Synthesis of substituted benzyl homo-C-ribonucleosides and -nucleotides as carba analogues of phosphoribosylanthranilate

Article abstract of DOI:10.1002/ejoc.201200819

New 2-substituted benzyl C-ribonucleosides and -nucleotides were designed as carba analogues of phosphoribosylanthranilate, a key intermediate in tryptophan biosynthesis. The synthesis was based on the preparation of TBS-protected 2-bromobenzyl C-ribonucleoside 4a by addition of (2-bromobenzyl)magnesium bromide to ribonolactone followed by reduction and subsequent functional group transformations. Pd-catalyzed hydrogenation, cross-couplings, amination or hydroxylation, as well as lithiation followed by reaction with CO₂ and amidations, gave a large series of 2-alkyl-, 2-(het)aryl, 2-amino, 2-hydroxy, 2-carboxy and 2-carbamoyl derivatives that were deprotected to afford free homo-C-ribonucleosides. Some of the title nucleosides were converted to 5'-O-phosphates. Novel benzyl C-nucleosides were designed and prepared as carba analogues of phosphoribosylanthranilate, an important intermediate in the biosynthesis of tryptophan. Copyright

Full text of DOI:10.1002/ejoc.201200819

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
FULL PAPER
DOI: 10.1002/ejoc.201200819
Synthesis of Substituted Benzyl Homo-C-Ribonucleosides and -Nucleotides as
Carba Analogues of Phosphoribosylanthranilate
[a]
[a]
[a,b]
ˇ
ˇ
Tomás Kubelka, Lenka Slavetínská, and Michal Hocek*
Keywords: Nucleosides / Nucleotides / Cross-coupling / Phosphoribosylanthranilate / Amides
New 2-substituted benzyl C-ribonucleosides and -nucleo-
tides were designed as carba analogues of phosphoribosyl-
anthranilate, a key intermediate in tryptophan biosynthesis.
The synthesis was based on the preparation of TBS-protected
2-bromobenzyl C-ribonucleoside 4a by addition of (2-bromo-
benzyl)magnesium bromide to ribonolactone followed by
reduction and subsequent functional group transformations.
Pd-catalyzed hydrogenation, cross-couplings, amination or
hydroxylation, as well as lithiation followed by reaction with
CO2 and amidations, gave a large series of 2-alkyl-, 2-(het)-
aryl, 2-amino, 2-hydroxy, 2-carboxy and 2-carbamoyl deriva-
tives that were deprotected to afford free homo-C-ribonu-
cleosides. Some of the title nucleosides were converted to 5Ј-
O-phosphates.
Introduction
Phosphoribosylanthranilate (PRA) is an important inter-
mediate in the biosynthesis of the essential amino acid tryp-
tophan.[1] It is transformed by PRA isomerase to 1-(2-carb-
oxyphenylamino)-1Ј-deoxyribulose-5Ј-phosphate
(CdRP,
Scheme 1). Since tryptophan biosynthesis does not occur in
humans but is crucial for prokaryotes, targeting of this en-
zyme might constitute a viable approach to selective anti-
biotics. There is a clear evolutionary relationship[2] between
PRA isomerase and ProFAR isomerase involved in biosyn-
thesis of histidine. In mycobacteria (i.e. Mycobacterium tu-
berculosis) the enzyme PriA isomerase catalyzes both trans-
formations carried out by PRA and ProFAR isomerases;
this enzyme also is a potential target for antimycobacterial
therapy. The mechanism consists of protonation of the fur-
anose oxygen atom followed by ring opening to form a
Schiff base, which – after isomerization to enolamine and
further tautomerization – gives CdRP. Therefore, we have
designed carba analogues of PRA based on homo-C-nu-
cleosides as potential inhibitors of these enzymes.
Scheme 1. Biotransformation catalyzed by PRA isomerase or PriA
isomerase and the design of carba analogues of the substrate
(PRA).
rivatives have been reported to possess important biological
activities, and others have been used in chemical biology
studies such as in the use of novel base-pairs for extending
the genetic alphabet[4] and as model substrates for studying
of mechanisms of polymerases.[5] There are many ap-
proaches[3] to the synthesis of C-nucleosides, but some of
C-Nucleosides[3] are an important class of nucleoside an-
alogues characterized by replacement of the chemically and
enzymatically labile nucleosidic C–N bond by the more
stable C–C bond. Many hetaryl and aryl-C-nucleoside de-
[a] Institute of Organic Chemistry and Biochemistry, Academy of them suffer from poor stereoselectivities or low transforma-
Sciences of the Czech Republic, Gilead Sciences & IOCB
tion efficiencies, and none of them is truly general. In our
Research Center
laboratory, we have developed a modular approach[6] con-
Flemingovo nam. 2, 16610 Prague 6, Czech Republic
Fax: +420-220-183-559
E-mail: hocek@uochb.cas.cz
Homepage: http://www.uochb.cas.cz/hocekgroup
[b] Department of Organic Chemistry, Faculty of Science, Charles
University in Prague
sisting of the synthesis of a central halo-(het)aryl C-nu-
cleoside intermediate followed by further functional group
transformations such as Pd-catalyzed C–C or C–X cou-
plings. Here we report the first application of this modular
approach for the synthesis of 2-substituted benzyl C-nu-
cleosides as carba analogues of PRA.
Hlavova 8, 12843 Prague 2, Czech Republic
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200819.
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T. Kubelka, L. Slaveˇtínská, M. Hocek
FULL PAPER
Results and Discussion
Our synthetic strategy for the preparation of the target
benzyl C-nucleosides was based on the synthesis of 2-
bromobenzyl C-ribonucleoside key intermediate and fol-
low-up functional group transformations. For the synthesis
of this intermediate, we decided to use nucleophilic addition
of commercially available (2-bromobenzyl)magnesium
bromide (2) to protected ribonolactone 1. More reactive
organolithium species are typically used for such additions,
which proceed with β-stereoselectivity,[3] but only one exam-
ple of an addition of arylmagnesium bromide has been re-
ported in the literature.[7]
Starting ribonolactone[8] is easily available in two steps
from d-ribose in multigram scale in very good overall yield
(79%). The addition of the Grigard reagent 2 to lactone 1
proceeded very smoothly and stereoselectively to give de-
sired hemiketal 3 in excellent 88% yield exclusively as the
β-anomer (Scheme 2). The reaction was very facile and was
performed at room temperature under air in multigram
scale (up to 10 g). Reduction of the hemiketal 3 by Et3SiH
in the presence of BF3·Et2O gave the desired TBS-protected
2-bromobenzyl C-ribonucleoside key intermediate 4a only
Scheme 2. Reagents and conditions: (i) 2, THF, room temp., 1 h;
(ii) Et3SiH, BF3·Et2O, DCM, 0 °C, 10 min; (iii) TBSCl, imidazole,
DMF, 24 h.
Having key intermediate 4a in hand, we performed a sys-
in 36% yield accompanied by a mixture of two inseparable tematic study of functional group transformations (hydro-
by-products lacking one of the TBS groups at 3Ј- or 2Ј- genation, cross-coupling, amination and hydroxylation) to
position (5 and 6, respectively) in 40% yield. However, the generate a series of 2-substituted benzyl C-nucleoside deriv-
mixture of 5 and 6 was easily converted into the desired atives (Scheme 3, Table 1).
fully silylated nucleoside 4a by further silylation. Therefore,
Catalytic hydrogenation of 4a was performed at atmo-
the combined overall yield of 4a was an acceptable 72% spheric pressure in the presence of palladium on carbon in
after reduction and re-silylation. Two-dimensional ROESY a mixture of ethanol, THF, water, and Et3N. The hydrogen-
NMR spectra of compound 4a confirmed the desired β- ation proceeded smoothly to give the 2-unsubstituted
configuration.
benzyl C-ribonucleoside 4b in very good 85% yield
Scheme 3. Synthesis of 2-substituted benzyl C-ribonucleosides.
Table 1. Functional group transformations of 2-bromobenzyl C-ribonucleoside 4a followed by deprotection.
Entry
Reagent
Catalyst
Ligand/base
Solvent
Conditions [h, °C] Reaction (yield [%])
Deprotection
(yield [%])
1
2
3
4
5
7a (80)
7b (80)
7c (70)
7d (82)
7e (74)
H2
Me3Al
PhB(OH)2
KN(SiMe3)2,
Ph3SiNH2
Me2NH2
Pd/C
Et3N
EtOH/THF/H2O
THF
12, r.t.
24, 70
12, 90
18, 100
4b (85)
4c (91)
4d (87)
4e (37)
Pd(PPh3)4
Pd(PPh3)4
Pd2dba3
K2CO3
toluene
toluene
CyJohnPhos[a]
6
7
8
9
10
Pd2dba3
Pd2dba3
Pd2dba3
PdCl2
Pd(PPh3)2Cl2
JohnPhos[b]
tButylXPhos[c]
tButylXPhos[c]
JohnPhos[b]
THF/toluene
dioxane/H2O
dioxane/H2O
toluene
24, 60
2, 100
2, 100
24, 130
24, 130
4f (85)
4g (80)
4h (84)
4i (80)
4j (86)
7f (75)
7g (82)
7h (82)
7i (85)
7j (88)
KOH
1. KOH, 2. MeI
2-Bu3Sn-Th[d]
2-Bu3Sn-Fur[e]
DMF
[a] CyJohnPhos = (biphenyl-2-yl)dicyclohexylphosphane. [b] JohnPhos = (biphenyl-2-yl)di-tert-butylphosphane. [c] tButylXPhos =
(2Ј,4Ј,6Ј-triisopropylbiphenyl-2-yl)di-tert-butylphosphane. [d] 2-Bu3Sn-Th = 2-(tributylstannyl)thiophene. [e] 2-Bu3Sn-Fur = 2-(tributyl-
stannyl)furan.
2
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Carba Analogues of Phosphoribosylanthranilate
(Table 1, Entry 2). The cross-coupling reaction of 4a with gave pure nucleosides 7a–j in good yields (70–88%, Table 1,
trimethylaluminum was used for the introduction of a Entries 1–10).
methyl group. Under standard conditions in the presence of
In order to prepare a series of diversely substituted carb-
Pd(PPh3)4 in THF, the desired protected 2-methylbenzyl C- oxamides, we attempted to use a recently developed meth-
nucleoside 4c was obtained in excellent 91% yield (Table 1, odology for Pd-catalyzed aminocarbonylations.[14] How-
Entry 3). 2-Phenylbenzyl C-ribonucleoside 4d was prepared ever, in the case of ortho-substituted aryl halides, this meth-
by the Suzuki–Miyaura cross-coupling of 4a with phenyl- odology was found to be inefficient. Pd-catalyzed amino-
boronic acid in toluene in the presence of K2CO3 and carbonylations of 4a at atmospheric pressure of CO and
Pd(PPh3)4 at 90 °C in 87% yield (Table 1, Entry 4).
amines suffered from very low yields, and the reactions were
Hartwig-Buchwald reactions were employed for the in- not reproducible. Therefore, we changed our synthetic strat-
troduction of N-substituents. We tried to prepare unsubsti- egy and decided to prepare carboxylic acid 4k and to at-
tuted 2-aminobenzyl derivative 4e using potassium bis(tri- tempt conversion to amides (Scheme 4). Carboxylic acid 4k
methylsilyl)amide in the presence of Pd2dba3 and Buch- was prepared in a one-pot two-step sequence consisting of
wald-type ligand (biphenyl-2-yl)dicyclohexylphosphane lithiation of 4a with BuLi in THF at –78 °C followed by a
(CyJohnPhos).[9] However, we observed only traces of the reaction with dry ice. These reactions proceeded very well
desired product, even after prolonged reaction time and at to afford 4k in good 70% yield on a 3 g scale. Starting from
elevated temperature. For the amination of ortho-substi- carboxylic acid 4k, a series of amides 4l–o was prepared
tuted aryl halides, Buchwald had developed[10] a procedure (Scheme 4, Table 2). The procedure involved activation of
using aminotriphenylsilane. By this approach, we were able 4k by peptide synthesis activators HOBt and EDC in DCM
to prepare the 2-aminobenzyl derivative 4e in a moderate followed by reactions with NH4Cl, amines or amine hydro-
but acceptable 37% yield (Table 1, Entry 5). For introduc- chlorides. The desired unsubstituted or N-substituted car-
tion of the dimethylamino group, we used the Buchwald boxamides 4l–o were obtained in excellent yields (88–97%).
reaction of 4a with dimethylamine.[11] The reaction was per- Deprotection of acid 4k and amides 4l–o was performed
formed under standard conditions using Pd2dba3 and (bi- using a mixture of trifluoroacetic acid/water (9:1). Free acid
phenyl-2-yl)di-tert-butylphosphane (JohnPhos) to give 2- 7k and amides 7l–o were obtained in ca. 80% yield (Table 2)
(dimethylamino)benzyl C-ribonucleoside 4f in very good after purification by silica gel flash chromatography.
85% yield.
The recently developed[12] palladium-catalyzed hydroxyl-
ation using KOH, Pd2dba3 and Buchwald-type ligand
(2Ј,4Ј,6Ј-triisopropylbiphenyl-2-yl)di-tert-butylphosphane
(tButylXPhos) was used for the synthesis of hydroxybenzyl
C-ribonucleoside 4g. The reaction proceeded in a mixture
of 1,4-dioxane/water (1:1) at 100 °C within 2 h to furnish
the desired phenol nucleoside 4g in excellent 80% yield. In
order to introduce a methyl ether group, we performed a
one-pot palladium-catalyzed hydroxylation followed by
treatment with methyl iodide in the presence of phase-trans-
fer catalyst Aliquat[12] to afford 2-methoxybenzyl derivative
4h in 84% yield (Table 1, Entry 8).
