Regioselective glycosylation: Synthesis of α-indoline nucleosides

Article abstract of DOI:10.1081/NCN-200067398

Novel indoline ribonucleosides with the α-N-glycoside configuration are synthesized with very high regioselectivity in 90-96% yield, using TMS protected indolines and 2,3-O-(1-methylethylidene)-5-O-(triphenylmethyl)- α/β-D-ribofuranose. The structures of

Full text of DOI:10.1081/NCN-200067398

Nucleosides, Nucleotides, and Nucleic Acids, 24 (8):1147–1165, (2005)
Copyright D Taylor & Francis, Inc.
ISSN: 1525-7770 print/ 1532-2335 online
DOI: 10.1081/NCN-200067398
REGIOSELECTIVE GLYCOSYLATION: SYNTHESIS OF
a-INDOLINE NUCLEOSIDES
5
Kenneth L. Brown, Tilak Chandra, and Shawn Zou
Department of Chemistry and
Biochemistry, Ohio University, Athens, Ohio, USA
5
Edward J. Valente
Department of Chemistry, Mississippi College, Clinton, Mississippi,
USA
5
Novel indoline ribonucleosides with the a-N-glycoside configuration are synthesized with very high
regioselectivity in 90---96% yield, using TMS protected indolines and 2,3-O-(1-methylethylidene)-5-O-
(triphenylmethyl)-a/b-D-ribofuranose. The structures of these ribonucleosides were elucidated with
X-ray crystallography as well as 2D (NOESY, COSY, and HMQC) NMR spectroscopy.
Keywords Coenzyme B12, Biosynthesis, Regioselective, Glycosylation
INTRODUCTION
Studies of the role of the axial nucleotide in the enzymatic activation of 5’-
deoxyadenosylcobalamin (coenzyme B12, AdoCbl, Figure 1) require coenzyme
analogs with altered axial nucleotides.[1] Although some such analogs may be
obtained by guided biosynthesis,[2] using fermentation of appropriate bacteria on
media supplemented with the desired axial base, analogs with indole axial nu-
cleotides (which mimic the natural structure but lack the coordinating nitrogen)
cannot, as these organisms fail to glycosylate indoles to make the required nucleo-
side precursor.[3] It is thus necessary to develop a chemical method for the semi-
synthesis of AdoCbl analogs with altered axial nucleotides by coupling the desired
nucleoside to the nucleotide-free cobinamide, Factor-B,[4] or cobyric acid.[4,5] For this
Received 19 October 2004, accepted 22 April 2005.
Address correspondence to Kenneth L. Brown, Department of Chemistry and Biochemistry, Ohio University,
Athens, Ohio 45701, USA; Fax: 740-594-0148; E-mail: brownk3@ohiou.edu
1147
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1148
K. L. Brown et al.
FIGURE 1 Structure of coenzyme B12 and B3-deazaAdoCbl.
purpose, a critical step is the synthesis of the nucleoside, which has the unusual a-N-
glycosidic bond configuration. Since indoles are poor nucleophiles, the typical
strategy is to glycosylate the reduced indoline, followed by reoxidation to give the
indole nucleoside.[6,7] Thus, synthesis of indoline ribonucleosides with the unusual
a-configuration is a priority in this work.
While many routes exist for synthesis of b-N-glycosides, there are few methods
available for the a-anomers. Mukaiyama et al.[8] showed that the reaction of
1-hydroxy sugars such as 2,3-O-(1-methylethylidene)-5-O-(triphenylmethyl)-a/b-D-
ribofuranose[9] or 5-O-benzoyl-2,3-O-(1-methylethylidene)-D-ribofuranose[10] with
trimethylsylated benzimidazole and other nitrogenous bases including nucleoside
bases and azides, using 2-fluoro-1-methylpyridinium tosylate as condensing reagent,
gives predominantly alpha ribonucleosides. However, as much as 47% of the b-
anomer is obtained, requiring difficult separations of these isomeric mixtures by
column chromatography. So far, no full characterization and isolation of these
compounds has been reported. There are reports[10,11] of the use of ribofuranosyl
chlorides for a-glycosylation, but these also produce mixtures of a- and b-N-
glycosides. To date, there has not been a single report of reactions that produce the

Synthesis of a-Indoline Nucleosides
1149
a-nucleoside exclusively. We now report the synthesis of a-indoline ribonucleosides
in excellent yield without the formation of any detectable b-ribonucleoside.
RESULTS AND DISCUSSION
Scheme 1 shows the synthetic route for the synthesis of protected indolines and
their coupling to protected D-ribofuranose to form the a-indoline ribonucleosides
exclusively. The dimethyl indole base 2 was synthesized in fairly good yield by a
literature method[12,13] starting from readily available 5-nitropseudocumene.[12]
5-Nitropseudocumene was converted into 2,4,5-trimethylaniline[12] by tin chloride
reduction in hydrochloric acid. The amine was further converted to the formamide
in 90% yield by refluxing in formic acid. Thermal cyclization of the amide using
freshly prepared tert-butoxide affords the indole in fairly good yield (40%). The
dimethylindole was converted to the dimethyindoline 5 in 90% yield using sodium
cyanoborohydride in acetic acid at ambient temperature.[14] For the coupling
reaction, the free base was protected with trimethylsilyl chloride to give the silylated
base[15] in excellent yield. 5,6-Dimethyl-1-trimethylsilanyl-2,3-dihydro-1H-indole
8 was prepared in 98% yield from dimethylindoline at À70°C. Similarily, the
TMS-bromoindoline 9 was prepared in 95% yield from corresponding 5-bromoin-
doline base. 2,3-O-(1-Methylethylidene)-5-O-(triphenylmethyl)-a/b-D-ribofuranose
was easily prepared in fairly good yield from D-ribose in two steps.[9]
Freshly prepared, silylated dimethyindoline base 8 was then coupled to an
anomeric mixture of the protected sugar 2,3-O-(1-methylethylidene)-5-O-(triphenyl-
methyl)-a/b-D-ribofuranose, 10 (a mixture of a- and b-anomers),[9] using 2-fluoro-1-
methylpyridinium p-toluene sulfonate as a condensing agent[8] (Scheme 1). For this
SCHEME 1 Reagents and conditions: (i) sodiumcyanoborohydride, AcOH; (ii) butyllithium, trimethylsilyl-
chloride, À70°C; (iii) 2-fluoromethylpyridinium tosylate, N,N’-diisopropylethylamine, methylene chloride, 0 to
À30°C.

1150
K. L. Brown et al.
SCHEME 2 Reagents and conditions: (i) 2-fluoromethylpyridinium tosylate, N,N’-diisopropylethylamine,
methylene chloride, 0 to À30°C.
coupling reaction, 2-fluoro-1-methylpyridinium p-toluene sulfonate and the sugar
were stirred in methylene chloride under basic condition, using N,N-di-
isopropylethylamine as a base, for 2–3 h at À30°C, and the silylated indoline
was added to the reaction mixture at À10°C in dry methylene chloride under argon
atmosphere. The reaction proceeds smoothly and can be monitored by NMR. The
reaction was highly regioselective and crude reaction mixtures showed exclusively
a-ribonucleosides with no trace of b-nucleosides by NMR. After completion of the
reaction, the organic layer was thoroughly washed with water, and the solvent was
removed under reduced pressure. The unreacted base was removed by washing
with hexane, and the resulting solid was dried under reduced pressure to afford the
pure a-ribonucleoside in 96% yield. The method does not require further
complicated purification. a-Indoline and 5-bromoindoline ribonucleosides were
FIGURE 2 ORTEP diagram of compound 11.

