Biochemistry 1969, 8,
2342.
(8) (a) Silva, D. J .; Goodnow, R.; Kahne, D. Biochemistry 1993, 32,
463. (b) Silva, D. J .; Kahne, D. E. J . Am. Chem. Soc. 1993, 115, 7962.
(9) Silva, D. J .; Kahne, D. J . Am. Chem. Soc. 1994, 116, 2641.
(10) (a) Ramesh, S.; Franck, R. W. J . Chem. Soc., Chem. Commun.
1989, 960. (b) Ramesh, S.; Kaila, N.; Grewal, G.; Franck, R. W. J . Org.
Chem. 1990, 55, 5. (c) Grewal, G,; Kaila, N.; Franck; R. W. J . Org.
Chem. 1992, 57, 2084. (d) Franck, R. W.; Kaila, N. Carbohydr. Res.
1993, 239, 71.
† Dedicated to Erwin Fleissner on the occasion of his retirement as
Dean of the Division of Sciences and Mathematics at Hunter College.
* Professor Richard Franck: phone (212)772-5340. E-mail
rfranck@shiva.hunter.cuny.edu. Dr. Cecilia Marzabadi: phone
(212)772-5339. E-mail cmarza@aol.com.
(1) Remers, W. A. In The Chemistry of Antitumor Antibiotics;
Wiley-Interscience: New York, 1979; pp 133-175. (b) Remers, W. A.;
Iyengar, B. S. In Cancer Chemotherapeutic Agents; W. O. Foye, Ed.;
American Chemical Society, 1995; p 578.
(2) Lee, M. D.; Dunne, T. S.; Chang, C. C.; Siegel, M. M.; Morton,
G. O.; Ellestad, G. A.; McGahren, W. J .; Borders, D. B. J . Am. Chem.
Soc. 1992, 114, 985. (b) Nicolau, K. C.; Dai, W. M. Agnew. Chem. Int.
Ed. Engl. 1991, 30, 1387.
(3) Henderson, F. G. In Digitalis; C. Fish and Surawicz, Eds.; Grune
& Stratton; New York, 1969; pp 3-21.
(4) Rohr, J .; Thiericke, P. Nat. Prod. Rep. 1992, 9, 103.
(5) Thiem, J .; Klaffke, W. Top. Curr. Chem. 1990, 154, 285; (b)
Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
(11) (a) Sebesta, D. P.; Roush, W. R. J . Org. Chem. 1992, 57, 4799.
(b) Roush, W. R.; Lin, X. J . Am. Chem. Soc. 1995, 117, 2236. (c) Roush,
W. R.; Briner, K.; Kesler, B. S.; Murphy, M. J . Org. Chem. 1996, 61,
6098.
S0022-3263(97)01934-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/12/1998

2198 J . Org. Chem., Vol. 63, No. 7, 1998
Franck and Marzabadi
Sch em e 1
tion to the developing oxocarbenium ion, such as an
acetate group, a more stable dioxolenium ion 4 may be
generated. Then, nucleophillic attack at the anomeric
center produces exclusively the 1,2-trans glycoside 5â.
Recently, vinyl (alkenyl) glycosides21-26 6 have also
been shown to possess excellent donor properties. These
compounds have been prepared by: (1) methylenation of
anomeric acetates;21a,22 (2) the reaction of organometallic
species with glycosyl bromides;21b,23 (3) isomerization of
allyl glycosides;24 (4) E1 chemistry;25 and (5) anomeric
alkoxide addition to methyl phenylpropiolate.26 The
mechanism of activation of these donors 6 is believed to
involve the initial reaction of the electrophilic species (E+)
with the vinyl ether double bond leading to the formation
of a cation 7. This cation then collapses to produce an
oxocarbenium ion 3 which reacts to produce a glycoside
5. Again, neighboring group participation plays an
important role in dictating the stereochemical outcome
of the glycosylation reaction. In some cases, the glycosyl
acceptor reacts directly with the activated double bond
to give glycoside 8 which may then be rearranged to the
anomeric position.25
for the synthesis of 2-deoxy-â-glycosides.12 This method
utilizes a single sugar donor and gives glycosides for a
variety of acceptors, including those types found in the
aureolic acid antibiotics.
Ba ck gr ou n d . The most common method for glycosyl
transfer involves the electrophilic activation of an ano-
meric carbon which contains a good leaving group
(Scheme 1). Examples of leaving groups which have been
successfully utilized include the anomeric halides,13,14
acetates,15 sulfides,16 sulfoxides,17 phosphates and phos-
phites,18 trichloroacetimidates,19 and pentenyl glyco-
sides.20
Upon activation, the anomeric group of the donor 2
departs and an oxocarbenium ion 3 is formed. This
intermediate 3 is trapped by an alcohol acceptor, giving
rise to a mixture of glycosides 5r and 5â. Often, when
the sugar donor contains an equatorial protecting group
at C-2 which is capable of providing anchimeric stabiliza-
(12) A preliminary report of this work has appeared: Marzabadi,
C. H.; Franck, R. W. J . Chem. Soc., Chem. Commun. 1996, 2651.
(13) For examples see: (a) Koenigs, W.; Knorr, E. Chem. Ber. 1901,
34, 957. (b) Lemieux, R. U.; Hayami, J . L. Can. J . Chem. 1965, 43,
2162. (c) Paulsen, H.; Lockoff, O. Chem. Ber. 1981, 114, 3102.
(14) (a) Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett. 1981, 431.
(b) Nicolau, K. C.; Dolle, R. E.; Papahatjis, D. P.; Randall, J . L. J . Am.
Chem. Soc. 1984, 106, 4189.
(15) (a) Helferich, B,; Shimitz-Hillebrecht, E. Chem. Ber. 1933, 66,
378. (b) Lemeiux, R. U.; Shyluk, W. P. Can. J . Chem. 1953, 31, 528.
(c) Hanessian, S.; Banoub, J . Carbohydr. Res. 1977, 59, 261. (d)
Dahmen, J .; Frejd, T.; Magnusson, G.; Noori, G. Carbohydr. Res. 1983,
114, 328. (e) Ogawa, T.; Beppu, K.; Nakabayashi, S. Carbohydr. Res.
1981, 93, C6.
(16) (a) Ferrier, R. J .; Hay, R. W.; Vethaviyasar, N. Carbohydr. Res.
1983, 116, 162. (b) Ito, Y.; Ogawa, T. Tetrahedron Lett. 1988, 29, 1061.
(c) Nicolau, K. C.; Seitz, S. P.; Papahatjis, D. P. J . Am. Chem. Soc.
1983, 105, 2430. (d) Konradsson, P. Udodong, U. E.; Fraser-Reid, B.
Tetrahedron Lett. 1990, 31, 4313. (e) Veeneman, G. H.; van Leeuwen,
S. H.; van Boom, J . H. Tetrahedron Lett. 1990, 31, 1331. (f) Dasgupta,
F.; Garegg, P. J . Carbohydr. Res. 1988, 177, C13. (g) Fugedi, P.;
Garregg, P. J . Carbohydr. Res. 1986, 149, C9.
None of the methods described above are particularly
useful for the direct synthesis of the 2-deoxy-â-glycosidic
linkage. The lack of a participating C-2 substituent
makes a highly stereocontrolled and efficient glycosyla-
tion difficult. The intermediate oxocarbenium ion which
is generated favors the trapping of acceptor in the axial
direction due to a developing anomeric effect.27 In
addition, glycosidic bonds of 2-deoxy sugars possess low
stability under acidic conditions due to the lack of a C-2
electron-withdrawing group, and hydrolysis and anomer-
ization readily occurs.28
For these reasons, the most frequently employed
strategy for accessing 2-deoxy-â-glycosides uses tempo-
rary equatorial blocking groups at C-2 which can be
(17) Kahne, D.; Walker, S.; Chang, Y.; van Enger, D. J . Am. Chem.
Soc. 1989, 111, 6881.
(21) (a) Chenault, H. K.; Chafin, L. F. J . Org. Chem. 1994, 59, 6167.
(b) Chenault, H. K.; Castro, A.; Chafin, L. F.; Yang, J . J . Org. Chem.
1996, 61, 5024.
(22) Marra, A.; Esnault, J .; Veyrieres, A.; Sinay, P. J . Am. Chem.
Soc. 1992, 114, 6354.
(23) de Raadt, A.; Ferrier, R. J . Carbohydr. Res. 1991, 216, 93.
(24) (a) Boons, G. J .; Isles, S. Tetrahedron Lett. 1994, 35, 3593. (b)
Boons, G. J .; Isles, S. J . Org. Chem. 1996, 61, 4262.
(25) Senaidman, M. L.; J ohnson, S. C.; Crasto, C.; Hecht, S. M. J .
Org. Chem. 1995, 60, 3942.
(26) Vankar, Y. D.; Vankar, P. S.; Behrendt, M.; Schmidt, R. R.
Tetrahedron 1991, 47, 9985.
(27) (a) Deslongchamps, P. In Stereoelectronic Effects in Organic
Chemistry; Pergammon Press: Oxford, 1983; pp 4-29. (b) Kirby, A. J .
The Anomeric Effect and Related Stereoelectronic Effects at Oxygen;
Springer-Verlag: New York, 1983. (c) J uaristi, E.; Cuevas, G. Tetra-
hedron 1992, 48, 5019.
(18) (a) Boger, D. L.; Honda, T. J . Am. Chem. Soc. 1994, 116, 5647.
(b) Kondo, H.; Aoki, S.; Ichikawa, Y.; Halcomb, R. L.; Ritzen, H.; Wong,
C.-H., J . Org. Chem. 1994, 59, 864. (c) Muller, T.; Schneider, R.;
Schmidt, R. R. Tetrahedron Lett. 1994, 35, 4763. (d) Watanabe, Y.;
Nakamoto, C.; Yammamoto, S.; Ozaki, S. Tetrahedron 1994, 50, 6523.
(e) Yamanoi, T.; Nakamura, K.; Takeyama, H.; Yanagihara, Y. Bull.
Chem. Soc. J pn. 1994, 67, 1359. (f) Muller, T.; Hummel G.; Schmidt,
R. R.; Liebigs Ann. Chem. 1994, 325. (g) Singh, K.; Fernandez-
Mayorlas, A.; Martin-Lomas, M. J . Chem. Soc. Chem. Commun. 1994,
775.
(19) Schmidt, R. R.; Michel, J . Agnew. Chem. Int. Ed. Engl. 1980,
19, 731.
(20) (a) Fraser-Reid, B.; Konradsson, P.; Mootoo, D. R., Udodong,
U. J . Chem. Soc., Chem. Commun. 1988, 823. (b) Mootoo, D. R.;
Konradsson, P.; Udodong, U.; Fraser-Reid, B. J . Am. Chem. Soc. 1988,
110, 5583. (c) Mootoo, D. R.; Konradsson, P.; Fraser-Reid, B. J . Am.
Chem. Soc. 1989, 111, 8540.
(28) Feather, M. S.; Harris, J . F. J . Org. Chem. 1965, 30, 153.

Bicyclic Donors for the Synthesis of 2-Deoxy-â-Glycosides
J . Org. Chem., Vol. 63, No. 7, 1998 2199
Sch em e 2
Sch em e 3
removed following glycosylation. Halo-,29,30 thiophenyl-
31
,
selenophenyl-,32 and formylamido-33 groups have all
been employed as temporary protecting groups. These
moieties help stabilize the resulting glycosidic bond and
are also believed to participate in the stabilization of
oxocarbenium ion intermediates analogous to 3. Often
the â-stereoselectivity obtained is excellent.
Previous work in our group focused on this type of
approach to 2-deoxy-â-glycosides.10b Addition of aryl-
bis(arylthio)sulfonium salts and alcohols to glycals gave
in some cases excellent stereoselectivities for the 2-deoxy-
2-(arylthio)-â-glucosides (Scheme 2). The arylthio group
at C-2 could then be removed with Raney nickel. Un-
fortunately, this method was not uniformly â-selective
and required the use of harsh reagents, low tempera-
tures, and anhydrous reaction conditions. With these
problems in mind, we sought to develop a method which
was both facile and highly selective.
