Total synthesis of uradl polyoxin c

Article abstract of DOI:10.1055/s-1998-4499

An improved synthesis of methyl (methyl 5-azido-5deoxy-2,3-O-isopropylidene-β-D-allofuranosid)uronate (7) from methyl 2,3-0-isopropylidene-β-D-rifro-pentodialdo-l,4-furanoside (6), using vinylmagnesium bromide in the key step, and its application to the total synthesis of uracil polyoxin C (1) are described.

Full text of DOI:10.1055/s-1998-4499

SYNTHESIS
October 1998
1527
Total Synthesis of Uracil Polyoxin C
Keisuke Kato, Cheng Yu Chen, Hiroyuki Akita*
School of Pharmaceutical Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba, 274-8510, Japan
Fax +81(474)721825; E-mail: akita@phar.toho-u.ac.jp
Received 27 January 1998; revised 13 March 1998
Abstract: An improved synthesis of methyl (methyl 5-azido-5-
Nucleophilic 1,2-addition of allyl organometallics to the
5-aldehyde 6 has been reported to give preferential prod-
uct A the result of re-face attack on the unchelated alde-
hyde (non-chelation) with a C4–C5 conformation depicted
in structure of 6.4 Taking into account the effect of coex-
isting metal halides, the β-chelation of the metal ion may
give the re-face attack product A as a major component,
while the α-chelation of the metal ion would afford the si-
face attack product B as a major product.
deoxy-2,3-O-isopropylidene-β-D-allofuranosid)uronate (7) from
methyl 2,3-O-isopropylidene-β-D-ribo-pentodialdo-1,4-furano-
side (6), using vinylmagnesium bromide in the key step, and its
application to the total synthesis of uracil polyoxin C (1) are
described.
Key words: total synthesis, diastereoselective vinylation, α-hydroxy
ester, uracil polyoxin C
Polyoxins are pyrimidine nucleoside peptide antibiotics
produced by Streptomyces cacaoi var asoensis.1 They ex-
hibit selective activity against phytopathogenic fungi, but
are not toxic to bacteria, plants, or animals because of in-
hibition of chitin synthase.1 They are also reported to be
therapeutically useful against Candida albicans, a medi-
cally important human fungal pathogen.2 All members of
the polyoxin family possess the 1-(5-amino-5-deoxy-β-D-
allofuranuronosyl)pyrimidine unit, such as uracil polyox-
in C (1) and thymine polyoxin C (2), as a basic com-
ponent. In a previous paper,3 we reported a short path
synthesis of an important intermediate, ethyl (methyl 5-
azido-5-deoxy-2,3-O-isopropylidene-β-D-allofuranosid)-
uronate (3) for the syntheses of 1 or 2. It was derived from
ethyl (methyl 2,3-O-isopropylidene-β-D-allofuranosid)-
uronate (4) or ethyl (methyl 2,3-O-isopropylidene-α-L-
talofuranosid)uronate (5). The α-hydroxy esters (5S)-4
and (5R)-5 are obtained from the reaction of methyl 2,3-
O-isopropylidene-β-D-ribo-pentodialdo-1,4-furanoside
(6) and 1-ethoxyvinyllithium followed by ozonolysis and
subsequent reductive treatment in overall yield of 31%
and 10%, respectively. Although both (5S)-4 and (5R)-5
were converted to the desired α-azide ester 3, the overall
yield of 3 from 6 is quite low (13%). We now report the
improved synthesis of α-azido ester (5S)-7 from 6 and its
application to the total synthesis of uracil polyoxin C (1).
Scheme 2
Initially, reaction of the aldehyde 6 with vinylmagnesium
bromide examined and the reaction mixture was subjected
to acetylation to give a 3.7:1 diastereomeric mixture of
acetoxy compounds 8 and 9 by NMR analysis based on
comparison of the integral intensity due to the methoxy
groups of 8 (δ = 3.31) and 9 (δ = 3.30) in 71% overall
yield. Oxidative treatment of this mixture with RuCl4 and
NaIO4 followed by esterification and subsequent hydroly-
sis afforded a mixture of α-hydroxy esters 10 and 11,
which were separated to the more polar (5S)-10 (64%
overall yield) and the less polar (5R)-11 (22% overall
yield). Physical data [NMR and [α]D27 –56.4 (c = 1.40,
CHCl3)] of the minor isomer (5R)-11 were identical with
those [NMR and [α]D28 –56.7 (c = 1.47, CHCl3)] of an au-
thentic sample of (5R)-11 obtained by the transesterifica-
tion of the known (5R)-5.3 Therefore, the C5 configuration
of the major 10 may be S. This assumption was confirmed
by the following conversion reactions. Treatment of 10
with iodine and triphenylphosphine in the presence of im-
idazole gave the inverted α-iodo ester 12 [92% yield,
[α]D24 +12.7 (c = 0.59, CHCl3)] which was treated with
NaN3 to afford the α-azido ester 7 in 98% yield. The phys-
ical data [NMR and [α]D24 –53.3 (c = 1.41, CHCl3)] of syn-
thetic 7 were identical with those [NMR and [α]D –55.3 (c
Scheme 1

SYNTHESIS
Papers
1528
= 0.89, CHCl3)] of known (5S)-7.5 On the other hand, tri- lation effect. On the other hand, addition of trimethylsilyl-
flation of (5R)-11 followed by treatment of the triflate 13 acetylide to the α-oxygenated aldehyde in the presence of
with NaN3 afforded (5S)-7 in overall 87% yield. Thus the titanium complex was reported to give diastereoselec-
overall yield of the desired 7 from 6 was totally improved tively the anti-alkynyl addition product.6 By applying this
to 55% in comparison with the previous case3 (13%) or method, the addition of trimethylsilylacetylide to 6 was
the reported procedure (38%) by Barrett et al.5 From these investigated and the results are listed in Table 2.
experiments, the chemical shifts δ = 3.31 and 3.30 were
ascribed to those of methoxy groups of the major 8 and the
minor 9, respectively.