Synthesis of a-Indoline Nucleosides
1151
similarily prepared in 90 and 92% yield, respectively, from corresponding TMS
protected indoline bases. The indoline ribonucleoside was easily purified by stirring
in hexane at room temperature. These a-ribonucleosides can be easily converted to
the corresponding indole nucleosides in excellent yield at moderate temperature
using manganese dioxide and molecular sieves in benzene.[7]
The dimethylbenzimidazole and benzimidazole a-ribonucleosides were simila-
rily prepared from 5,6-dimethyl-1-(trimethylsilyl)-1H-benzimidazole[16] or 1-(trime-
thylsilyl)-1H-benzimidazole and 10 using 2-fluoro-1-methylpyridinium p-toluene
sulfonate as a condensing agent[8] (Scheme 2) and isolated in pure form for
spectroscopic comparison. The reaction of trimethylsilylated benzimidazole with 2,3-
O-(1-methylethylidene)-5-O-(triphenylmethyl)-a/b-D-ribofuranose gives the a-anomer
in 70–80% yield and b-anomer in 20–30% yield. The spectroscopic data and
characterization of these ribonucleosides has been not reported in the literature,[8] so
it is necessary to characterize these ribonucleosides by 2D NMR. The isomers were
separated with some difficulty.
The anomeric configuration of 11 was confirmed by X-ray crystallography
(Figure 2). Suitable crystals for X-ray diffraction were grown by slow crystallization
at low temperature in ethyl acetate/hexane (1:1). A summary of crystallographic
data for the indoline nucleoside 11 is given in Table 1. The indoline moiety is
˚
nearly planar, the glycosidic bond length is 1.444 A (Table 2), and the glycosidic
TABLE 1 Crystal Data and Structure Refinement for Compound 11
Empirical formula
Formula weight
C35 H35 N O4
533.64
Temperature
293(2) K
Wavelength
0.71073 A
Crystal system, space group
Unit cell dimensions
Orthorhombic, P2(1)2(1)2(1)
a = 6.964(7) A alpha = 90°
b = 16.69(2) A beta = 90
c = 24.63(2) A gamma = 90°
2863(5) A3
Volume
Z, Calculated density
Absorption coefficient
F(000)
4, 1.238 Mg/m3
0.080 mmÀ1
1136
Crystal size
Theta range for data collection
Index ranges
Reflections collected/unique
Completeness to 2theta =
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2sigma(I)]
R indices (all data)
0.15 Â 0.15 Â 0.8 mm
2.06 to 20.01 deg.
0 ꢀ h ꢀ 6, 0 ꢀ k ꢀ 16, 0 ꢀ l ꢀ 23
1583/1577 [R(int) = 0.1602]
20.01 99.7%
Full-matrix least-squares on F2
1577/210/361
0.568
R1 = 0.0555, wR2 = 0.1105
R1 = 0.1888, wR2 = 0.1544
À9(7) (Undetermined)
0.179 and À0.191 e.AÀ3
Absolute structure parameter
Largest diff. peak and hole

1152
K. L. Brown et al.
˚
TABLE 2 Bond Lengths (A) and Angles (°) for Compound 11
O(1)–C(1)
O(2)–C(2)
O(3)–C(3)
O(5)–C(20)
N(1)–C(1)
C(2)–C(3)
C(4)–C(5)
C(6)–C(7)
1.443(14)
1.413(14)
1.440(15)
1.484(14)
1.444(15)
1.525(17)
1.553(16)
1.536(18)
1.534(19)
1.503(17)
111.5(10)
106.7(11)
115.4(12)
115.3(12)
103.8(11)
107.1(12)
105.3(11)
106.8(12)
112.0(11)
107.6(11)
O(1)–C(4)
O(3)–C(6)
O(5)–C(5)
N(1)–C(12)
C(1)–C(2)
C(3)–C(4)
C(6)–C(8)
C(12)–C(13
1.437(14)
1.439(15)
1.399(14)
1.480(16)
1.565(17)
1.523(16)
1.494(16)
1.571(15)
1.379(17)
1.528(17)
107.1(11)
119.5(10)
113.1(11)
110.6(11)
117.4(12)
113.1(11)
108.3(12)
105.4(11)
111.5(11)
105.0(12)
C(13)–C(14)
C(20)–C(41)
C(14)–C(15)
C(20)–C(31)
C(1)–O(1)–C(4)
C(6)–O(3)–C(3)
C(19)–N(1)–C(1)
C(1)–N(1)–C(12)
O(1)–C(1)–C(2)
O(2)–C(2)–C(3)
C(3)–C(2)–C(1)
C(4)–C(3)–C(2)
O(1)–C(4)–C(5)
O(5)–C(5)–C(4)
C(6)–O(2)–C(2)
C(5)–O(5)–C(20)
C(19)–N(1)–C(12)
O(1)–C(1)–N(1)
N(1)–C(1)–C(2)
O(2)–C(2)–C(1)
O(3)–C(3)–C(4)
O(1)–C(4)–C(3)
C(3)–C(4)–C(5)
O(2)–C(6)–O(3)
torsion angle, C(19)–N(1)–C(1)–O(1) is À79.9°, slightly outside the narrow range
of À30° to À72° observed for other a-ribonucleosides.[17]
In the NMR, the anomeric protons of the a-indoline ribonucleosides appeared
at d 5.32–5.45 ppm and the 1’–2’ coupling constant was 3.8 Hz for each compound.
For comparison, the protected a- and b-ribonucleosides of benzimidazole and 5,6-
dimethylbenzimidazole (Scheme 2) had J1’–2’ = 3.8 Hz for the a-anomers, but 3.0
or 3.2 Hz for the b-anomers. While literature reports[18–20] suggest that the anomeric
configuration of such nucleosides can be established based on the chemical shift
difference of the isopropylidene methyl groups, the indoline ribonucleosides do not
follow this rule. Thus, while the benzimidazole a-ribosides have isopropylidene
methyl group chemical shift separations of ꢀ 0.2 ppm (0.16 and 0.20 ppm) and the
b-ribosides have a 0.27 ppm methyl separation, the a-indoline ribosides have an
isopropylidene separation of 0.22 or 0.23 ppm.
EXPERIMENTAL SECTION
General Information
Unless otherwise noted, all reactions were conducted in flame-dried glassware
with magnetic stirring under an atmosphere of dry nitrogen. Solvents were distilled
prior to use. Dichloromethane, benzene, and ether were distilled from calcium
hydride. Flash column chromatography was performed using silica gel 230–400
mesh. Compounds on thin-layer chromatography were visualized by illumination