Later reductive removal of sulfur at C-2 would give a
2-deoxy-â-glycoside 13.
The heterodiene system which led to the development
of our new method described in this paper is the diacyl
thione 17, which is generated in situ from the phthal-
imidosulfenyl precursor 16 (eq 2).35 In turn, 16 is easily
formed from 2,4-pentanedione 15 and phthalimidosulfe-
nyl chloride 14.36
The genesis for our new concept for glycosyl transfer
came from earlier work in the inverse electron demand
Bradsher cycloaddition reactions of isoquinolinium salts
with glycals34 (eq 1). These reactions were both easy to
carry out and gave the cis-1,2-dideoxy-C-glucosides as a
single diastereoisomer.
Diacyl thione 17 undergoes cycloaddition reactions
with a variety of glycals under mild conditions.35c,37-39
With tri-O-benzyl-D-glucal 18, adduct 19 is obtained in
80% yield (5 days) (eq 3). A small amount of a minor
diastereoisomer 20 is also formed (5%) and is easily
separated from 19 by column chromatography. The
adduct 22 obtained from tri-O-benzyl-D-galactal 21 is
isolated as a single diastereoisomer (73%; 3 days) (eq 4).
The conversion of these adducts into useful glycosyl
donors for the highly stereoselective synthesis of 2-deoxy-
â-glycosides is the subject of this paper. Applications of
the method described to the construction of important
linkages found in the aureolic acid family of antibiotics
will also be discussed.
We visualized an extension of this approach to the
cycloaddition reaction of a heterodiene such as 10 with
a glycal 9 (Scheme 3). The resulting heterocycle 11 would
be a vinyl glycoside which should possess excellent donor
properties. Reaction with an electrophilic catalyst could
conceivably cause cleavage of the C1-oxygen bond and
in the presence of an appropriate acceptor molecule, a
glycoside 12 could be formed. The acyl side chain or the
C-2 sulfur could provide neighboring group participation,
making the glycosylation process highly stereoselective.
Resu lts
(29) (a) Bock, K.; Pedersen, M.; Thiem, J . Carbohydr. Res. 1979,
73, 85. (b) Thiem, J .; Gerken, M. J . Org. Chem. 1985, 50, 954.
(30) (a) Thiem, J .; Gerken, M.; Schottmer, B.; Weigand, J . Carbo-
hydr. Res. 1987, 164, 327. (b) Thiem, J .; Schottmer, B. Agnew. Chem.,
Int. Ed. Engl. 1987, 26, 555.
Our initial attempts at glycosyl transfer focused on the
cleavage of the anomeric carbon-oxygen bond of adduct
(31) (a) Nicolau, K. C.; Ladduwahetty, T.; Randal, J . L.; Chu-
cholowski, A. J . Am. Chem. Soc. 1986, 108, 2466. (b) Toshima, K.;
Mukaiyama, S.; Ishiyama, T.; Tatsuta, K. Tetrahedron Lett. 1990, 31,
3339. See also ref 5b.
(32) Perez, M.; Beau, J . M. Tetrahedron Lett. 1989, 30, 75.
(33) Tavecchia, P.; Trumtel, M.; Veyieres, A.; Sinay, P. Tetrahedron
Lett. 1989, 30, 2533.
(35) For example see: (a) Capozzi, G.; Nativi, C.; Menichetti, S.; Rosi,
A.; Valle, G. Tetrahedron 1992, 48, 9023. (b) Capozzi, G.; Menichetti,
S.; Nativi, C.; Rossi, A.; Franck, R. W. Tetrahedron Lett. 1993, 34, 4253.
(c) Capozzi, G.; Franck, R. W.; Menichetti, S.; Mattioli, M.; Nativi, C.;
Valle, G. J . Org. Chem. 1995, 60, 6416.
(36) Ley, S. V.; Bombala, M. U. J . Chem. Soc., Perkin Trans. 1 1979,
3013.
(34) Gupta, R. B.; Franck, R. W. J . Am. Chem. Soc. 1989, 111, 7668.

2200 J . Org. Chem., Vol. 63, No. 7, 1998
Franck and Marzabadi
19 (eq 5).37 Although the adduct cleanly opened to give
â-methyl glucoside 23 when using a p-toluenesulfonic
acid (p-TsOH) catalyst in methanol, a reduction in the
quantity of acceptor employed or the use of the less
nucleophilic acceptor, 1,2:3,4-diisopropylidenegalactopy-
ranose (DIPG) 24, failed to give the desired glycoside.
Similarly, a change in acid catalyst to trifluoroacetic acid
(TFA) or triflic acid (TfOH) failed to effect glycosylation.
resonance of the sugar derived from the acceptor (H-1′)
was a doublet centered at 5.52 ppm ( J 1′,2′ ) 5.1 Hz). The
H-2′ resonance was a doublet of doublets centered at 4.28
ppm (J ) 4.8, 2.2 Hz). The H-1 resonance of the newly
formed glycosidic linkage appeared as a doublet centered
at 4.41 ppm. The H-2 resonance was a doublet of
doublets centered at 2.78 ppm. The assignment of â
stereochemistry for the glycosidic linkage of 28 was based
on the values of J 1,2 (8.4 Hz) and J 2,3 (9.0 Hz) which were
indicative of a trans-trans diaxial arrangement of the
protons at H-1 through H-3. In addition, 13C-1H con-
nectivities for the anomeric carbons were determined by
HETCOR experiments. The C-1′ resonance was assigned
at 96.2 ppm and C-1 at 103.3 ppm. One bond carbon-
hydrogen coupling constants (1J (13C1H)) were determined
for both anomeric carbons. The coupling constant for C-1′
1
was found to be 156 Hz, whereas J for C-1 had a larger
We next looked at possible methods for activating the
adducts.37,38 Olefination of the cycloadduct 19 to produce
a diene would generate an extended vinyl glycoside.
Treatment of 19 with methyl Wittig reagent gave diene
26 (53%). Higher yields of diene were, however, realized
using commercially available Nysted Reagent40 25 acti-
vated by TiCl4 (76%) (eq 6). Similarly, the galactose-
derived cycloadduct 22 underwent methylenation with
this reagent to produce 27 (69%).
Dienes 26 and 27 were easy to handle compounds
which proved to be relatively stable. No decomposition
of these materials was observed even after a year when
they were stored at low temperatures (-20 °C).
value of 178 Hz. These values are consistent with an
axial and equatorial glycosidic linkage, respectively.41
A range of other promoters were also assayed for their
effectiveness using the coupling of 26 and glycosyl
acceptor 24 as a representative reaction (Table 1). With
most of the other acid promoters, only â-glycoside 28 was
again detected in the reaction mixtures. None of the
glycoside resulting from addition of acceptor to the vinyl
ether double bond was observed. In addition to disac-
charides, unreacted starting materials and to a lesser
extent (<5%) mixtures of free sugars derived by hydroly-
sis of 26 accounted for the mass balance from these
reactions.
The methylenated compounds proved to be superior
glycosyl donors. Donor 26 when reacted with 2 equiv of
DIPG 24 and 1 equiv of p-TsOH afforded modest yields
of glycoside 28 (Table 1, entry 1). None of the R-glycosidic
product was observed either in the 1H NMR (CDCl3)
spectrum of the crude reaction mixture or from the
analysis of fractions from column chromatography.
Structural assignments for 28 were established in part
Falck’s catalyst (PPh3HBr),42 gave an R:â mixture of
glycosides (Table 1, entry 6). When aluminum(III)
chloride was used as the promoter, substantial amounts
of de-isopropylidenated material was obtained (Table 1,
entry 5). No reaction occurred when trifluoroacetic acid
was used (Table 1, entry 8). N-Iodosuccinimide failed to
cause scission of the heterocyclic ring (Table 1, entry 9).
Instead, mixtures of alkoxy iodides were obtained as a
result of the addition of reagent and acceptor to both
endocyclic and exocyclic double bonds.
1
using H-COSY (400 MHz) experiments. The anomeric
(37) (a) Presented in part: 209th National ACS Meeting, Anaheim,
CA; April 1995; CARB 033. (b) Presented in part: 211th National ACS
Meeting, New Orleans, LA; March 1996; ORGN 300.
(38) Capozzi, G.; Mannocci, F.; Menichetti, S.; Nativi, C.; Paoletti,
S. J . Chem. Soc., Chem. Commun. 1997, 2291.
The lanthanide triflates have been shown to be effec-
tive glycosylation catalysts.43 However, with donor 26,
and a Yb(OTf)3 catalyst, glycoside formation occurred
(39) (a) Capozzi, G.; Dios, A.; Franck, R. W.; Geer, A.; Marzabadi,
C.; Menichetti, S.; Nativi, C.; Tamarez, M. Agnew. Chem., Int. Ed. Engl.
1996, 35, 7.
(40) Watson, A. T.; Park, K.; Wiemer, D. P.; Scott, W. J . J . Org.
Chem. 1995, 60, 5102 and ref 17 therein.
(41) Bock, K.; Pedersen, C. J . Chem. Soc., Perkin Trans. 2 1974,
293.
(42) Bolitt, V.; Mioskowski, C.; Lee, S. G.; Falck, J . R. J . Org. Chem.
1990, 55, 5812.

Bicyclic Donors for the Synthesis of 2-Deoxy-â-Glycosides
J . Org. Chem., Vol. 63, No. 7, 1998 2201
Ta ble 1. Th e Effect of P r om oter on Isola ted Yield s of Disa cch a r id e 28
entry
equiv of acceptor
equiv of donor
promoter
solvent
temp (°C)
time, h
yield (%) of 28a
1
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
1
1
p-TsOH
TMSOTf
TfOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
5
5
5
44
5
40
3
-20
-20 to 5
1
76
4
BF3‚Et2O
4
42
5
AlCl3
5
25
25
25
5
1
62b
63c
43
6
PPh3HBr
1
d
7
Yb(OTf)3
CF3CO2H
NIS
48
24
2
8
NR
NRe
NR
9
10
Bu4NOTf
25
24
a
b
Yields reported are isolated yields and are calculated using the donor 26 as the limiting reagent. Significant amounts of
de-isopropylidenated material was also detected. c A mixture of disaccharides was obtained (1:10 R:â). 0.3 equiv of catalyst was used.
d
e Complex mixtures of alkoxy halides were formed.
Ta ble 2. Rea ction of th e Glu co Dien e Cycloa d d u ct 26
tion, none of the R-disaccharide was observed when this
solvent was employed.
w ith DIP G 24. Tr iflic Acid a s th e P r om oter
Donor 26 also reacted well with a variety of other
acceptors (Table 3) under our optimized reaction condi-
tions (1 equiv of donor, 2 equiv of acceptor, and 1 equiv
of TfOH). Methyl glucoside 29 was obtained cleanly in
74% yield (Table 3, entry 1). Protected glycerol (1-O-
hexadecyl-2-O-methyl-sn-glycerol) prepared by Bittman45
gave glycoside 30 in 73% yield (Table 3, entry 2).
Disaccharide 31 was obtained in modest yields (57%)
from the reaction of 26 with methyl 2,3,4-tri-O-methyl-
R-D-glucopyranoside.46 The less-nucleophilic secondary
sugar alcohol, methyl 6-O-benzyl-2,3-di-O-methyl-R-D-
glucopyranoside,47 produced disaccharide 32 in 67%
isolated yield.
isolated
temp (%) yield
equiv of equiv of
equiv of
CF3SO3H solvent
entry acceptor
donor
(°C)
of 28
1
2
3
4
5
6
7
8
9
1
1.5
2
3
2
2
2
2
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0.5
0.1
0.2c
1.2
1
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
Et2O
-20
-20
-20
-20
-20
-20
-20
-20
-20
-20
22a
53
76
73
NR
<10b
64
53d
53e
45f
10
2
1
Polymeric material was present in the crude mixture. bMo-
a
lecular sieves were excluded from the reaction mixture. c With 1
The â-glucopyranose acceptor48 (Table 3, entry 5) gave
disappointingly low yields of â-disaccharide 33 (28%)
presumably due to steric effects. In addition to recovered
starting materials, R-disaccharide (3%) and â-benzyl
glycoside 34 (12%) were recovered from the reaction
d
equiv of Bu4NOTf. De-isopropylidenated material was formed
under these conditions. e Two-hour reaction time. f Four-hour reac-
tion time.
very sluggishly at room temperature to afford only a 43%
yield of disaccharide after 2 days (Table 1, entry 7).