Table 2. Reaction of 6 and Trimethylsilylacetylide in the Presence of
Additive
Entry Additive
Conditions
Yield (%) Ratio
14+15
(14/15)
1
2
3
none
Et2AlCl
TiCl4/Ti(O-iPr)4 –78°C, 2 h
(1:1)
–78°C, 1.5 h
–78°C~0°C, 3.5 h 26
62
1:1.5
1.6:1
1.2:1
62
In each case, an improvement in the selectivity was not
found and the ratio of the diastereomeric mixture of 14
and 15 was determined by NMR analysis based on the
comparison of the integral intensity due to the methoxy
groups of 14 (δ = 3.44) and 15 (δ = 3.49). In order to de-
termine the structure of each diastereomer in the case of
Table 2, entry 1, the 1:1.5 diastereomeric mixture of 14
and 15 was treated with fluoride ion (F–) followed by
acetylation and subsequent partial reduction to give a
1:1.5 mixture of 8 and 9 in 91% overall yield. From these
experiments, the configurations of the newly generated
chiral centers (C5-position) of 14 and 15 should be R and
S, respectively. The addition of other carbanions to 6 was
then investigated and the results are shown in Table 3.
Scheme 3
For the purpose of improving the diastereoselectivity, the
effect of a coexisting metal halide in the addition to 6 was
examined and the results are shown in Table 1.
Table 1. Reaction of 6 and Vinylmagnesium Bromide in the Presence
of Additive
In the case of the addition of the methoxy(phenylthio)me-
thyl carbanion (Table 3, entry 1), the crude addition prod-
uct 16 was subjected to successive conversion reactions
[(1) acetylation, (2) Jones oxidation, (3) esterification, (4)
hydrolysis] and α-hydroxy esters 10 and 11 were obtained
in 9.5% and 9.7% overall yield, respectively. In the case
of the addition of the tris(methylthio)methyl carbanion
(Table 3, entries 2–5), the resulting diastereomeric mix-
ture 17 was treated with Hg2+ in MeOH to give α-hydroxy
esters 10 and 11 in moderate overall yields. The use of
Et2AlCl led to an enhanced α-chelation effect (Table 3,
entry 3). In the case of the addition of the cyanide ion to
6, the crude diastereomeric mixture of cyanohydrins was
treated with K2CO3 in 15% aqueous H2O2 to provide the
Entry Additive Conditions
Yield 8+9 (%) Ratio (8/9)
1
2
3
none
CeCl3
ZnBr2
–78°C ~ –20°C, 1.5 h 71
3.7:1
4.4:1
1.7:1
–78°C, 1.5 h
0°C, 1.5 h
53
52
In comparison to the reaction where no additive was
present (Table 1, entry 1), the addition of a metal ion (en-
tries 2 and 3) decreased the overall yield of products 8 and
9 and the additive CeCl3 (entry 2) may enhance the β-che-

SYNTHESIS
October 1998
1529
Table 3. Reaction of
6 and Methoxy(phenylthio)methyl- or
nesium bromide with dialdose derivatives was reported to
exhibit low diastereofacial preference (2:1–1:1.5).4 In the
formation of 8 and 9 from 6 via 3-trimethylsilylprop-1-
ene-1-yl-furanoside 20 on a small scale, high diastereose-
lectivity (8/9 8:1) was observed, but the total conversion
yield was moderate (44% from 6, Scheme 5). From the
point of view of synthetic effectiveness (diastereoselectiv-
ity and conversion yield), the present synthetic route to the
desired α-azide ester 7 by way of (5R)-8 and (5S)-9
seemed to be useful in comparison with the reported
procedures3–5 because both (5R)-8 and (5S)-9 were finally
converted to the important intermediate 7 despite the low
diastereoselectivity.
Tris(methylthilo)methyl Carbanion in the Presence of Additivea
Entry R
Additive
Conditions Yield (%)b Ratio
(10/11)
10
11
1
2
3
4
5
PhS(MeO)CH– none
–78°C, 1.5 h
–78°C, 1.5 h 32.9 5.6 6:1
0°C, 2 h
0°C, 2 h
9.5 9.7 1:1
(MeS)3C–
(MeS)3C–
(MeS)3C–
none
Et2AlCl
ZnBr2
35.5 5.3 6.7:1
27.1 7.3 3.7:1
5.5 0.3 18:1
(MeS)3C– TiCl4/Ti(O-iPr)4 0°C, 2 h
(1:1)
a
Method a) for 16; (1) Ac2O, pyridine; (2) CrO3. H+, (3) CH2N2; (4)
K2CO3, MeOH. Method b) for 17: HgO, HgCl2, MeOH/H2O (4:1).
Overall yield from 6.
b
Scheme 5
Thus obtained (5S)-7 was treated with Dowex 50W H+
resin in MeOH followed by acetylation to afford the diac-
etate 21. Treatment of 21 with acetic anhydride and acetic
acid in the presence of a catalytic amount of H2SO4
smoothly gave the triacetate 22 (69% overall yield from 7)
in which no C5 epimerization could be detected. Reaction
of the triacetate 22 with 2,4-bis(trimethylsiloxy)pyr-
imidine7 under the conditions reported by Vorbrüggen8
(TMSOTf, 1,2-dichloroethane, reflux) afforded exclu-
sively the β-nucleoside 23 (89% yield). Hydrogenation of
the azide 23 in the presence of 10% Pd-C afforded the
α-amino acid ester which was treated with benzyloxycar-
bonyl chloride in the presence of 7% aqueous NaHCO3 to
give (5S)-24 (66% yield). Alkaline hydrolysis of 24 fol-
lowed by hydrogenation gave uracil polyoxin C (1; 53%
yield). The synthetic material 1 ([α]D +16.7 (c = 1.57,
less polar amide 18 and the more polar amide 19 in 33%
and 35% overall yield, respectively. Both amides were in-
dependently subjected to successive conversion reactions
[(1) acid hydrolysis, (2) acetonide formation, (3) esterifi-
cation] and α-hydroxy esters 10 and 11 were obtained in
12% overall yield from 18 and 26% overall yield from 19,
respectively. From these experiments, the configurations
of the newly generated chiral centers (C5-position) of 18
and 19 were found to be S and R, respectively.
Scheme 4
In order to improve the diastereoselectivity and yield in
the addition of nucleophiles to the aldehyde 6, four types
of carbanion and the cyanide ion were used, but diastereo-
selectivity was not always improved, with the exception
of vinylmagnesium bromide (3.7:1–4.4:1; Table 1, entries
1 and 2) or tris(methylthio)methyllithium (6:1–6.7:1; Ta-
ble 3, entries 2 and 3). However, the reaction of vinylmag- Scheme 6

SYNTHESIS
Papers
1530
1H NMR: δ = 1.31 (s, 3H), 1.48 (s, 3H), 3.43 (s, 3H), 3.82 (s, 3H),
3.92 (d, 1H, J = 3.4 Hz), 4.32 (dd, 1H, J = 3.4, 3.9 Hz), 4.57 (d, 1H, J
= 3.9 Hz), 4.60 (d, 1H, J = 6.4 Hz), 4.90 (d, 1H, J = 6.4 Hz). 5.00 (s,
1H).