Synthesis of a-Indoline Nucleosides
1153
under UV light (254 nm). Evaporations were carried out under reduced pressure
with a water bath below 40°C. All solvents were dried and purified before use. All
reagents were commercially available and used without further purification. All
reactions were monitored by thin-layer chromatography (TLC) using Merck silica
gel 60, F-254.
Physical Measurements
1H NMR and 13C NMR spectra were recorded on a Varian INOVA-500 and
VXR-400 NMR spectrometers using the residual proton resonance of the solvent as
an internal reference at 25°C. Two-dimensional NMR (COSY, NOESY, and
HMQC) spectra were obtained at 25°C on a Varian INOVA-500 NMR
spectrometer using TMS as internal reference. Chemical shifts are reported in
parts per million (d), and signals are expressed as s (singlet), d (doublet), t (triplet), q
(quartet), and m (multiplet). The multiplicities of the 13C NMR signals were
determined by the HMQC and DEPT technique. Mass data (FD, MALDI and
FAB) were obtained at the University of Illinois using a micromass Quattro-I mass
spectrometer. Melting points are uncorrected.
5,6-Dimethylindole (2). To dry precooled, vigorously stirred tert-butyl
alcohol (50 mL), clean potassium metal (2 g) was added in small portions under a
nitrogen atmosphere. After complete dissolution, the mixture was stirred at 40°C
for 10 min and N-(2,4,5-trimethylphenyl)formamide (3.8 g, 23 mmol) was added
and the temperature was slowly raised to remove the excess solvent completely. At
a temperature of 270–280°C, fumes evolved, and heating was continued at this
temperature until the fuming ceased. The reaction mixture was cooled to room
temperature, the residue was dissolved in a mixture of methylene chloride and
methanol (1:1), and silica gel (10 g) was added to the flask. Following removal of the
solvent under reduced pressure, the resulting powder was loaded onto a silica gel
column and was eluted with a 5–30% methylene chloride: hexane concentration
1
gradient, which yielded a yellow low melting solid.[12,13] Yield: 1.35 g, 40%; H
NMR (CDCl3): d 2.40 (s, 3H, CH3), 2.41 (s, 3H, CH3), 6.48 (t, J = 2Hz, 1H, indole),
7.10 (t, J = 2.5 Hz, 1H, indole), 7.18 (s, 1H, indole), 7.45 (s, 1H, indole), 7.63 (bs,
1H, NH); 13C NMR (CDCl3): d 20.00 (CH3), 20.40 (CH3), 101.69 (CH), 111.34
(CH), 120.63 (CH), 123.31 (CH), 126.10 (Cquat), 128.30 (Cquat), 130.85 (Cquat),
134.71 (Cquat); MS (EI) m/z: 145 (M+), 119, 94; HRMS: m/z: 146.0972 (calcd for
C10H12N; 146.0976) (M + H).
5,6-Dimethyl-2,3-dihydro-1H-indole (5). A solution of dimethylin-
dole 2 (0.470 g, 3.2 mmol) in acetic acid was stirred for 10 min at 12°C and sodium
cyanoborohydride (0.8 g, 12 mmol) was added portion-wise under a nitrogen
atmosphere at the same temperature. The reaction mixture was stirred for 2 h and was
monitored by TLC. After completion of the reaction, the mixture was neutralized

1154
K. L. Brown et al.
with 50% sodium hydroxide (10 mL). Finally, ether (50 mL) was added and the
mixture was stirred for 30 min. The ether layer was separated, the extraction was
repeated two more times, and the combined ether layers were washed with brine.
After removal of the ether layer, a viscous oil was obtained that was purified on silica
gel column. Yield: 0.428 g, 90%; mp 35–38°C dec; white solid; 1H NMR (CDCl3): d
2.14 (s, 3H, CH3), 2.17 (s, 3H, CH3), 2.98 (t, J = 8.4 Hz, 2H, CH2), 3.30 (bs, 1H, NH),
3.53 (t, J = 8.8 Hz, 2H, CH2), 6.544 (s, 1H, Ar), 6.93 (s, 1H, Ar); 13C NMR (CDCl3): d
19.19 (CH3), 19.93 (CH3), 29.67 (CH2), 47.53 (CH2), 111.52 (CH), 125.82 (CH),
126.86 (Cquat), 127.05 (Cquat), 135.10 (Cquat), 149.16 (Cquat); MS (EI) m/z: 147
(M+), 132, 117; HRMS: m/z: 148.1127 (calcd for C10H14N; 148.1125) (M + H).
5-Bromo-2,3-dihydro-1H-indole (6). 5-Bromo-2,3-dihydro-1H-indole
6 was prepared from 5-bromoindole as described for 5,6-dimethylindoline 5,
1
above. Yield: 0.9 g, 90%; low melting solid. H NMR (CDCl3): d 2.99 (t, J = 8 Hz,
2H, CH2), 3.53 (t, J = 8.5 Hz, 2H, NCH2), 3.7 (bs, 1H, NH), 6.46 (d, J = 8.5 Hz, 1H,
Ar), 7.06 (d, J = 6.5 Hz, 1H, Ar), 7.17 (s, 1H, Ar); 13C NMR (CDCl3): d 29.62
(CH2), 47.47 (CH2), 110.01 (Cquat), 110.50 (Cquat), 127.44 (CH), 129.68 (CH),
131.71 (CH), 150.55 (Cquat); MS (EI) m/z: 198 (M+), 118 (M-Br); HRMS: m/z:
271.02149 (calcd for C11H16SiBrN; 271.0214).
1-(Trimethylsilanyl)-2,3-dihydro-1H-indole (7). To a solution of
indoline 4 (5.0 g, 42 mmol) in ether, a solution of n-butyllithium (1.6 M) (25 mL, 39
mmol) was added dropwise during 30 min maintaining the temperature at À70°C.
After addition, a solid separated out and the mixture was stirred for an additional
15 min. Finally, a solution of chlorotrimethylsilane (4.2 g, 39 mmol) in dry ether (25
mL) was added over one h at the same temperature and the reaction mixture was
stirred for 10 h at 25°C. After completion of the reaction, which was monitored by
1H-NMR, the reaction mixture was filtered through a Buchner funnel under a
nitrogen atmosphere, and the filtrate was concentrated under reduced pressure.
The viscous residue was distilled under vacuum at 90°C. Yield: 7.6 g, 95%; 1H NMR
(CDCl3): d 0.34 (s, 9H, CH3), 3.071 (t, J = 9 Hz, 2H, CH2), 3.68 (t, J = 8.5 Hz, 2H,
CH2), 6.64–6.66 (m, 2H, Ar), 7.04 (t, J = 7.5 Hz, 1H, Ar), 7.12 (d, J = 7.5 Hz, 1H,
Ar), 13C NMR (CDCl3): d 0.722 (CH3, SiMe3), 29.87 (CH2), 48.97 (CH2), 108.77
(CH), 116.71 (CH), 124.47 (CH), 127.02 (CH), 131.73 (Cquat), 152.09 (Cquat); MS
(EI) m/z: 191 (M+), 176 (M-15), 118, 91.
5,6-Dimethyl-1-trimethylsilanyl-2,3-dihydro-1H-indole (8). 5,6-
Dimethyl-1-trimethylsilanyl-2,3-dihydro-1H-indole was prepared from 8 as described
for 7, above. Yield: 0.63 g, 98%; 1H NMR (CDCl3): d 0.34 (s, 9H, CH3), 2.14 (s, 3H,
CH3, Ar), 2.17 (s, 3H, CH3, Ar), 2.93 (t, J = 9 Hz, 2H, CH2, indoline), 3.57 (t, J = 8.5 Hz,
2H, CH2, indoline), 6.4 (s, 1H, Ar), 6.42 (s, 1H, Ar); 13C NMR (CDCl3): dÀ0.624
(CH3), 18.98 (CH3, Ar), 20.26 (CH3, Ar), 29.78 (CH2, indoline), 49.23 (CH2, indoline),
110.43 (CH), 124.35 (Cquat), 125.85 (CH), 129.28 (Cquat), 134.65 (Cquat), 150.20

