Synthesis of the shimofuridin nucleoside disaccharide

Full text of DOI:10.1021/jo960727z

6744
J . Org. Chem. 1996, 61, 6744-6747
Syn th esis of th e Sh im ofu r id in Nu cleosid e
Disa cch a r id e
Spencer Knapp* and Vijay K. Gore
Department of Chemistry, RutgerssThe State University of
New J ersey, P.O. Box 939, Piscataway, New J ersey 08855
Received April 19, 1996
In tr od u ction
Many complex nucleoside antibiotics, such as ezomycin
A1 and liposidomycin C (shown below), contain O-glyco-
sylated nucleoside substructures.1-3 Synthetic approaches
to these compounds must include an O-glycosylation step
(to form the disaccharide), or an N-glycosylation step (to
form the nucleoside), or both. While there are plenty of
examples of efficient nucleoside formation from simple,
elaborated, or disaccharidal glycosyl donors, there are
fewer cases of successful O-glycosylation of a nucleoside.1-3
In most of these reactions, the nucleoside pyrimidine or
purine base is more reactive toward the glycosyl donor
than the desired hydroxyl site, and, although base-
glycosylation may be reversible, an excess of donor is
usually required.4,5 A base-glycosylated product that is
formed initially may be less reactive toward further
glycosylation and can hydrolyze back to the original
nucleoside acceptor upon quench4 or hydrolysis5 or (in
the case of purine nucleoside acceptors) may depurinate
under the reaction conditions.5,6 Frequently glycosylation
yields are low, even with a primary hydroxyl acceptor
site,4,7 and successful nucleoside glycosylations at a
hindered secondary hydroxyl site, mostly pyrimidine
examples, can be counted on the fingers of one hand.4,8-11
In 1993, Kobayashi and co-workers reported the isola-
tion of several milligrams of a complex nucleoside from
the Okinawan marine tunicate Aplidium multiplica-
tum.12 The compound, shimofuridin A, exhibited cyto-
toxic, antimicrobial, and protein kinase C inhibitory
activities and was shown by degradation studies and by
1H NMR, 13C NMR, mass, infrared, and ultraviolet
spectroscopy to possess the unusual fatty acyl-fucopy-
ranosyl-inosine structure 1. A small quantity of 1 was
hydrolyzed under basic conditions to give fatty acid
components and the shimofuridin nucleoside disaccharide
2, and further acidic degradation of 2 enabled assignment
of the absolute configuration of the D-ribose and L-fucose
subunits.
(1) Knapp, S. Chem. Rev. 1995, 95, 1859-1876.
(2) Garner, P. Synthetic Approaches to Complex Nucleoside Anti-
biotics. In Studies in Natural Products Chemistry; Atta-ur-Rahman,
Ed.; Elsevier: Amsterdam, 1988; Part A, Vol. 1, pp 397-434.
(3) (a) Lerner, L. M. Synthesis and Properties of Various Disaccha-
ride Nucleosides. In Chemistry of Nucleosides and Nucleotides;
Townsend, L. B., Ed.; Plenum Press: New York, 1991; Vol 2, pp 27-
79. (b) Isono, K. J . Antibiot. 1988, 41, 1711-1739. (c) Isono, K.
Pharmacol. Ther. 1991, 52, 269-286.
(4) Knapp, S.; Nandan, S. R. J . Org. Chem. 1994, 59, 281-283.
(5) (a) Lichtenthaler, F. W.; Sanemitsu, Y.; Nohara, T. Angew.
Chem., Int. Ed. Engl. 1978, 17, 772-774. (b) Lichtenthaler, F. W.;
Kitahara, K. Angew. Chem., Int. Ed. 1975, 14, 815-816.
(6) Review of purine transglycosylation: Boryski, J . Nucleoside
Nucleotide 1996, 15, 771-791.
We viewed the structure of shimofuridin in the context
of complex nucleoside synthesis as a challenge for gly-
cosylation chemistry: attachment of a fucopyranosyl
subunit at O-2′ of inosine would represent a rare example
of O-glycosylation of a purine nucleoside at a secondary
hydroxyl11 and would require surmounting the double
obstacle of steric hindrance and competing depurination.