Triflic acid proved to be the promoter of choice with
regards to reaction rate, product yield, and cleanliness
of the reaction (Table 1, entry 3). Attempts to reduce
the quantity of triflic acid resulted in prolonged reaction
times and/or reduced yields (Table 2). Removal of
molecular sieves from the reaction pot (Table 2, entry 6)
appeared to reduce the quantity of acid required to effect
glycosyl transfer, as did the addition of Bu4NOTf (Table
2, entry 7).
mixture. Similar results were obtained using methyl
mannoside48 35 as the acceptor. Seemingly, debenzyla-
tion of the sugar acceptor (at the primary OR) occurs
preferentially to the nucleophilic attack by the congested
C-2 hydroxy group.49 Addition of Bu4NOTf in conjunction
with a reduction in TfOH (0.4 equiv) appeared to sup-
press the formation of R-disaccharide, although the
A change in solvent system to acetonitrile (Table 2,
entry 9) or diethyl ether (Table 2, entry 10) also gave
rise to reduced yields of disaccharide 28 when triflic acid
was used. Acetonitrile has previously been shown to be
an effective â-selective glycosylation solvent.22 Interme-
diate R-acetonitrilium species are believed to be involved.
However, for our representative reaction, only a 53%
yield of â-glycoside 28 was realized even after doubling
the reaction time (2 h). The use of diethyl ether as a
solvent has previously been shown to enhance the ratio
of 1,2-cis disaccharides obtained.44 For our model reac-
(44) Igarashi, K.; Irisawa, J .; Honma, T. Carbohydr. Res. 1975, 39,
213-225.
(45) Marino-Albernas, J . R.; Bittman, R.; Peters, A.; Mayhew, E. J .
Med. Chem. 1996, 39, 3241.
(46) Dziewiszek, K.; Zamoiski, A. Carbohydr. Res. 1986, 150, 163.
(47) Garegg, M. E. P. J .; Hultberg, H.; Oscarson, S. J . Carbohydr.
Chem. 1983, 2, 305.
(48) Marzabadi, C. H.; Spilling, C. D. J . Org. Chem. 1993, 58, 3761.
(49) A similar debenzylation of a primary benzyloxy group has
recently been reported: Pozgay, V.; Dubois, E. P.; Lotter, H.; Nezmelyi,
A. Carbohydr. Res. 1997, 303, 165.
(43) Inanaga, J .; Yokoyama, Y.; Hanamoto, T. Tetrahedron Lett.
1993, 34, 2791.

2202 J . Org. Chem., Vol. 63, No. 7, 1998
Franck and Marzabadi
Ta ble 3. Rea ction s of th e Glu co Dien e Cycloa d d u ct 26
w ith Oth er Alcoh ol Accep tor s
Ta ble 4. Rea ction of th e Glu co Dien e Cycloa d d u ct 26
w ith â-Na p h th ol 41
%
%
%
entry
promoter
reaction time 42a 43a 44a
1
2
3
4
1.0 equiv TfOH
1.0 equiv TfOH
1.0 equiv TfOH
0.2 equiv TfOH +
1.0 equiv Bu4NOTf
40 min
1 h
1 h, 30 min
1.5 h
36
29
-
12
11
-
16
-
67
b
b
69
a
Isolated yields from column chromatography using donor 26
as the limiting reagent. Not isolated. Less than 5% by 1H NMR.
b
phenolic moiety, and the construction of the 2-deoxy-â-
glycoside in a galactose-based sugar framework.
Toward these ends we prepared the racemic model
acyloin 39 using Kahne’s procedure.50 Using only 1.5
equiv of racemic acyloin 39 with 1 equiv of donor 26 and
with 1 equiv of triflic acid, resulted in a 69% yield of a
1.3:1 mixture of glycosides 40a ,b both with the â-config-
uration about C-1 and R,S-isomeric about C-2′ (eq 8).
These diastereoisomers were isolated by careful column
chromatography.
a
b
Calculated using donor 26 as the limiting reagent. 1 equiv
of triflic acid was used. c 0.4 equiv of TfOH + 1 equiv of Bu4NOTf.
â-benzyl glycoside was still formed in comparable amounts,
and no significant improvements in yield were observed.
Ketone cycloadduct 37 (Table 3, entry 6) was prepared
by cycloaddition of acylthione 17 with 4,6-di-O-benzyl-
D-glucal 36 (eq 7). This acceptor also acts as an efficient
glycosylating agent producing â-disaccharide 38 (53%),
as well as its R-anomer (10%). Access to 38 opens the
possibility for an “armed-disarmed” 20 (or “latent-ac-
tive” 24) approach to 2-deoxy-â-oligosaccharide synthesis.
Reaction of 26 with â-naphthol 41 proved to be
troublesome (Table 4). When the reaction was allowed
to proceed until complete consumption of 26 was indi-
cated by thin-layer chromatography, only the â-C-
glycosidic product 44 was observed (Table 4, entry 3).
Using shorter reaction times (Table 4, entries 1 and 2),
mixtures of R- and â-O- and C-aryl glycosides (42-44)
were obtained in low yield. Apparently, using our
standard reaction conditions, epimerization at the C-1
glycosidic bond readily occurs to give the R-O-glycoside.
Also, the O-glycosides undergo rapid rearrangement to
their C-glycosyl analogues as previously observed by
Kometani.51 Ultimately, only the more stable â-C-
glycoside 44 results. We were able to circumvent this
acid-catalyzed rearrangement process by a reduction in
the quantity of triflic acid used (0.2 equiv) and with the
addition of 1 equiv of tetra-N-butylammonium triflate.
Th e Au r eolic Acid F a m ily of An tibiotics. As part
of our continuing efforts aimed at the synthesis of
members of the aureolic acid family of antibiotics, we
directed our glycosylation studies toward constructing
2-deoxy-â-glycosidic likages which were characteristic of
this family. In particular, we were interested in the
construction of the 2-deoxy-â linkages present with the
acyloin portion of the molecule, the linkage with the
(50) Silva, D. J .; Kraml, C. M.; Kahne, D. Biorg., & Med. Chem.
1994, 2, 1251.
(51) Kometani, U.; Kondo, H.; Fujimori, Y. Synthesis 1988, 1005.

Bicyclic Donors for the Synthesis of 2-Deoxy-â-Glycosides
J . Org. Chem., Vol. 63, No. 7, 1998 2203
Ta ble 5. Rea ction of th e Ga la cto Dien e Cycloa d d u ct 27
w ith DIP G 24
was accomplished using Raney nickel (W2) (Table 6). In
most cases the yields were good for the reduction of 28-
30, 33, and 42, although some variation in yield and
reaction time was observed depending on the age and
quality of the Raney nickel and upon the nature of the
compound undergoing reduction.
Methyl glucoside52 46 was obtained in 66% isolated
yield from the reduction of 29, whereas a 95% yield was
realized for the glycerol glycoside 47 derived from 30.45
Disaccharides 4810c (from 28) and 49 (from 33) were also
obtained in respectable yields (76 and 73%, respectively)
following treatment with Raney nickel.
yield of
entry
acid/equiv
TfOH/1.0
Ph3PHBr/1.0
CF3CO2H/1.0
temp (°C)
disaccharidea
1
2
3
4
-20
5
5
-20
nd (dec)
35% (1:5; R:â)
â-Naphthol O-glycoside 42 proved to be the most
problematic example, giving only a 35% isolated yield of
2-deoxy-glycoside 50.11b Tri-O-benzyl-D-glucal and 1,2-
dideoxy-3,4,6-tri-O-benzyl-D-arabino-hexopyranose were
isolated in substantial quantities as the result of the
facile overreduction of this substrate. Cooling the reac-
tion mixture and using other solvents failed to reduce
this process. Similar low yields have been obtained by
other groups when attempting to desulfurize related
compounds,53,11b and, in some cases, the reduction was
improved by changing the reducing agent to Bu3SnH/
AIBN. Unfortunately, switching reducing agents to
Bu3SnH/AIBN failed to cause desulfurization of our
glycoside.
nd
TfOH/0.4 + Bu4NOTf/1.0
64% (only â)
a
Isolated yields; calculated with donor 27 as the limiting
reagent.
Ta ble 6. Ra n ey Nick el Desu fu r iza tion of Glycosid es
Sch em e 4
Using this modified procedure, â-O-glycoside 42 was
obtained very cleanly (69%), with only baseline quantities
of other detectable products.
Discu ssion
Our next goal was to see if our glycosylation protocol
would be suitable for other sugar donors. The galactose-
derived diene cycloadduct 27 was reacted with 2 equiv
of DIPG 24 and 1 equiv of triflic acid at -20 °C (Table 5;
entry 1). Unfortunately, only rapid decomposition of the
donor was observed under these conditions. Several
other acids were tried and also gave poor results. Only
when PPh3HBr was used (Table 5, entry 2) was any
detectable quantity of disaccharide 45 observed (35%).
As was seen for the gluco case when the Falck catalyst
was used, a mixture of R- and â-disaccharides was
obtained (1:3). Using a modified protocol (0.4 equiv of
TfOH/1.0 equiv of Bu4NOTf) (Table 5, entry 4) we again
saw a dramatic improvement in both the isolated yield
(64%) and observed diastereoselectivity (only â-disaccha-
ride 45â was detected) of glycosylation.
A proposed mechanism for glycosyl transfer for the
heterocycles described is shown in Scheme 4. Initially,
electrophilic activation of the exocyclic double bond leads
to the formation of a carbocation 51. This carbocation
can be viewed as a delocalized structure with oxonium
ion 52 as a major contributing form. Oxocarbenium ion
52 then further rearranges to produce 53. Or, 53 is
formed directly from 26. This oxocarbenium ion 53 may
be stabilized by electrostatic interaction with the newly
liberated 2-thioacyl side chain. Or, participation by the
equatorial C-2 sulfur may give rise to an intermediate
thiiranium ion 54. Either intermediate would form on
the axial face of the sugar ring and therefore block this
(52) (a) Crich, D.; Ritchie, T. J . J . Chem. Soc., Chem. Commun. 1988,
1461. (b) Crich, D.; Ritchie, T. Carbohydr. Res. 1989, 190, C1. (c) Crich,
D.; Ritchie, T. J . J . Chem. Soc., Perkins Trans. 1 1990, 945.
(53) Hashimoto, S.; Yanagiya, Y.; Honda, T.; Ikegami, S. Chem. Lett.
1992, 1511.
R a n ey Nick el Desu lfu r iza t ion of Glycosid es.
Completion of the 2-deoxy-â-glycoside synthesis required
the efficient removal of the 2-thioacyl substituent. This

2204 J . Org. Chem., Vol. 63, No. 7, 1998
Franck and Marzabadi
Con clu sion s
face from attack by incoming nucleophiles. Then, exclu-
sive backside attack to produce the 1,2-trans glycoside
55 occurs.
We have described a new method for the synthesis of
2-deoxy-â-glycosides which is both facile and highly
stereoselective and which is at least comparable with
existing methods for the preparation of these compounds.
This method utilizes a single sugar donor type and
affords glycosides for a variety of alcohol acceptors.
Several disaccharides have been prepared from both
primary and secondary sugar acceptors, and we have
demonstrated the utility of this method to a possible
“armed-disarmed” 20 motif. Post-glycosylation processing
of the disaccharides gives, in most cases, good yields of
the 2-deoxy glycosides.