1
H2O), mp 242–248°C, H NMR) was consistent with an
authentic sample ([α]D +16.5 (c = 0.97, H2O),5 mp 241–
245°C,5 1H NMR9).
MS (FAB): m/z = 263 (M+ + 1).
All mps were measured on a Yanaco MP-S3 micro melting point ap-
paratus and are uncorrected. NMR spectra were measured on a JEOL
EX-400 spectrometer and spectra were taken as 5–10% (w/v) solu-
tions in CDCl3 with TMS as an internal reference. IR spectra were
measured on a JASCO FT/IR-300 spectrophotometer. FAB-MS were
obtained with a JEOL JMS-DX 303 instrument. Optical rotations
were measured on a JASCO DIP-370 digital polarimeter. All the re-
actions were carried out in an atmosphere of argon. All evaporations
were performed under reduced pressure.
11: yield: 2.27 g (22% overall yield); [α]D27 –56.4 (c = 1.40, CHCl3).
C11H18O7 calcd
(262.25) found
C
50.37
50.27
H
6.92
7.03
IR (neat): ν = 3419, 1747 cm–1.
1H NMR: δ = 1.32 (s, 3H), 1.47 (s,3H), 3.42 (s, 3H, 3.79 (s, 3H), 4.26
(s, 1H), 4.26 (d, 1H, J = 2 Hz), 4.60 (d, 1H, J = 5.9 Hz), 4.78 (d, 1H,
J = 2 Hz), 4.90 (d, 1H, J = 5.9 Hz), 4.94 (s, 1H).
MS (FAB): m/z = 263 (M+ + 1).
Reaction of Methyl 2,3-O-Isopropylidene-â-D-ribo-pentodialdo-1,4-
furanoside (6) and Vinylmagnesium Bromide (Table 1, Entry 1):
To a solution of 6 (11 g, 54.5 mmol) in THF (200 mL) at –78°C was
added 1 M vinylmagnesium bromide in THF (65.3 mL, 65.3 mmol).
The mixture was stirred at –20°C for 1.5 h, diluted with water (150 mL)
and extracted with EtOAc (2 × 300 mL). The extract was washed with
brine (100 mL), dried (MgSO4) and concentrated. To a solution of the
crude product in pyridine (11 mL, 139 mmol) at r.t. was added Ac2O
(1 mL, 100 mmol) and DMAP (611 mg, 5 mmol). The mixture was
stirred for 12 h, diluted with water (200 mL) and extracted with EtOAc
(200 mL). The organic layer was washed with 10% HCl (100 mL),
brine (100 mL), dried (MgSO4) and evaporated. The residue was chro-
matographed (silica gel, 200 g, hexane/EtOAc 10:1) to give a mixture
of 8 and 9 (8/9 3.7:1) as a colorless oil; yield: 10.5 g (71%).
Methyl (Methyl 2,3-O-Isopropylidene-α-L-talofuranosid)uronate
(11):
Ti(O-iPr)4 (0.17 mL, 0.57 mmol) was added to a solution of 53
(198 mg, 0.71 mmol) in a mixed solvent of benzene (6 mL), MeOH
(2.94 mL) and the whole mixture was refluxed for 16 h. It was diluted
with water (20 mL), extracted with Et2O (2 × 20 mL). The organic
layer was dried (MgSO4) and evaporated. The residue was chromato-
graphed (silica gel, 20 g, hexane/EtOAc, 10:1) to give 11 as a color-
less oil; yield: 158 mg (84%); [α]D28 –56.7 (c = 1.47, CHCl3).
Methyl (Methyl 5-Deoxy-5-iodo-2,3-O-isopropylidene-α-L-talo-
furanosid)uronate (12):
To a mixture of 10 (100 mg, 0.38 mmol), Ph3P (250 mg, 0.95 mmol)
and imidazole (65 mg. 0.96 mmol) in benzene (5 mL) was added I2
(194 mg. 0.76 mmol) at r.t. and the mixture was stirred for 2 h. It was
diluted with water (20 mL), extracted with EtOAc (2 × 20 mL). The
organic layer was dried (MgSO4) and concentrated. The residue was
chromatographed (silica gel, 20 g, hexane/EtOAc 5:1) to afford 12 as
C13H20O6 calcd
(272.29) found
C
57.34
57.02
H
7.40
7.69
IR (neat): ν = 1745, 1231, 1097 cm–1.
MS (FAB): m/z = 273 (M+ + 1).
1H NMR major diastereomer 8: δ = 1.33 (s, 3H), 1.48 (s, 3H), 2.11 (s,
3H), 3.31 (s, 3H), 4.24 (d, 1H, J = 6.8 Hz), 4.58 (d, 1H, J = 5.9 Hz),
4.68 (d, 1H, J = 5.9 Hz), 4.96 (s, 1H), 5.23–5.45 (m, 3H), 5.87 (ddd,
1H, J = 17.6, 10.7, 6.3 Hz).
α]24 +12.7 (c = 0.59, CHCl3).
a colorless oil; yield: 131 mg (92%); [
D
C11H17O8 calcd
(372.01) found
C
35.48
35.47
H
4.61
4.29
IR (neat): ν = 1738, 1514, 1098 cm–1.
1H NMR minor diastereomer 9: δ = 1.32 (s, 3H), 1.48 (s, 3H), 2.11 (s,
3H), 3.30 (s, 3H), 4.23 (dd, 1H, J = 1.4, 5.9 Hz), 4.58 (d, 1H, J = 5.9
Hz), 4.65 (dd, 1H, J = 1.4, 5.9 Hz), 5.01 (s, 1H), 5.23–5.45 (m, 3H),
5 78 (ddd, 1H, J = 10.3, 7.3 Hz).
1H NMR: δ = 1.32 (s, 3H), 1.49 (s, 3H), 3.45 (s, 3H), 3.78 (s, 3H),
4.52 (d, 1H, J = 10.2 Hz), 4.63 (d, 1H, J = 10.2 Hz), 4.65 (d, 1H, J =
6.2 Hz), 4.75 (d, 1H, J = 6.2 Hz), 5.01 (s, 1H).
MS (FAB): m/z = 373 (M+ + 1).