In this Note we report the synthesis of the shimofuridin
degradation product 2 by fucosylation of a suitably
protected inosine derivative under mild conditions.
(7) (a) Whitfield, D. M.; Douglas, S. P.; Tang, T.-H.; Csizmadia, I.
G.; Pang, H. Y. S.; Moolten, F. L.; Krepinsky, J . J . J . Can. Chem. 1994,
72, 2225-2238. (b) Wijsman, E. R.; van den Berg, O.; Kuyl-Yeheskiely,
E.; van der Marel, G. A.; van Boom, J . H. Recl. Trav. Chim. Pays-Bas
1994 113, 337-338.
(8) Suami, T.; Sasai, H.; Matsuno, K.; Suzuki, N. Carbohydr. Res.
1985, 143, 85-96.
(9) (a) Ikemoto, N.; Schreiber, S. L. J . Am. Chem. Soc. 1990, 112,
9657-9659. (b) Ikemoto, N.; Schreiber, S. L. J . Am. Chem. Soc. 1992,
114, 2524-2536.
Resu lts a n d Discu ssion
(10) Stevens, C. L.; Nemec, J .; Ransford, G. H. J . Am. Chem. Soc.
1972, 94, 3280-3281.
Protection of the 2′ hydroxyl of 3′,5′-O-(tetraisopropy-
ldisiloxane-1,3-diyl)inosine13 (3, Scheme 1) as its acetate
(11) Halmos, T.; Filippi, J .; Bach, J .; Antonakis, K. Carbohydr. Res.
1982, 99, 180-188.
(12) Ishibashi, M.; Doi, Y.; Kobayashi, J . J . Org. Chem. 1994, 59,
255-257.
(13) Kawase, Y.; Koizumi, M.; Iwai, S.; Ohtsuka, E. Chem. Pharm.
Bull. 1989, 37, 2313-2317.
S0022-3263(96)00727-X CCC: $12.00 © 1996 American Chemical Society

Notes
Sch em e 1. Syn th esis of th e Sh im ofu r id in
J . Org. Chem., Vol. 61, No. 19, 1996 6745
Sch em e 2. Tr a n s P u r in yla tion by Sch m id t Don or
Nu cleosid e Disa cch a r id e 2
materials and formation of a glycosylated product that
1
can be formulated as 8 on the basis of its H NMR, 13C
NMR, exact mass, IR, and UV spectra. In particular, the
fucopyranosyl anomeric H-1′′ appears as a doublet with
J ) 4.3, indicating the R-anomer. The use of fewer
equivalents of fucopyranosyl donor or lower reaction
temperature resulted in much less disaccharide product
8, and attempted glycosylation of the (N-1)-unprotected
acceptor 3 failed to produce any isolable disaccharide,
perhaps because of preferential glycosylation at O-6.5
By comparison to the successful glycosylation by 7, a
peracetylated fucopyranosyl donor, 2,3,4-tri-O-acetyl-(R/
â)-L-fucopyranosyl trichloroacetimidate17 (10), reacted
with 6 by the trans-purinylation pathway6 to give a
â-fucopyranosyl hypoxanthine product 12 in 38% yield
(Scheme 2). The position of glycosylation in 12 was
established unambiguously as N-7 by comparison of the
hypoxanthine C-4 and C-5 chemical shifts in the 13C NMR
spectrum (156.9 and 114.5 ppm, respectively) with those
of N-7 (157.7 and 114.7 ppm) and N-9 (148.4 and 124.6
ppm) ribosylated hypoxanthine.18 The peracetylated
donor 10 may be more reactive for trans-purinylation vs
O-glycosylation than the perbenzylated donor because it
is more electron-withdrawing once attached to the hy-
poxanthine N-7, as in 11.5
Stepwise removal of the disiloxan-1,3-diyl (with fluo-
ride ion) and benzyl and BOM (by hydrogenolysis)
protecting groups gave the desired shimofuridin nucleo-
side disccharide 2. Its spectroscopic characteristics (1H
NMR, 13C NMR, HR-FAB-MS, IR, and UV) are fully
consistent with the assigned structure. However, an
authentic sample of the natural shimofuridin degradation
product was unavailable, and no 1H or 13C NMR spectra
had been taken due to the limited amount of material
isolated in the degradation experiments.12 Thus, syn-
thetic 2 could only be compared with natural 1.
ester allowed N-1 alkylation with (benzyloxy)methyl
chloromethyl ether, leading to inosine derivative 5.