Synthesis of a-Indoline Nucleosides
1155
(Cquat); MS (EI) m/z: 219 (M+), 204 (M-15), 189, 174, 159, 144, 130, 118, 91; HRMS:
m/z: 220.1525 (calcd for C13H22SiN; 220.1520) (M + H).
5-Bromo-1-trimethylsilanyl-2,3-dihydro-1H-indole (9). Yield:
1
2.19 g, 95%; low melting solid. H NMR (CDCl3): d 0.288 (s, 9H, CH3), 3.005 (t,
J = 8.8 Hz, 2H, CH2), 3.638 (t, J = 9.6 Hz, 2H, CH2), 6.43 (t, J = 8.4Hz, 1H, Ar),
7.05 (d, J = 9.2 Hz, 1H, Ar), 7.15 (s, 1H, Ar); 13C NMR (CDCl3): d À0.844 (CH3),
29.70 (CH2), 49.33 (CH2), 108.17 (Cquat), 109.84 (CH), 127.29 (CH), 129.56 (CH),
134.35 (Cquat), 151.50 (Cquat); MS (EI) m/z: 270 (M+), 190, 175, 160.
2,3-O-(1-Methylethylidene)-5-O-(triphenylmethyl)-a/b-D-ribo-
furanose (mixture of a/b anomers) (10). Yield: 4.25 g, 85%;
1
amorphous solid; mp 95–98°C dec; H NMR (CDCl3): d 1.34 (s, 3H, CH3), 1.36
(s, 3H, CH3), 1.477 (s, 3H, CH3), 1.54 (s, 3H, CH3), 3.01 (dd, J = 3.0, 7.5 Hz), 3.33
(dd, J = 3.5, 6.5 Hz, 1H), 3.39–3.45 (m, 1H), 3.78 (d, J = 9.5 Hz, 1H), 3.94 (d,
J = 11.50 Hz, 1H), 4.18 (broad triplet, 1H), 4.346 (t, J = 3Hz, 1H), 4.58 (d, J = 5.5
Hz, 1H), 4.64 (d, J = 6 Hz, 1H), 4.71–4.73 (m, 1H), 4.77 (d, J = 6 Hz, 1H), 5.32 (d,
J = 9.5 Hz, 1H), 5.70 (dd, J = 3.5, 7.0 Hz, 1H), 7.22–7.40 (m, 15 H, trityl); 13C NMR
(CDCl3): 24.69 (CH3), 25.03 (CH3), 26.08 (CH3), 26.45 (CH3), 64.99 (CH2, 5’), 65.35
(CH2), 79.35(CH), 80.00 (CH), 81.89 (CH), 82.09 (CH), 85.95 (CH), 86.89 (CH),
87.43 (CH), 88.03 (CH), 97.93 (CH), 103.39 (CH), 112.15 (Cquat), 113.04 (Cquat),
127.12 (CH), 127.38 (CH), 127.90 (CH), 127.99 (CH), 128.49 (CH), 128.59 (CH),
142.79 (Cquat), 143.40 (Cquat); HRMS: m/z: 433.2215 (calcd for C27H29O5;
433.2014) (M + H); MS: (FAB) m/z 433, 243.[9]
1-(5-O-Triphenylmethyl-2,3-O-isopropylidene-a-D-ribofurano-
syl) indoline (11). To a precooled mixture of 2-fluoro-1-methylpyridinium
tosylate (1.7 g, 6.0 mmol) in dry, degassed methylene chloride (10 mL) at À30 to
À40°C was slowly added, a mixture of 2,3-O-(1-methylethyledene)-5-O-(triphenyl-
methyl)-a/b-D-ribofuranose[9,21] 10 (1.8 g, 4.2 mmol) in methylene chloride (10 mL)
and N,N-diisopropylethylamine (0.5 mL) under nitrogen, and this mixture was
stirred for 3 h at À30°C. During addition of the sugar, the reaction temperature was
maintained carefully. After 3 h, the temperature was raised to À10°C, the cooling
bath was removed from the reaction mixture and it was replaced with ice bath. A
solution of 1-(trimethylsilyl)-2,3-dihydro-1H-indole, 7 (2.0 g, 10 mmol) was prepared
in degassed dry methylene chloride and slowly added to the above mixture at
À10°C and the resulting solution was stirred for 6 h and then further stirred for 6 h
at room temperature. Complete conversion of the starting material was confirmed
1
by TLC (benzene: ether 8:2) as well as H NMR. After completion, the reaction
mixture was poured into water (50 mL) the organic layer was separated and dried
over anhydrous sodium sulfate, and the methylene chloride was removed under
reduced pressure. The residue was washed with hexane thoroughly by stirring in
hexane and the resulting solid was dried under reduced pressure to afford the