Our studies have led us to discover the benefits of
adding tetra-N-butylammonium triflate to our triflate-
promoted glycosylations, particularly when acid-sensitive
functionalities are present or when secondary acid pro-
cesses are possible.
The fact that these reactions are not catalytic in triflic
acid and are augmented by the addition of tetra-N-
butylammonium triflate suggests that the conjugate base
(TfO-) may play a role in stabilizing intermediates which
are formed in the course of the reaction thereby giving
rise to enhanced yields. Triflate may serve as a stabiliz-
ing counterion for thiaranium ion 54 or for oxonium ion
53. Or, the triflate anion may interact directly with the
intermediate which is formed as a nucleophile to produce
an anomeric triflate 56. Because of a large anomeric
effect,27 the anomeric triflate 56 would be predicted to
exist mainly as the axial (R) anomer. Then, in an SN2-
like fashion, nucleophilic attack by the acceptor would
produce the â-glycoside 55.
We have been able to forge three important linkages
found in the aureolic acid family of antibiotics: with an
acyloin, with â-naphthol, and between two galactose
moieties. An extension of this method to the synthesis
of the C-D-E trisaccharide present in the aureolic acid
antibiotic, mithramycin,1 is currently being investigated.
Studies aimed at optimization of the cleavage of the C-2
carbon-sulfur bond are ongoing. The reactions of the
bicyclic donors with other nucleophiles is also being
examined.
Tetra-alkylammonium salts of halides have been used
for many years as additives in the R-selective glycosyla-
tion reactions of anomeric halides with alcohol accep-
tors.54 Oxonium ion-halide ion pairs or â-glycosyl
halides were suggested to be intermediates in the glyco-
sylation process.
Crich and Sun have proposed55a and have recently
shown55b that anomeric triflates are the reactive inter-
mediates in the synthesis of â-mannosides from anomeric
sulfoxides using a modified Kahne glycosylation proto-
col.17 They observed a pronounced decrease in â-selectiv-
ity when the alcohol protecting group at C-2 of the donor
was bulky. The authors attributed this poor selectivity
to the sluggish reactivity of the anomeric triflate in a
sterically crowded environment and to its subsequent
decomposition to an oxocarbenium ion.
The poor selectivity and low yields obtained for disac-
charide 33 may be the result of retarded triflate displace-
ment for steric reasons and the resulting decomposition
of the triflate to the oxocarbenium ion 53, followed by
trapping of the alcohol acceptor in the axial direction.
Likewise, this may account for the mixtures of glycosides
obtained when bulky acceptor 37 was used.
Conversely, the triflate salt may help buffer the
reaction medium and prevent acid-catalyzed epimeriza-
tion of the glycosidic bond. In addition to suppressing
R-glycoside formation in 34, the salt also substantially
reduced anomerization in the reaction of galactose donor
27 with DIPG 24 and in the reaction of donor 26 with
â-naphthol 41. The acid-catalyzed O- to C-rearrange-
ment which is frequently observed in activated phenols
was also prevented by the addition of tetra-N-butylam-
monium triflate.
Exp er im en ta l Section
Gen er a l In for m a tion . All 1D and 2D 1H spectra were
recorded at 300 or 400 MHz, and all 13C spectra were recorded
at 75 MHz using CDCl3 as a solvent. Melting points are
uncorrected. Optical rotations were recorded under standard
conditions. Low resolution mass spectra were obtained by
chemical ionization (NH3).
All reactions were performed under an inert atmosphere.
Solvents were dried and distilled prior to use: diethyl ether
and THF from sodium/benzophenone ketyl, CH2Cl2 and CHCl3
from P2O5 , and CH3CN from CaH2. Anhydrous methanol,
anhydrous DMF, 2,4-pentanedione, tri-O-acetyl-D-glucal, and
Nysted reagent40 were purchased from Aldrich Chemical Co.
1,2:3,4-Diisopropylidene-R-D-galactopyranose (DIPG) was pur-
chased from Pfansthiel Chemical Company. Raney nickel
(W2) was prepared as described in the literature56 or was used
as supplied by Aldrich. 3,4,6-Tri-O-benzyl-D-galactal,57 methyl
6-O-benzyl-2,3-di-O-methyl-R-D-glucopyranoside,47 methyl 2,3,4-
tri-O-methyl-R-D-glucopyranoside,46 and methyl 3,4,6-tri-O-
benzyl-â-D-glucopyranoside48 were prepared using published
procedures. Thiophthalimide 16 and cycloadduct 19 were
prepared as reported elsewhere.35c Molecular sieves (3A) were
purchased from Aldrich Chemical Co. and were powdered and
activated (150 °C oven for 12 h) prior to use. Crude products
were purified by flash column chromatography on silica gel
(Merck; 230-400 mesh) or on neutral alumina (BA I).
P r ep a r a tion of 4,6-Di-O-ben zyl-D-glu ca l (36). To a
suspension of NaH (1.73 g, 43 mmol) in DMF (50 mL) was
added D-glucal58 (3.16 g, 22 mmol) portionwise as a solution
in DMF (25 mL). After stirring at room temperature for 40
min, the mixture was cooled to 5 °C, and tetra-N-butylammo-
nium iodide (0.31 g) and benzyl bromide (5.2 mL, 44 mmol)
were added. The mixture was slowly warmed to room tem-
perature (2 h) and was stirred an additional 48 h. The mixture
was quenched with water (10 mL) and was extracted with
(54) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; J ames, K. J . Am.
Chem. Soc. 1975, 97, 4056.
(55) (a) Crich, D.; Sun, S. J . Org. Chem. 1997, 62, 1198. (b) While
this manuscript was undergoing revision the existence of anomeric
triflates as reactive intermediates was convincingly shown: Crich, D.;
Sun, S. J . Am. Chem. Soc. 1997, 119, 11217.
(56) Mozingo, R. Org. Synth. Coll. Vol. 3, 1955, 181.
(57) Kozikowski, A. P.; Lee, J . J . Org. Chem. 1990, 55, 863.
(58) Prepared by methanolysis of tri-O-acetyl-D-glucal using Am-
berlite IRA-400 resin.

Bicyclic Donors for the Synthesis of 2-Deoxy-â-Glycosides
J . Org. Chem., Vol. 63, No. 7, 1998 2205
CH2Cl2 (3×, 75 mL). The combined organic fractions were
extracted with additional water (5×, 100 mL) and with brine
(100 mL) to afford after concentration in vacuo a mixture of
glucals. Column chromatography (SiO2; 15-40% ethyl acetate
in petroleum ether) gave as the major products: 3,4,6-tri-O-
benzyl-D-glucal59 (1.65 g) and 36 (0.96 g): an oil; [R]D +42.4°
(c ) 0.8, CHCl3 ); IR (thin film) 3409, 3031, 2871, 1647, 1597,
at room temperature afforded from chromatography (SiO2; 25-
50% EtOAc in petroleum ether): R-gluco cycloadduct 37 as an
oil (0.08 g, 63%): IR (thin film) 3432, 2919, 1673, 1629, 1570,
1483, 1409, 1354, 1239, 1103, 1038 cm-1 1H NMR δ 7.54-
;
7.21 (m, 10H), 5.21 (d, 1H, J ) 3.3 Hz), 4.83 (d, 1H, J ) 11.1
Hz), 4.67 (d, 1H, J ) 12.3 Hz), 4.58 (d, 1H, J ) 10.8 Hz), 4.55
(d, 1H, J ) 12.3 Hz), 3.95 (dd, 1H, J ) 6.9, 2.1 Hz), 3.81 (dd,
1H, J ) 11.1, 3.3 Hz), 3.74-3.70 (m, 2H), 3.13 (dd, 1H, J )
10.2, 3.0 Hz), 2.69 (s, 1H). 2.27 (s, 3H), 2.05 (s, 3H); MS (DEP/
CI) m/z (rel intensity) 474 (M + NH4) (100), 344 (71), 326 (41);
and â-manno cycloadduct as a white powder (0.03 g, 24%).
Gen er a l P r oced u r e for Meth ylen a tion of Keton e Cy-
cloa d d u cts. To a slurry of Nysted reagent40 (4 equiv) and
ketone cycloadduct (1 equiv) in THF at -78 °C was added a
1.0 M solution of TiCl4 (3 equiv) in CH2Cl2 over 5 min. The
reaction mixture was warmed to room temperature and was
stirred overnight (18 h). The mixture was cooled to 5 °C, and
triethylamine (20 equiv) was added as a single portion,
followed by the rapid addition of SiO2 (Merck; 230-400 mesh).
The mixture was warmed to room temperature and was
filtered through a plug of SiO2 using ethyl acetate as a wash.
The filtrate was concentrated in vacuo to afford a crude
product which was purified by column chromatography (SiO2;
5% EtOAc/petroleum ether).
1
1450, 1362, 1236, 1103 cm-1; H NMR δ 7.29-7.19 (m, 10H),
6.33 (dd, 1H, J ) 6.0, 0.9 Hz), 4.74-4.48 (m, 5H), 4.28-4.26
(m, 1H), 3.93-3.89 (m, 1H), 3.75-3.74 (m, 2H), 3.61 (dd, 1H,
J ) 8.9, 6.3 Hz), 1.83 (br s, 1H); 13C NMR δ 144.6, 128.5, 128.4,
127.9, 127.8, 127.7, 102.7, 97.4, 77.3, 76.8, 73.7, 73.6, 69.1, 68.9;
MS (DEP/CI) m/z (rel intensity) 344 (M + NH4) (58), 326 (100),
309 (75), 168 (61). Anal. Calcd for C20H22O4: C, 73.59; H, 6.79.
Found: C, 73.52; H, 6.94. Also obtained was 3,6-di-O-benzyl-
D-glucal60 (0.08 g). No 3,4-di-O-benzyl-D-glucal59 was isolated
from the mixture.
Allylic oxidation61 of 36 (0.087 g, 0.3 mmol) with MnO2 (1.03
g, 12 mmol) in CHCl3 (15 mL) afforded after 24 h, 4,6-d i-O-
ben zyl-h ex-1-en op yr a n o-3-u lose (57) as a clear oil (0.054
g, 0.17 mmol, 56%), with properties consistent with similar
known compounds.
1-O,2-S-(2-Isop r op en yl-1-m eth yl-1,2-eth en ed iyl)-3,4,6-
tr i-O-ben zyl-2-deoxy-2-th io-r-D-glu copyr an oside (26). Nyst-
ed reagent (3.84 mL, 2 mmol) and ketone cycloadduct 19 (0.29
g, 0.54 mmol) in THF (2 mL) and TiCl4 (1.8 mL, 1.8 mmol) in
CH2Cl2 were treated with triethylamine (1.73 mL, 12 mmol)
and SiO2 (0.18 g) to afford after filtration and chromatography
26 as a white solid (0.22 g, 0.4 mmol, 76%): mp 99-101 °C;
[R]D + 7.7° (c ) 0.5, CHCl3); IR (thin film) 3064, 3030, 2920,
Gen er a l P r oced u r e for Cycloa d d ition Rea ction s. 2,6-
Lutidine (1.0 equiv) was added to a suspension of glycal (1.0
equiv), thiophthalimide 16 (1-2 equiv), and powdered, acti-
vated, 3A molecular sieves (typically, a portion equal in weight
to the weight of the combined reactants) in dry solvent (0.5-
1.0 mM). The mixture was stirred at room temperature, and
the reaction progress was monitored at intervals by taking an
1651, 1496, 1454, 1360, 1261, 1218, 1053 cm-1 1H NMR δ
;
7.42-7.26 (m, 14H), 7.17-7.14 (m, 1H), 5.57 (d, 1H, J ) 2.7
Hz), 5.57-4.51 (series of overlapping apparent AB quartets,
8H), 4.05 (dd, 1H, J ) 6.9, 2.1 Hz), 3.83-3.69 (m, 4H), 3.17
(dd, 1H, J ) 7.5, 2.7 Hz), 1.90 (s, 6H); 13C NMR δ 142.3, 140.8,
138.3, 138.0, 137.9, 128.4, 128.1, 127.9, 127.8, 127.7, 117.8,
100.8, 94.8, 78.9, 78.6, 76.5, 75.3, 73.6, 72.6, 68.3, 43.0, 22.9,
18.6; MS (NCI/DEP) m/z (rel intensity) 545 (10), 544 (29), 543
(81), 224 (100). Anal. Calcd for C33H36O5S: C, 72.77; H, 6.66;
S, 5.89. Found: C, 72.63; H, 6.89; S, 5.67.