Deacetylation at O-2′ gave the glycosylation acceptor 6.
The benzyl-protected fucopyranosyl donor 7 was prepared
according to the literature procedure;14 the nonpartici-
pating benzyloxy group at C-2′′ was expected to direct
R-glycosylation.15
Activation of the donor 7 (5.75 equiv) with N-iodosuc-
cinimide and triflic acid16 at 23 °C in the presence of
acceptor 6 (1 equiv) led to the consuption of both starting
Figure 1 displays graphically the ∆δ values calculated
1
as the 13C and H chemical shifts of synthetic 2 minus
(16) (a) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J . H.
Tetrahedron Lett. 1990, 31, 1331-1334. (b) Knapp, S.; J aramillo, C.;
Freeman, B. J . Org. Chem. 1994, 59, 4800-4804.
(14) Hasegawa, A.; Kiso, M.; Ishida, H.; Kameyama, A. J . Carbo-
hydr. Chem. 1991, 10, 549-560.
(15) Recent reviews of glycosylation methods: (a) Toshima, K.;
Tatsuta, K. Chem. Rev. 1993, 93, 1503-1531. (b) Barresi, F.; Hinds-
gaul, O. Mod. Synth. Methods 1995, 7, 281-330. (c) Whitfield, D. M.;
Douglas, S. P. Glycoconjugate J . 1996, 13, 5-17.
(17) Wegmann, B.; J ung, K.-H.; Schmidt, R. R. Liebigs Ann. Chem.
1991, 121-124.
(18) Chenon, M-T.; Pugmire, R. J .; Grant, D. M.; Panzica, R. P.;
Townsend, L. B. J . Am. Chem. Soc. 1975, 97, 4627-4636.

6746 J . Org. Chem., Vol. 61, No. 19, 1996
Notes
2′-O-Acetyl-1-N-[(ben zyloxy)m eth yl]-3′,5′-O-(tetr a isop r o-
p yld isiloxa n e-1,3-d iyl)in osin e (5). A solution of 125 mg (0.22
mmol) of the inosine acetate 4 in 5 mL of dichloromethane
containing dry 4 Å sieves and 0.2 mL (1.15 mmol) of N,N-
diisopropylethylamine was treated with 0.05 mL (0.29 mmol)
of benzyl chloromethyl ether at 0 °C for 2.5 h. TLC analysis of
the reaction mixture at this point indicated complete disappear-
ance of the starting material and formation of a higher Rf
product. The reaction was quenched with 3 mL of water, stirred
for 0.5 h, and then diluted with dichloromethane. The organic
layer was washed with water and then brine, dried over sodium
sulfate, and concentrated. Chromatography of the residue with
30:1 dichloromethane/methanol as the eluant gave 110 mg (73%)
of the N-protected nucleoside 5 as a colorless oil: 1H NMR δ
8.10 (s, H-8), 8.04 (s, H-2), 7.37-7.39 (m, 5 Ar-H), 6.03 (d, J )
0.9, H-1′), 5.72 (d, J ) 5.1, H-2′), 5.66 and 5.62 (ABq, J ) 10.5,
NCH2O), 4.91-4.95 (m, H-3′), 4.73 (s, PhCH2), 4.07-4.26 (m, 2
H-5′, H-4′), 2.23 (s, OCOCH3), 1.07-1.16 (m, 4 CH(CH3)2); 13C
NMR δ 169.2, 156.6, 147.4, 146.5, 138.5, 136.7, 128.5, 128.1,
127.9, 127.8, 125.1, 87.5, 82.1, 75.7, 74.3, 71.9, 68.6, 60.2, 20.6,
17.4, 16.8, 13.3, 12.8; IR (film) 1753, 1706 cm-1; HR-FAB-MS
m/ z 673.3080 (calculated for M + H 673.3089); UV λmax 246 nm.