1156
K. L. Brown et al.
nucleoside in excellent yield. Yield: 2.0 g, 90%; mp 120–22°C dec; Rfj. 0.6; White
1
solid; H NMR (CDCl3): d 1.39 (s, 3H, CH3, isopropylidene), 1.61 (s, 3H, CH3,
isopropylidene), 2.93–2.99 (m, 2H, CH2, indoline), 3.28 (dd, J = 4.5, 5.0 Hz, 1H,
5’), 3.35 (dd, J = 4.5, 5 Hz, 1H, 5@), 3.51–3.58 (m, 1H, CH of NCH2, indoline), 3.60
(q, 1H, CH, indoline), 4.19–4.20 (m, 1H, CH, 4’), 4.70–4.72 (m, 1H, CH, 3’), 4.85–
4.87 (m, 1H, CH, 2’), 5.45 (d, J = 3.78 Hz, 1H, CH, 1’), 6.76 (t, J = 7.5 Hz, 1H, CH,
Ar), 6.81 (d, J = 8 Hz, 1H, Ar), 7.06–7.12 (m, 2H, Ar), 7.25–7.48 (m, 15H, Ar,
trityl); 13C NMR (CDCl3): d 25.56 (CH3), 27.48 (CH3), 28.26 (CH2), 47.31 (CH2),
63.89 (CH2), 80.67 (C 3’), 81.49 (C 2’), 82.00 (C 4’), 86.04 (Cquat), 92.83 (C 1’),
108.92 (CH, Ar), 114.01 (Cquat), 119.19 (CH), 124.60 (CH), 126.98 (CH), 127.75
(CH), 128.70 (CH), 136.23 (Cquat), 144.05 (Cquat), 149.05 (Cquat); HRMS: m/z:
534.2644 (calcd for C35H36NO4; 534.2643) (M + H); MS: (FAB) m/z: 534, 491, 430,
355, 281, 243, 165.
1-(5-O-Triphenylmethyl-2,3-O-isopropylidene-a-D-ribofurano-
syl)-5,6-dimethylindoline (12). The dimethylindoline nucleoside was
prepared from 8 as described for compound 11. Purification was carried out
using methylene chloride as eluent. Yield: 96%. White foam. Rf; 0.6 (methylene
1
chloride), H NMR (CDCl3): d 1.38 (s, 3H, CH3, isopropylidene), 1.60 (s, 3H,
CH3, isopropylidene), 2.17 (s, 3H, CH3, Ar), 2.19 (s, 3H, CH3, Ar), 2.85–2.90 (m,
2H, CH2, indoline), 3.26 (dd, J = 4.5, 5.5 Hz, 1H, 5’), 3.32 (dd, J = 4.5, 6.0 Hz,
1H, 5@), 3.45 (q, 1H, indoline), 3.53 (q, 1H, indoline), 4.19 (q, J = 4.5 Hz, 1H, 4’),
4.64–4.66 (m, 1H, 3’), 4.80–4.82 (m, 1H, H 2’), 5.41 (d, J = 3.7 Hz, 1H, 1’), 6.61 (s, 1H,
Ar), 6.88 (s, 1H, Ar), 7.22–7.28 (m, 9H, trityl), 7.45 (d, 6H, trityl); 13C NMR (CDCl3): d
19.16 (CH3, Ar), 20.20 (CH3, Ar), 25.56 (CH3, isopropylidene), 27.511 (CH3,
isopropylidene), 28.10 (CH2, indoline), 47.26 (CH2, indoline), 64.02 (CH2, 5’), 80.91
(C 3’), 81.58 (C 2’), 81.93 (C 4’), 86.64 (Cquat), 93.20 (C 1’), 110.60 (CH), 113.89
(Cquat), 125.83 (CH), 127.02 (CH), 127.83 (CH), 128.57 (CH), 135.01 (Cquat), 143.61
(Cquat), 143.79 (Cquat), 148.15 (Cquat), HRMS: m/z: 562.2966 (calcd for
C37H40NO4; 562.2967) (M + H); MS: (FAB), m/z: 562, 561, 338, 337, 244, 243; Anal.
1
ˇ
Calcd. for C37H39NO4Á /2 H2O: C, 77.85; H, 7.06; N, 2.45. Found: C, 77.97; H, 6.53;
N, 2.24.
1-(5-O-Triphenylmethyl-2,3-O-isopropylidene-a-D-ribofurano-
syl)-5-bromoindoline (13). Yield: 92%. White foam. Rf; 0.7 (methylene
chloride); 1H NMR (CDCl3): d 1.38 (s, 3H, CH3, isopropylidene), 1.60 (s, 3H, CH3,
isopropylidene), 2.85–2.90 (m, 2H, CH2, indoline), 3.24 (dd, J = 4.5 Hz, 1H, 5’),
3.41 (dd, 1H, 5@), 3.47–3.49 (q, 1H, NCH2, indoline), 3.56 (q, 1H, NCH2, indoline),
4.14–4.17 (m, 1H, CH, 4’), 4.65–4.67 (m, 1H, CH, 3’), 4.77–4.79 (m, 1H, CH, 2’),
5.32 (d, J = 3.8 Hz, 1H, CH, 1’), 6.63 (d, J = 8.5 Hz, 1H, Ar), 7.10 (d, J = 8.5 Hz, 1H,
Ar), 7.12 (s, 1H, Ar), 7.18–7.25 (m, 9H, trityl), 7.41 (d, J = 7 Hz, 6H, trityl); 13C
NMR (CDCl3): d 25.53 (CH3, isopropylidene), 27.46 (CH3, isopropylidene), 28.03
(CH2, indoline), 47.49 (CH2, indoline), 63.80 (CH2, 5’), 80.67 (C 3’), 81.33 (C 2’),

Synthesis of a-Indoline Nucleosides
1157
82.06 (C 4’), 86.74 (Cquat), 92.77 (C 1’), 110.30 (CH), 110.93, 114.17 (Cquat), 127.05
(CH), 127.78 (CH), 128.68 (CH), 129.92 (Cquat), 132.82, 143.68, 149.10 (Cquat);
HRMS: m/z: 612.1735 (calcd for C35H34BrNO4; 612.1747) (M + H); MS: m/z: 615,
614, 613, 612, 611, 243.
1-(5-O-Triphenylmethyl-2,3-O-isopropylidene-a-D-ribofurano-
syl)-benzimidazole (16). Yield: 1.72 g, 70%; white crystalline solid; mp 195–
198°C; Rf. 0.6; 1H NMR (CDCl3): d 1.31 (s, 3H, CH3), 1.47 (s, 3H, CH3), 3.29 (dd,
J = 2.5, 8.3 Hz, 1H, 5’), 3.65 (dd, J = 2.5, 7.5 Hz, 1H, 5@), 4.58 (bt, 1H, 4’), 4.86 (d,
J = 6.5 Hz, 1H, 3’), 5.06 (t, J = 4.5 Hz, 1H, 2’), 6.70 (d, J = 3.8 Hz, 1H, 1’), 7.28–7.32
(m, 6H, Ar & trityl), 7.35 (t, 6H, Ar), 7.45 (d, J = 8.0 Hz, 6H, Ar), 7.84 (d, J = 8Hz,
1H, Ar), 8.34 (s, 1H, imidazole); 13C NMR (CDCl3): d 24.37 (CH3), 25.88 (CH3),
65.83 (CH2, 5’), 80.07 (2’), 82.02 (4’), 82.70 (3’), 87.16 (1’), 87.88 (Cquat), 109.33 (CH),
113.59 (Cquat), 120.31 (CH), 122.46 (Cquat), 123.12 (CH), 127.47 (CH), 128.12
(CH), 128.52 (CH), 133.09 (Cquat), 142.46 (Cquat), 142.91 (Cquat), 143.25 (CH);
HRMS: m/z: 533.2433 (calcd for C34H33N2O4; 533.2439) (M + H); MS: (FAB) m/z:
535, 534, 533, 381, 365, 337, 243; Anal. Calcd. for C34H33N2O4: C, 76.65; H, 6.05; N,
5.26. Found: C, 76.38; H, 5.84; N, 5.11.
1-(5-O-Triphenylmethyl-2,3-O-isopropylidene-b-D-ribofurano-
syl)-benzimidazole (18). Yield: 0.49 g, 20%; white solid; mp 80–85°C; Rf.
1
0.5; H NMR (CDCl3): d 1.39 (s, 3H, CH3), 1.65 (s, 3H, CH3), 3.42 (dd, J = 4.53,
6.42 Hz, 1H, 5’), 3.49 (dd, J = 3.39, 7.18 Hz, 1H, 5@), 4.48 (m, 1H, 4’), 4.83 (q,
J = 1H, 3’), 5.03 (q, 1H, 2’), 6.02 (d, J = 3.4 Hz, 1H, 1’), 7.24–7.40 (m, 16H, trityl,
Ar), 7.47 (d, J = 7.71 Hz, 1H, Ar), 7.62 (d, J = 7.93 Hz, 1H, Ar), 7.85 (d, J = 8.31
Hz, 1H, Ar), 8.11 (s, 1H, imidazole); 13C NMR (CDCl3): d 25.39 (CH3), 27.29
(CH3), 63.46 (CH2, 5’), 81.09 (3’), 84.36 (2’), 84.55 (4’), 87.34 (Cquat), 92.41 (1’),
111.88 (CH), 114.98 (Cquat), 120.28 (CH), 123.04 (Cquat), 123.57 (Cquat), 127.27
(CH), 127.95 (CH), 128.15 (CH), 128.60 (CH), 133.09 (Cquat), 140.36 (CH),
143.18 (CH); HRMS: m/z: 533.2445 (calcd for C34H33N2O4; 533.2439) (M + H);
MS: (FAB), m/z: 535, 534, 533, 381, 365, 337, 243; Anal. Calcd. for C34H33N2O4:
C, 76.65; H, 6.05; N, 5.26. Found: C, 76.39; H, 5.81; N, 5.11.
CONCLUSIONS
We have shown for the first time that the reaction of trimethylsilyl indoline with
2,3-O-(1-methylethylidene)-5-O-(triphenylmethyl)-a/b-D-ribofuranose, in the presence
of 2-fluoro-1-methylpyridinium tosylate under basic conditions, produces a-ribonu-
cleosides exclusively, the anomeric configuration of which was confirmed by X-ray
crystallography (for 11) as well as 2D NMR spectroscopy. The new finding here is
that the all of these glycosylation reactions are absolutely stereoselective for the a-
anomer, which is easily purified without any complication.