1
aliquot from the suspension for analysis by H NMR (CDCl3).
When the composition of the reaction mixture showed no
additional change (3-7 days), the mixture was quenched with
saturated aqueous NH4Cl and was extracted with CH2Cl2 (3×).
The organics were dried (Na2SO4), filtered, and concentrated
in vacuo. The crude mixtures were chromatographed (SiO2)
using gradients of ethyl acetate in petroleum ether. Removal
of residual phthalimide impurities from the chromatographed
fractions was accomplished by stirring with 0.1 M NaOH,
followed by extraction with ethyl acetate.
1-O,2-S-(2-Isop r op en yl-1-m eth yl-1,2-eth en ed iyl)-3,4,6-
tr i-O-ben zyl-2-d eoxy-2-th io-r-D-ga la ctop yr a n osid e (27).
Galacto ketone cycloadduct 22 (0.44 g, 0.81 mmol) and Nysted
reagent (5.8 mL, 3.0 mmol) in THF (4 mL) and TiCl4 (0.29
mL, 2.6 mmol) in CH2Cl2 were treated with triethylamine (2.2
mL, 16 mmol) and SiO2 (0.26 g) to afford after filtration and
column chromatography 27 as a white, oily solid at room
temperature (0.31 g, 0.56 mmol, 69%): [R]D +24.2° (c ) 0.2,
CHCl3); IR (neat) 2916, 1650, 1495, 1453, 1348, 1224, 1140,
1-O,2-S-(2-Acetyl-1-m eth yl-1,2-eth en ed iyl)-3,4,6-tr i-O-
ben zyl-2-d eoxy-2-th io-r-D-ga la ctop yr a n osid e (22). 3,4,6-
Tri-O-benzyl-D-galactal (21) (0.48 g, 1.2 mmol), 16 (0.64 g, 2.3
mmol), and 2,6-lutidine (0.14 mL, 1.2 mmol) in CHCl3 (4.7 mL)
afforded 22 as an oil (0.46 g, 0.8 mmol, 73%, 4 days) following
column chromatography (SiO2, 20% EtOAc/petroleum ether):
[R]D +30.3° (c ) 0.8, CHCl3); IR (thin film) 3030, 2919, 2869,
1674, 1558, 1455, 1356, 1234, 1139, 1112, 1052 cm-1; 1H NMR
δ 7.36-7.26 (m, 15H), 5.62 (d, 1H, J ) 3.0 Hz), 4.89 (d, 1H, J
) 13.8 Hz), 4.71-4.39 (m, 5H), 4.13-4.07 (m, 1H), 4.00 (m,
1H), 3.73 (dd, 1H, J ) 10.8, 3.0 Hz), 3.60 (m, 2H), 3.53-3.44
(m, 1H), 2.29 (s, 3H), 2.25 (s, 3H); 13C NMR δ 195.4, 159.3,
138.2, 137.7, 137.5, 128.5, 128.3, 128.2, 128.1, 128.0, 127.9,
127.8, 127.7, 127.5, 101.9, 96.7, 75.0, 73.7, 73.6, 73.3, 72.9, 71.8,
68.4, 38.0, 30.1, 29.7; MS (DP/PCI) m/z (rel intensity) 564 (M
+ NH4) (11), 434 (64), 309 (45), 118 (100). Anal. Calcd for
1
1100, 1059 cm-1; H NMR δ 7.36-7.16 (m, 15H), 5.52 (br s,
1H), 5.21 (d, 1 H, J ) 3 Hz), 5.02-4.39 (series of apparent
overlapping AB quartets, 8 H), 4.11 (apparent t, 1H, J ) 6.4
Hz), 3.92 (s, 1H), 3.62 (s, 2H), 3.52 (d, 2H, J ) 6.3 Hz), 1.83 (s,
3H), 1.82 (s, 3H); 13C NMR δ 141.8, 140.8, 138.4, 138.1, 137.8,
128.4, 128.2, 127.9, 127.7, 127.6, 127.4, 117.5, 101.5, 95.3, 77.0,
75.6, 74.8, 73.9, 73.5, 71.3, 68.5, 39.4, 22.9, 18.5; MS (PCI/
DEP/NH3) m/z (rel intensity) 562 (M + NH4) (100), 545 (M +
H) (21), 434 (44), 242 (17), 168 (23). Anal. Calcd for C33H36O5S‚
H2O: C, 70.44; H, 6.81; S, 5.69. Found: C, 70.79; H, 6.62; S,
5.57.
Gen er a l P r oced u r e for Tr iflic Acid P r om oted Glyco-
syla tion . To a solution of sugar acceptor (1.5-2 equiv), diene
cycloadduct (1 equiv), and powdered 3 A molecular sieves in
CH2Cl2 at -20 °C was added triflic acid (1 equiv) as a single
portion. The mixture was stirred for 1 h and then was
quenched with saturated aqueous NaHCO3 and was warmed
to room temperature. The mixture was diluted with water
and was extracted with CH2Cl2 (3×). The combined organics
were dried (Na2SO4), filtered, and concentrated in vacuo. The
crude products were purified by column chromatography (SiO2,
230-400 mesh, 10-50% EtOAc in petroleum ether).
1,2:3,4-Diisopr opyliden e-6-O-{3,4,6-tr i-O-ben zyl-2-deoxy-
2-S-(4-m eth yl-3-th io-pen t-3-en -2-on e)-â-D-glu copyr an osyl}-
C
32H34O6S: C, 70.31; H, 6.52; S, 5.87. Found: C, 69.94; H,
6.64; S, 5.87.
1-O,2-S-(2-Acetyl-1-m eth yl-1,2-eth en ediyl)-4,6-di-O-ben -
zyl-2-d eoxy-2-th io-r-D-glu cop yr a n osid e (37). Glucal 36
(0.087 g, 0.27 mmol), thiophthalimide 16 (0.35 mmol), and 2,6-
lutidine (0.03 mL, 0.27 mmol) in CHCl3 (1.8 mL) after 6 days
(59) Blackburne, I. D.; Fredericks, D. M.; Guthrie, R. D. Aust. J .
Chem. 1976, 29, 381.
(60) Danishefsky, S. J .; Behar, V.; Randolph, J . T.; Lloyd, K. O. J .
Am. Chem. Soc. 1995, 117, 5701.
(61) Fraser-Reid, B.; Walker, D. L.; Tam, Y.-K.; Holder, N. L. Can.
J . Chem. 1973, 51, 3950.

2206 J . Org. Chem., Vol. 63, No. 7, 1998
Franck and Marzabadi
r-D-ga la ctop yr a n osid e (28). 1,2:3,4-Di-O-isopropylidene-R-
D-galactopyranose (24) (0.090 g, 0.36 mmol), gluco diene
cycloadduct 26 (0.097 g, 0.18 mmol), and triflic acid (0.016 mL,
0.18 mmol) in CH2Cl2 (2 mL) afforded 28 as a white semisolid
(0.11 g, 0.14 mmol, 76%): [R]D -44.7° (c ) 0.9, CHCl3); IR (thin
film) 2988, 2935, 1683, 1455, 1372, 1256, 1210, 1174, 1110,
79.1, 77.2, 74.9, 74.7, 73.5, 70.0, 69.1, 67.9, 60.7, 60.2, 58.9,
55.2, 53.7, 30.0, 23.1, 22.6; MS (NCI/DEP) m/z (rel intensity)
780 (M) (100), 147 (24), 129 (43), 127 (28). Anal. Calcd for
C43H56O11S: C, 66.13; H, 7.23; S, 4.11. Found: C, 66.05; H,
7.13; S, 3.85.
Met h yl 6-O-Ben zyl-2,3-d i-O-m et h yl-4-O-{3,4,6-t r i-O-
ben zyl-2-d eoxy-2-S-(4-m et h yl-3-t h io-p en t -3-en -2-on e)-â-
D-glu cop yr a n osyl}-r-D-glu cop yr a n osid e (32). Methyl 6-O-
benzyl-2,3-di-O-methyl-R-D-glucopyranose (0.095 g, 0.3 mmol),
26 (0.08 g, 0.15 mmol), and triflic acid (0.013 mL, 0.15 mmol)
in CH2Cl2 (1.8 mL) afforded disaccharide 32 as an oil (0.084
g, 0.1 mmol, 67%): [R]D +36.6° (c ) 2.1, CHCl3); IR (thin film)
3062, 3029, 2907, 1686, 1605, 1496, 1453, 1356, 1312, 1240,
1204, 1111, 1048 cm-1; 1H NMR δ 7.40-7.15 (m, 20H), 4.84-
4.47 (series of apparent unresolved ABq, 9H), 4.24 (d, 1H, J
) 8.7 Hz), 4.03-3.91 (m, 2H), 3.73-3.47 (m, 7H), 3.55 (s, 3H),
3.52 (s, 3H), 3.41 (s, 3H), 3.35-3.21 (m, 2H), 2.63 (dd, 1H, J )
12, 8.7 Hz), 2.33 (s, 3H), 1.86 (s, 3H), 1.75 (s, 3H); 13C NMR δ
201.4, 141.2, 138.6, 138.4, 138.3, 137.9, 130.5, 128.5, 128.3,
128.1, 127.8, 127.7, 127.6, 127.5, 127.3, 127.2, 101.1, 97.7, 83.1,
81.4, 81.1, 79.2, 77.2, 75.3, 75.1, 74.9, 74.7, 73.5, 69.7, 68.6,
60.9, 59.1, 55.0, 54.7, 30.1, 22.8, 22.4; MS (NCI/DEP) m/z (rel
intensity) 856 (7), 623 (100), 543 (35), 311 (42). Anal. Calcd
for C49H60O11S: C, 68.75; H, 6.95; S, 3.75. Found: C, 68.39;
H, 7.09; S, 3.73.
1
1071, 1002 cm-1; H NMR δ 7.38-7.24 (m, 13H), 7.15-7.06
(m, 2H), 5.52 (d, 1H, J ) 5.1 Hz), 4.88 (d, 1H, J ) 11.1 Hz),
4.85 (d, 1H, J ) 10.8 Hz), 4.73 (d, 1H, J ) 10.8 Hz), 4.63-
4.51 (m, 4H), 4.41 (d, 1H, J ) 8.8 Hz), 4.33 (dd. 1H, J ) 8.0,
1.5 Hz), 4.28 (dd, 1H, J ) 4.8. 2.2 Hz), 4.06-4.02 (m, 1H),
3.98-3.94 (m, 1H), 3.71 (apparent br d, 2H, J ) 2.8 Hz), 3.67-
3.60 (m, 2H), 3.48-3.42 (m, 2H), 2.79 (dd, 1H, J ) 8.8, 9.0
Hz), 2.42 (s, 3H), 1.99 (s, 3H), 1.85 (s, 3H), 1.55 (s, 3H), 1.42
(s, 3H), 1.33 (s, 6H); 13C NMR δ 202.1, 144.8, 138.4, 138.2,
138.1, 129.7, 128.3, 128.2, 127.8, 127.7, 127.6, 127.4, 109.0,
108.4, 103.3, 96.2, 83.1, 79.1, 75.3, 74.9, 74.7, 73.6, 71.0, 70.7,
70.6, 68.7, 68.1, 66.9, 53.9, 30.2, 26.2, 26.0, 24.9, 24.4, 23.4,
22.7; MS (NCI/DEP) m/z (rel intensity) 804 (M) (69), 592 (13),
367 (100), 210 (29), 129 (54). Anal. Calcd for C45H56O11S: C,
67.14; H, 7.01; S, 3.98. Found: C, 67.20; H, 7.08; S, 4.18.