1-N-[(Ben zyloxy)m eth yl]-3′,5′-O-(tetr a isop r op yld isilox-
a n e-1,3-d iyl)in osin e (6). A solution of 125 mg (0.186 mmol) of
the N1-[(benzyloxy)methyl]inosine 5 in 5 mL of methanol was
treated with 8 mg (0.148 mmol) of sodium methoxide, and the
reaction mixture was stirred at room temperature for 1.5 h. TLC
analysis of the reaction mixture at this point indicated complete
disappearance of the starting material, and a new spot with a
slightly lower Rf than the starting material was observed. The
reaction mixture was neutralized with Amberlite IR-120 (H+)
resin, filtered, and then concentrated to give the crude product,
which was chromatographed with 30:1 dichloromethane/metha-
nol as the eluant to give 88 mg (75%) of 6 as a colorless oil: 1H
NMR δ 8.10 (s, H-8), 8.00 (s, H-2), 7.38-7.39 (m, 5 Ph-H), 6.00
(d, J ) 1.3, H-1′), 5.66 and 5.63 (ABq, J ) 10.9, NCH2O), 4.94
(app t, J ) 5.6, H-3′), 4.74 (s, PhCH2), 4.51 (br d, J ) 5.6, H-2′),
4.10-4.21 (m, 2 H-5′, H-4′), 3.15 (d, J ) 1.3, OH), 1.07-1.16
(m, 4 CH(CH3)2); 13C NMR δ 157.0, 147.2, 138.8, 136.7, 128.5,
128.1, 127.9, 125.3, 89.5, 82.1, 75.3, 74.3, 71.2, 70.4, 61.4, 17.3,
16.9, 13.3, 12.8; IR (film) 3418, 1706 cm-1; HR-FAB-MS m/ z
631.2988 (calculated for M + H 631.2983); UV λmax 248 nm.
1-N-[(Ben zyloxy)m eth yl]-3′,5′-O-(tetr a isop r op yld isilox-
a n e-1,3-d iyl)-2′-O-(2′′,3′′,4′′-t r i-O-b en zyl-r-L-fu cop yr a n o-
syl)in osin e (8). A stirred solution of 96 mg (0.207 mmol) of
phenyl 1,6-dideoxy-1-thio-2,3,4-tri-O-benzyl-â-L-fucopyranoside
(7) and 23 mg (0.036 mmol) of nucleoside acceptor 6 in 4 mL of
dichloromethane was treated sequentially with 75 mg of acti-
vated 3 Å sieves, 42 mg (0.187 mmol) of N-iodosuccinimide, and
0.30 mL (0.080 mmol) of a 4% dichloromethane solution of triflic
acid. After 15 min the reaction was quenched by adding 10%
aqueous sodium thiosulfate solution until the purple color was
discharged. The reaction mixture was diluted with dichlo-
romethane, washed sequentially with saturated aqueous sodium
bicarbonate, water, and brine, dried over sodium sulfate, con-
centrated, and then chromatographed with 3:2 hexane/ethyl
acetate as the eluant to give 14 mg (37%) of the protected
nucleoside disaccharide 8: 1H NMR δ 8.24 (s, H-8), 7.99 (s, H-2),
7.26-7.41 (m, 20 PhH), 5.99 (s, H-1′), 5.69 (d, J ) 4.3, H-1′′),
5.61 and 5.55, (ABq, J ) 10.3, NCH2O), 4.63-5.01 (m, 8 PhCH2),
4.56 (dd, J ) 3.4, 4.3, H-3′), 4.46 (d, J ) 3.4, H-2′), 4.20-4.35
(m, H-3′′, H-4′), 4.14-4.19 (m, H-5′′, H-5′), 4.00-4.07 (m, H-5′,
H-2′′), 3.78 (d, J ) 1.3, H-4′′), 0.96-1.11 [m, 3 H-6′′, 4 CH(CH3)2];
13C NMR δ 156.7, 147.0, 146.1, 138.9, 138.6, 138.4, 137.8, 136.8,
128.8, 128.5, 128.3, 128.2, 128.1, 127.9, 127.7, 127.6, 127.4, 95.9,
88.9, 81.4, 79.0, 76.1, 75.5, 74.8, 74.3, 73.4, 72.0, 71.8, 69.5, 67.0,
59.3, 17.5, 17.3, 16.9, 16.8, 16.7, 13.4, 13.0, 12.9, 12.4; IR (film)
1708 cm-1; HR-FAB-MS m/ z 1047.4965 (calculated for M + H
1047.4971); UV λmax 246 nm.