For the synthesis of hetaryl-substituted derivatives, the
Stille cross-coupling reaction was used. Reaction of 4a with
tributyl(2-furyl)stannane (Table 1, Entry 10) in the presence
of Pd(PPh3)Cl2 in DMF was very slow and required a
higher temperature (130 °C) and a longer reaction time
(24 h) to reach complete conversion and to give the desired
2-(2-furyl)benzyl C-ribonucleoside 4j in very good 86%
yield. When we applied the same conditions to the reaction
of 4a with tributyl(2-thienyl)stannane, only an inseparable
Scheme 4. Reagents and conditions: (i) 1. BuLi, THF, –78 °C,
60 min; 2. CO2, –78 °C 60 min; (ii) TFA, H2O, room temp., 4 h;
mixture of starting material and product was isolated. The
desired 2-(2-thienyl)benzyl C-ribonucleoside 4j was then
prepared using PdCl2 and JohnPhos in toluene at 130 °C
for 24 h in 80% yield.
For the final deprotection of silylated nucleosides 4a–j,
treatment with triethylamine trihydrofluoride in tetra-
hydrofuran was used.[13] Stirring of the reaction mixture at
40 °C for 2 d followed by treatment with NaHCO3 resulted
in the formation of the desired free nucleosides 7a–j. Chro-
matographic purification by silica flash chromatography
(iii) 1. HOBt, EDC, DCM, room temp., 60 min; 2. amine, Et3N,
room temp., 30 min.
Table 2. Synthesis of carboxamides (Scheme 4).
Entry
Amine
Reaction (yield [%]) Deprotection (yield [%])
1
2
3
4
NH4Cl
MeNH2·HCl
Me2NH·HCl
BnNH2
4l (94)
4m (91)
4n (88)
4o (97)
7l (74)
7m (79)
7n (76)
7o (76)
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T. Kubelka, L. Slaveˇtínská, M. Hocek
FULL PAPER
Since the substrate for PRA isomerase is a 5Ј-phosphate sides 7k–o. This general methodology has the potential for
(nucleotide), we decided to convert selected examples of nu- further applications in the synthesis of other types of homo-
cleosides (amino derivatives 7e and 7f and amides 7l and C-nucleosides relevant to medicinal chemistry or chemical
7n) to their corresponding 5Ј-phosphates to assess for en- biology.
zyme inhibition (Scheme 4). The reaction of 7e,f,l and n
with POCl3 in PO(OMe)3 at 0 °C followed by conversion
to the corresponding sodium salts afforded a series of 5Ј-
monophosphate 2-substituted benzyl C-ribonucleosides
Experimental Section
General: All cross-coupling reactions were carried out in evacuated
flame-dried glassware with magnetic stirring under argon. THF,
toluene, and hexanes were dried and distilled from sodium/benzo-
phenone. Other reagents were purchased from commercial suppli-
ers and used as received. NMR spectra were recorded with a
400 MHz spectrometer (1H at 400 MHz, 13C at 100.6 MHz),
500 MHz spectrometer (1H at 500 MHz, 13C at 125.8 MHz), and/
or 600 MHz spectrometer (1H at 600 MHz, 13C at 151 MHz). The
samples were measured in CDCl3 using TMS as an internal stan-
dard or in [D6]DMSO referenced to the residual solvent signal (1H
NMR: δ = 2.50 ppm; 13C NMR: δ = 39.7 ppm). Chemical shifts
are given in ppm (δ scale), coupling constants (J) in Hz. Complete
assignment of all NMR signals was performed using a combination
of 2D NMR (H,H-COSY, H,C-HSQC, and H,C-HMBC) experi-
ments, and configurations were established by two-dimensional
ROESY spectra. Testing of PriA isomerase inhibitor candidates
was performed according to a literature procedure.[15]
8e,f,l,n in ca. 40% isolated yields. In the case of the prepara-
tion of 5Ј-monophosphate from primary amide 7l using
POCl3, dehydration was found to lead to nitrile by-product
8p isolated in 12% yield from the reaction mixture.
(Scheme 5).
1β-(2-Bromobenzyl)-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-ribo-
furanose (3): (2-Bromobenzyl)magnesium bromide solution (2)
(24 mL, 6.0 mmol, 2 equiv., 0.25 m in Et2O) was added to a flask
containing ribonolactone 1 (1.5 g, 3.0 mmol, 1 equiv.), and the re-
sulting reaction mixture was stirred at room temp. for 60 min. Then
a saturated solution of NaHCO3 was added (200 mL), and the mix-
ture was extracted with diethyl ether (3ϫ 150 mL), solvents were
removed, and the product was filtered through silica gel to give the
crude hemiketal 3 in 88% yield as colorless oil. The crude product
was used without further purification in the next step. 1H NMR
(500 MHz, CDCl3): δ = 0.05, 0.08, 0.090, 0.092, 0.10 and 0.11 (6ϫ
s, 6 ϫ 3 H, CH3Si); 0.89, 0.93 and 0.94 [3ϫ s, 3 ϫ 9 H, (CH3)3C];
2.99 (dd, Jgem = 14.0, JCH2a,OH = 1.1 Hz, 1 H, CH2a); 3.32 (d, Jgem
= 14.0 Hz, 1 H, CH2b); 3.62 (dd, Jgem = 11.1, J5Јa,4Ј = 4.2 Hz, 1 H,
Scheme 5. Synthesis 5Ј-monophosphates. Reagents and conditions:
(i) 1. POCl3, PO(OMe)3, 0 °C, 3 h; 2. DOWEX Na+.
All nucleosides 7a–l and nucleotides 8e,f,l,n,p were tested
for the inhibition of PriA isomerase from Mycobacterium
tuberculosis.[15] None of the compounds evaluated showed
any significant enzyme inhibition up to concentrations of
0.5 mm, although there still could be some potential use in
testing of these compounds with PRA isomerases from
other prokaryotic pathogens. Since compounds 7 and 8 5Ј-Ha); 3.66 (dd, Jgem = 11.1, J5Јb,4Ј = 3.1 Hz, 1 H, 5Ј-Hb); 3.96 (d,
J2Ј,3Ј = 4.6 Hz, 1 H, 2Ј-H); 4.04 (dt, J4Ј,5Јa = 4.2, J4Ј,3Ј = J4Ј,5Јb
3.1 Hz, 1 H, 4Ј-H); 4.18 (dd, J3Ј,2Ј = 4.6, J3Ј,4Ј = 3.0 Hz, 1 H, 3Ј-
H); 4.45 (d, JOH,CH2a = 1.1 Hz, 1 H, O1Ј-H); 7.05 (td, J4,3 = J4,5
7.7, J4,6 = 1.8 Hz, 1 H, 4-H); 7.23 (td, J5,4 = J5,6 = 7.5, J5,3
1.3 Hz, 1 H, 5-H); 7.53 (dd, J3,4 = 8.0, J3,5 = 1.3 Hz, 1 H, 3-H),
7.63 (dd, J6,5 = 7.7, J6,4 = 1.8 Hz, 1 H, 6-H) ppm. 13C NMR
(125.7 MHz, CDCl3): δ = –5.5, –5.3, –4.9, –4.5, –4.5 and –4.0
(CH3Si); 17.9, 18.1 and 18.4 [(CH3)3C]; 25.86, 25.89 and 26.0
[(CH3)3C]; 42.8 (CH2); 62.7 (CH2-5Ј); 73.2 (CH-3Ј); 75.0 (CH-2Ј);
83.4 (CH-4Ј); 103.7 (C-1Ј); 125.7 (C-2); 126.9 (CH-5); 127.9 (CH-
4); 132.5 (CH-3); 132.8 (CH-6); 136.3 (C-1) ppm. HRMS (ESI) for
C30H57BrO5Si3: [M + Na]+ calcd. 683.2589, found 683.2588.
=
were designed as carba analogues of the substrate, we en-
vision future PriA inhibitors that will serve as transition-
state analogs or that will emulate intermediates of this bio-
transformation.
=
=
Conclusions
We have developed a facile approach for the synthesis of
diverse 2-substituted derivatives of benzyl C-ribonucleo-
sides and -nucleotides. The key intermediate 4a was pre-
pared by addition of (2-bromobenzyl)magnesium bromide
to TBS-protected ribonolactone followed by reduction and
re-silylation. Pd-catalyzed hydrogenation, cross-couplings,
aminations and hydroxylation gave corresponding 2-unsub-
stituted or 2-alkyl-, 2-aryl-, 2-hetaryl-, 2-amino and 2-hy-
droxy derivatives 4b–j that were deprotected to free nucleo-
sides 7a–j. Lithiation of 4a followed by reaction with CO2
gave carboxylic acid 4k, which was transformed into car-
1β-(2-Bromobenzyl)-2,3,5-tri-O-(tert-butyldimethylsilyl)-1-deoxy-
D
-ribofuranose (4a): Et3SiH (4.5 mL, 28.4 mmol, 3 equiv.) was
added in one portion to a stirred solution of hemiketal 3 (6.27 g,
9.45 mmol) in dry DCM (40 mL) under argon at 0 °C (ice bath).
After 5 min, BF3·Et2O (1.34 mL, 11.3 mmol, 1.2 equiv.) was slowly
added in one portion, and the resulting mixture was stirred for an
additional 5 min. Subsequently, Et3N (30 mL) was added, and the
reaction mixture was concentrated under reduced pressure. The
crude product was directly chromatographed on silica gel eluting
boxamides 4l–o, which were also deprotected to free nucleo- with a gradient of hexanes to 7% EtOAc in hexanes to give 4a
4
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Carba Analogues of Phosphoribosylanthranilate
(2.1 g, 36%) as a colorless oil and inseparable mixture of com-
pounds 5 and 6 (1.9 g, 40%) as a colorless oil.
Compound 4a: 1H NMR (500 MHz, CDCl3): δ = –0.07, –0.02,
0.087, 0.089, 0.093 and 0.10 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.88, 0.90 and
Procedure for the Re-Silylation of the Mixture of Compounds 5 and
6: Imidazole (486 mg, 7.14 mmol, 2 equiv.) and then TBDMSCl
(1.08 g, 7.14 mmol, 2 equiv.) were added to a flame-dried flask con-
taining a solution of the mixture of nucleosides 5 and 6 (1.9 g,
3.57 mmol) in dry DMF (50 mL) at 0 °C under argon, the solution
was warmed to room temp. and stirred for 16 h. The reaction mix-
ture was then poured into a saturated solution of NaCl (100 mL)
and extracted with EtOAc (3ϫ 30 mL). the collected organic frac-
tions were washed with a saturated NaCl solution, dried with
MgSO4, and the solvents were evaporated under vacuum. The
crude product was chromatographed on silica gel eluting with a
gradient of hexanes to 7% EtOAc in hexanes to give the nucleoside
4a (2.1 g, 91%) as a colorless oil.
0.94 [3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.80 (dd, Jgem = 14.1, JCH2a,1Ј
=
8.0 Hz, 1 H, CH2a); 3.05 (dd, Jgem = 14.1, JCH2b,1Ј = 5.8 Hz, 1 H,
CH2b); 3.65 (dd, Jgem = 11.2, J5Јa,4Ј = 3.1 Hz, 1 H, 5Ј-Ha); 3.73
(dd, Jgem = 11.2, J5Јb,4Ј = 3.4 Hz, 1 H, 5Ј-Hb); 3.88 (t, J2Ј,1Ј = J2Ј,3Ј
= 4.3 Hz, 1 H, 2Ј-H); 3.83 (dt, J4Ј,3Ј = 5.2, J4Ј,5Јa = J4Ј,5Јb = 3.2 Hz,
1 H, 4Ј-H); 4.13 (ddd, J1Ј,CH2a = 8.0, J1Ј,CH2b = 5.8, J1Ј,2Ј = 4.3 Hz,
1 H, 1Ј-H); 4.14 (t, J3Ј,2Ј = J3Ј,4Ј = 4.7 Hz, 1 H, 3Ј-H); 7.07 (ddd,
J4,3 = 7.9, J4,5 = 7.4, J4,6 = 1.8 Hz, 1 H, 4-H); 7.25 (td, J5,4 = J5,6
= 7.5, J5,3 = 1.3 Hz, 1 H, 5-H); 7.35 (dd, J6,5 = 7.7, J6,4 = 1.8 Hz,
1 H, 6-H); 7.54 (dd, J3,4 = 8.0, J3,5 = 1.3 Hz, 1 H, 3-H) ppm. 13C
NMR (125.7 MHz, CDCl3): δ = –5.4, –5.2, –4.8, –4.6, –4.5 and
–4.3 (CH3Si); 18.0, 18.1 and 18.4 [(CH3)3C]; 25.85, 25.92 and 26.0
[(CH3)3C]; 40.2 (CH2); 62.6 (CH2-5Ј); 72.1 (CH-3Ј); 75.7 (CH-2Ј);
82.4 (CH-1Ј); 83.6 (CH-4Ј); 124.8 (C-2); 127.3 (CH-5); 128.0 (CH-
4); 131.5 (CH-6); 132.8 (CH-3); 138.2 (C-1) ppm. HRMS (ESI) for
C30H57BrO4Si3: [M + Na]+ calcd. 667.2640, found 667.2639. IR
1β-Benzyl-2,3,5-tri-O-(tert-butyldimethylsilyl)-1-deoxy-D-ribo-
furanose (4b): 10% Pd/C (150 mg) was added to a solution of 4a
(400 mg, 0.69 mmol) in a mixture of THF (15 mL), EtOH (15 mL),
H2O (1.5 mL), and Et3N (1.0 mL). The reaction flask was then
sealed with a septum, evacuated, and filled with H2 (101 kPa). Af-
ter the reaction was completed (12 h), the Pd catalyst was filtered
off, the filtrate was poured into H2O, and crude product was ex-
tracted with EtOAc. Chromatography (silica gel, elution with a gra-
dient of hexanes to 5% EtOAc in hexanes) gave 4b (300 mg, 85%)
as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = –0.02, 0.02,
0.06, 0.08, 0.09 and 0.10 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.900, 0.902 and
(CCl ): ν = 3069, 2956, 2897, 1593, 1568, 1472, 1463, 1440, 1406,
˜
4
1390, 1362, 1255, 1276, 1219, 1128, 1118, 1088, 1048, 1032, 1021,
1003, 940, 838, 701, 680, 661, 540, 496 cm–1.