Methyl (Methyl 2,3-O-Isopropylidene-â-D-allofuranosid)uronate
(10) and Methyl (Methyl 2,3-O-Isopropylidene-α-L-talofura-
nosid)uronate (11):
Methyl (Methyl 5-Azido-5-deoxy-2,3-O-isopropylidene-â-D-allo-
furanosid)uronate (7):
To a solution of 12 (2.04 g 5.48 mmol) in DMF (12 mL) was added
NaN3 (1.07 g, 16.46 mmol) at 0°C and the mixture was stirred at r.t.
for 3 h. It was diluted with water (30 mL) and extracted with EtOAc
(2 × 20 mL). The organic layer was dried (MgSO4) and evaporated.
The residue was chromatographed (silica gel, 25 g, hexane/EtOAc
15:1) to give 7 as a colorless oil; yield: 1.54 g (98%); [α]D24 –53.3 (c
= 1.41, CHCl3).
To a solution of mixture of 8 and 9 (10.5 g, 38.6 mmol) in a mixed
solvent of MeCN (150 mL), CCl4 (150 mL), and pH 7.6 phosphate
buffer (150 mL) at r.t. was added RuCl3 (161 mg, 0.78 mmol) and
NaIO4 (41.3 g, 193 mmol). The mixture was stirred at r.t. for 5 h, to
which was added brine (150 mL) and 10% HCl (70 mL). It was ex-
tracted with EtOAc (2 × 300 mL). The organic layer was washed with
brine (50 mL), dried (MgSO4) and evaporated. A solution of residue
in Et2O (50 mL) was treated with an excess of CH2N2/Et2O solution
at 0°C. The mixture was stirred at r.t. for 2 h and evaporated. To a
mixture of the resulting residue in MeOH (40 mL) was added K2CO3
(5.4 g, 39.1 mmol) at 0°C for 1 h. The mixture was diluted with brine
(100 mL) and extracted with CHCl3 (2 × 150 mL). The CHCl3 layer
was washed with brine (50 mL), dried (MgSO4) and concentrated.
The residue was chromatographed (silica gel, 300 g, hexane/EtOAc
8:1) to give the less polar fraction 11 as a colorless oil and the more
polar fraction 10 as a colorless oil.
C11H17O6N3 calcd
(287.27) found
C
45.99
46.35
H
5.97
6.02
N
14.63
14.21
IR (neat): ν = 2939, 2112, 1747, 1438 cm–1.
1H NMR: δ = 1.33 (s, 3H), 1.49 (s, 3H), 3.34 (s, 3H), 3.82 (d, 1H, J =
9 Hz), 3.84 (s, 3H), 4.45 (dd, 1H, J = 1.9 Hz), 4.59 (d, 1H, J = 6 Hz),
4.87 (dd, 1H, J = 1, 6 Hz), 4.98 (s, 1H).
MS (FAB): m/z = 288 (M+ + 1).
Methyl (Methyl 5-Azido-5-deoxy-2,3-O-isopropylidene-â-D-allo-
furanosid)uronate (7):
To a solution of 11 (3.25 g, 12.4 mmol) in a mixed solvent of pyridine
(4.9 mL, 62 mmol) and CH2Cl2 (35 mL) was added Tf2O (3.12 mL,
18.6 mmol) at 0°C. After stirring for 15 min, the mixture was diluted
with water (30 mL). The organic layer was washed with 10% HCl
(40 mL) and brine (40 mL), dried (MgSO4) and concentrated. To a
10: yield: 6.51 g (64% overall yield); [α]D25 –47.2 (c = 1.29, CHCl3).
C11H18O7 calcd
(262.25) found
C
50.37
50.12
H
6.92
7.13
IR (neat): ν = 3396, 1736 cm–1.

SYNTHESIS
October 1998
1531
solution of crude 13 in DMF (30 mL) was added NaN3 (1.2 g,
18.5 mmol) at r.t. After stirring for 2 h, the mixture was diluted with
water (40 mL) and extracted with EtOAc (2 × 20 mL). The organic
layer was dried (MgSO4) and concentrated. The residue was chro-
matographed (silica gel, 150g, hexane/EtOAc 20:1) to provide 7 as a
colorless oil; yield: 3.1 g (87%).
stirred at 0°C for 2 h. The mixture was diluted with water (20 mL) and
EtOAc (20 mL). After filtration (Celite), the filtrate was separated and
water layer was again extracted with EtOAc (20 mL) and dried
(MgSO4). The combined EtOAc layer was dried (MgSO4), and con-
centrated. The organic layer was treated by the same way as case of
entry 1 (Table 2) to give a mixture of 14 and 15 (14/15 1.6:1) as a
colorless oil; yield: 96 mg (26%).
Reaction of 6 and Vinylmagnesium Bromide in the Presence of
CeCl3 (Table 1, Entry 2):
Reaction of 6 and Lithium Trimethylsilylacetylide in the Presence
of TiCl4 and Ti(O-iPr)4 (Table 2 Entry 3):
To a mixture of CeCl3 (493 mg, 2 mmol) in THF (5 mL) at –78°C was
added 1 M vinylmagnesium bromide in THF (2 mL, 2 mmol). After
stirring at –78°C for 0.5 h, a solution of 6 (202 mg, 1 mmol) in THF
(2 mL) was added to the above mixture and the whole mixture was
stirred at –78°C for 1.5h. The reaction was stopped by adding sat.
NH4Cl (10 mL), diluted with water (20 mL) and extracted with
EtOAc (2 × 20 mL). The organic layer was dried (MgSO4) and evap-
orated. To a solution of crude product in pyridine (1 mL, 12.7 mmol)
at r.t. was added Ac2O (1 mL, 10.6 mmol) and DMAP (12 mg, 0.1
mmol). The mixture was stirred for 12 h, diluted with water (25 mL)
and extracted with EtOAc (30 mL). The organic layer was purified by
the same way as case of entry 1 (Table 1) to give a mixture of 8 and 9
(8/9 4.4:1) as a colorless oil; yield: 145 mg (53%).
To a solution of lithium trimethylsilylacetylide prepared from tri-
methylsilylacetylene (304 mg, 3 mmol) by the same way as case of
entry 1 (Table 2) was added a mixture of TiCl4 (0.14 mL, 1.27 mmol)
and Ti(O-iPr)4 (0.37 mL, 1.25 mmol) in THF (4 mL), prepared be-
forehand in another flask, and the whole mixture was stirred at –78°C
for 15 min. A solution of 6 (250 mg, 1.24 mmol) in THF (4 mL) was
added to the above mixture, and the whole mixture was stirred at
–78°C for 2 h. The mixture was diluted with water (20 mL), extracted
with EtOAc (2 × 20 mL) and dried (MgSO4). The organic layer was
treated by the same way as case of entry 1 (Table 2) to give a mixture
of 14 and 15 (14/15 1.2:1) as a colorless oil; yield: 233 mg (62%).