Meth yl 3,4,6-Tr i-O-ben zyl-2-deoxy-2-S-(4-m eth yl-3-th io-
p en t-3-en -2-on e)-â-D-glu cop yr a n osid e (29). Methanol (8
µL, 0.19 mmol), 26 (0.05 g, 0.09 mmol), and triflic acid (8 µL,
0.09 mmol) in CH2Cl2 (2 mL) gave 29 as a colorless oil (0.04 g,
0.07 mmol, 74%): [R]D -24.6° (c ) 0.3, CHCl3); IR (thin film)
3030, 2912, 2866, 1684, 1540, 1456, 1362, 1206, 1113, 1074,
1049 cm-1; 1H NMR δ 7.33-7.19 (m, 13H), 7.09-7.06 (m, 2H),
4.86 (d, 1H, J ) 10.8 Hz), 4.78 (d, 2H, J ) 10.8 Hz), 4.69 (d,
1H, J ) 10.5 Hz), 4.55 (d, 1H, J ) 12.3 Hz), 4.48 (d, 1H, J )
10.5 Hz), 4.47 (d, 1 H, J ) 12.3 Hz), 4.19 (d, 1H, J ) 8.7 Hz),
3.65-3.64 (m, 2H), 3.58-3.52 (m, 1H), 3.42-3.32 (m, 1H), 3.37
(s, 3H), 2.68 (dd, 1H, J ) 10.8, 8.7 Hz), 2.31 (s, 3H), 1.99 (s,
3H), 1.85 (s, 3H); 13C NMR δ 202.0, 148.7, 138.3, 138.2, 138.0,
129.0, 128.4, 128.3, 128.2, 127.8, 127.7, 127.6, 127.5, 104.6,
82.6, 79.4, 75.7, 74.9, 74.8, 73.5, 68.8, 56.5, 55.0, 29.8, 23.8,
22.9; MS (DEP/PCI) m/z (rel intensity) 594 (M + NH4) (100),
536 (22), 466 (60), 258 (26), 180 (35), 116 (36). Anal. Calcd
for C34H40O6S: C, 70.81; H, 6.99; S, 5.60. Found: C, 70.90;
H, 6.78; S, 5.39.
Met h yl 3,4,6-Tr i-O-b en zyl-O-2-{3,4,6-t r i-O-b en zyl-2-
d eoxy-2-S-(4-m eth yl-3-th io-p en t-3-en -2-on e)-â-D-glu cop y-
r a n osyl}-r-D-glu cop yr a n osid e (33). Methyl 3,4,6-tri-O-
benzyl-R-D-glucopyranoside (0.24 g, 0.51 mmol), 26 (0.09 g, 0.18
mmol), and triflic acid (0.015 mL, 0.18 mmol) in CH2Cl2 (3 mL)
gave a crude mixture which following column chromatography
(SiO2, 20-40% EtOAc in petroleum ether) afforded benzyl
glycoside 34 as an oil (0.013 g, 1.9 × 10-5 mol; 11%): IR (neat)
3030, 2911, 2865, 1682, 1605, 1497, 1454, 1355, 1310, 1240,
1
1206, 1112, 1050, 1028 cm-1; H NMR δ 7.39-7.25 (m, 18H),
7.16-7.13 (m, 2H), 4.93-4.83 (m, 3H), 4.76 (d, 1H, J ) 10.8
Hz), 4.63-4.52 (m, 4H) 4.45 (d, 1H, J ) 8.4 Hz), 3.71-3.61
(m, 3H), 3.47-3.41 (m, 2H), 2.85 (dd, 1H, J ) 11.1, 8.4 Hz),
2.32 (s, 3H), 1.85 (s, 3H), 1.75 (s, 3H); 13C NMR δ 201.9, 145.8,
138.3, 138.2, 138.0, 137.4, 129.5, 128.4, 128.2, 128.1, 127.9,
127.8, 127.7, 127.6, 127.5, 127.4, 102.6, 82.8, 79.3, 77.2, 75.5,
74.9, 73.5, 70.5, 68.9, 54.1, 30.0, 23.4, 22.6; MS (DEP/PCI) m/z
(rel intensity) 670 (M + NH4) (2), 580 (15), 562 (24), 434 (32),
360 (78), 332 (72), 196 (47), 168 (100). Further elution afforded
the title compound 33 as an oil (0.05 g, 5.1 × 10-5 mol, 28%):
IR (thin film) 3063, 3031, 2910, 2864, 1684, 1497, 1455, 1361,
Hexa d ecyl-2-O-m eth yl-sn -glycer yl-3,4,6-tr i-O-ben zyl-2-
d eoxy-2-S-(4-m eth yl-3-th io-p en t-3-en -2-on e)-â-D-glu cop y-
r a n osid e (30). 1-O-Hexadecyl-2-O-methyl-sn-glycerol (0.08
g, 0.23 mmol), 26 (0.06 g, 0.12 mmol), and triflic acid (0.01
mL, 0.12 mmol) in CH2Cl2 (1.5 mL) afforded 30 as a waxy,
white solid (0.07 g, 0.09 mmol, 73%): [R]D -21.6° (c ) 0.4.
CHCl3); IR (neat) 3030, 2924, 2853, 1683, 1604, 1497, 1454,
1207, 1108 and 1028 cm-1 1H NMR δ 7.29-7.18 (m, 26H),
;
1
1355, 1261, 1205, 1113, 1028 cm-1, H NMR δ 7.38-7.24 (m,
7.10-7.06 (m, 4H), 4.96 (d, 1H, J ) 10.8 Hz), 4.82-4.46 (series
of overlapping ABq, 12H), 4.28 (d, 1H, J ) 7.2 Hz), 3.82
(apparent t, 1H, J ) 7.8 Hz), 3.70-3.56 (m, 8H), 3.43 (s, 3H),
3.41-3.23 (m, 2H), 2.71 (dd, 1H, J ) 10.5, 8.6 Hz), 2.30 (s,
3H), 1.87 (s, 3H), 1.71 (s, 3H); 13C NMR δ 201.7, 143.8, 138.9,
138.5, 138.4, 138.1, 137.9, 129.9, 128.4, 128.2, 128.0, 127.8,
127.7, 127.6, 127.5, 127.4, 127.2, 102.3, 101.1, 85.4, 83.1, 79.2,
78.3, 75.0, 74.8, 74.7, 74.6, 73.5, 68.9, 68.6, 56.6, 54.9, 30.1,
23.2, 22.5. Anal. Calcd for C61H68O11S‚1H2O: C, 71.32; H,
6.87; S, 3.12. Found: C, 71.29; H, 7.00; S, 3.18. Also isolated
was 7 mg (6.9 × 10-6 mol, 3%) of an oily material tentatively
identified as the isomeric R-gluco disaccharide based on its
anomeric proton resonance at 5.61 ppm (d, J ) 3.6 Hz).
1-O,2-S-(2-Acetyl-1-m eth yl-1,2-eth en ediyl)-4,6-di-O-ben -
zyl-O-3-{3,4,6-tr i-O-ben zyl-2-d eoxy-2-S-(4-m eth yl-3-th io-
p r op -3-en -2-on e)-â-D-glu cop yr a n osyl}-r-D-glu cop yr a n o-
sid e (38). Gluco diene cycloadduct 26 (0.05 g, 0.09 mmol), 37
(0.04 g, 0.09 mmol), and triflic acid (0.008 mL, 0.09 mmol) in
CH2Cl2 (1.5 mL) afforded 38 as a clear oil (SiO2; 10-40% ethyl
acetate in petroleum ether) (0.05 g, 0.05 mmol, 53%): [R]D
+15.2 (c ) 0.6, CHCl3); IR (neat) 3031, 2919, 1683, 1558, 1497,
13H), 7.15-7.12 (m, 2H), 4.92-4.51 (series of overlapping ABq,
6H), 4.35 (d, 1H, J ) 8.4 Hz), 3.87-3.85 (m, 1H), 3.70-3.68
(m, 1H), 3.65-3.38 (m, 8H), 3.44 (s, 3H), 2.76 (dd, 1H, J )
10.8, 8.7 Hz), 2.39 (s, 3H), 2.00 (s, 3H), 1.87 (s, 3H), 1.64-
1.52 (m, 4H), 1.25 (br s, 25H), 0.90-0.86 (m, 4H); 13C NMR δ
201.6, 145.6, 138.4, 138.2, 138.0, 129.6, 128.3, 128.2, 127.8,
127.7, 127.5, 127.4, 103.7, 82.9, 79.3, 79.2, 75.4, 74.9, 74.8, 74.7,
73.5, 71.7, 70.6, 69.2, 68.9, 58.0, 54.2, 31.9, 29.9, 29.7, 29.5,
29.3, 26.1, 23.5, 22.7, 22.6, 14.0; MS (NCI/DEP) m/z (rel
intensity) 874 (1), 365 (21), 226 (17), 202 (100), 129 (78). Anal.
Calcd for C53H78O8S: C, 72.73; H, 8.98. Found: C, 72.80; H,
9.00.
Met h yl 2,3,4-Tr i-O-m et h yl-O-6-{3,4,6-t r i-O-b en zyl-2-
d eoxy-2-S-(4-m eth yl-3-th io-p en t-3-en -2-on e)-â-D-glu cop y-
r a n osyl}-r-D-glu cop yr a n osid e (31). Methyl 2,3,4-tri-O-
methyl-R-D-glucopyranoside (69 mg, 0.29 mmol), 26 (77 mg,
0.14 mmol), and triflic acid (0.012 mL, 0.14 mmol) in CH2Cl2
(1.5 mL) afforded 31 as a colorless oil (61 mg, 0.08 mmol,
57%): [R]D +24.0° (c ) 0.9, CHCl3); IR (thin film) 2928, 1684,
1497, 1454, 1355, 1261, 1204, 1101 cm-1 1H NMR δ 7.37-
;
1
7.11 (m, 15H), 4.92-4.48 (m, 6H), 4.79 (d, 1H, J ) 3.6 Hz),
4.42 (d, 1H, J ) 10.2 Hz), 4.09-4.00 (m, 1H), 3.77-3.44 (m,
8H), 3.61 (s, 3H), 3.54 (s, 3H), 3.50 (s, 3H), 3.41 (s, 3H), 3.19
(dd, 1H, J ) 9.0, 3.6 Hz), 3.20-3.08 (m, 1H), 2.83 (dd, 1H, J
) 9.3, 9.9 Hz), 2.41 (s, 3H), 1.95 (s, 3H), 1.80 (s, 3H); 13C NMR
δ 202.0, 143.8, 138.4, 138.2, 138.0, 129.4, 128.3, 128.2, 127.9,
127.7, 127.5, 127.3, 127.2, 102.8, 97.2, 83.5, 83.3, 81.8, 79.8,
1454, 1355, 1206, 1107, 1049 cm-1; H NMR δ 7.36-7.14 (m,
25H), 5.54 (d, 1H, J ) 3.0 Hz), 5.23 (d, 1H, J ) 8.4 Hz), 4.95-
4.73 (series of overlapping ABq, 6H), 4.60-4.52 (m, 4H), 4.50-
4.41 (m, 2H), 4.15-4.09 (m, 1H), 3.94-3.90 (m, 1H), 3.69-
3.61 (m, 4H), 3.57-3.46 (m, 1H), 3.35 (dd, 1H, J ) 4.2, 2.1
Hz), 3.20 (dd, 1H, J ) 9.9, 3.0 Hz), 2.77 (dd, 1H. J ) 10.5, 4.2
Hz), 2.42 (s, 3H), 2.30 (s, 3H), 2.17 (s, 3H), 2.02 (s, 3H), 1.88

Bicyclic Donors for the Synthesis of 2-Deoxy-â-Glycosides
J . Org. Chem., Vol. 63, No. 7, 1998 2207
(s, 3H); 13C NMR δ 201.0, 194.9, 160.0, 144.3, 138.7, 138.3,
138.2, 138.1, 138.0, 130.7, 128.6, 128.4, 128.3, 128.2, 128.0,
127.9, 127.8, 127.7. 127.6, 127.5, 127.4, 102.6, 102.0, 97.4, 96.4,
83.0, 79.6, 77.8, 77.7, 77.2, 75.9, 75.3, 74.9, 73.6, 73.5, 73.2,
72.8, 68.7, 55.3, 40.8, 30.3, 30.0, 23.6, 22.7, 21.4. Anal. Calcd
for C58H64O11S2: C, 69.58; H, 6.44; S, 6.41. Found: C, 69.46;
H, 6.38; S, 6.68. Further elution afforded 9 mg (9.0 × 10-6
mol, 10%) of an oily material tentatively identified as the
R-gluco disaccharide based on the observation of an anomeric
resonance at 5.16 ppm (d, J ) 3.6 Hz).