1β-(2-Bromobenzyl)-2,5-di-O-(tert-butyldimethylsilyl)-1-deoxy-D-
ribofuranose (5): Spectra taken from the mixture of 5 + 6. 1H NMR
(500 MHz, CDCl3): δ = 0.05, 0.07, 0.09 and 0.11 (4ϫ s, 4 ϫ 3 H,
CH3Si); 0.91 and 0.94 [2ϫ s, 2 ϫ 9 H, (CH3)3C]; 2.61 (br. d, JOHЈ,3Ј
= 5.2 Hz, 1 H, O3Ј-H); 2.83 (dd, Jgem = 14.1, JCH2a,1Ј = 8.7 Hz, 1
H, CH2a); 3.10 (dd, Jgem = 14.1, JCH2b,1Ј = 4.4 Hz, 1 H, CH2b);
3.71 (dd, Jgem = 11.2, J5Јa,4Ј = 3.1 Hz, 1 H, 5Ј-Ha); 3.78 (dd, Jgem
0.94 [3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.70 (dd, Jgem = 13.8, JCH2a,1Ј
=
8.2 Hz, 1 H, CH2a); 2.85 (dd, Jgem = 13.8, JCH2b,1Ј = 4.9 Hz, 1 H,
CH2b); 3.62 (dd, Jgem = 11.1, J5Јa,4Ј = 3.5 Hz, 1 H, 5Ј-Ha); 3.65
(dd, Jgem = 11.1, J5Јb,4Ј = 3.6 Hz, 1 H, 5Ј-Hb); 3.79 (dd, J2Ј,1Ј = 5.4,
J2Ј,3Ј = 4.4 Hz, 1 H, 2Ј-H); 3.88 (br. dt, J4Ј,3Ј = 4.2, J4Ј,5Јa = J4Ј,5Јb
= 3.5 Hz, 1 H, 4Ј-H); 4.02 (t, J3Ј,2Ј = J3Ј,4Ј = 4.3 Hz, 1 H, 3Ј-H);
4.06 (dt, J1Ј,CH2a = 8.3, J1Ј,CH2b = J1Ј,2Ј = 5.1 Hz, 1 H, 1Ј-H); 7.21–
7.32 (m, 5 H, 2,3,4-H) ppm. 13C NMR (125.7 MHz, CDCl3): δ =
–5.4, –5.2, –4.7, –4.5, –4.4 and –4.3 (CH3Si); 18.1 and 18.4
[(CH3)3C]; 25.88, 25.91 and 26.0 [(CH3)3C]; 40.4 (CH2); 63.0 (CH2-
5Ј); 72.5 (CH-3Ј); 75.9 (CH-2Ј); 83.1 (CH-1Ј); 84.0 (CH-4Ј); 126.2
(CH-4); 128.3 (CH-3); 129.3 (CH-2); 139.0 (C-1) ppm. HRMS
(ESI) for C30H58O4Si3: [M + H]+ calcd. 567.3716, found 567.3717.
= 11.2, J5Јb,4Ј = 2.7 Hz, 1 H, 5Ј-Hb); 3.90 (dt, J4Ј,3Ј = 4.3, J4Ј,5Јa
=
J4Ј,5Јb = 2.9 Hz, 1 H, 4Ј-H); 4.01 (t, J2Ј,1Ј = J2Ј,3Ј = 5.2 Hz, 1 H, 2Ј-
H); 4.05 (m, 1 H, 3Ј-H); 4.10 (ddd, J1Ј,CH2a = 8.6, J1Ј,2Ј = 5.1,
J1Ј,CH2b = 4.5 Hz, 1 H, 1Ј-H); 7.08 (br. ddd, J4,3 = 7.9, J4,5 = 7.5,
J4,6 = 1.8 Hz, 1 H, 4-H); 7.24 (td, J5,4 = J5,6 = 7.5, J5,3 = 1.3 Hz,
1 H, 5-H); 7.35 (dd, J6,5 = 7.7, J6,4 = 1.8 Hz, 1 H, 6-H); 7.53 (dd,
J3,4 = 8.0, J3,5 = 1.3 Hz, 1 H, 3-H) ppm. 13C NMR (125.7 MHz,
CDCl3): δ = –5.5, –5.3, –4.9 and –4.7 (CH3Si); 18.0 and 18.4
[(CH3)3C]; 25.7 and 26.0 [(CH3)3C]; 39.9 (CH2); 63.4 (CH2-5Ј); 71.9
(CH-3Ј); 76.2 (CH-2Ј); 81.8 (CH-1Ј); 84.5 (CH-4Ј); 124.6 (C-2);
127.3 (CH-5); 128.1 (CH-4); 131.6 (CH-6); 132.7 (CH-3); 137.9 (C-
1) ppm. HRMS (ESI) for C24H43BrO4Si2: [M – H]– calcd. 529.1811,
found 529.1817.
IR (CCl ): ν = 3099, 3066, 3030, 2955, 2896, 1605, 1586, 1496,
˜
4
1472, 1463, 1455, 1406, 1390, 1362, 1255, 1311, 1090, 1079, 1023,
1004, 940, 838, 699, 680, 671 cm–1.
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-(2-methylbenzyl)-
D-ribofuranose (4c): Me3Al (0.23 mL, 0.47 mmol, 1.5 equiv., 2 m in
toluene) was added to a vigorously stirred solution of 4a (200 mg,
0.31 mmol) and Pd(PPh3)4 (18 mg, 0.015 mmol, 5 mol-%) in THF
(5 mL) under argon. The mixture was stirred at 70 °C for 24 h,
quenched by pouring into saturated NaH2PO4 (50 mL), and ex-
tracted with EtOAc (3ϫ 50 mL). The crude product was chromato-
graphed on silica gel eluting with a gradient of hexanes to 1%
EtOAc in hexanes to give 4c (163 mg, 91%) as colorless oil. 1H
NMR (500 MHz, CDCl3): δ = –0.04, 0.00, 0.075, 0.084, 0.09 and
1β-(2-Bromobenzyl)-3,5-di-O-(tert-butyldimethylsilyl)-1-deoxy-D-
ribofuranose (6): Spectra taken from the mixture of 5 + 6. 1H NMR
(500 MHz, CDCl3): δ = 0.07, 0.08, 0.12 and 0.13 (4ϫ s, 4 ϫ 3 H,
CH3Si); 0.91 [s, 2ϫ 9 H, (CH3)3C]; 2.59 (d, JOHЈ,2Ј = 7.6 Hz, 1 H,
O2Ј-H); 2.91 (dd, Jgem = 14.3, JCH2a,1Ј = 7.8 Hz, 1 H, CH2a); 3.17
(dd, Jgem = 14.3, JCH2b,1Ј = 5.2 Hz, 1 H, CH2b); 3.63 (dd, Jgem
11.1, J5Јa,4Ј = 4.1 Hz, 1 H, 5Ј-Ha); 3.66 (dd, Jgem = 11.1, J5Јb,4Ј
=
=
3.4 Hz, 1 H, 5Ј-Hb); 3.79 (br. dt, J2Ј,OH = 7.6, J2Ј,1Ј = J2Ј,3Ј = 5.8 Hz, 0.10 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.89, 0.90 and 0.94 [3ϫ s, 3 ϫ 9 H,
1 H, 2Ј-H); 3.83 (q, J4Ј,5Јa = J4Ј,5Јb = J4Ј,3Ј = 3.7 Hz, 1 H, 4Ј-H); (CH3)3C]; 2.33 (s, 3 H, CH3-2); 2.69 (dd, Jgem = 14.1, JCH2a,1Ј
4.04 (ddd, J1Ј,CH2a = 7.8, J1Ј,2Ј = 6.0, J1Ј,CH2b = 5.2 Hz, 1 H, 1Ј-H); 8.4 Hz, 1 H, CH2a); 2.85 (dd, Jgem = 14.1, JCH2b,1Ј = 5.1 Hz, 1 H,
4.24 (dd, J3Ј,2Ј = 5.5, J3Ј,4Ј = 3.8 Hz, 1 H, 3Ј-H); 7.07 (br. ddd, J4,3 CH2b); 3.64 (dd, Jgem = 11.1, J5Јa,4Ј = 3.2 Hz, 1 H, 5Ј-Ha); 3.67
= 8.0, J4,5 = 7.5, J4,6 = 1.8 Hz, 1 H, 4-H); 7.24 (td, J5,4 = J5,6 (dd, Jgem = 11.1, J5Јb,4Ј = 3.6 Hz, 1 H, 5Ј-Hb); 3.81 (dd, J2Ј,1Ј = 5.5,
J2Ј,3Ј = 4.4 Hz, 1 H, 2Ј-H); 3.87 (br. q, J4Ј,3Ј = J4Ј,5Јa = J4Ј,5Јb
=
=
7.5, J5,3 = 1.3 Hz, 1 H, 5-H); 7.34 (dd, J6,5 = 7.7, J6,4 = 1.8 Hz, 1
H, 6-H); 7.54 (dd, J3,4 = 8.0, J3,5 = 1.3 Hz, 1 H, 3-H) ppm. 13C
NMR (125.7 MHz, CDCl3): δ = –5.5, –5.3, –4.9 and –4.5 (CH3Si);
18.0 and 18.4 [(CH3)3C]; 25.8 and 26.0 [(CH3)3C]; 39.6 (CH2); 62.7
=
3.6 Hz, 1 H, 4Ј-H); 4.06 (dt, J1Ј,CH2a = 8.5, J1Ј,CH2b = J1Ј,2Ј = 5.3 Hz,
1 H, 1Ј-H); 4.11 (t, J3Ј,2Ј = J3Ј,4Ј = 4.2 Hz, 1 H, 3Ј-H); 7.09–7.17
(m, 3 H, 3,4,5-H); 7.21 (m, 1 H, 6-H) ppm. 13C NMR (125.7 MHz,
(CH2-5Ј); 72.5 (CH-3Ј); 74.8 (CH-2Ј); 82.1 (CH-1Ј); 84.4 (CH-4Ј); CDCl3): δ = –5.5, –5.3, –4.8, –4.5, –4.41 and –4.36 (CH3Si); 18.00,
124.8 (C-2); 127.2 (CH-5); 128.0 (CH-4); 131.5 (CH-6); 132.7 (CH-
3); 137.8 (C-1) ppm. HRMS (ESI) for C24H43BrO4Si2: [M – H]–
calcd. 529.1811, found 529.1817.
18.04 and 18.4 [(CH3)3C]; 19.7 (CH3-2); 25.86, 25.90 and 26.0
[(CH3)3C]; 37.6 (CH2); 63.0 (CH2-5Ј); 72.5 (CH-3Ј); 76.1 (CH-2Ј);
82.2 (CH-1Ј); 84.2 (CH-4Ј); 125.9 (CH-5); 126.4 (CH-4); 129.9
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
T. Kubelka, L. Slaveˇtínská, M. Hocek
FULL PAPER
(CH-6); 130.2 (CH-3); 136.3 and 137.3 (C-1,2) ppm. HRMS (ESI)
2897, 1624, 1606, 1586, 1499, 1472, 1462, 1406, 1390, 1362, 1313,
1277, 1256, 1188, 1090, 1080, 1053, 1005, 940, 928, 864, 838, 712,
678, 672, 529, 505 cm–1.
for C31H60O4Si3: [M + H]+ calcd. 581.3872, found 581.3874. IR
(CCl ): ν = 3065, 3019, 2955, 2897, 1606, 1584, 1509, 1472, 1463,
˜
4
1406, 1389, 1380, 1362, 1277, 1254, 1087, 1041, 1003, 939, 865,
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-[2-(dimethylamino)-
benzyl]-D-ribofuranose (4f): Toluene (0.6 mL) and Me2NH (1.2 mL,
838, 819, 721, 696, 679, 671, 589, 542 cm–1.