1
F igu r e 1. 13C and H chemical shift differences (∆δ) between
synthetic 2 and natural 1.
the chemical shifts12 of the corresponding atoms of 1 in
DMSO-d6 solution. A small positive or negative ∆δ value
corresponds to a close match in chemical shift. The
carbons of synthetic 2 were assigned by a HETCOR-2D
NMR experiment (see supporting information) and by
comparison to the 13C NMR spectrum of authentic methyl
R-L-fucopyranoside.19 Thus, 2 can be seen as a fucosy-
lated inosine that closely matches 1 at all carbons ([∆δ]
< 1 ppm) except for C-5′′ and the supposed point of
acylation, C-4′′. The upfield shift of C-5′′ (∆δ ) 4.2 ppm)
in response to acylation at C-4′′ (as in 1) finds precedent
in a 4-O-benzoylated R-fucopyranoside described by Bin-
kley.19 The downfield shifts of C-4′′ (∆δ ) -2.2 ppm) and
H-4′′ (-1.6 ppm) upon acylation at that site are reason-
able values.19 Therefore, based on the spectroscopic
correlations and the method of synthesis, the structure
of synthetic 2 corresponds to the nucleoside disaccharide
core of shimofuridin 1.
Exp er im en ta l Section
2′-O-Acet yl-3′,5′-O-(t et r a isop r op yld isiloxa n e-1,3-d iyl)-
in osin e (4). A solution of 250 mg (0.489 mmol) of 3′,5′-O-
(tetraisopropyldisiloxane-1,3-diyl)inosine in 5 mL of pyridine was
treated with 1 mL (10.6 mmol) of acetic anhydride. The reaction
mixture was stirred at room temperature for 6 h, cooled to 0 °C,
quenched with 5 mL of water, and stirred for another 0.5 h.
Concentration under high vacuum gave a residue that was
partitioned between 100 mL of ethyl acetate and 30 mL of water.
The organic layer was separated and then extracted sequentially
with 20% aqueous citric acid, water, and brine. The organic
layer was dried over sodium sulfate, concentrated, and then
chromatographed with 19:1 dichloromethane/methanol as the
eluant to give 260 mg (96%) of the pure acetate 4: 1H NMR (400
MHz, CDCl3) δ 13.18 (br s, NH), 8.14 (s, H-8), 8.10 (s, H-2), 6.08
(d, J ) 0.9, H-1′), 5.75 (d, J ) 5.1, H-2′), 4.97 (dd, J ) 5.6, 5.13,
H-3′), 4.08-4.26 (m, 2 H-5′, H-4′), 2.24 (s, OCOCH3), 1.07-1.17
(m, 4 CH(CH3)2); 13C NMR (100 MHz, CDCl3) δ 169.2, 159.2,
148.1, 144.9, 138.7, 125.6, 87.6, 82.2, 75.7, 68.7, 60.3, 20.6, 17.4,
16.9, 13.3, 12.8; IR (film) 1751, 1699 cm-1; HR-FAB-MS m/ z
553.2513 (calculated for M + H 553.2514); UV (MeOH) λmax 246
nm.