1158
APPENDIX
K. L. Brown et al.
TABLE A1 Atomic Coordinates (Â 104) and Equivalent Isotropic Displacement Parameters (A2Â 103) for
Compound 11
x
y
z
U(eq)
O(1)
O(2)
O(3)
O(5)
N(1)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
322(13)
1109(16)
3388(14)
À1065(13)
À1453(17)
À960(2)
120(2)
1630(2)
1490(2)
600(2)
2930(2)
4557(5)
6443(5)
5693(6)
4272(5)
5507(7)
5236(8)
5840(9)
5342(8)
4493(8)
3912(8)
6496(9)
6716(8)
7071(7)
5700(9)
5450(9)
5038(8)
4639(8)
4275(8)
4297(8)
4706(8)
5059(8)
3803(7)
3157(9)
2495(8)
1958(9)
2104(8)
2737(8)
3281(8)
3401(9)
2702(9)
2321(8)
2651(9)
3322(9)
3719(8)
4415(9)
5244(8)
5779(10)
5546(10)
4749(9)
4195(9)
9807(3)
9689(4)
9300(4)
8700(3)
10,318(4)
9779(6)
9400(5)
9104(5)
9327(5)
8903(5)
9469(6)
9923(5)
9004(5)
10,675(5)
11,254(5)
11,148(6)
11,493(5)
11,293(6)
10,744(6)
10,391(6)
10,583(6)
8343(5)
8682(5)
8456(6)
8751(7)
9300(6)
9539(6)
9240(6)
7887(5)
7999(6)
7584(6)
7057(6)
6967(5)
7362(6)
8114(5)
8144(5)
7914(5)
7681(5)
7634(5)
7852(5)
34(3)
44(3)
46(3)
32(3)
34(3)
45(5)
38(5)
37(5)
32(4)
39(5)
40(5)
65(6)
63(6)
51(5)
56(5)
38(5)
43(5)
53(5)
48(5)
45(5)
28(4)
23(4)
36(4)
40(5)
71(6)
54(5)
55(5)
48(5)
34(4)
50(5)
60(6)
61(6)
43(5)
43(5)
34(4)
44(5)
56(6)
45(5)
52(5)
37(5)
4340(2)
2980(2)
190(2)
C(8)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
C(26)
C(31)
C(32)
C(33)
C(34)
C(35)
C(36)
C(41)
C(42)
C(43)
C(44)
C(45)
C(46)
À540(2)
À2470(2)
À3700(2)
À5290(2)
À5740(2)
À4480(2)
À2900(2)
À2370(2)
À3420(2)
À4220(2)
À5410(3)
À5540(2)
À4780(2)
À3660(2)
À1230(2)
À110(2)
970(2)
1030(2)
À50(2)
À1200(2)
À3720(2)
À3340(2)
À4590(2)
À6240(2)
À6690(2)
À5420(2)
U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

Synthesis of a-Indoline Nucleosides
1159
˚
TABLE A2 Bond Lengths (A) and Angles
(°) for 11
O(1)–C(1)
1.443(14)
O(1)–C(4)
O(2)–C(6)
O(2)–C(2)
O(3)–C(6)
O(3)–C(3)
O(5)–C(5)
O(5)–C(20)
N(1)–C(19)
N(1)–C(1)
N(1)–C(12)
C(1)–C(2)
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(6)–C(8)
1.437(14)
1.381(17)
1.413(14)
1.439(15)
1.440(15)
1.399(14)
1.484(14)
1.413(16)
1.444(15)
1.480(16)
1.565(17)
1.525(17)
1.523(16)
1.553(16)
1.494(16)
1.536(18)
1.571(15)
1.534(19)
1.379(17)
1.425(16)
1.358(18)
1.387(16)
1.412(17)
1.336(18)
1.503(17)
1.528(17)
1.549(16)
1.356(17)
1.399(15)
1.422(19)
1.378(16)
1.321(17)
1.403(17)
1.398(16)
1.432(17)
1.417(17)
1.412(17)
1.368(18)
1.422(17)
1.394(18)
1.412(17)
1.371(17)
1.339(18)
1.372(18)
1.385(17)
111.5(10)
107.1(11)
106.7(11)
119.5(10)
115.4(12)
113.1(11)
C(6)–C(7)
C(12)–C(13)
C(13)–C(14)
C(14)–C(15)
C(14)–C(19)
C(15)–C(16)
C(16)–C(17)
C(17)–C(18)
C(18)–C(19)
C(20)–C(41)
C(20)–C(31)
C(20)–C(21)
C(21)–C(22)
C(21)–C(26)
C(22)–C(23)
C(23)–C(24)
C(24)–C(25)
C(25)–C(26)
C(31)–C(36)
C(31)–C(32)
C(32)–C(33)
C(33)–C(34)
C(34)–C(35)
C(35)–C(36)
C(41)–C(46)
C(41)–C(42)
C(42)–C(43)
C(43)–C(44)
C(44)–C(45)
C(45)–C(46)
C(1)–O(1)–C(4)
C(6)–O(2)–C(2)
C(6)–O(3)–C(3)
C(5)–O(5)–C(20)
C(19)–N(1)–C(1)
C(19)–N(1)–C(12)
(continued)