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-(2-phenylbenzyl)-
2.32 mmol, 6 equiv; 2 m solution in THF) were added to a flame-
dried and argon-purged flask containing 4a (249 mg, 0.39 mmol),
Pd2(dba)3 (18 mg, 0.019 mmol, 5 mol-%), (biphenyl-2-yl)di-tert-but-
ylphosphane (23 mg, 0.077 mmol, 20 mol-%), and sodium tert-but-
oxide (37 mg, 0.39 mmol, 1 equiv.). The reaction mixture was
stirred at 60 °C for 24 h, concentrated under reduced pressure, and
the crude product was chromatographed on silica gel eluting with
a gradient of hexanes to 1% EtOAc in hexanes, to give 4f (200 mg,
85%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = –0.16,
D
-ribofuranose (4d): K2CO3 (106 mg, 0.77 mmol), Pd(PPh3)4
(59 mg, 0.05 mmol, 10 mol-%), PhB(OH)2 (125 mg, 1.02 mmol,
2 equiv.) and starting nucleoside 4a (330 mg, 0.51 mmol) were dis-
solved in toluene (6 mL) under argon, and the mixture was stirred
at 90 °C for 12 h. The reaction mixture was concentrated under
reduced pressure, and the crude product was chromatographed on
silica gel eluting with a gradient of hexanes to 1% EtOAc in hex-
anes to give 4d (287 mg, 87 %) as a colorless oil. 1H NMR
(500 MHz, CDCl3): δ = –0.23, –0.10, –0.01, 0.00, 0.067 and 0.070 –0.09, 0.08, 0.09, 0.10 and 0.11 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.85, 0.90
(6 ϫ s, 6 ϫ 3 H, CH3Si); 0.78, 0.87 and 0.92 [3 ϫ s, 3 ϫ 9 H, and 0.94 [3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.67 [s, 6 H, (CH3)2N]; 2.71
(CH3)3C]; 2.69 (dd, Jgem = 14.3, JCH2a,1Ј = 8.0 Hz, 1 H, CH2a); 2.92 (dd, Jgem = 13.8, JCH2a,1Ј = 6.9 Hz, 1 H, CH2a); 3.03 (dd, Jgem
(dd, Jgem = 14.3, JCH2b,1Ј = 5.5 Hz, 1 H, CH2b); 3.56 (dd, J2Ј,1Ј 13.8, JCH2b,1Ј = 6.9 Hz, 1 H, CH2b); 3.65 (dd, Jgem = 11.2, J5Јa,4Ј
4.8, J2Ј,3Ј = 3.8 Hz, 1 H, 2Ј-H); 3.57–3.65 (m, 2 H, 5Ј-H); 3.81–3.85
(m, 2 H,3Ј,4Ј-H); 3.96 (ddd, J1Ј,CH2a = 8.0, J1Ј,CH2b = 5.5, J1Ј,2Ј
4.8 Hz, 1 H, 1Ј-H); 7.22 (dd, J3,4 = 7.4, J3,5 = 1.7 Hz, 1 H, 3-H);
=
=
=
3.1 Hz, 1 H, 5Ј-Ha); 3.76 (dd, Jgem = 11.2, J5Јb,4Ј = 3.1 Hz, 1 H, 5Ј-
Hb); 3.84 (br. t, J2Ј,1Ј = J2Ј,3Ј = 3.9 Hz, 1 H, 2Ј-H); 3.89 (dt, J4Ј,3Ј
=
= 6.1, J4Ј,5Јa = J4Ј,5Јb = 3.1 Hz, 1 H, 4Ј-H); 4.08 (td, J1Ј,CH2a
=
7.26 (td, J4,3 = J4,5 = 7.4, J4,6 = 1.4 Hz, 1 H, 4-H); 7.30–7.36 (m, J1Ј,CH2b = 6.9, J1Ј,2Ј = 3.5 Hz, 1 H, 1Ј-H); 4.11 (dd, J3Ј,4Ј = 6.0, J3Ј,2Ј
4 H, 5-H,o,p-C6H5); 7.39 (m, 2 H, H-m-C6H5); 7.48 (dd, J6,5 = 7.7, = 4.3 Hz, 1 H, 3Ј-H); 7.02 (td, J5,4 = J5,6 = 7.4, J5,3 = 1.4 Hz, 1 H,
J6,4 = 1.5 Hz, 1 H, 6-H) ppm. 13C NMR (125.7 MHz, CDCl3): δ = 5-H); 7.10 (dd, J3,4 = 8.1, J3,5 = 1.4 Hz, 1 H, 3-H); 7.18 (br. ddd,
–5.4, –5.3, –5.0, –4.6, –4.5 and –4.3 (CH3Si); 17.9, 18.0 and 18.4
[(CH3)3C]; 25.8, 25.9 and 26.0 [(CH3)3C]; 37.1 (CH2); 62.7 (CH2-
J4,3 = 7.9, J4,5 = 7.4, J4,6 = 1.7 Hz, 1 H, 4-H); 7.31 (dd, J6,5 = 7.5,
J6,4 = 1.7 Hz, 1 H, 6-H) ppm. 13C NMR (125.7 MHz, CDCl3): δ =
5Ј); 72.0 (CH-3Ј); 75.8 (CH-2Ј); 83.4 (CH-1Ј); 83.6 (CH-4Ј); 126.1 –5.4, –5.2, –4.9, –4.64, –4.60 and –4.3 (CH3Si); 18.0, 18.1 and 18.4
(CH-4); 126.8 (CH–p-C6H5); 127.3 (CH-5); 128.2 (CH–m–C6H5); [(CH3)3C]; 25.8, 25.9 and 26.0 [(CH3)3C]; 35.3 (CH2); 45.3
129.5 (CH–o-C6H5); 130.1 (CH-3); 130.3 (CH-6); 136.2 (C-1); 141.7 [(CH3)2N]; 62.4 (CH2-5Ј); 71.8 (CH-3Ј); 75.6 (CH-2Ј); 82.9 (CH-
(C-i-C6H5); 142.1 (C-2) ppm. HRMS (ESI) for C36H63O4Si3: [M +
4Ј); 84.5 (CH-1Ј); 119.4 (CH-3); 123.4 (CH-5); 127.1 (CH-4); 131.0
H]+ calcd. 643.4029, found 643.4031. IR (CCl ): ν = 3061, 3026,
(CH-6); 133.7 (C-1); 152.9 (C-2) ppm. HRMS (ESI) for
˜
4
2956, 2896, 1599, 1587, 1500, 1480, 1472, 1463, 1450, 1405, 1435,
C
32H64O4NSi3: [M + H]+ calcd. 610.4138, found 610.4138. IR
1389, 1361, 1255, 1087, 1024, 1003, 940, 838, 702, 680, 671 cm–1.
(CCl ): ν = 3062, 3023, 2955, 2896, 2827, 2787, 1599, 1580, 1494,
˜
4
1472, 1462, 1453, 1406, 1389, 1362, 1306, 1254, 1187, 1081, 1034,
1β-(2-Aminobenzyl)-2,3,5-tri-O-(tert-butyldimethylsilyl)-1-deoxy-
946, 940, 838, 699, 680 cm–1.
D-ribofuranose (4e): KN(SiMe3)2 (4.05 mL, 2.02 mmol, 2.5 equiv.
0.5 m solution in toluene) was added to a flame-dried and argon-
purged flask containing 4a (519 mg, 0.81 mmol), Ph3SiNH2
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-(2-hydroxybenz-
yl)-D-ribofuranose (4g): Water (1.0 mL) and 1,4-dioxane (1.0 mL)
(446 mg, 1.62 mmol), Pd2(dba)3, (43 mg, 0.041 mmol, 5 mol-%), were added to a septum-sealed flask containing 4a (430 mg,
and (biphenyl-2-yl)dicyclohexylphosphane (57 mg, 0.162 mmol,
20 mol-%), and the mixture was stirred at 100 °C for 18 h. After
cooling to room temp., the reaction mixture was diluted with Et2O
(30 mL), washed with 2 m HCl (10 mL) and 1 m NaOH (15 mL).
The crude product was chromatographed on silica gel eluting with
a gradient of hexanes to 2% EtOAc in hexanes to give 4e (173 mg,
37%) as a colorless oil. 1H NMR (500 MHz, [D6]acetone): δ =
–0.04, 0.01, 0.11, 0.12, 0.128 and 0.132 (6ϫ s, 6 ϫ 3 H, CH3Si);
0.89, 0.92 and 0.95 [3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.45 (dd, Jgem = 13.7,
0.67 mmol), Pd2dba3 (31 mg, 0.034 mmol, 5.0 mol-%), (2Ј,4Ј,6Ј-tri-
isopropylbiphenyl-2-yl)di-tert-butylphosphane (57 mg, 0.13 mmol,
20 mol-%) and KOH (114 mg, 2.0 mmol, 3 equiv.) under argon.
The reaction mixture was heated at 100 °C for 2 h, cooled to room
temp., and concentrated under reduced pressure. The crude product
was purified by flash chromatography on silica gel eluting with a
gradient of hexanes to 3 % EtOAc in hexanes, furnishing 4g
(312 mg, 80%) as a colorless oil. 1H NMR (500 MHz, [D6]DMSO):
δ = –0.20, 0.14, 0.056, 0.058, 0.064 and 0.07 (6 ϫ s, 6 ϫ 3 H,
CH3Si); 0.80, 0.87 and 0.89 [3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.55 (dd,
JCH2a,1Ј = 7.7 Hz, 1 H, CH2a); 2.72 (dd, Jgem = 13.7, JCH2b,1Ј
=
5.9 Hz, 1 H, CH2b); 3.67 (dd, Jgem = 11.2, J5Јa,4Ј = 3.3 Hz, 1 H, 5Ј- Jgem = 13.2, JCH2a,1Ј = 6.4 Hz, 1 H, CH2a); 2.72 (dd, Jgem = 13.2,
Ha); 3.74 (dd, Jgem = 11.2, J5Јb,4Ј = 3.4 Hz, 1 H, 5Ј-Hb); 3.79 (dt, JCH2b,1Ј = 7.5 Hz, 1 H, CH2b); 3.56 (dd, Jgem = 11.1, J5Јa,4Ј
J4Ј,3Ј = 5.0, J4Ј,5Јa = J4Ј,5Јb = 3.4 Hz, 1 H, 4Ј-H); 3.92 (ddd, J1Ј,CH2a 4.2 Hz, 1 H, 5Ј-Ha); 3.68–3.74 (m, 2 H, 4Ј-H,5Ј-Hb); 3.90 (dd, J2Ј,3Ј
= 7.7, J1Ј,CH2b = 6.0, J1Ј,2Ј = 4.5 Hz, 1 H, 1Ј-H); 3.99 (t, J2Ј,1Ј = 4.2, J2Ј,1Ј = 2.6 Hz, 1 H, 2Ј-H); 3.92 (ddd, J1Ј,CH2a = 7.5, J1Ј,CH2b
J2Ј,3Ј = 4.4 Hz, 1 H, 2Ј-H); 4.13 (br. t, J3Ј,4Ј = J3Ј,2Ј = 4.7 Hz, 1 H, = 6.5, J1Ј,2Ј = 2.6 Hz, 1 H, 1Ј-H); 4.08 (dd, J3Ј,4Ј = 6.6, J3Ј,2Ј
3Ј-H); 6.53 (dd, J3,4 = 7.8, J3,5 = 1.4 Hz, 1 H, 3-H); 6.97 (td, J5,4 4.1 Hz, 1 H, 3Ј-H); 6.70 (td, J5,4 = J5,6 = 7.4, J5,3 = 1.2 Hz, 1 H,
=
=
=
= J5,6 = 7.5, J5,3 = 1.4 Hz, 1 H, 5-H); 7.13 (td, J4,3 = J4,5 = 7.6,
J4,6 = 1.5 Hz, 1 H, 4-H); 7.28 (dd, J6,5 = 7.6, J6,4 = 1.5 Hz, 1 H, 6-
H) ppm. 13C NMR (125.7 MHz, [D6]acetone): δ = –5.2, –5.00, –4.4,
–4.2, –4.1 and –3.9 (CH3Si); 18.6 and 19.0 [(CH3)3C]; 26.36 and
26.43 [(CH3)3C]; 36.4 (CH2); 63.6 (CH2-5Ј); 73.2 (CH-3Ј); 76.6
5-H); 6.79 (dd, J3,4 = 8.1, J3,5 = 1.2 Hz, 1 H, 3-H); 7.01 (br. ddd,
J4,3 = 8.0, J4,5 = 7.4, J4,6 = 1.7 Hz, 1 H, 4-H); 7.05 (dd, J6,5
=
7.5, J6,4 = 1.8 Hz, 1 H, 6-H); 9.35 (s, 1 H, O2-H) ppm. 13C NMR
(125.7 MHz, [D6]DMSO): δ = –5.3, –5.1, –4.77, –4.75, –4.7 and
–4.3 (CH3Si); 17.8, 17.9 and 18.2 [(CH3)3C]; 25.8, 25.96 and 26.00
(CH-2Ј); 83.7 (CH-1Ј); 84.3 (CH-4Ј); 119.7 (CH-3); 123.7 (CH-5); [(CH3)3C]; 34.6 (CH2); 62.2 (CH2-5Ј); 71.3 (CH-3Ј); 75.0 (CH-2Ј);
127.6 (CH-4); 129.2 (C-1); 131.6 (CH-6); 151.2 (C-2) ppm. HRMS 81.7 (CH-4Ј); 83.5 (CH-1Ј); 115.1 (CH-3); 118.9 (CH-5); 124.4 (C-
(ESI) for C30H59O4NSi3: [M + H]+ calcd. 582.3825, found 1); 127.5 (CH-4); 131.2 (CH-6); 155.4 (C-2) ppm. HRMS (ESI) for
582.3826. IR (CCl ): ν = 3447, 3354, 3071, 3053, 3026, 3005, 2956,
C30H58O5Si3: [M + Na]+ calcd. 605.3484, found 605.3483. IR
˜
4
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
Carba Analogues of Phosphoribosylanthranilate
(CCl ): ν = 3610, 3348, 3069, 3035, 2955, 2897, 1616, 1585, 1507,
H) ppm. 13C NMR (125.7 MHz, CDCl3): δ = –5.4, –5.3, –4.9, –4.6,
–4.5 and –4.3 (CH3Si); 17.9, 18.0 and 18.4 [(CH3)3C]; 25.8, 25.9
and 26.0 [(CH3)3C]; 37.3 (CH2); 62.8 (CH2-5Ј); 72.2 (CH-3Ј); 75.9
(CH-2Ј); 83.1 (CH-1Ј); 83.8 (CH-4Ј); 125.3 (CH-5-thienyl); 126.2
(CH-4); 126.8 (CH-3-thienyl); 127.1 (CH-4-thienyl); 128.0 (CH-5);
130.6 (CH-6); 131.2 (CH-3); 134.2 (C-2); 137.3 (C-1); 142.6 (C-
2-thienyl) ppm. HRMS (ESI) for C34H60O4SSi3: [M + H]+ calcd.