1-N-[(Ben zyloxy)m eth yl]-2′-O-(2′′,3′′,4′′-tr i-O-ben zyl-r-L-
fu cop yr a n osyl)in osin e (9). A solution of 28.5 mg (0.027 mmol)
of the disaccharide 8 in 3 mL of dry THF was treated with 0.035
mL (0.035 mmol) of a 1 M solution of tetra-n-butylammonium
fluoride in THF. The reaction mixture was stirred at room
temperature for 2.5 h and then concentrated. The crude product
was extracted into ethyl acetate, which was washed with water
followed by brine, dried over sodium sulfate, and then concen-
trated to a residue, which was triturated with hexane (2 × 25
(19) Binkley, R. W.; Goewey, G. S.; J ohnston, J . C. J . Org. Chem.
1984, 49, 992-996.

Notes
J . Org. Chem., Vol. 61, No. 19, 1996 6747
mL). Chromatography with 16:1 dichloromethane/methanol as
the eluant gave 13.5 mg (62%) of 9: 1H NMR δ 8.13 (s, H-8), 7.8
(s, H-2), 7.28-7.40 (m, 20 PhH), 5.87 (d, J ) 7.7, H-1′), 5.61
and 5.53 (ABq, J ) 10.7, NCH2O), 5.14 (d, J ) 11.1, 5′-OH),
4.91 (t, J ) 11.2, PhCH2), 4.80 (dd, J ) 7.7, 5.1, H-2′), 4.77 (s,
PhCH2), 4.71 (d, J ) 4.3, H-1′′), 4.57 and 4.68 (ABq, J ) 12.0,
PhCH2), 4.67 (s, PhCH2), 4.38 (d, J ) 5.1, H-3′), 4.35 (s, 3′-OH),
4.02 (dd, J ) 10.2, 3.4, H-5′), 3.88-3.94 (m, H-2′′, H-3′′, H-4′),
3.74 (t, J ) 11.1, H-5′), 3.60 (s, H-4′′), 3.39 (q, J ) 6.8, H-5′′),
0.74 (d, J ) 6.8, 3 H-6′′); IR (film) 3447, 1715 cm-1; HR-FAB-
MS m/ z 805.3446 (calculated for M + H 805.3448); UV λmax 248
nm.
2′-O-(r-L-F u cop yr a n osyl)in osin e (2). A solution of 12 mg
(0.015 mmol) of the nucleoside disaccharide 9 in 6 mL of
methanol was stirred with 8 mg of 20% palladium hydroxide on
carbon at room temperature under hydrogen atmosphere for 6
h. The catalyst was removed by filtration through a Celite pad,
and the filter cake was washed twice with 20 mL of methanol.
The combined filtrate was concentrated to give 4.5 mg (73%) of
the pure nucleoside disaccharide 2: 1H NMR (DMSO-d6) δ 12.42
(br s, NH), 8.36 (s, H-8), 8.09 (s, H-2), 6.02 (d, J ) 6.8, H-1′),
5.14 (br t, J ) 5, 5′-OH), 5.01 (d, J ) 3.9, H-1′′), 4.73 (dd, J )
6.8, 4.9, H-2′), 4.72 (br d, J ) 11.7, 2 OH), 4.60 (br s, OH), 4.43
(d, J ) 4.9, H-3′), 4.29 (br d, OH), 3.99 (br d, J ) 2, H-4′), 3.63
(m, 2 H-5′), 3.50 (br m, H-2′′, H-5′′), 3.29-3.33 (m, H-3′′, H-4′′),
0.58 (d, J ) 5.9, 3 H-6′′); 13C NMR (DMSO-d6) δ 146.0 (C-2),
148.2 (C-4), 124.4 (C-5), 156.4 (C-6), 138.8 (C-8), 85.5 (C-1′), 80.2
(C-2′), 69.6 (C-3′), 85.9 (C-4′), 61.3 (C-5′), 100.1 (C-1′′), 67.9 (C-
2′′), 66.6 (C-3′′), 71.4 (C-4′′), 69.4 (C-5′′), 15.7 (C-6′′); IR (film)
3427 and 1600 cm-1; HR-FAB-MS m/ z 415.1479 (calculated for
M + 1 415.1465); UV λmax 246 nm (MeOH, pH 7), 250 nm (pH
2), 254 nm (pH 11).