Reaction of 6 and Vinylmagnesium Bromide in the Presence of
ZnBr2 (Table 1, Entry 3):
Preparation of a Mixture of 8 and 9 from a Mixture of 14 and 15:
Bu4NF (383 mg, 1.46 mmol) was added to a solution of a mixture of
14 and 15 (14/15 1:1.5, 220 mg. 0.73 mmol) in DMSO (5 mL) at r.t.
and the mixture stirred for 20 min. It was diluted with water (20 mL)
and extracted with EtOAc (2 × 20 mL). The organic layer was dried
(MgSO4) and concentrated. To a solution of the residue in pyridine
(1 mL, 12.7 mmol) at r.t. was added Ac2O (0.5 mL, 5.3 mmol) and
DMAP (12 mg, 0.1 mmol). The mixture was stirred at r.t. for 15 min,
diluted with water (20 mL) and extracted with EtOAc (30 mL). The
organic layer was washed with 10% HCl (20 mL), brine (20 mL),
dried (MgSO4) and evaporated. A mixture of residue and 5% Pd-
BaSO4 (70 mg) in CH2Cl2 (4 mL) was subjected to catalytic hydroge-
nation at r.t. and the mixture was filtered with the aid of Celite. The
filtrate was evaporated to give the residue, which was chromato-
graphed (silica gel, 50 g, hexane/EtOAc 9:1) to provide a mixture of
8 and 9 (8/9 1:1.5) as a colorless oil; yield: 182 mg (91%).
To a mixture of ZnBr2 (450 mg, 2 mmol) in THF (5 mL) at 0°C was
added 1 M vinylmagnesium bromide in THF (2 mL, 2 mmol). After
stirring at 0°C for 0.5 h, a solution of 6 (202 mg, 1 mmol) in THF
(2 mL) was added to the above mixture and the whole was stirred at
0°C for 1.5 h. The reaction was stopped by adding sat. NaHCO3
(30 mL) and extracted with EtOAc (2 × 20 mL). The organic layer
was subjected to acetylation and subsequent purification by the same
way as case of entry 2 (Table 1) to give a mixture of 8 and 9 (8/9
1.7:1) as a colorless oil; yield: 140 mg (52%).
Reaction of 6 and Lithium Trimethylsilylacetylide (Table 2, En-
try 1):
To a solution of trimethylsilylacetylene (304 mg, 3 mmol) in THF
(10 mL) at –78°C was added 1.5 M BuLi in hexane (1.65 mL,
2.48 mmol), and the mixture was stirred for 20 min. A solution of 6
(250 mg, 1.24 mmol) in THF (4 mL) was added to the acetylide solu-
tion and the mixture was stirred for 1.5 h. The mixture was diluted
with water (20 mL), extracted with EtOAc (2 × 20 mL). The organic
layer was dried (MgSO4) and concentrated. The residue was chro-
matographed (silica gel, 50 g, hexane/EtOAc 10:1) to give a mixture
of 14 and 15 (14/15 1:1.5) as a colorless oil; yield: 232 mg (62%).
Reaction of 6 and Methoxy(phenylthio)methyllithium (Table 3,
Entry 1):
To a solution of methoxymethyl phenyl sulfide (616 mg, 4 mmol) in
THF (10 mL), at –78°C was added 1.2 M BuLi in hexane (2.5 mL,
3 mmol), and the mixture was stirred for 0.5 h. A solution of 6
(405 mg, 2 mmol) in THF (4 mL) was added to the above mixture,
and the mixture was stirred for 1.5 h. The mixture was diluted with
water (25 mL) and extracted with EtOAc, (2 × 25 mL). The extract
was dried (MgSO4) and concentrated. To a solution of the residue in
pyridine (1 mL, 12.7 mmol) at r.t. was added Ac2O (1 mL, 10.6
mmol) and DMAP (12 mg, 0.1 mmol). The organic layer was
washed with 10% HCl (20 mL), brine (25 mL), dried (MgSO4) and
evaporated. Jones reagent (2 mL) was added a solution of residue in
acetone (20 mL) at –20°C, and the mixture was stirred at 0°C for
2 h. The reaction was stopped by adding iPrOH (1 mL), diluted with
brine (20 mL) and extracted with EtOAc (3 × 30 mL). The organic
layer was evaporated. A solution of residue in Et2O (20 mL) was
treated with an excess of CH2N2/Et2O solution at 0°C. The mixture
was stirred at r.t. for 1 h and evaporated. To a solution of the result-
ing residue in MeOH (6 mL) was added K2CO3 (276 mg, 2 mmol)
at 0°C and the mixture was stirred for 0.5 h. The mixture was diluted
with water (25 mL) and extracted with CHCl3 (2 × 20 mL). The
CHCl3 layer was dried (MgSO4) and concentrated. The residue was
chromatographed (silica gel, 40 g, hexane/EtOAc 7:1) to give the
less polar fraction 11 as a colorless oil and the more polar fraction
10 as a colorless oil.
C14H24O5Si calcd
(300.42) found
C
55.97
55.90
H
8.06
8.34
IR (KBr): ν = 3429, 2958, 2177, 1094 cm–1.
MS (FAB): m/z = 301 (M+ + 1).
1H NMR: δ = 0.17 (s, 1.8H in 15), 0.19 (s, 1.2H in 14), 1.31 (s, 1.8H
in 15), 1.34 (s, 1.2H in 14), 1.47 (s, 1.8H in 15), 1.49 (s, 1.2H in 15),
3.44 (s, 1.2H in 14), 3 49 (s, 1.8H in 15), 3.81 (d. 0.4H, J = 2.0 Hz in
14), 3.91 (d, 0.6H, J = 10.7 Hz in 15), 4.32 (dd, 0.6H, J = 3.9, 10.7 Hz
in 15), 4.42–4.46 (m, 1.4H in 14 and 15), 4.58 (d, 1H, J = 5.9 Hz in
14 and 15), 4.81 (d, 0.6H, J = 5.9 Hz in 15), 4.98 (d, 0.4H, J = 5.9 Hz
in 14), 4.99 (s, 0.4H in 14), 5.00 (s, 0.6H in 15).
Reaction of 6 and Lithium Trimethylsilylacetylide in the Presence
of Et2AlCl (Table 2, Entry 2):
To a solution of lithium trimethylsilylacetylide prepared from tri-
methylsilylacetylene (304 mg, 3 mmol) by the same way as case of
entry 1 (Table 2) was added 1 M Et2AlCl in hexane (2.4 mL,
2.4 mmol), and the mixture was stirred at –78°C for 20 min. A solu-
tion of 6 (250 mg, 124 mmol) in THF (4 mL) was added to the above
mixture, and the whole mixture was stirred at –78°C for 30 min and

SYNTHESIS
Papers
1532
10; yield: 50 mg (9.5% overall yield from 6).