˜
4
1472, 1463, 1444, 1405, 1390, 1362, 1255, 1240, 1160, 1111, 1100,
1089, 1006, 940, 838, 680 cm–1.
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-(2-methoxybenzyl)-
D-ribofuranose (4h): Water (0.5 mL) and 1,4-dioxane (0.5 mL) were
added to a septum-sealed flask containing 4a (147 mg, 0.23 mmol),
Pd2dba3 (11 mg, 0.012 mmol, 5.0 mol-%), (2Ј,4Ј,6Ј-triisopropylbi-
phenyl-2-yl)di-tert-butylphosphane (20 mg, 0.046 mmol, 20 mol-%)
and KOH (39 mg, 0.69 mmol, 3 equiv.) under argon. The reaction
mixture was heated at 100 °C for 2 h. Then it was cooled to room
temp., and tetrabutylammonium bromide (8 mg, 0.023 mmol),
KOH (26 mg, 0.46 mmol) and methyl iodide (29 μL, 0.46 mol) were
added, and reaction mixture was heated at 100 °C for an additional
2 h. After cooling to room temp., the reaction mixture was concen-
trated under reduced pressure. The crude product was purified by
flash chromatography on silica gel eluting with a gradient of hex-
anes to 1% EtOAc in hexanes, furnishing 4h (136 mg, 84%) as a
649.3593, found 649.3595. IR (CCl ): ν = 3066, 3021, 2956, 2897,
˜
4
1602, 1484, 1472, 1463, 1448, 1431, 1406, 1389, 1362, 1255, 1220,
1086, 1023, 1004, 940, 853, 838, 696, 679, 591, 498 cm–1.
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-[2-(2-furyl)benz-
yl]-D-ribofuranose (4j): DMF (3.0 mL) was added to a flame-dried
and argon-purged flask, containing 4a (306 mg, 0.48 mmol), and
PdCl2(PPh3)2 (17 mg, 0.024 mmol, 5 mol-%). After 5 min of stir-
ring at room temp., tributyl(2-furyl)stannane (0.23 mL, 0.72 mmol,
1.5 equiv.) was added, and mixture was heated to 130 °C for 24 h.
The crude reaction mixture was diluted with Et2O (300 mL),
washed with 2 m HCl (80 mL) and saturated NaHCO3 (100 mL).
After evaporation of the solvents under reduced pressure, the crude
product was chromatographed on silica gel eluting with a gradient
of hexanes to 2% EtOAc in hexanes to obtain 4i (258 mg, 86%) as
a colorless oil. 1H NMR (500 MHz, CDCl3): δ = –0.12, –0.04,
0.046, 0.049, 0.09 and 0.10 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.85, 0.88 and
1
colorless oil. H NMR (500 MHz, CDCl3): δ = –0.18, –0.09, 0.07,
0.08, 0.09 and 0.10 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.84, 0.90 and 0.93
[3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.72 (dd, Jgem = 13.5, JCH2a,1Ј = 6.8 Hz,
1 H, CH2a); 2.85 (dd, Jgem = 13.5, JCH2b,1Ј = 7.3 Hz, 1 H, CH2b);
3.63 (dd, Jgem = 11.3, J5Јa,4Ј = 3.3 Hz, 1 H, 5Ј-Ha); 3.77 (dd, Jgem
= 11.3, J5Јb,4Ј = 2.8 Hz, 1 H, 5Ј-Hb); 3.81 (s, 3 H, CH3O-2); 3.84
(dd, J2Ј,3Ј = 4.3, J2Ј,1Ј = 2.8 Hz, 1 H, 2Ј-H); 3.89 (br. dt, J4Ј,3Ј = 6.7,
0.94 [3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.89 (dd, Jgem = 14.1, JCH2a,1Ј
=
J4Ј,5Јa = J4Ј,5Јb = 3.1 Hz, 1 H, 4Ј-H); 4.088 (dd, J3Ј,4Ј = 6.7, J3Ј,2Ј
4.3 Hz, 1 H, 3Ј-H); 4.091 (td, J1Ј,CH2a = J1Ј,CH2b = 7.0, J1Ј,2Ј
=
=
8.1 Hz, 1 H, CH2a); 3.15 (dd, Jgem = 14.1, JCH2b,1Ј = 5.3 Hz, 1 H,
CH2b); 3.63 (dd, Jgem = 11.2, J5Јa,4Ј = 3.2 Hz, 1 H, 5Ј-Ha); 3.69
2.8 Hz, 1 H, 1Ј-H); 6.84 (dd, J3,4 = 8.7, J3,5 = 1.1 Hz, 1 H, 3-H);
6.89 (td, J5,4 = J5,6 = 7.4, J5,3 = 1.1 Hz, 1 H, 5-H); 7.16–7.22 (m,
2 H, 4,6-H) ppm. 13C NMR (125.7 MHz, CDCl3): δ = –5.4, –5.2,
–4.9, –4.8, –4.7 and –4.3 (CH3Si); 18.0, 18.1 and 18.5 [(CH3)3C];
25.8, 25.9 and 26.1 [(CH3)3C]; 34.8 (CH2); 55.1 (CH3O-2); 62.4
(CH2-5Ј); 71.6 (CH-3Ј); 75.5 (CH-2Ј); 82.4 (CH-4Ј); 83.8 (CH-1Ј);
110.2 (CH-3); 120.4 (CH-5); 127.6 (C-1); 128.3 (CH-4); 131.2 (CH-
6); 157.4 (C-2) ppm. HRMS (ESI) for C31H60O5Si3: [M + Na]+
(dd, Jgem = 11.2, J5Јb,4Ј = 3.6 Hz, 1 H, 5Ј-Hb); 3.76 (br. dd, J2Ј,1Ј
=
5.0, J2Ј,3Ј = 4.4 Hz, 1 H, 2Ј-H); 3.87 (dt, J4Ј,3Ј = 4.4, J4Ј,5Јa = J4Ј,5Јb
= 3.4 Hz, 1 H, 4Ј-H); 4.03 (t, J3Ј,2Ј = J3Ј,4Ј = 4.4 Hz, 1 H, 3Ј-H);
4.10 (dt, J1Ј,CH2a = 8.1, J1Ј,CH2b = J1Ј,2Ј = 5.2 Hz, 1 H, 1Ј-H); 6.46
(dd, J4,3 = 3.3, J4,5 = 1.8 Hz, 1 H, 4-H-furyl); 6.59 (br. dd, J3,4
=
3.3, J3,5 = 0.8 Hz, 1 H, 3-H-furyl); 7.24–7.28 (m, 2 H, 5,4-H); 7.37
(m, 1 H, 6-H); 7.49 (dd, J5,4 = 1.8, J5,4 = 0.8 Hz, 1 H, 5-H-furyl);
7.59 (m, 1 H, 3-H) ppm. 13C NMR (125.7 MHz, CDCl3): δ = –5.4,
–5.3, –4.9, –4.5 and –4.4 (CH3Si); 17.98, 18.01 and 18.4 [(CH3)3C];
25.8, 25.9 and 26.0 [(CH3)3C]; 38.0 (CH2); 62.8 (CH2-5Ј); 72.3 (CH-
3Ј); 76.0 (CH-2Ј); 82.4 (CH-1Ј); 83.9 (CH-4Ј); 108.7 (CH-3-furyl);
111.3 (CH-4-furyl); 126.5 (CH-4); 127.8 (CH-5); 128.3 (CH-3);
130.5 (C-2); 131.2 (CH-6); 136.0 (C-1); 141.9 (CH-5-furyl); 153.5
(C-2-furyl) ppm. HRMS (ESI) for C34H60O5Si3: [M + H]+ calcd.
calcd. 619.3641, found 619.3638. IR (CCl ): ν = 3067, 2956, 2929,
˜
4
2897, 2857, 2838, 1603, 1588, 1494, 1472, 1463, 1439, 1405, 1389,
1362, 1251, 1242, 1081, 1037, 1003, 940, 838, 680 cm–1.
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-[2-(2-thienyl)-
benzyl]-D-ribofuranose (4i): Toluene (3 mL) was added to a flame-
dried and argon-purged flask containing 4a (287 mg, 0.45 mmol),
PdCl2 (8 mg, 0.045 mmol) and (biphenyl-2-yl)di-tert-butylphos-
phane (32 mg, 0.09 mmol). After 5 min of stirring at room temp.,
tributyl(thiophen-2-yl)stannane (220 μL, 0.68 mmol) was added,
and the mixture was heated to 130 °C for 24 h. The crude reaction
mixture was diluted with Et2O (300 mL), washed with 2 m HCl
(80 mL) and saturated NaHCO3 (100 mL). After evaporation of
the solvents under reduced pressure, the crude product was chro-
matographed on silica gel eluting with a gradient of hexanes to 1%
EtOAc in hexanes to obtain 4i (231 mg, 80%) as a colorless oil. 1H
NMR (500 MHz, CDCl3): δ = –0.18, –0.07, 0.02, 0.03, 0.076 and
0.082 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.81, 0.88 and 0.92 [3ϫ s, 3 ϫ 9 H,
(CH3)3C]; 2.79 (dd, Jgem = 14.2, JCH2a,1Ј = 8.1 Hz, 1 H, CH2a); 3.08
633.3821, found 633.3824. IR (CCl ): ν = 3120, 3065, 3020, 2956,
˜
4
2896, 1605, 1594, 1505, 1485, 1472, 1463, 1440, 1406, 1389, 1377,
1362, 1285, 1253, 1217, 1156, 1085, 1022, 1005, 940, 884, 838, 733,
680, 596, 510 cm–1.
General Procedure for the Deprotection of the TBS Group.
Method A: Et3N·3HF (400 μL, 2.4 mmol, 6 equiv.) was added to
the solution of silylated compound 4a–j (0.40 mmol) in THF
(2.00 mL), and the resulting mixture was stirred at 40 °C for 2 d.
After the reaction was finished (monitored by TLC eluting with
CHCl3/MeOH, 10:1), the solvent was removed under reduced pres-
sure, the crude product was dissolved in water, and solid NaHCO3
was added until pH = 8. The solvents were removed under reduced
pressure, and the crude product was chromatographed on silica gel
(20 g) eluting with a gradient of CHCl3 to 15% MeOH in CHCl3
to give free C-ribonucleosides 7a–j.
(dd, Jgem = 14.2, JCH2b,1Ј = 5.4 Hz, 1 H, CH2b); 3.61 (dd, Jgem
11.2, J5Јa,4Ј = 3.2 Hz, 1 H, 5Ј-Ha); 3.66 (dd, Jgem = 11.2, J5Јb,4Ј
=
=
3.6 Hz, 1 H, 5Ј-Hb); 3.67 (br. dd, J2Ј,1Ј = 5.0, J2Ј,3Ј = 4.4 Hz, 1 H,
2Ј-H); 3.85 (dt, J4Ј,3Ј = 4.6, J4Ј,5Јa = J4Ј,5Јb = 3.4 Hz, 1 H, 4Ј-H);
3.93 (t, J3Ј,2Ј = J3Ј,4Ј = 4.5 Hz, 1 H, 3Ј-H); 4.03 (dt, J1Ј,CH2a = 8.0,
J1Ј,CH2b = J1Ј,2Ј = 5.2 Hz, 1 H, 1Ј-H); 7.05 (br. dd, J3,4 = 3.5, J3,5
1β-(2-Bromobenzyl)-1-deoxy-
D-ribofuranose (7a): Compound 7a
was prepared from 4a (200 mg, 0.31 mmol) according to the gene-
1
= 1.5 Hz, 1 H, 3-H-thienyl); 7.06 (br. dd, J4,5 = 4.9, J4,3 = 3.5 Hz, ral procedure (method A) in 80% yield as a white solid. H NMR
1 H, 4-H-thienyl); 7.23 (td, J4,5 = J4,3 = 7.5, J4,6 = 1.5 Hz, 1 H, 4- (500 MHz, CD3OD): δ = 2.95 (dd, Jgem = 14.3, JCH2a,1Ј = 7.9 Hz,
H); 7.31 (td, J5,4 = J5,6 = 7.4, J5,3 = 1.5 Hz, 1 H, 5-H); 7.32 (dd, 1 H, CH2a); 3.11 (dd, Jgem = 14.3, JCH2b,1Ј = 5.2 Hz, 1 H, CH2b);
5,4 = 4.9, J5,3 = 1.5 Hz, 1 H, 5-H-thienyl); 7.37 (dd, J3,4 = 7.6, J3,5 3.58 (dd, Jgem = 11.9, J5Јa,4Ј = 4.8 Hz, 1 H, 5Ј-Ha); 3.67 (dd, Jgem
= 1.5 Hz, 1 H, 3-H); 7.45 (dd, J6,5 = 7.7, J6,4 = 1.5 Hz, 1 H, 6-
J
= 11.9, J5Јb,4Ј = 3.6 Hz, 1 H, 5Ј-Hb); 3.79 (br. td, J4Ј,5Јa = J4Ј,3Ј
=
7
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
T. Kubelka, L. Slaveˇtínská, M. Hocek
5.1, J4Ј,5Јb = 3.6 Hz, 1 H, 4Ј-H); 3.84 (t, J2Ј,1Ј = J2Ј,3Ј = 5.5 Hz, 1 H, (125.7 MHz, CD3OD): δ = 37.9 (CH2); 63.6 (CH2-5Ј); 72.5 (CH-
FULL PAPER
2Ј-H); 3.97 (t, J3Ј,2Ј = J3Ј,4Ј = 5.5 Hz, 1 H, 3Ј-H); 4.08 (dt, J1Ј,CH2a
7.9, J1Ј,CH2b = J1Ј,2Ј = 5.3 Hz, 1 H, 1Ј-H); 7.11 (ddd, J4,3 = 8.0, J4,5
= 7.4, J4,6 = 1.8 Hz, 1 H, 4-H); 7.27 (td, J5,4 = J5,6 = 7.5, J5,3
=
3Ј); 75.8 (CH-2Ј); 84.9 (CH-1Ј); 85.2 (CH-4Ј); 127.2 (CH-4); 127.9
(CH-p-C6H5); 128.3 (CH-5); 129.2 (CH–m-C6H5); 130.6 (CH–o-
C6H5); 131.0 (CH-3); 131.2 (CH-6); 137.1 (C-1); 143.2 (C-i-C6H5);
143.8 (C-2) ppm. HRMS (ESI) for C18H20O4: [M + Na]+ calcd.