with lower Rf. The reaction was quenched with 2 mL of
saturated aqueous sodium bicarbonate and extracted with 25
mL of dichloromethane. The organic layer was dried over
sodium sulfate and then concentrated to a residue, which was
chromatographed with 49:1 dichloromethane/methanol as the
eluant to afford 8.6 mg (38%) of the fucosylated hypoxanthine
12. 1H NMR (CDCl3) δ 8.24 (s, H-8), 8.15 (s, H-2), 7.29-7.36
(m, 5 Ph-H), 6.29 (d, J ) 9.4, H-1′), 5.68 (t, J ) 9.7, H-2′), 5.68
(s, NCH2O), 5.39 (d, J ) 3.3, H-4′), 5.27 (dd, J ) 10.0, 3.4, H-3′),
4.68 (s, OCH2Ph), 4.16 (q, J ) 6.4, H-5′), 2.26, 2.01, and 1.85 (3
s, OCOCH3), 1.26 (d, J ) 6.4, three H-6′); 13C NMR (50 MHz,
CDCl3) δ 170.4 , 169.8, 169.2 (3 OCOCH3’s), 156.9 (C-4), 154.0
(C-6), 146.9 (C-2), 142.1 (C-8), 136.4 (ipso-Ph), 128.6, 128.3, 127.9
(o-, m-, p-Ph), 114.5 (C-5), 82.8 (C-1′), 74.1, 72.5, 71.8, 71.6, 70.0,
68.1, 20.7, 20.5, 20.3 (3 OCOCH3), 16.1 (C-6′); HR-FAB-MS m/z
529.1950 (calculated for M + 1 529.1934).
Meth yl (r a n d â)-L-F u cop yr a n osid e. A reference sample
of the two fucopyranoside anomers was synthesized from L-
fucose and methanol according to the literature procedure,19
resulting in a 2:1 R/â mixture that could be analyzed as such by
1H and 13C NMR spectroscopy. R-Anomer 1H NMR (partial,
DMSO-d6) δ 4.48 (d, J ) 2.6, H-1); 13C NMR (DMSO-d6) δ 100.5
(C-1), 71.8 (C-4), 69.9 (C-5), 68.3 (C-2), 65.9 (C-3), 54.8 (OCH3),
16.7 (C-6). â-Anomer 1H NMR (partial, DMSO-d6) δ 4.00 (d, J
) 7.6, H-1); 13C NMR (DMSO-d6) δ 104.5 (C-1), 73.7 (C-4), 71.3
(C-5), 70.4 (C-2), 70.2 (C-3), 56.0 (OCH3), 19.6 (C-6).
Ack n ow led gm en t. We are grateful to American
Cyanamid and Hoffmann-La Roche for support of this
research, and Gino Sasso, George Elgar, Vance Bell, and
Richard Szypula of the Physical Chemistry Department
of Hoffmann-La Roche for obtaining NMR and mass
spectra.
Tr a n s-P u r in yla t ion w it h Sch m id t Don or . 1-N-[(Ben -
zyloxy)m eth yl]-7-(2,3,4-tr i-O-a cetyl-â-L-fu cop yr a n osyl)h y-
p oxa n th in e (12). A solution of 17 mg (0.027 mmol) of the
inosine acceptor 6 and 19 mg (0.044 mmol) of 2,3,4-tri-O-acetyl-
L-fucopyranosyl trichloroacetimidate (10) in 3.0 mL of dichlo-
romethane was cooled to 0 °C and then treated with 0.008 mL
(0.044 mmol) of trimethylsilyl trifluoromethanesulfonate. The
reaction mixture was stirred for 1 h, during which time the bath
temperature rose to 15 °C. TLC analysis indicated complete
consumption of the acceptor and the formation of a new product
Su p p or tin g In for m a tion Ava ila ble: HETCOR-2D NMR
spectrum of 2 (4 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 O960727Z