11; yield: 51 mg (9.7% overall yield from 6).
(Table 3) to provide the less polar fraction 11 as a colorless oil and the
more polar fraction 10 as a colorless oil.
10; yield: 14.4 mg (5.5% overall yield from 6).
11; yield: 0.8 mg (0.3% overall yield from 6).
Reaction of 6 and Tris(methylthio)methyllithium (Table 3, Entry
2):
To a solution of tris(methylthio)methane (386 mg, 2.5 mmol) in THF
(8 mL) at –78°C was added 1.2 M BuLi in hexane (1.7 mL, 2 mmol),
and the mixture was stirred for 15 min. A solution of 6 (202 mg,
1 mmol) in THF (4 mL) was added to the above mixture, and the mix-
ture was stirred for 1.5 h. The mixture was diluted with sat. NH4Cl
(20 mL) and extracted with EtOAc (2 × 20 mL). The organic layer
was dried (MgSO4) and concentrated. HgCl2 (570 mg, 2.1 mmol) and
HgO (227 mg, 1.1 mmol) was added to a solution of the above residue
in a mixed solvent of MeOH (12 mL), water (1 mL) at r.t. and the
whole mixture was stirred for 0.5 h. After filtration, the filtrate was
diluted with sat. NH4Cl (25 mL) and extracted with CHCl3 (2 ×
30 mL). The CHCl3 was dried (MgSO4) and concentrated. The resi-
due was chromatographed (silica gel, 20 g, hexane/EtOAc 8:1) to give
the less polar fraction 11 as a colorless oil and the more polar fraction
10 as a colorless oil.
Methyl (Methyl 2,3-O-Isopropylidene-â-D-allofuranosid)urona-
mide (18) and Methyl (Methyl 2,3-O-Isopropylidene-α-L-talo-
furanosid)uronamide (19):
To a solution of 6 (1.906 g, 9.43 mmol) in MeOH (20 mL) was added
NaCN (0.71 g, 14.5 mmol) and K2CO3 (1.92 g, 13.9 mmol) at 0°C for
5 min, and 15% H2O2 (20 mL) was added to the above mixture at 0°C
and the whole mixture was allowed to stir for 30 min at 0°C. The
mixture was diluted with water (5 mL) and 10% Na2SO3 (20 mL) and
extracted with EtOAc (3 × 20 mL). The organic layer was washed
with brine (20 mL), dried (MgSO4) and evaporated. The residue was
chromatographed (silica gel, 60 g, hexane/EtOAc 1:1–1:2) to give the
less polar fraction 18 as colorless crystals and the more polar fraction
19 as colorless crystals.
10; yield: 86.2 mg (32.2% overall yield from 6).
11; yield: 14.8 mg (5.6% overall yield from 6).
18: recrystallized from hexane/EtOAc to give colorless needles
(779 mg, 33% overall yield); mp 146–147°C; [α]D25 –95.5 (c = 1.28,
CHCl3).
Reaction of 6 and Tris(methylthio)methyllithium in the Presence
of Et2AlCl (Table 3, Entry 3):
C10H17O6N
(247.24)
calcd
found
C
48.58
48.35
H
6.93
6.92
N
5.67
5.64
To a solution of lithium tris(methylthio)methyl carbanion prepared
from tris(methylthio)methane (386 mg, 2.5 mmol) by the same way
as case of entry 2 (Table 3) was added 1 M Et2AlCl in hexane (2 mL,
2 mmol), and the mixture was stirred at 0°C for 10 min. A solution of
6 (202 mg, 1 mmol) in THF (4 mL) was added to the above mixture,
and the whole mixture was stirred at 0°C for 2 h. It was diluted with
water (30 mL) and extracted with EtOAc (30 mL) and filtered with
the aid of Celite. The filtrate was separated and organic layer was
dried (MgSO4), evaporated. The residue was treated by the same way
as case of entry 2 (Table 3) to afford the less polar fraction 11 as a
colorless oil and the more polar fraction 10 as a colorless oil.
10; yield: 93 mg (35.5% overall yield from 6).
IR (neat): ν = 3393, 3192, 1633 cm–1.
1H NMR: δ = 1.31 (s, 3H), 1.47 (s, 3H), 3.47 (s, 3H), 4.21 (dd, 1H, J
= 1.6, 3.3 Hz), 4.49 (d, 1H. J = 1.6 Hz), 4.59 (d, 1H, J = 5.8 Hz), 4.77
(d, 1H, J = 3.3 Hz), 4.79 (d, 1H, J = 5.8 Hz), 5.02 (s, 1H), 6.18 (brs,
1H), 6.77 (brs, 1H).
MS (FAB): m/z = 248 (M+ + 1).
19: recrystallized from hexane/EtOAc to give colorless needles
(819 mg, 35% overall yield); mp 144–145°C; [α]D26 –5.09 (c = 1.12.
CHCl3).
C10H17O6N
(247.24)
calcd
found
C
48.58
48.40
H
6.93
6.94
N
5.67
5.68
11; yield: 14 mg (5.4% overall yield from 6).
IR (neat): ν = 3420, 3281, 1631 cm–1.
Reaction of 6 and Tris(methylthio)methyllithium in the Presence
of ZnBr2 (Table 3, Entry 4):
NMR: δ = 1.33 (s, 3H), 1.48 (s, 3H), 3.46 (s, 3H), 4.10 (dd, 1H, J =
3.0, 10.1 Hz), 4.57 (d, 1H, J = 10.1 Hz), 4.60 (d, 1H, J = 5.8 Hz), 4.90
(dd, 1H, J = 0.6, 5.8 Hz), 4.99 (s, 1H), 5.00 (d, 1H, J = 3.0 Hz), 6.36
(brs, 1H), 6.73 (brs, 1H).
To a solution of lithium tris(methylthio)methyl carbanion prepared
from tris(methylthio)methane (386 mg, 2.5 mmol) by the same way
as case of entry 2 (Table 3) was added a solution of ZnBr2 (450 mg.
2 mmol) in THF (3 mL), and the mixture was stirred at 0°C for 10 min
A solution of 6 (202 mg, 1 mmol) in THF (4 mL) was added to the
above mixture, and the whole mixture was stirred at 0°C for 2 h. The
reaction was stopped by adding sat. NH4Cl (25 mL) and the mixture
was extracted with EtOAc (2 × 25 mL). The organic layer was dried
(MgSO4) and evaporated. The residue was treated by the same way as
case of entry 2 (Table 3) to provide the less polar fraction 11 as a
colorless oil and the more polar fraction 10 as a colorless oil.