1160
K. L. Brown et al.
Table A2 Continued
C(1)–N(1)–C(12)
O(1)–C(1)–N(1)
O(1)–C(1)–C(2)
N(1)–C(1)–C(2)
O(2)–C(2)–C(3)
O(2)–C(2)–C(1)
C(3)–C(2)–C(1)
O(3)–C(3)–C(4)
O(3)–C(3)–C(2)
C(4)–C(3)–C(2)
O(1)–C(4)–C(3)
O(1)–C(4)–C(5)
C(3)–C(4)–C(5)
O(5)–C(5)–C(4)
O(2)–C(6)–O(3)
O(2)–C(6)–C(8)
O(3)–C(6)–C(8)
O(2)–C(6)–C(7)
115.3(12)
110.6(11)
103.8(11)
117.4(12)
107.1(12)
113.1(11)
105.3(11)
108.3(12)
101.8(10)
106.8(12)
105.4(11)
112.0(11)
111.5(11)
107.6(11)
105.0(12)
111.4(14)
111.8(12)
108.5(13)
107.0(13)
112.8(13)
103.3(11)
104.4(11)
119.0(15)
131.1(14)
109.8(14)
120.0(14)
121.7(16)
118.3(15)
120.6(14)
131.2(14)
120.4(15)
108.4(13)
104.4(10)
110.5(11)
110.3(12)
109.8(11)
112.2(12)
109.6(11)
118.4(14)
122.7(12)
118.9(14)
122.8(14)
115.4(16)
123.6(17)
120.4(15)
119.1(15)
118.4(14)
121.5(14)
120.0(13)
121.2(14)
120.3(15)
116.8(16)
125.5(14)
117.8(14)
O(3)–C(6)–C(7)
C(8)–C(6)–C(7)
N(1)–C(12)–C(13)
C(14)–C(13)–C(12)
C(15)–C(14)–C(19)
C(15)–C(14)–C(13)
C(19)–C(14)–C(13)
C(16)–C(15)–C(14)
C(15)–C(16)–C(17)
C(16)–C(17)–C(18)
C(19)–C(18)–C(17)
C(18)–C(19)–N(1)
C(18)–C(19)–C(14)
N(1)–C(19)–C(14)
O(5)–C(20)–C(41)
O(5)–C(20)–C(31)
C(41)–C(20)–C(31)
O(5)–C(20)–C(21)
C(41)–C(20)–C(21)
C(31)–C(20)–C(21)
C(22)–C(21)–C(26)
C(22)–C(21)–C(20)
C(26)–C(21)–C(20)
C(21)–C(22)–C(23)
C(24)–C(23)–C(22)
C(25)–C(24)–C(23)
C(24)–C(25)–C(26)
C(25)–C(26)–C(21)
C(36)–C(31)–C(32)
C(36)–C(31)–C(20)
C(32)–C(31)–C(20)
C(33)–C(32)–C(31)
C(32)–C(33)–C(34)
C(35)–C(34)–C(33)
C(34)–C(35)–C(36)
C(31)–C(36)–C(35)
(continued)

Synthesis of a-Indoline Nucleosides
1161
Table A2 Continued
C(46)–C(41)–C(42)
C(46)–C(41)–C(20)
C(42)–C(41)–C(20)
C(43)–C(42)–C(41)
C(44)–C(43)–C(42)
C(43)–C(44)–C(45)
C(44)–C(45)–C(46)
C(45)–C(46)–C(41)
116.3(15)
121.9(14)
121.7(15)
119.7(15)
122.2(16)
120.8(17)
118.0(16)
122.9(14)
TABLE A3 Anisotropic Displacement Parameters (A2Â 103) for 11
U11
U22
U33
U23
U13
U12
O(1)
O(2)
O(3)
O(5)
N(1)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
44(7)
57(9)
44(8)
37(7)
24(8)
45(9)
36(8)
38(8)
32(8)
41(9)
50(9)
56(11)
57(12)
59(9)
63(9)
40(8)
59(9)
60(9)
45(9)
47(9)
34(8)
23(7)
38(8)
44(8)
69(10)
50(9)
62(9)
42(9)
38(8)
57(9)
74(10)
71(10)
47(9)
48(9)
37(8)
50(9)
63(9)
46(9)
41(9)
42(9)
35(6)
36(7)
33(7)
30(6)
35(8)
47(8)
46(8)
44(8)
33(7)
33(8)
26(7)
67(11)
69(11)
51(8)
61(9)
28(7)
41(8)
53(9)
42(8)
44(8)
24(7)
18(7)
43(8)
40(8)
62(9)
49(8)
59(9)
44(8)
36(8)
52(8)
47(8)
55(9)
48(8)
35(8)
45(8)
37(8)
52(9)
51(8)
60(9)
35(8)
23(5)
40(7)
60(7)
31(6)
44(8)
43(8)
34(8)
30(7)
31(7)
44(8)
44(8)
71(11)
63(10)
44(8)
45(8)
44(8)
29(7)
48(8)
58(8)
45(8)
28(8)
27(7)
29(7)
36(8)
81(9)
62(9)
45(8)
57(8)
28(7)
41(8)
59(9)
56(9)
35(8)
47(8)
20(7)
46(8)
52(8)
37(8)
54(8)
34(7)
0(5)
À3(6)
À11(6)
8(5)
11(6)
8(7)
À12(7)
À7(6)
4(8)
8(6)
À1(7)
À6(7)
À3(6)
16(8)
À5(8)
16(7)
À4(7)
1(7)
À8(7)
À6(7)
À26(10)
À11(10)
1(8)
À20(8)
0(7)
À9(8)
1(7)
4(7)
À6(7)
À1(7)
8(7)
À3(7)
À16(10)
À7(10)
0(7)
À9(7)
À17(7)
À5(7)
À2(7)
À4(7)
7(7)
4(7)
À9(7)
7(7)
À8(8)
À14(10)
10(10)
2(8)
C(8)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
C(26)
C(31)
C(32)
C(33)
C(34)
C(35)
C(36)
C(41)
C(42)
C(43)
C(44)
C(45)
C(46)
À1(7)
À1(8)
5(7)
9(7)
5(7)
16(8)
0(7)
À1(7)
À8(7)
9(7)
2(7)
À4(8)
À2(7)
5(7)
8(7)
3(7)
À12(7)
À8(7)
À12(8)
À21(7)
3(8)
7(7)
À10(7)
7(7)
À5(7)
0(7)
6(8)
5(7)
À5(8)
À2(8)
4(8)
6(8)
4(7)
11(8)
11(7)
À3(7)
À2(7)
À8(7)
À17(7)
À4(7)
À2(7)
2(7)
À4(7)
6(7)
À4(8)
7(8)
6(8)
8(8)
6(7)
0(8)
À5(8)
À12(7)
À5(8)
18(7)
À6(8)
À4(8)
4(7)
À1(7)
1(7)
0(8)
10(7)
À7(7)
12(7)
À3(7)
3(7)
À1(7)
À7(8)
13(8)
4(8)
0(8)
4(7)
À9(7)
The anisotropic displacement factor exponent takes the form: À2 pi2 (h2 a*,2 U11 +. . . +2 h k a* b* U12).