=
1.3 Hz, 1 H, 5-H); 7.42 (br. dd, J6,5 = 7.7, J6,4 = 1.8 Hz, 1 H, 6-
H); 7.54 (dd, J3,4 = 8.0, J3,5 = 1.3 Hz, 1 H, 3-H) ppm. 13C NMR 323.1254, found 323.1254. IR (KBr): ν = 3414, 3059, 3024, 2599,
˜
(125.7 MHz, CD3OD): δ = 40.8 (CH2); 63.5 (CH2-5Ј); 72.6 (CH- 2579, 2568, 1500, 1480, 1450, 1438, 1313, 1202, 1101, 1118, 1073,
3Ј); 75.9 (CH-2Ј); 83.5 (CH-1Ј); 85.4 (CH-4Ј); 125.6 (C-2); 128.5 1050, 907, 774, 751, 723, 704, 617 cm–1.
(CH-5); 129.2 (CH-4); 133.0 (CH-6); 133.7 (CH-3); 139.2 (C-
1β-(2-Aminobenzyl)-1-deoxy-D-ribofuranose (7e): Compound 7e
1) ppm. HRMS (ESI) for C12H15BrO4: [M – H]– calcd. 301.0081,
was prepared from 4e (215 mg, 0.37 mmol) according to the general
found 301.0083. IR (KBr): ν = 3425, 3392, 3269, 1567, 1472, 1460,
˜
procedure (method A) in 74% yield as a yellow solid. 1H NMR
1205, 1160, 1122, 1111, 1071, 1057, 1045, 1029, 941, 862, 771, 748,
(500 MHz, [D6]DMSO): δ = 2.53 (dd, Jgem = 14.6, JCH2a,1Ј
8.1 Hz, 1 H, CH2a); 2.70 (dd, Jgem = 14.6, JCH2b,1Ј = 3.7 Hz, 1 H,
CH2b); 3.37 (m, 2 H, 5Ј-H); 3.60 (br. q, J2Ј,1Ј = J2Ј,OH = J2Ј,3Ј
=
659, 595, 536, 447 cm–1.
1β-(2-Benzyl)-1-deoxy-D-ribofuranose (7b): Compound 7b was pre-
=
pared from 4b (255 mg, 0.45 mmol) according to the general pro-
cedure (method A) in 80 % yield as a white gum. 1H NMR
(500 MHz, CD3OD): δ = 2.80 (dd, Jgem = 14.2, JCH2a,1Ј = 7.4 Hz,
5.8 Hz, 1 H, 2Ј-H); 3.61 (br. q, J4Ј,3Ј = J4Ј,5Јa = J4Ј,5Јb = 4.6 Hz, 1
H, 4Ј-H); 3. 74 (br. td, J3Ј,2Ј = J3Ј,OH = 5.4, J3Ј,4Ј = 4.5 Hz, 1 H, 3Ј-
H); 3.81 (ddd, J1Ј,CH2a = 8.1, J1Ј,2Ј = 6.1, J1Ј,CH2b = 3.7 Hz, 1 H,
1 H, CH2a); 2.94 (dd, Jgem = 14.2, JCH2b,1Ј = 4.6 Hz, 1 H, CH2b); 1Ј-H); 4.64 (t, JOH,5Јa = JOH,5Јb = 5.6 Hz, 1 H, O5Ј-H); 4.71 (d,
3.53 (dd, Jgem = 11.9, J5Јa,4Ј = 5.0 Hz, 1 H, 5Ј-Ha); 3.60 (dd, Jgem JOH,3Ј = 5.3 Hz, 1 H, O3Ј-H); 4.76 (br. d, JOH,2Ј = 6.1 Hz, 1 H,
= 11.9, J5Јb,4Ј = 3.8 Hz, 1 H, 5Ј-Hb); 3.73 (t, J2Ј,1Ј = J2Ј,3Ј = 5.7 Hz, O2Ј-H); 4.78 (br. s, 2 H, NH2); 6.50 (td, J5,4 = J5,6 = 7.3, J5,3
1 H, 2Ј-H); 3.77 (dt, J4Ј,3Ј = J4Ј,5Јa = 5.0, J4Ј,5Јb = 3.7 Hz, 1 H, 4Ј- 1.3 Hz, 1 H, 5-H); 6.61 (dd, J3,4 = 7.9, J3,5 = 1.3 Hz, 1 H, 3-H);
H); 3.82 (br. t, J3Ј,2Ј = J3Ј,4Ј = 5.3 Hz, 1 H, 3Ј-H); 3.98 (ddd, J1Ј,CH2a 6.89 (br. td, J4,3 = J4,5 = 7.6, J4,6 = 1.6 Hz, 1 H, 4-H); 6.94 (dd,
= 7.4, J1Ј,2Ј = 5.9, J1Ј,CH2b = 4.6 Hz, 1 H, 1Ј-H); 7.15–7.20 (m, 1
J6,5 = 7.5, J6,4 = 1.6 Hz, 1 H, 6-H) ppm. 13C NMR (125.7 MHz,
H, 4-H); 7.23–7.29 (m, 4 H, 2,3-H) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 35.1 (CH2); 62.1 (CH2-5Ј); 71.1 (CH-3Ј); 74.4
CD3OD): δ = 40.5 (CH2); 63.7 (CH2-5Ј); 72.7 (CH-3Ј); 75.5 (CH- (CH-2Ј); 82.6 (CH-1Ј); 84.6 (CH-4Ј); 115.3 (CH-3); 116.7 (CH-5);
=
2Ј); 84.8 (CH-1Ј); 85.6 (CH-4Ј); 127.2 (CH-4); 129.2 (CH-3); 130.6 123.4 (C-1); 126.9 (CH-4); 130.5 (CH-6); 146.8 (C-2) ppm. HRMS
(CH-2); 139.8 (C-1) ppm. HRMS (ESI) for C12H16O4: [M + Na]+ (ESI) for C12H17NO4: [M + Na]+ calcd. 262.1050, found 262.1049.
calcd. 247.0941, found 247.0941. IR (KBr): ν = 3435, 3410, 3253,
IR (KBr): ν = 3060, 3425, 3346, 3310, 3240, 3024, 1625, 1610, 1583,
˜
˜
3087, 3064, 3030, 3004, 1603, 1584, 1496, 1455, 1308, 1201, 1112,
1498, 1458, 1259, 1118, 1102, 1063, 1010, 755, 656, 603 cm–1.
1098, 1070, 1057, 1030, 904, 842, 762, 744, 704, 531 cm–1.
1-Deoxy-1β-[2-(dimethylamino)benzyl]-D-ribofuranose (7f): Com-
1-Deoxy-1β-(2-methylbenzyl)-
D
-ribofuranose (7c): Compound 7c
pound 7f was prepared from 4f (210 mg, 0.34 mmol) according to
the general procedure (method A) in 75% yield as a white gum. 1H
NMR (500 MHz, CD3OD): δ = 2.65 [s, 6 H, (CH3)2N]; 2.92 (dd,
Jgem = 14.2, JCH2a,1Ј = 7.9 Hz, 1 H, CH2a); 2.97 (dd, Jgem = 14.2,
was prepared from 4c (160 mg, 0.28 mmol) according to the general
procedure (method A) in 70% yield as a white solid. 1H NMR
(500 MHz, CD3OD): δ = 2.34 (s, 3 H, CH3-2); 2.83 (dd, Jgem
=
14.4, JCH2a,1Ј = 7.6 Hz, 1 H, CH2a); 2.95 (dd, Jgem = 14.4, JCH2b,1Ј
JCH2b,1Ј = 5.2 Hz, 1 H, CH2b); 3.57 (dd, Jgem = 12.0, J5Јa,4Ј
=
= 4.9 Hz, 1 H, CH2b); 3.55 (dd, Jgem = 11.9, J5Јa,4Ј = 4.9 Hz, 1 H, 4.4 Hz, 1 H, 5Ј-Ha); 3.68 (dd, Jgem = 12.0, J5Јb,4Ј = 3.3 Hz, 1 H, 5Ј-
5Ј-Ha); 3.61 (dd, Jgem = 11.9, J5Јb,4Ј = 3.9 Hz, 1 H, 5Ј-Hb); 3.77 Hb); 3.79 (ddd, J4Ј,3Ј = 6.0, J4Ј,5Јa = 4.4, J4Ј,5Јb = 3.3 Hz, 1 H, 4Ј-
(td, J4Ј,3Ј = J4Ј,5Јa = 4.9, J4Ј,5Јb = 3.9 Hz, 1 H, 4Ј-H); 3.77 (t, J2Ј,1Ј H); 3.83 (dd, J2Ј,3Ј = 5.4, J2Ј,1Ј = 4.4 Hz, 1 H, 2Ј-H); 4.00 (t, J3Ј,4Ј
= J2Ј,3Ј = 5.8 Hz, 1 H, 2Ј-H); 3.92 (br. dd, J3Ј,2Ј = 5.5, J3Ј,4Ј = 5.0 Hz,
1 H, 3Ј-H); 3.99 (ddd, J1Ј,CH2a = 7.6, J1Ј,2Ј = 6.0, J1Ј,CH2b = 4.8 Hz,
= J3Ј,2Ј = 5.7 Hz, 1 H, 3Ј-H); 4.09 (br. ddd, J1Ј,CH2a = 7.9, J1Ј,CH2b
= 5.2, J1Ј,2Ј = 4.5 Hz, 1 H, 1Ј-H); 7.02 (m, 1 H, 5-H); 7.15–7.19 (m,
1 H, 1Ј-H); 7.07–7.10 (m, 2 H, 4,5-H); 7.11 (m, 1 H, 3-H); 7.23 (m, 2 H, 3,4-H); 7.32 (dm, J6,5 = 7.7 Hz, 1 H, 6-H) ppm. 13C NMR
1 H, 6-H) ppm. 13C NMR (125.7 MHz, CD3OD): δ = 19.9 (CH3- (125.7 MHz, CD3OD): δ = 35.9 (CH2); 45.8 [(CH3)2N]; 63.3 (CH2-
2); 37.7 (CH2); 63.6 (CH2-5Ј); 72.7 (CH-3Ј); 75.8 (CH-2Ј); 84.2 5Ј); 72.4 (CH-3Ј); 76.2 (CH-2Ј); 85.1 (CH-4Ј); 85.7 (CH-1Ј); 120.8
(CH-1Ј); 85.6 (CH-4Ј); 126.8 (CH-5); 127.4 (CH-4); 131.0 and (CH-3); 125.0 (CH-5); 128.3 (CH-4); 131.8 (CH-6); 135.0 (C-1);
131.1 (CH-3,6); 137.7 and 138.1 (C-1,2) ppm. HRMS (ESI) for
154.3 (C-2) ppm. HRMS (ESI) for C14H21NO4: [M + H]+ calcd.
C13H18O4: [M + Na]+ calcd. 261.1097, found 261.1098. IR (KBr):
268.1543, found 268.1544. IR (KBr): ν = 3380, 3061, 3025, 2828,
˜
ν = 3402, 3065, 3021, 1606, 1583, 1494, 1461, 1379, 1126, 1111,
2786, 1598, 1580, 1494, 1477, 1452, 1406, 1304, 1187, 1156, 1100,
˜
1074, 1055, 771, 743, 698 cm–1.
1049, 1036, 947, 827, 767, 703, 529 cm–1.