10; yield: 71 mg (27.1% overall yield from 6)
MS (FAB): m/z = 248 (M+ + 1).
Methyl (Methyl 2,3-O-Isopropylidene-â-D-allofuranosid)uronate
(10) from 18:
A mixture of 18 (101 mg, 0.40 mmol), Dowex 50W H+ resin (61 mg)
in a mixed solvent (dioxane/H2O 4:1, 3 mL) was allowed to stir at
90°C for 18 h. The mixture was filtered with the aid of Celite and the
Celite was washed with acetone (10 mL). The whole filtrate was dried
(MgSO4) and evaporated. A mixture of the above residue in a mixed
solvent of acetone (2 mL) and MeOH (2 mL) in the presence of concd
HCl (2 drops) was refluxed with stirring for 12 h. After cooling, the
mixture was directly dried (MgSO4) and evaporated. The residue was
chromatographed (silica gel, 10 g, hexane/EtOAc 8:1) to give 10 as a
colorless oil; yield: 13.1 mg (12% overall yield).
11; yield: 19 mg (7.3% overall yield from 6)
Reaction of 6 and Tris(methylthio)methyllithium in the Presence
of TiCl4 and Ti(O-iPr)4 (Table 3, Entry 5):
To a solution of lithium tris(methylthio)methyl carbanion prepared
from tris(methylthio)methane (386 mg, 2.5 mmol) by the same way
as case of entry 2 (Table 3) was added a mixture of TiCl4 (0.11 mL,
1 mmol) and Ti(O-iPr)4 (0.3 mL, 1 mmol) in THF (3 mL) prepared
beforehand in another flask, and the mixture was stirred at –78°C for
0.5 h. A solution of 6 (202 mg, 1 mmol) in THF (4 mL) was added to
the above mixture, and the whole mixture was stirred at –78°C for 1
h and at 0°C for 2 h. It was diluted with water (25 mL), extracted with
EtOAc (2 × 25 mL). The organic layer was dried (MgSO4) and evap-
orated. The residue was treated by the same way as case of entry 2
Methyl (Methyl 2,3-O-Isopropylidene-α-L-talofuranosid)uronate
(11) from 19:
A mixture of 19 (101 mg, 0.40 mmol), Dowex 50W H+ resin (64 mg)
in a mixed solvent (dioxane/H2O 4:1, 3 mL) was allowed to stir at
90°C for 18 h. The mixture was worked up by the same way as case
of conversion of 18 to 10 to afford 11 as a colorless oil 11; yield:
28.3 mg (26% overall yield).

SYNTHESIS
October 1998
1533
Methyl (5-Azido-5-deoxy-1,2,3-tri-O-acetyl-D-allofuranosid)ur-
onate (22):
mixture was filtered with the aid of Celite. The filtrate was evaporated
to give the residue. A mixture of the residue, benzyl chloroformate
(0.4 mL, 1 mmol), and 7% NaHCO3 (0.7 mL) in dioxane (4 mL) was
stirred at r.t. for 1 h, and diluted with brine (20 mL). The mixture was
extracted with EtOAc (3 × 10 mL), dried (MgSO4) and evaporated.
The residue was chromatographed (silica gel, 20 g, hexane/EtOAc
1:2) to afford 24 as a colorless amorphous product; yield: 146 mg
(66%); mp 78–80°C; [α]D26 +16.0 (c = 1.043, CHCl3).
To a solution of 7 (669 mg, 2.33 mmol) in MeOH (15 mL) was added
Dowex 50W H+ resin (1.37 g), and the mixture was refluxed for 16 h.
The solution was filtered with the aid of Celite, and the Celite was
washed with MeOH (20 mL) and CH2Cl2 (20 mL), and the whole
filtrate was evaporated. A mixture of the residue and Ac2O (5.3 mL,
56.1 mmol) in pyridine (21 mL, 260 mmol) was stirred at r.t. for 1 h.
The mixture was poured into ice (10 g), allowed to stir for 0.5 h, and
extracted with EtOAc (3 × 20 mL). The organic layer was washed
with 2 N HCl (20 mL), 7% NaHCO3 (30 mL), and brine (30 mL). The
organic layer was dried (MgSO4) and concentrated to give a crude
residue 21, which was used for the next reaction without further puri-
fication. To a solution of a crude 21 in a mixed solvent of CH2Cl2
(6 mL) and AcOH (6 mL) at 0°C was added Ac2O (1.6 mL, 16.9
mmol) followed by a catalytic amount of H2SO4 (5 drops). The mix-
ture was allowed to stir at 0°C for 40 min then warmed at r.t. and
allowed to stir for a further 1 h. The mixture was poured into ice (10
g), allowed to stir for 0.5 h, and extracted with Et2O (3 × 30 mL). The
organic layer was washed with 7% NaHCO3 (30 mL), and brine (30
mL). The organic layer was dried (MgSO4) and evaporated. The res-
idue was chromatographed (silica gel, 30g, hexane/EtOAc 4:1) to
provide 22 as a colorless oil; yield: 581 mg (69% overall yield).
C23H25O11N3 calcd
(519.45) found
C
53.18
53.38
H
4.85
4.63
N
8.09
8.06
IR (Nujol): ν = 3190, 1748, 1693 cm–1.
1H NMR: δ = 2.09 (s, 3H), 3.80 (s, 3H), 4.41 (dd, 1H, J = 3.9, 5.1 Hz),
4.83 (d, 1H, J = 5.1 Hz), 5.14 (d, 2H, J = 6.6 Hz), 5.50 (dd, 1H, J =
5.3, 6.2 Hz), 5.66 (d, 1H, J = 8.2 Hz), 5.80 (d, 1H, J = 8.4 Hz), 5.91
(d, 1H, J = 5.3 Hz), 6.44 (d, 1H, J = 4.4 Hz), 7.20 (d, 1H, J = 8.2 Hz),
7.32–7.37 (m, 5H), 8.58 (brs, 1H).
MS (FAB): m/z = 520 (M+ + 1), 558 (M+ + K).