Prolonged reaction times resulted in the formation of
mixtures of R- and â-O-glycosides, as well as, â-C-glycosides.
For example, when 26 (84 mg, 0.15 mmol), 41 (44 mg, 0.31
mmol), and triflic acid (13 µL, 0.15 mmol) were reacted in
CH2Cl2 (2 mL) at -20 °C for 1 h, 15 min and then worked up
and chromatographed as described above, 42 was isolated (31
mg, 4.5 × 10-5 mol, 29%). Further elution of the column
afforded the R-O-naphthyl glycoside 43 (12 mg, 1.7 × 10-5 mol)
as an oil: [R]D +78.7° (c ) 0.2, CHCl3); IR (thin film) 3064,
3030, 2912, 2864, 1682, 1629, 1600, 1514, 1497, 1466, 1454,
1389, 1357, 1252, 1212, 1176, 1108, 1047, 1027 cm-1; 1H NMR
δ 7.71-7.64 (m, 3H), 7.42-7.02 (m, 19H), 5.54 (d, 1H, J ) 3.3
Hz), 4.87 (d, 1H, J ) 8.7 Hz), 4.81 (d, 1H, J ) 9 Hz), 4.72 (d,
1H, J ) 10.8 Hz), 4.54 (d, 1H, J ) 12 Hz), 4.43 (d, 1H, J )
10.8 Hz), 4.35 (d, 1H, J ) 12 Hz), 4.08-3.97 (m, 1H), 3.88-
3.85 (m, 1H), 3.78-3.64 (m, 2H), 3.53-3.49 (m, 1H), 3.03 (dd,
1H, J ) 11.3, 3.3 Hz), 2.28 (s, 3H), 1.77 (s, 3H), 1.68 (s, 3H);
MS (NCI/DEP) m/z (rel intensity) 688 (1), 652 (4), 543 (4), 472
(12), 287 (46), 143 (100); then, the â-C-glycoside 44 as a solid
(17 mg, 2.5 × 10-5 mmol, 16%): mp 112-114 °C (Et2O/
hexanes); [R]D +7.4 (c ) 0.4, CHCl3); IR (thin film) 3356, 3063,
3031, 2913, 2867, 1684, 1623, 1600, 1521, 1497, 1455, 1398,
1264, 1214, 1114, 1049 cm-1; 1H NMR δ 8.06 (m, 1H), 7.94 (s,
1H), 7.71-7.66 (m, 3H), 7.47-7.12 (m, 17H), 5.40 (d, 1H, J )
10.5 Hz), 4.98 (d, 1H, J ) 11.1 Hz), 4.84 (d, 1H, J ) 12.3 Hz),
4.82 (d, 1 H, J ) 10.8 Hz), 4.59-4.52 (m, 2H), 4.44 (d, 1H, J
) 12.3 Hz), 4.00 (apparent t, 1H, J ) 9 Hz), 3.79-3.64 (m,
3H), 3.40 (apparent t, 1 H, J ) 10.8 Hz), 1.97 (s, 3H), 1.27 (s,
3H), 0.83 (s, 3H); MS (PCI/DEP) m/z (rel intensity) 706 (M +
NH4) (7), 196 (15), 180 (100), 148 (40), 131 (40), 99 (18).
Reaction of th e Galactose Don or 27 with DIP G: Tr iph -
en ylp h osp h in e Hyd r ogen Br om id e a s a P r om oter . To a
solution of 24 (32 mg, 0.13 mmol), 27 (34 mg, 6.3 × 10-5 mol),
and powdered 3A molecular sieves in CH2Cl2 (0.9 mL) at 5
°C, was added triphenylphosphine hydrogen bromide (21 mg,
6.3 × 10-5 mol) as a single portion. The reaction mixture was
stirred for 6 h and then quenched with saturated aqueous
NaHCO3 (5 mL). It was diluted with CH2Cl2 (10 mL) and was
washed with water (3×, 10 mL). The organics were dried
(MgSO4), filtered, and concentrated in vacuo. The crude
product mixture was chromatographed (Neutral alumina (BA
I); 10-20% ethyl acetate in petroleum ether) to give 1,2:3,4-
Diisop r op ylid en e-O-6-{3,4,6-tr i-O-ben zyl-2-d eoxy-2-S-(4-
m eth yl-3-th io-p en t-3-en -2-on e)-r-D-ga la ctop yr a n osyl}-r-
D-ga la ctop yr a n osid e (45r) as a colorless oil (4 mg, 6.2 ×
10-6 mol, 9%): 1H NMR δ 7.25 (m, 15H), 5.51 (d, 1H, J ) 5.1
Hz), 4.94-4.93 (m, 1H), 4.83 (d, 1H, J ) 11.1 Hz), 4.74 (d, 1H,
J ) 11.7 Hz), 4.66-4.59 (m, 2H), 4.51-4.37 (m, 3H), 4.11-
3.94 (m, 3H), 3.83 (dd, 1H, J ) 10.8, 2.4 Hz), 3.76-3.61 (m,
2H), 3.60-3.52 (m, 4H), 3.34 (dd, 1H, J ) 12.0, 3.3 Hz), 2.32
(s, 3H), 1.93 (s, 3H), 1.79 (s, 3H), 1.42 (s, 3H), 1.34 (s, 3H),
1.32 (s, 3H), 1.26 (s, 3H). Further elution afforded 1,2:3,4-
Diisop r op ylid en e-O-6-{3,4,6-tr i-O-ben zyl-2-d eoxy-2-S-(4-
m eth yl-3-th io-p en t-3-en -2-on e)-â-D-ga la ctop yr a n osyl}-r-
D-ga la ctop yr a n osid e (45â) as a white solid (12 mg, 1.8 ×
10-5 mol, 26%): mp 58-60 °C; [R]D -31.4° (c ) 0.7, CHCl3);
IR (neat) 3003, 2934, 1684, 1660, 1456, 1374, 1258, 1209, 1167,
1-O-(2,8,9-Tr ih yd r oxy-1-oxo-1,2,3,4-tetr a h yd r oa n th r a -
cen -2-yl)- 3,4,6-tr i-O-ben zyl-2-d eoxy-2-S-(4-m eth yl-3-th io-
p en t-3-en -2-on e)-â-D-glu cop yr a n osid e (40). To a suspen-
sion of 26 (42 mg, 8.5 × 10-5 mol), acyloin 39 (27 mg, 0.11
mmol), and powdered 3A molecular sieves (0.101 g) in CH2Cl2
(2.5 mL) at -20 °C was added triflic acid (7 µL, 8.5 × 10-5
mol) as a single portion. The reaction mixture was stirred for
40 min and then was quenched with saturated aqueous
NaHCO3 and was worked up as previously described. Column
chromatography (SiO2, 5-10% acetone in benzene) afforded
the major diastereoisomer 40a as an orange, glassy solid (26
mg, 3.3 × 10-5 mol, 39%): [R]D +34.0° (c ) 0.6, CHCl3); IR
(thin film) 3406, 3063, 3030, 2925, 2866, 1683, 1634, 1602,
1575, 1455, 1354, 1301, 1206, 1110, 1070, 1047 cm-1; 1H NMR
δ 15.73 (s, 1H), 9.65 (s, 1H), 7.51-7.00 (m, 18 H), 6.84 (d, 1H,
J ) 7.8 Hz), 4.98 (d, 1H, J ) 8.4 Hz), 4.92 (d, 1H, J ) 10.8
Hz), 4.83 (d, 1H, J ) 10.8 Hz), 4.79 (d, 1H, J ) 10.8 Hz), 4.64-
4.52 (m, 4H), 3.73-3.69 (m, 2H), 3.67 (d, 1H, J ) 8.7 Hz),
3.55-3.47 (m, 1H), 3.47-3.44 (m, 1H), 3.35-3.27 (m, 1H),
2.86-2.81 (m, 1H), 2.78 (dd, 1H, J ) 10.8, 8.4 Hz), 2.38-2.17
(m, 2H), 2.32 (s, 3H), 1.58 (s, 3H), 1.51 (s, 3H); 13C NMR δ
202.0, 201.9, 167.0, 158.6, 144.4, 140.2, 138.8, 138.7, 138.6,
138.5, 133.6. 130.7, 129.1, 129.0, 128.9, 128.8, 128.4, 128.3,
128.2, 128.1, 128.0, 118.8, 117.9, 113.1, 111.4, 110.1, 102.8,
83.2, 79.9, 77.8, 76.7, 75.5, 75.3, 74.3, 74.0, 69.3, 55.0, 30.5,
30.3, 25.9, 23.5, 22.9. Anal. Calcd for C47H48O9S‚H2O: C,
69.96; H, 6.24. Found: C, 70.10; H, 5.87. Further elution
afforded slightly impure minor diastereoisomer 40b as an
orange, glassy solid (20 mg, 2.5 × 10-5 mol, 30%): IR (thin
film) 3734, 2924, 1683, 1634, 1454, 1362, 1307, 1261, 1207 and
1
1106 cm-1; H NMR δ 15.43 (s, 1H), 9.55 (s, 1H), 7.40 (t, 1H,
J ) 7.8 Hz), 7.36-6.93 (m, 17H), 6.75 (d, 1H, J ) 7.8 Hz),
4.82 (d, 1H, J ) 10.8 Hz), 4.76 (d, 1H, J ) 10.8 Hz), 4.65 (d,
1H, J ) 10.8 Hz), 4.60 (d, 1H, J ) 8.1 Hz), 4.47 (d, 1H, J )
10.8 Hz), 4.27 (d, 1H, J ) 12.3 Hz), 4.25-4.23 (m, 2H), 4.14
(d, 1H, J ) 12.3 Hz), 3.67-3.56 (m, 2H), 3.48-3.42 (m, 2H),
3.31-3.17 (m, 1H), 2.81-2.75 (m, 2H), 2.31 (s, 3H), 2.17-2.14
(m, 2H), 1.95 (s, 3H), 1.79 (s, 3H).