1-Deoxy-1β-(2-phenylbenzyl)-
D
-ribofuranose (7d): Compound 7d
1-Deoxy-1β-(2-hydroxybenzyl)-D-ribofuranose (7g): Compound 7g
was prepared from 4d (280 mg, 0.44 mmol) according to the gene-
ral procedure (method A) in 82% yield as a white solid. H NMR
was prepared from 4g (300 mg, 0.51 mmol) according to the gene-
ral procedure (method A) in 82% yield as a white solid. H NMR
1
1
(500 MHz, CD3OD): δ = 2.84 (dd, Jgem = 14, JCH2a,1Ј = 7.8 Hz, 1 (500 MHz, [D6]DMSO): δ = 2.60 (dd, Jgem = 14.0, JCH2a,1Ј
=
H, CH2a); 2.89 (dd, Jgem = 14.5, JCH2b,1Ј = 5.5 Hz, 1 H, CH2b); 7.7 Hz, 1 H, CH2a); 2.76 (dd, Jgem = 14.0, JCH2b,1Ј = 5.4 Hz, 1 H,
3.50 (dd, Jgem = 11.8, J5Јa,4Ј = 5.1 Hz, 1 H, 5Ј-Ha); 3.60 (dd, Jgem CH2b); 3.36 (dd, Jgem = 11.6, J5Јa,OH = 6.1, J5Јa,4Ј = 5.1 Hz, 1 H,
= 11.8, J5Јb,4Ј = 3.6 Hz, 1 H, 5Ј-Hb); 3.61 (br. t, J2Ј,1Ј = J2Ј,3Ј
5.4 Hz, 1 H, 2Ј-H); 3.71 (ddd, J4Ј,3Ј = 5.4, J4Ј,5Јa = 5.1, J4Ј,5Јb
3.5 Hz, 1 H, 4Ј-H); 3.76 (t, J3Ј,2Ј = J3Ј,4Ј = 5.5 Hz, 1 H, 3Ј-H); 3.90
(dt, J1Ј,CH2a = 7.8, J1Ј,CH2b = J1Ј,2Ј = 5.4 Hz, 1 H, 1Ј-H); 7.16 (dd,
J3,4 = 7.5, J3,5 = 1.6 Hz, 1 H, 3-H); 7.24 (td, J4,3 = J4,5 = 7.5, J4,6
= 1.5 Hz, 1 H, 4-H); 7.29 (td, J5,4 = J5,6 = 7.4, J5,3 = 1.6 Hz, 1 H,
=
=
5Ј-Ha); 3.46 (dd, Jgem = 11.6, J5Јb,OH = 5.3, J5Јb,4Ј = 3.8 Hz, 1 H,
5Ј-Hb); 3.59 (br. td, J4Ј,3Ј = J4Ј,5Јa = 5.4, J4Ј,5Јb = 3.8 Hz, 1 H, 4Ј-
H); 3.63 (br. q, J2Ј,3Ј = J2Ј,1Ј = J2Ј,OH = 5.2 Hz, 1 H, 2Ј-H); 3.76
(br. q, J3Ј,4Ј = J3Ј,2Ј = J3Ј,OH = 5.7 Hz, 1 H, 3Ј-H); 3.87 (br. dt,
J1Ј,CH2a = 7.7, J1Ј,2Ј = J1Ј,CH2b = 5.1 Hz, 1 H, 1Ј-H); 4.59 (br. t,
JOH,5Јa = JOH,5Јb = 5.7 Hz, 1 H, O5Ј-H); 4.63 (d, JOH,2Ј = 5.5 Hz,
5-H); 7.30–7.35 (m, 3 H, H-o,p-C6H5); 7.40 (m, 2 H, H-m-C6H5); 1 H, O2Ј-H); 4.67 (d, JOH,3Ј = 5.9 Hz, 1 H, O3Ј-H); 6.70 (td, J5,4
7.46 (dd, J6,5 = 7.7, J6,4 = 1.5 Hz, 1 H, 6-H) ppm. 13C NMR = J5,6 = 7.4, J5,3 = 1.3 Hz, 1 H, 5-H); 6.76 (dd, J3,4 = 8.1, J3,5
=
8
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
Carba Analogues of Phosphoribosylanthranilate
1.3 Hz, 1 H, 3-H); 7.00 (br. td, J4,3 = J4,5 = 7.7, J4,6 = 1.8 Hz, 1 H,
4-H); 7.11 (dd, J6,5 = 7.5, J6,4 = 1.8 Hz, 1 H, 6-H); 9.18 (s, 1 H,
O2-H) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 34.3 (CH2);
J4,3 = 3.4, J4,5 = 1.9 Hz, 1 H, 4-H-furyl); 6.66 (dd, J3,4 = 3.4, J3,5
= 0.9 Hz, 1 H, 3-H-furyl); 7.23–7.28 (m, 2 H, 5,4-H); 7.42 (m, 1
H, 6-H); 7.57 (m, 1 H, 3-H); 7.59 (dd, J5,4 = 1.9, J5,4 = 0.8 Hz, 1
62.2 (CH2-5Ј); 71.1 (CH-3Ј); 74.3 (CH-2Ј); 82.5 (CH-1Ј); 83.8 (CH- H, 5-H-furyl) ppm. 13C NMR (125.7 MHz, CD3OD): δ = 39.0
4Ј); 115.0 (CH-3); 118.9 (CH-5); 125.2 (C-1); 127.2 (CH-4); 131.1 (CH2); 63.6 (CH2-5Ј); 72.6 (CH-3Ј); 76.0 (CH-2Ј); 84.5 (CH-1Ј);
(CH-6); 155.4 (C-2) ppm. HRMS (ESI) for C12H16O5: [M + Na]+ 85.3 (CH-4Ј); 109.7 (CH-3-furyl); 112.3 (CH-4-furyl); 127.5 (CH-
calcd. 263.0890, found 263.0890. IR (KBr): ν = 3416, 3065, 3035,
4); 128.8 (CH-5); 129.1 (CH-3); 131.9 (C-2); 132.5 (CH-6); 136.9
(C-1); 143.3 (CH-5-furyl); 154.9 (C-2-furyl) ppm. HRMS (ESI) for
˜
1612, 1595, 1586, 1506, 1491, 1457, 1242, 1154, 1103, 1043, 906,
828, 752 cm–1.
C H O : [M – H]– calcd. 289.1082, found 289.1082. IR (KBr): ν
˜
16 18
5
= 3411, 3120, 3065, 3028, 1604, 1573, 1504, 1485, 1464, 1407, 1283,
1-Deoxy-1β-(2-methoxybenzyl)-D-ribofuranose (7h): Compound 7h
1215, 1156, 1103, 1051, 1010, 886, 763, 596 cm–1.
was prepared from 4h (190 mg, 0.32 mmol) according to the gene-
1
ral procedure (method A) in 82% yield as a white solid. H NMR
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1β-(2-carboxybenzyl)-1-de-
(500 MHz, CD3OD): δ = 2.83 (dd, Jgem = 13.8, JCH2a,1Ј = 7.1 Hz,
oxy-D-ribofuranose (4k): nBuLi (2.62 mL, 4.2 mmol, 1.6 m solution
1 H, CH2a); 2.89 (dd, Jgem = 13.8, JCH2b,1Ј = 6.2 Hz, 1 H, CH2b); in hexane, 1.5 equiv.) was added to a vigorously stirred solution of
3.55 (dd, Jgem = 11.9, J5Јa,4Ј = 5.0 Hz, 1 H, 5Ј-Ha); 3.66 (dd, Jgem compound 4a (3.0 g, 2.79 mmol) in dry THF (26 mL) under argon
= 11.9, J5Јb,4Ј = 3.4 Hz, 1 H, 5Ј-Hb); 3.77 (ddd, J4Ј,3Ј = 6.2, J4Ј,5Јa at –78 °C and stirred at –78 °C for 60 min. Dry ice was placed in
= 5.0, J4Ј,5Јb = 3.4 Hz, 1 H, 4Ј-H); 3.81 (dd, J2Ј,3Ј = 5.5, J2Ј,1Ј
4.4 Hz, 1 H, 2Ј-H); 3.82 (s, 3 H, CH3O); 3.90 (br. dd, J3Ј,4Ј = 6.1, the reaction mixture through cannula for 60 min. The resulting
J3Ј,2Ј = 5.5 Hz, 1 H, 3Ј-H); 4.07 (ddd, J1Ј,CH2a = 7.1, J1Ј,CH2b = 6.1, mixture was slowly warmed up to room temp., quenched by pour-
J1Ј,2Ј = 4.4 Hz, 1 H, 1Ј-H); 6.86 (td, J5,4 = J5,6 = 7.4, J5,3 = 1.2 Hz, ing into a solution of NH4Cl in water (150 mL) and extracted with
1 H, 5-H); 6.92 (dd, J3,4 = 8.2, J3,5 = 1.2 Hz, 1 H, 3-H); 7.18 (ddd, Et2O (3 ϫ 250 mL). After evaporation of the solvents and
J4,3 = 8.2, J4,5 = 7.5, J4,6 = 1.8 Hz, 1 H, 4-H); 7.21 (dd, J6,5 = 7.4, chromatography eluting with a gradient of hexanes to 16% EtOAc
=
a the flame-dried flask (sealed with a septum) and introduced into
J6,4 = 1.8 Hz, 1 H, 6-H) ppm. 13C NMR (125.7 MHz, CD3OD): δ
in hexanes, compound 4k (1.99 g, 70%) was obtained as a white
= 35.3 (CH2); 55.8 (CH3O); 63.6 (CH2-5Ј); 72.6 (CH-3Ј); 75.8 (CH- solid. 1H NMR (500 MHz, CDCl3): δ = 0.05, 0.075, 0 078, 0.09
2Ј); 84.6 (CH-1Ј); 84.1 (CH-4Ј); 111.4 (CH-3); 121.4 (CH-5); 127.6 and 0.11 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.88, 0.92 and 0.93 [3ϫ s, 3 ϫ 9
(C-1); 128.7 (CH-4); 132.2 (CH-6); 159.0 (C-2) ppm. HRMS (ESI)
for C13H18O5: [M + Na]+ calcd. 277.1046, found 277.1045. IR 3.22 (dd, Jgem = 13.9, JCH2b,1Ј = 3.5 Hz, 1 H, CH2b); 3.61 (dd, Jgem
(KBr): ν = 3076, 3034, 2961, 2933, 2845, 1600, 1587, 1496, 1466, = 11.2, J5Јa,4Ј = 4.0 Hz, 1 H, 5Ј-Ha); 3.64 (dd, Jgem = 11.2, J5Јb,4Ј
H, (CH3)3C]; 2.96 (dd, Jgem = 13.9, JCH2a,1Ј = 9.8 Hz, 1 H, CH2a);
=
˜
1446, 1247, 1118, 1035.933, 756, 608 cm–1.
3.5 Hz, 1 H, 5Ј-Hb); 3.89 (dd, J2Ј,1Ј = 7.2, J2Ј,3Ј = 4.5 Hz, 1 H, 2Ј-
H); 3.94 (td, J4Ј,5Јa = J4Ј,5Јb = 3.8, J4Ј,3Ј = 2.6 Hz, 1 H, 4Ј-H); 4.07
(dd, J3Ј,2Ј = 4.5, J3Ј,4Ј = 2.6 Hz, 1 H, 3Ј-H); 4.12 (dd, J1Ј,CH2a = 9.8,
J1Ј,2Ј = 7.2, J1Ј,CH2b = 3.5 Hz, 1 H, 1Ј-H); 7.30–7.35 (m, 2 H, 4,6-
H); 7.48 (td, J5,4 = J5,6 = 7.5, J5,3 = 1.5 Hz, 1 H, 5-H); 7.85 (dd,
J3,4 = 8.1, J3,5 = 1.5 Hz, 1 H, 5-H) ppm. 13C NMR (125.7 MHz,
CDCl3): δ = –5.7, –5.4, –4.7, –4.5, –4.4 and –4.1 (CH3Si); 18.0, 18.1
and 18.4 [(CH3)3C]; 25.8, 25.9 and 26.0 [(CH3)3C]; 37.4 (CH2); 62.7
(CH2-5Ј); 73.2 (CH-3Ј); 75.9 (CH-2Ј); 83.0 (CH-1Ј); 86.2 (CH-4Ј);
126.9 (CH-4); 130.9 (CH-6); 131.0 (CH-3); 132.0 (CH-5); 132.3 (C-
2); 137.8 (C-1); 170.3 (CO) ppm. HRMS (ESI) for C31H58O6Si3:
1-Deoxy-1β-[2-(2-thienyl)benzyl]- -ribofuranose (7i): Compound 7i
D
was prepared from 4i (210 mg, 0.32 mmol) according to the general
1
procedure (method A) in 85% yield as an orange solid. H NMR
(500 MHz, CD3OD): δ = 2.97 (dd, Jgem = 14.4, JCH2a,1Ј = 8.0 Hz,
1 H, CH2a); 3.06 (dd, Jgem = 14.5, JCH2b,1Ј = 5.2 Hz, 1 H, CH2b);
3.54 (dd, Jgem = 11.9, J5Јa,4Ј = 5.0 Hz, 1 H, 5Ј-Ha); 3.64 (dd, Jgem
= 11.9, J5Јb,4Ј = 3.7 Hz, 1 H, 5Ј-Hb); 3.71 (t, J2Ј,1Ј = J2Ј,3Ј = 5.5 Hz,
1 H, 2Ј-H); 3.75 (td, J4Ј,3Ј = J4Ј,5Јa = 5.2, J4Ј,5Јb = 3.8 Hz, 1 H, 4Ј-
H); 3.85 (t, J3Ј,2Ј = J3Ј,4Ј = 5.5 Hz, 1 H, 3Ј-H); 3.96 (dt, J1Ј,CH2a
=
8.0, J1Ј,CH2b = J1Ј,2Ј = 5.3 Hz, 1 H, 1Ј-H); 7.09 (dd, J4,5 = 5.0, J4,3
= 3.5 Hz, 1 H, 4-H-thienyl); 7.10 (dd, J3,4 = 3.5, J3,5 = 1.3 Hz, 1
H, 3-H-thienyl); 7.23 (td, J4,5 = J4,3 = 7.5, J4,6 = 1.5 Hz, 1 H, 4-
H); 7.30 (td, J5,6 = J5,4 = 7.6, J5,3 = 1.6 Hz, 1 H, 5-H); 7.33 (dd,
[M + H]+ calcd. 611.3614, found 611.3614. IR (CCl ): ν = 3535,
˜
4
3075, 3028, 2956, 2897, 1738, 1694, 1603, 1576, 1491, 1472, 1463,
1448, 1405, 1390, 1362, 1303, 1256, 1188, 1084, 1022, 940, 838,
717, 707, 680, 463 cm–1.