1-(5'-Amino-5'-deoxy-â-D-allofuranosyluronic acid)uracil
(Uracil Polyoxin C) (1):
A mixture of 24 (27.7 mg. 0.053 mmol) and LiOH H2O (13 mg,
•
0.51 mmol) in a mixed solvent (THF/H2O 4:1, 3 mL) was stirred at
0°C for 1.5 h. The mixture was diluted with water (2 mL) and extract-
ed with CH2Cl2 (5 mL). The water layer was adjusted with 1 N HCl
to pH 2–3 and extracted with EtOAc (5 × 10 mL). The EtOAc layer
was dried (MgSO4) and evaporated. A mixture of the residue and 10%
Pd-C (30 mg) in MeOH (2 mL) was subjected to catalytic hydrogena-
tion at r.t. and the mixture was filtered with the aid of Celite (50 mg)
and activated carbon (30 mg). The filtrate was evaporated and the
residue was crystallized from water to give 1 as a pale tan solid; yield:
8.2 mg (53% overall yield); mp 242–248°C; [α]D25 +16.7 (c = 1.145,
H2O).
C13H17O9N3 calcd
(359.29) found
IR (neat): ν = 2958, 2116, 1747 cm–1.
C
43.46
43.57
H
4.77
4.55
N
11.70
11.79
1H NMR α-anomer: δ = 2.08 (s, 3. H), 2.1 1 (s, 3H), 2.13 (s, 3H), 3.84
(s, 3H), 4.42 (d, 1H, J = 2.9 Hz), 4.61 (t, 1H, J = 2.9 Hz), 5.23 (dd,
1H, J = 4.4, 6.8 Hz), 5.33 (dd, 1H, J = 2.4, 6.8 Hz), 6.44 (d, 1H, J =
4.4 Hz).
1H NMR β-anomer: δ = 2.04 (s, 3H), 2.13 (s, 6H), 3.80 (s, 3H), 4.34
(d, 1H, J = 4.4 Hz), 4.61 (dd, 1H, J = 4.4, 6.8 Hz), 5.36 (d, 1H, J = 4.9
Hz), 5.54 (dd, 1H, J = 4.9, 6.8 Hz), 6.16 (s, 1H).
MS (FAB): m/z = 300 (M+ – OAc).
HRMS (FAB): calcd for C10H14O7N3 (M+ + 1) 288.0832; found
288.0855
1-(Methyl 2',3'-Di-O-acetyl-5'-azido-5'-deoxy-â-D-allofuranosyl-
uronate)uracil (23):
IR (KBr): ν = 3429–3167 (br), 1687, 1632, 1465 cm–1.
1H NMR: (3% DCl in D2O): δ = 4.23 (dd, 1H, J = 2.6, 6.5 Hz), 4.30
(dd, 1H, J = 4, 6.5 Hz), 4.45 (d, 1H, J = 2.6 Hz), 4.54 (t, 1H, J = 6.5
Hz), 5.61 (d, 1H, J = 4 Hz), 5.73 (d, 1H, J = 8 Hz), 7.37 (d, 1H, J = 8
Hz).
A mixture of uracil (143 mg, 1.28 mmol), 1,1,1,3,3,3-hexamethyldis-
ilazane (3.8 mL, 18.0 mmol) and TMSCl (0.41 mL, 3.22 mmol) was
refluxed for 7 h, cooled and evaporated. The residue was dissolved in
1,2-dichloroethane (4 mL), the resulting clear solution which was
used for subsequent reactions. To a solution of 22 (99 mg, 0.276
mmol) in 1,2-dichloroethane (2 mL) was added the above solution
and the mixture was allowed to stir for 5 min. After addition of
TMSOTf (0.3 mL, 1.66 mmol), the mixture was allowed to stir at
100°C for 2 h and then quenched by addition of 7% NaHCO3 (5 mL).
The mixture was extracted with CH2Cl2 (3 × 10 mL), dried (MgSO4),
and evaporated. The residue was chromatographed (silica gel, 20 g,
hexane/EtOAc 1:1) to give 23 as a colorless amorphous product;
yield: 101 mg (89%); mp 144–146°C; [α]D25 –74.0 (c = 1.077, CHCl3).
This work was supported by a grant for the “Biodesign Research
Program” from Riken (The Institute of Physical and Chemical
Research) to H. A.
(1) Isono K.; Asahi K.; Suzuki S. J. Am. Chem. Soc. 1969, 91, 7490.
Isono K.; Suzuki S. Heterocycles 1979, 13, 333.
(2) Becker J. M.; Covert N. L.; Shenbagamurthi P. S.; Steinfeld A.;
Naider F. Antimicrob. Agents Chemother. 1983, 23, 926.
(3) Akita H.; Uchida K.; Chen Cheng Yu. Heterocycles 1997, 46, 87.
(4) Danishefsky S. J.; DeNinno M. P.; Phillips G. B.; Zelle R. E.; Lar-
tey P. A. Tetrahedron 1986, 42, 2809.
(5) Barrett A. G. M.; Lebold S. A. J. Org. Chem. 1990, 55, 3853.
(6) Mukaiyama T.; Suzuki K.; Yamada T.; Tabusa F. Tetrahedron
1990, 46, 265.
(7) Iwai I.; Nishimura T. Chem. Pharm. Bull. 1964, 12, 352.
(8) Vorbrüggen H.; Krolikiewicz K.; Bennua B. Chem. Ber. 1981,
114, 1234.
(9) Uramoto M.; Kobinata K.; Isono K.; Higashijima T.; Miyazawa
T.; Jenkins E. E.; McCloskey J. A. Tetrahedron 1982, 38, 1599.
C15H17O9N5 calcd
(411.33) found
C
43.89
43.68
H
4.17
3.90
N
17.03
16.63
IR (Nujol): ν = 2922, 2117, 1749, 1718, 1686 cm–1.
1H NMR: δ = 2.08 (s, 3H), 2.12 (s, 3H), 3.87 (s, 3H), 4.46 (dd, 1H, J
= 2.9, 3.4 Hz), 4.53 (d, 1H, J = 3.4 Hz), 5.32 (dd, 1H, J = 5.9, 6.8 Hz),
5.38 (dd, 1H, J = 2.9, 5.9 Hz), 5.86 (d, 1H, J = 8 Hz), 6.19 (d, 1H, J =
6.8 Hz), 7.53 (d, 1H, J = 8 Hz), 9.65 (brs, 1H).
MS (FAB): m/z = 412 (M+ + 1), 450 (M+ + K).
1-(Methyl 2',3'-Di-O-acetyl-5'-benzyloxycarbonylamino-5'-
deoxy-â-D-allofuranosyluronate)uracil (24):
A mixture of 23 (175 mg, 0.426 mmol) and 10% Pd-C (50 mg) in
MeOH (8 mL) was subjected to catalytic hydrogenation at r.t. and the