2-O-Na p h th yl-3,4,6-tr i-O-ben zyl-2-d eoxy-2-S-(4-m eth yl-
3-th io-p en t-3-en -2-on e)-â-D-glu cop yr a n osid e (42). To a
cooled suspension (-20 °C) of 26 (0.24 g, 0.45 mmol), 41 (0.15
g, 0.9 mmol), and powdered 3A molecular sieves (0.18 g) in
CH2Cl2 (4.5 mL) was added triflic acid (0.04 mL, 0.45 mmol)
as a single portion. The reaction mixture was stirred for 40
min and then was diluted with 0.1 M NaOH (5 mL) and was
warmed to room temperature. The mixture was diluted with
CH2Cl2 (10 mL) and was washed with 0.1 M NaOH (10 mL)
and with water (3×, 10 mL). The organics were dried (MgSO4),
filtered, and concentrated in vacuo. Flash column chroma-
tography on the crude residue (SiO2; 5-20% ethyl acetate in
petroleum ether) afforded 42 (0.11 g, 0.16 mmol, 36%) as an
oil: [R]D -53.9° (c ) 0.5, CHCl3); IR (neat) 3062, 3030, 2918,
2866, 1680, 1631, 1600, 1512, 1497, 1467, 1454, 1390, 1355,
1
1104, 1069 cm-1; H NMR δ 7.30-7.17 (m, 15H), 5.44 (br d,
1H, J ) 5.1 Hz), 4.74 (d, 1H, J ) 11.7 Hz), 4.65 (d, 1H, J )
12.3 Hz), 4.51 (d, 1H, J ) 11.7 Hz), 4.49-4.42 (series of
overlapping ABq, 2H), 4.36 (d, 1H, J ) 6.0 Hz), 4.27 (d, 1H, J
) 9 Hz), 4.21-4.18 (m, 4H), 3.97-3.88 (m, 2H), 3.82 (d, 1H, J
) 2.1 Hz), 3.55-3.41 (m, 3H), 3.32 (dd, 1H, J ) 11.4, 2.7 Hz),
3.07 (dd, 1H, J ) 10.8, 9 Hz), 2.35 (s, 3H), 1.88 (s, 3H), 1.76
(s, 3H), 1.44 (s, 3H), 1.34 (s, 3H), 1.24 (s, 6H); 13C NMR δ 202.9,
145.4, 138.5, 138.0, 133.9, 133.6, 129.6, 128.5, 128.4, 128.3,
128.2, 128.1, 127.9, 127.7, 127.5, 127.4, 127.2, 109.0, 108.4,
103.1, 97.4, 96.2, 81.3, 74.4, 73.5, 73.3, 72.1, 71.8, 71.2, 70.7,
68.7, 68.6, 67.2, 51.1, 30.2, 26.2, 26.0, 25.0, 24.4, 23.5, 22.6;
MS (NCI/DEP) m/z (rel intensity) 804 (9), 286 (13), 194 (33),
143 (100). Anal. Calcd for C45H56O11S: C, 67.15; H, 7.01.
Found: C, 66.94; H, 7.25.
1254, 1214, 1178, 1104, 1053, 1028 cm-1 1H NMR δ 7.79-
;
7.66 (m, 4H), 7.43-7.15 (m, 18H), 5.21 (d, 1H, J ) 8.4 Hz),
4.99-4.80 (m, 3H), 4.62-4.47 (m, 3H), 3.83-3.55 (m, 5H), 3.12
(dd, 1H, J ) 8.7, 12 Hz), 2.40 (s, 3H), 1.91 (s, 3H), 1.83 (s,
3H); 13C NMR δ 201.6, 154.7, 147.9, 138.1, 138.0, 137.9, 134.3,
129.7, 129.2, 129.0, 128.4, 128.3, 128.1, 127.8, 127.7, 127.6,
127.56, 127.51, 127.2, 126.3, 126.2, 124.1, 118.9, 109.9, 101.2,
82.5, 79.3, 76.0, 75.2, 75.0, 73.5, 68.8, 54.3, 29.9, 23.7, 22.9;
MS (NCI/DEP) m/z (rel intensity) 688 (2), 238 (29), 210 (41),
202 (38), 194 (45), 143 (40), 129 (100). Anal. Calcd for
Mod ified Tr iflic Acid P r om oted Glycosyla tion P r oto-
col. To a solution of donor (1 equiv), acceptor (2 equiv), and
powdered 3A molecular sieves in CH2Cl2 at -20 °C were added
C
43H44O6S: C, 74.89; H, 6.38; S, 4.64. Found: C, 74.69; H,
6.37; S, 4.36.

2208 J . Org. Chem., Vol. 63, No. 7, 1998
Franck and Marzabadi
tetra-N-butylammonium triflate (1 equiv) and then triflic acid
(0.2-0.4 equiv). The mixture was stirred at this temperature
until consumption of starting materials was indicated by thin-
layer chromatography. The mixture was worked up as previ-
ously described, and the crude products were chromatographed
using gradients of ethyl acetate in petroleum ether.
2-O-Na p h th yl Glycosid e (42). â-Naphthol 41 (27 mg, 0.18
mmol), 26 (48 mg, 0.09 mmol), Bu4NOTf (9.5 mg, 0.09 mmol),
and triflic acid (16 µL, 0.02 mmol) afforded 42 (42 mg, 0.12
mmol, 69%) from chromatography.
and the resulting crude product was chromatographed (SiO2;
5% ethyl acetate in dichloromethane) to give 48 as a colorless
oil (25 mg, 3.7 × 10-5 mol, 74%) with spectral characteristics
consistent with those previously described.10c
Met h yl 3,4,6-Tr i-O-b en zyl-O-2-(3,4,6-t r i-O-b en zyl-2-
d e oxy-â-D -a r a b in o-h e xop yr a n osyl)-â-D -glu cop yr a n o-
sid e (49). To a suspension of Raney nickel (200 mg) in
benzene (3 mL) at room temperature was added a solution of
disaccharide 33 (34 mg, 3.3 × 10-5 mol) in benzene (4 mL).
After 2 h, the mixture was filtered through a mixed pad of
Celite/SiO2, and the pad was washed with benzene (100 mL)
and then with acetone (300 mL). The combined filtrate was
concentrated in vacuo. The crude mixture was chromato-
graphed (SiO2; 10-20% ethyl acetate in petroleum ether) to
afford 49 as a colorless oil (22 mg, 2.5 × 10-5 mol, 73%): [R]D
-3.9° (c ) 0.3, CHCl3); IR (neat) 3030, 2928, 2866, 1497, 1454,
Ga la ctose Disa cch a r id e (45). DIPG 24 (0.12 g, 0.44
mmol), 27 (0.12 g, 0.22 mmol), Bu4NOTf (0.09 g, 0.22 mmol),
and triflic acid (8 µL, 0.09 mmol) gave 45 (0.11 g, 0.14 mmol,
64%) following column chromatography.
Gen er a l P r oced u r e for Ra n ey Nick el Desu lfu r iza tion .
The Raney nickel suspension (freshly prepared or commer-
cially supplied) was transferred by pipet to a two-necked
round-bottom flask and was washed with water (3×, 5 mL, or
until the pH of the resulting supernatant was neutral to litmus
paper). The slurry was then washed (2×, 5 mL) with the
solvent used for carrying out the reaction. It was resuspended
in solvent and, where necessary, cooled in an ice-water bath.
A solution of glycoside was prepared and added to the Raney
nickel suspension. The mixture was stirred until consumption
of starting materials was indicated by TLC (SiO2; vanilin/H2-
SO4 or palladium(II) chloride/HCl). The mixture was filtered
through a mixed pad of Celite/SiO2, and the pad was rinsed
with a large excess of solvent. The filtrate was concentrated
in vacuo, and the resulting crude product was chromato-
graphed on SiO2 using either gradients of ethyl acetate in
petroleum ether or ethyl acetate in dichloromethane.
Meth yl 3,4,6-Tr i-O-ben zyl-2-d eoxy-â-D-a r a bin o-h exop y-
r a n osid e (46). To a suspension of Raney nickel (200 mg) in
benzene (3 mL) at room temperature was added a solution of
glycoside 29 (20 mg, 3.5 × 10-5 mol) in benzene (4 mL). After
30 min, the mixture was filtered through a mixed pad of Celite/
SiO2, and the pad was washed with benzene (100 mL) and with
acetone (400 mL). The combined filtrate was concentrated in
vacuo. Column chromatography (SiO2, 15% ethyl acetate in
petroleum ether) afforded 46 (10 mg, 2.3 × 10-5 mol, 66%) with
spectroscopic properties consistent with those described in the
literature.33
Hexa d ecyl-2-O-m eth yl-sn -glycer yl 3,4,6-tr i-O-ben zyl-
2-d eoxy-â-D-a r a bin o-h exop yr a n osid e (47). To a suspen-
sion of Raney nickel (250 mg) in benzene (2 mL) at room
temperature was added a solution of glycoside 30 (0.04 g, 0.05
mmol) in benzene (2 mL). After 1 h, the mixture was filtered
through a pad of Celite which was rinsed successively with
benzene (100 mL) and then with acetone (450 mL). The
combined filtrates were concentrated in vacuo, and the crude
material was chromatographed (SiO2, 15% ethyl acetate in
petroleum ether) to afford 47 (0.03 g, 97%) with spectral
characteristics consistent with those previously reported.45
1,2:3,4-Diisopr opyliden e-6-O-(3,4,6-tr i-O-ben zyl-2-deoxy-
â-D-a r a bin o-h exop yr a n osyl)-r-D-ga la ctop yr a n osid e (48).
To a suspension of Raney nickel (400 mg) in benzene (5 mL)
was added a solution of disaccharide 28 (38 mg, 4.7 × 10-5
mol) in benzene (4 mL). The mixture was stirred at room
temperature for 1.5 h and then was filtered through a pad of
Celite using benzene (100 mL) and acetone (600 mL) as
washes. The combined filtrates were concentrated in vacuo,
1
1362, 1094, 1062, 1028 cm-1; H NMR δ 7.29-7.19 (m, 25H),
7.17-7.11 (m, 5H), 4.83-4.66 (series of overlapping ABq, 5H),
4.60-4.40 (series of overlapping ABq, 8H), 4.28 (br d, 1H, J )
6.6 Hz), 3.69-3.50 (m, 7H), 3.49-3.28 (m, 4H), 3.42 (s, 3H),
2.19-2.14 (m, 1H), 1.57 (ddd, 1H, J ) 12.6, 6.3, 2.4 Hz); 13C
NMR δ 138.5, 138.4, 138.2, 138.0, 128.5, 128.4, 128.3, 128.1,
128.0, 127.9, 127.8, 127.7, 127.6, 127.4, 102.8, 100.6, 85.1, 80.4,
79.6, 78.0, 77.9, 77.4, 77.2, 77.0, 75.6, 75.4, 74.9, 73.5, 71.3,
69.3, 68.9, 56.6, 36.9. Anal. Calcd for C55H60O10‚H2O: C,
73.03; H, 6.66. Found: C, 73.48; H, 6.95.
2-O-Na p h th yl 3,4,6-Tr i-O-ben zyl-2-d eoxy-â-D-a r a bin o-
h exop yr a n osid e (50). To a suspension of Raney nickel (200
mg) in abs ethanol (2 mL) at 5 °C was added a solution of
glycoside 42 (41 mg, 6.0 × 10-5 mol) in benzene/ethanol (4 mL,
1:1). After 1 h, the mixture was filtered through a pad of
Celite/SiO2, and the pad was washed with ethanol (100 mL),
benzene (100 mL), and acetone (200 mL). The combined
filtrate was concentrated in vacuo. Repetitive column chro-
matography (2×) on the crude product (SiO2; 5-10% ethyl
acetate in petroleum ether) afforded slightly impure 2-deoxy-
glycoside 50 (12 mg, 2.1 × 10-5 mol) with spectroscopic
properties consistent with those described in the literature.11b
Ack n ow led gm en t. We are grateful to Professor R.
Bittman for suggesting glycoside 47 as a target and for
the gift of protected glycerol. We thank Nelu Kaila,
Maria Tamarez, and Angeles Dios for carrying out
preliminary experiments related to this work. We also
thank Dr. Clifford Soll for obtaining the mass spectral
data contained in this paper and Dr. Michael Blumen-
stein for assistance with NMR experiments pertinent
to this work. The financial support for this work from
NIH grants GM 51216 and RR 03037 and PSC/CUNY
funds is gratefully appreciated.
Su p p or tin g In for m a tion Ava ila ble: 1H and/or 13C NMR
spectra for all compounds and 1H-COSY, 1H-13C-HETCOR
1
and a portion of the undecoupled H-13C spectra for compound
28 (47 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 O971934H