1162
K. L. Brown et al.
TABLE A4 Hydrogen Coordinates (Â 104) and Isotropic Displacement Parameters (A2Â 103) for
Compound 11
x
y
z
U(eq)
H(1A)
H(2A)
H(3A)
H(4A)
H(5A)
H(5B)
H(7A)
H(7B)
H(7C)
H(8A)
H(8B)
H(8C)
H(12A)
H(12B)
H(13A)
H(13B)
H(15A)
H(16A)
H(17A)
H(18A)
H(22A)
H(23A)
H(24A)
H(25A)
H(26A)
H(32A)
H(33A)
H(34A)
H(35A)
H(36A)
H(42A)
H(43A)
H(44A)
H(45A)
H(46A)
À2136
À776
1505
2769
1505
289
4248
4037
5627
2059
4244
2685
497
1323
357
5067
6080
5367
4304
3814
3404
6330
7239
6718
6913
7070
7599
6266
5394
5085
5917
4619
4004
4048
4730
2386
1538
1738
2821
3719
2495
1852
2424
3536
4175
5426
6321
5930
4585
3654
9596
9140
8708
9428
8612
54
46
45
38
47
47
78
78
78
75
75
75
62
62
67
67
52
64
58
54
48
85
64
67
57
60
72
73
52
52
53
67
53
62
45
9073
10,211
10,061
9782
8736
8846
9132
10,661
10,572
11,427
11,484
11,863
11,530
10,613
10,022
8092
8584
9514
9908
9410
8349
7660
6784
6619
7274
8319
7919
7549
À701
À3438
À6106
À6840
À4755
À3968
À6061
À6203
À4974
À3095
À82
1639
1775
À36
À1896
À2240
À4287
À7086
À7806
À5715
7461
7823
TABLE A5 Torsion Angles [deg] for 11
C(4)–O(1)–C(1)–N(1)
C(4)–O(1)–C(1)–C(2)
C(19)–N(1)–C(1)–O(1)
C(12)–N(1)–C(1)–O(1)
C(19)–N(1)–C(1)–C(2)
C(12)–N(1)–C(1)–C(2)
C(6)–O(2)–C(2)–C(3)
C(6)–O(2)–C(2)–C(1)
O(1)–C(1)–C(2)–O(2)
N(1)–C(1)–C(2)–O(2)
O(1)–C(1)–C(2)–C(3)
À154.3(11)
À27.5(14)
À79.9(15)
55.0(16)
161.3(12)
À63.9(17)
17.4(15)
132.9(13)
À99.2(13)
23.2(19)
17.4(15)
(continued)

Synthesis of a-Indoline Nucleosides
1163
Table A5 Continued
N(1)–C(1)–C(2)–C(3)
139.8(13)
À136.3(11)
À24.0(13)
4.5(13)
C(6)–O(3)–C(3)–C(4)
C(6)–O(3)–C(3)–C(2)
O(2)–C(2)–C(3)–O(3)
C(1)–C(2)–C(3)–O(3)
O(2)–C(2)–C(3)–C(4)
C(1)–C(2)–C(3)–C(4)
C(1)–O(1)–C(4)–C(3)
C(1)–O(1)–C(4)–C(5)
O(3)–C(3)–C(4)–O(1)
C(2)–C(3)–C(4)–O(1)
O(3)–C(3)–C(4)–C(5)
C(2)–C(3)–C(4)–C(5)
À116.1(11)
118.0(12)
À2.6(16)
26.2(14)
À95.2(13)
95.7(13)
À13.2(15)
À142.6(11)
108.4(13)
À171.4(10)
69.0(13)
À48.8(15)
À32.6(15)
88.5(13)
À146.7(11)
36.1(14)
À84.9(14)
151.2(11)
À10.3(16)
À146.2(12)
6.9(15)
C(20)–O(5)–C(5)–C(4)
O(1)–C(4)–C(5)–O(5)
C(3)–C(4)–C(5)–O(5)
C(2)–O(2)–C(6)–O(3)
C(2)–O(2)–C(6)–C(8)
C(2)–O(2)–C(6)–C(7)
C(3)–O(3)–C(6)–O(2)
C(3)–O(3)–C(6)–C(8)
C(3)–O(3)–C(6)–C(7)
C(19)–N(1)–C(12)–C(13)
C(1)–N(1)–C(12)–C(13)
N(1)–C(12)–C(13)–C(14)
C(12)–C(13)–C(14)–C(15)
C(12)–C(13)–C(14)–C(19)
C(19)–C(14)–C(15)–C(16)
C(13)–C(14)–C(15)–C(16)
C(14)–C(15)–C(16)–C(17)
C(15)–C(16)–C(17)–C(18)
C(16)–C(17)–C(18)–C(19)
C(17)–C(18)–C(19)–N(1)
C(17)–C(18)–C(19)–C(14)
C(1)–N(1)–C(19)–C(18)
C(12)–N(1)–C(19)–C(18)
C(1)–N(1)–C(19)–C(14)
C(12)–N(1)–C(19)–C(14)
C(15)–C(14)–C(19)–C(18)
C(13)–C(14)–C(19)–C(18)
C(15)–C(14)–C(19)–N(1)
C(13)–C(14)–C(19)–N(1)
C(5)–O(5)–C(20)–C(41)
C(5)–O(5)–C(20)–C(31)
C(5)–O(5)–C(20)–C(21)
O(5)–C(20)–C(21)–C(22)
C(41)–C(20)–C(21)–C(22)
C(31)–C(20)–C(21)–C(22)
O(5)–C(20)–C(21)–C(26)
C(41)–C(20)–C(21)–C(26)
C(31)–C(20)–C(21)–C(26)
C(26)–C(21)–C(22)–C(23)
C(20)–C(21)–C(22)–C(23)
173.9(15)
À1.9(16)
0(2)
À175.6(14)
0(2)
0(2)
0(2)
À179.0(13)
À1(2)
À36(2)
À172.3(14)
145.3(12)
9.5(16)
1(2)
177.2(13)
179.4(13)
À4.3(16)
À168.5(10)
À49.9(15)
71.1(14)
À158.9(13)
85.5(17)
À37(2)
24.8(18)
À90.8(17)
146.4(14)
5(2)
À171.0(14)
(continued)

1164
K. L. Brown et al.
Table A5 Continued
C(21)–C(22)–C(23)–C(24)
C(22)–C(23)–C(24)–C(25)
C(23)–C(24)–C(25)–C(26)
C(24)–C(25)–C(26)–C(21)
C(22)–C(21)–C(26)–C(25)
C(20)–C(21)–C(26)–C(25)
O(5)–C(20)–C(31)–C(36)
C(41)–C(20)–C(31)–C(36)
C(21)–C(20)–C(31)–C(36)
O(5)–C(20)–C(31)–C(32)
C(41)–C(20)–C(31)–C(32)
C(21)–C(20)–C(31)–C(32)
C(36)–C(31)–C(32)–C(33)
C(20)–C(31)–C(32)–C(33)
C(31)–C(32)–C(33)–C(34)
C(32)–C(33)–C(34)–C(35)
C(33)–C(34)–C(35)–C(36)
C(32)–C(31)–C(36)–C(35)
C(20)–C(31)–C(36)–C(35)
C(34)–C(35)–C(36)–C(31)
O(5)–C(20)–C(41)–C(46)
C(31)–C(20)–C(41)–C(46)
C(21)–C(20)–C(41)–C(46)
O(5)–C(20)–C(41)–C(42)
C(31)–C(20)–C(41)–C(42)
C(21)–C(20)–C(41)–C(42)
C(46)–C(41)–C(42)–C(43)
C(20)–C(41)–C(42)–C(43)
C(41)–C(42)–C(43)–C(44)
C(42)–C(43)–C(44)–C(45)
C(43)–C(44)–C(45)–C(46)
C(44)–C(45)–C(46)–C(41)
C(42)–C(41)–C(46)–C(45)
C(20)–C(41)–C(46)–C(45)
À7(2)
6(3)
À4(3)
2(2)
À3(2)
174.0(13)
À101.0(16)
14(2)
137.9(14)
76.2(16)
À168.9(13)
À44.9(19)
À2(2)
À179.5(14)
3(2)
À3(2)
1(2)
1(2)
177.8(13)
0(2)
À165.9(11)
75.4(16)
À47.1(17)
15.1(17)
À103.7(15)
133.9(14)
À1(2)
178.0(12)
3(2)
À4(2)
2(2)
0(2)
0(2)
À179.5(12)
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