J3,4 = 7.5, J3,5 = 1.6 Hz, 1 H, 3-H); 7.42 (dd, J5,4 = 5.0, J5,3
=
1.4 Hz, 1 H, 5-H-thienyl); 7.47 (dd, J6,5 = 7.7, J6,4 = 1.6 Hz, 1 H,
General Procedure for Amide Synthesis: Hydroxybenzotriazole
6-H) ppm. 13C NMR (125.7 MHz, CD3OD): δ = 38.2 (CH2); 63.6 (95 mg, 0.71 mmol, 1.5 equiv.), 1-ethyl-3-[3-(dimethylamino)propyl]-
(CH2-5Ј); 72.6 (CH-3Ј); 75.9 (CH-2Ј); 84.8 (CH-1Ј); 85.3 (CH-4Ј); carbodiimide (136 mg, 0.71 mmol, 1.5 equiv.) and starting nucleo-
126.4 (CH-5-thienyl); 127.3 (CH-4); 127.17 and 127.18 (CH-3,4-
thienyl); 129.0 (CH-5); 131.7 (CH-6); 132.1 (CH-3); 135.8 (C-2); (4 mL), and the mixture was stirred at room temp. for 60 min. Then
138.3 (C-1); 143.8 (C-2-furyl) ppm. HRMS (ESI) for C16H18O4S: a solution of the amine source (0.94 mmol, 2.0 equiv.) and Et3N
[M + Na]+ calcd. 329.0818, found 329.0817. IR (KBr): ν = 3106, (0.5 mL) in dry DCM (2 mL) were added, and the reaction mixture
side 4k (285 mg, 0.47 mmol, 1.0 equiv.) were dissolved in DCM
˜
3090, 3065, 1601, 1585, 1531, 1484, 1457, 1427, 1350, 1247, 1112,
was stirred for another 30 min. The reaction mixture was then
quenched by pouring into a solution of NaHCO3 (50 mL), ex-
tracting with DCM (3ϫ 50 mL) and drying with Na2SO4. After
evaporation of the solvents, the crude product was chromato-
graphed on silica gel eluting with a gradient of hexanes to 20%
EtOAc in hexanes to give free C-ribonucleosides 4l–o.
1048, 1030, 849, 775, 687, 610 cm–1.
1-Deoxy-1β-[2-(2-furyl)benzyl]-D-ribofuranose (7j): Compound 7j
was prepared from 4j (330 mg, 0.52 mmol) according to the general
procedure (method A) in 88% yield as a yellow solid. 1H NMR
(500 MHz, CD3OD): δ = 3.05 (dd, Jgem = 14.3, JCH2a,1Ј = 7.7 Hz,
1 H, CH2a); 3.17 (dd, Jgem = 14.3, JCH2b,1Ј = 5.3 Hz, 1 H, CH2b); 2,3,5-Tri-O-(tert-butyldimethylsilyl)-1β-(2-carbamoylbenzyl)-1-
3.57 (dd, Jgem = 11.9, J5Јa,4Ј = 4.8 Hz, 1 H, 5Ј-Ha); 3.67 (dd, Jgem deoxy- -ribofuranose (4l): Compound 4l was prepared from 4k
= 11.9, J5Јb,4Ј = 3.6 Hz, 1 H, 5Ј-Hb); 3.76 (br. ddd, J4Ј,3Ј = 5.3, (350 mg, 0.57 mmol) and ammonium chloride (61 mg, 1.14 mmol)
D
J4Ј,5Јa = 5.0, J4Ј,5Јb = 3.6 Hz, 1 H, 4Ј-H); 3.80 (t, J2Ј,1Ј = J2Ј,3Ј
5.5 Hz, 1 H, 2Ј-H); 3.93 (t, J3Ј,2Ј = J3Ј,4Ј = 5.5 Hz, 1 H, 3Ј-H); 4.01
(dt, J1Ј,CH2a = 7.7, J1Ј,CH2b = J1Ј,2Ј = 5.3 Hz, 1 H, 1Ј-H); 6.52 (dd,
=
according to the general procedure for amide synthesis in 94% yield
as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 0.03, 0.07,
0.08, 0.10 and 0.12 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.89, 0.92 and 0.95
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
T. Kubelka, L. Slaveˇtínská, M. Hocek
[3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.97–3.07 (m, 2 H, CH2); 3.54–3.61 (m, + H]+ calcd. 638.4087, found 638.4087. IR (CCl ): ν = 3065, 3022,
FULL PAPER
˜
4
2 H, 5Ј-H); 3.80 (dd, J2Ј,1Ј = 8.3, J2Ј,3Ј = 4.8 Hz, 1 H, 2Ј-H); 3.86
2955, 2896, 1645, 1602, 1578, 1503, 1485, 1472, 1463, 1447, 1405,
(td, J4Ј,5Јa = J4Ј,5Јb = 3.3, J4Ј,3Ј = 1.7 Hz, 1 H, 4Ј-H); 3.98 (dd, J3Ј,4Ј 1393, 1361, 1253, 1188, 1079, 1023, 1004, 940, 838, 702, 681,
= 4.8, J3Ј,4Ј = 1.7 Hz, 1 H, 3Ј-H); 4.12 (br. td, J1Ј,2Ј = J1Ј,CH2 = 8.6,
J1Ј,CH2 = 4.4 Hz, 1 H, 1Ј-H); 5.71 (br. s, 1 H, NH2a); 7.28 (m, 1 H,
4-H); 7.30 (br. d, J6,5 = 7.4 Hz, 1 H, 6-H); 7.42 (m, 1 H, 5-H); 7.67
(m, 1 H, 3-H); 7.99 (br. s, 1 H, NH2b) ppm. 13C NMR (125.7 MHz,
CDCl3): δ = –5.5, –5.4, –4.6, –4.5, –4.3 and –4.0 (CH3Si); 18.0; 18.1
and 18.3 [(CH3)3C]; 25.8, 25.9 and 26.0 [(CH3)3C]; 36.6 (CH2); 63.3
(CH2-5Ј); 73.5 (CH-3Ј); 76.5 (CH-2Ј); 83.0 (CH-1Ј); 86.7 (CH-4Ј);
126.7 (CH-4); 129.2 (CH-3); 130.0 (CH-6); 130.5 (CH-5); 136.0 and
136.1 (C-1, 2); 171.6 (CO) ppm. HRMS (ESI) for C31H59NO5Si3:
655 cm–1.
1β-[2-(N-Benzylcarbamoyl)benzyl]-2,3,5-tri-O-(tert-butyldimethyl-
silyl)-1-deoxy-D-ribofuranose (4o): Compound 4o was prepared
from 4k (330 mg, 0.54 mmol) and benzylamine (118 μL,
1.08 mmol) according to the general procedure for amide synthesis
in 97% yield as a colorless oil. H NMR (500 MHz, CDCl3): δ =
0.00, 0.02, 0.03, 0.07, 0.076 and 0.079 (6ϫ s, 6 ϫ 3 H, CH3Si); 0.88,
0.89 and 0.94 [3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.89 (dd, Jgem = 14.0,
1
JCH2a,1Ј = 9.7 Hz, 1 H, CH2a); 3.05 (dd, Jgem = 14.0, JCH2b,1Ј
=
[M + H]+ calcd. 610.3774, found 610.3775. IR (CCl ): ν = 3532,
˜
4
3.1 Hz, 1 H, CH2b); 3.32 (dd, Jgem = 10.8, J5Јa,4Ј = 5.5 Hz, 1 H, 5Ј-
Ha); 3.42 (dd, Jgem = 10.8, J5Јb,4Ј = 4.5 Hz, 1 H, 5Ј-Hb); 3.66 (dd,
J2Ј,1Ј = 7.8, J2Ј,3Ј = 4.6 Hz, 1 H, 2Ј-H); 3.81 (ddd, J4Ј,5Јa = 5.5, J4Ј,5Јb
= 4.5, J4Ј,3Ј = 2.0 Hz, 1 H, 4Ј-H); 3.93 (dd, J3Ј,4Ј = 4.6, J3Ј,4Ј
2.0 Hz, 1 H, 3Ј-H); 4.09 (ddd, J1Ј,CH2a = 9.7, J1Ј,2Ј = 7.8, J1Ј,CH2b
3485, 3411, 3380, 3334, 3180, 3074, 3022, 2955, 2897, 1678, 1604,
1578, 1490, 1472, 1463, 1450, 1408, 1389, 1362, 1256, 1152, 1124,
1086, 1015, 1006, 940, 882, 839, 680 cm–1.
=
=
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-[2-(N-methyl-
3.0 Hz, 1 H, 1Ј-H); 4.60 (dd, Jgem = 15.1, JCH2a,NH = 5.9 Hz, 1 H,
CH2a-Ph); 4.66 (dd, Jgem = 15.1, JCH2b,NH = 6.2 Hz, 1 H, CH2b-
Ph); 7.23–7.36 (m, 7 H, 4, 6-H, o,m,p-Ph); 7.38 (br. td, J5,4Ј = J5,6
= 7.5, J5,3 = 1.5 Hz, 1 H, 5-H); 7.58 (dd, J3,4 = 7.7, J3,5 = 1.5 Hz,
1 H, 3-H); 7.77 (br. t, JNH,CH2a = JNH,CH2b = 6.0 Hz, 1 H,
NH) ppm. 13C NMR (125.7 MHz, CDCl3): δ = –5.41, –5.39, –4.7,
–4.5, –4.3 and –4.0 (CH3Si); 18.0, 18.1 and 18.3 [(CH3)3C]; 25.8,
25.9 and 26.0 [(CH3)3C]; 36.2 (CH2); 43.4 (CH2-Ph); 63.6 (CH2-
5Ј); 73.1 (CH-3Ј); 75.8 (CH-2Ј); 82.8 (CH-1Ј); 85.8 (CH-4Ј); 126.6
(CH-4); 127.2 (CH-p-Ph); 127.3 (CH-o-Ph); 128.6 (CH-m-Ph);
128.7 (CH-3); 129.9 (CH-5); 130.3 (CH-6); 135.9 (C-1); 137.2 (C-
2); 138.9 (C-i-Ph); 169.5 (CO) ppm. HRMS (ESI) for
carbamoyl)benzyl]-D-ribofuranose (4m): Compound 4m was pre-
pared from 4k (285 mg, 0.47 mmol) and methylamine hydrochlor-
ide (64 mg, 0.94 mmol) according to the general procedure for
amide synthesis in 91 % yield as a colorless oil. 1H NMR
(500 MHz, CDCl3): δ = 0.04, 0.07, 0.078, 0.080, 0.09 and 0.10 (6ϫ
s, 6 ϫ 3 H, CH3Si); 0.89, 0.92 and 0.94 [3ϫ s, 3 ϫ 9 H, (CH3)3C];
2.79 (dd, Jgem = 13.9, JCH2a,1Ј = 10.0 Hz, 1 H, CH2a); 2.93 (d,
JCH3,NH = 4.7 Hz, 3 H, CH3NH); 3.01 (dd, Jgem = 13.9, JCH2b,1Ј
=
2.7 Hz, 1 H, CH2b); 3.55 (dd, Jgem = 11.0, J5Јa,4Ј = 4.4 Hz, 1 H, 5Ј-
Ha); 3.60 (dd, Jgem = 11.0, J5Јb,4Ј = 4.1 Hz, 1 H, 5Ј-Hb); 3.76 (dd,
J2Ј,1Ј = 8.0, J2Ј,3Ј = 4.6 Hz, 1 H, 2Ј-H); 3.87 (td, J4Ј,5Јa = J4Ј,5Јb
=
4.3, J4Ј,3Ј = 1.9 Hz, 1 H, 4Ј-H); 3.98 (dd, J3Ј,4Ј = 4.6, J3Ј,4Ј = 1.9 Hz,
1 H, 3Ј-H); 4.09 (ddd, J1Ј,CH2a = 10.0, J1Ј,2Ј = 8.0, J1Ј,CH2b = 2.6 Hz,
1 H, 1Ј-H); 7.26 (m, 1 H, 4-H); 7.27 (m, 1 H, 6-H); 7.37 (m, 1 H,
5-H); 7.48 (br. s, 1 H, NH); 7.56 (m, 1 H, 3-H) ppm. 13C NMR
(125.7 MHz, CDCl3): δ = –5.5, –5.3, –4.7, –4.5, –4.4 and –4.0
(CH3Si); 18.0; 18.1 and 18.4 [(CH3)3C]; 25.8, 25.9 and 26.0
[(CH3)3C]; 26.3 (CH3NH); 36.5 (CH2); 63.8 (CH2-5Ј); 73.2 (CH-
3Ј); 76.1 (CH-2Ј); 83.2 (CH-1Ј); 86.1 (CH-4Ј); 126.6 (CH-4); 128.8
(CH-3); 129.8 (CH-5); 130.1 (CH-6); 135.7 (C-1); 137.5 (C-2); 170.1
(CO) ppm. HRMS (ESI) for C32H61NO5Si3: [M + H]+ calcd.
C
38H65NO5Si3: [M + H]+ calcd. 700.4243, found 700.4245. IR
(KBr): ν = 3089, 3067, 3031, 2955, 2896, 1603, 1587, 1577, 1543,
˜
1500, 1482, 1472, 1463, 1455, 1406, 1389, 1361, 1275, 1256, 1089,
1025, 1005, 941, 839, 699, 680 cm–1.
General Procedure for the Deprotection of the TBS Group.
Method B: A mixture of CF3COOH/H2O (9:1) (2 mL) was added
to silylated compounds 4k–o (0.50 mmol), and the resulting homo-
geneous mixtures were stirred at room temp. for 4 h. After the reac-
tion was complete (monitored by TLC eluting with CHCl3/MeOH,
10:1), the solvents were removed under reduced pressure and the
crude products co-evaporated with 3ϫ 50 mL of toluene. Subse-
quent purification by chromatography on silica gel (20 g) eluting
with a gradient of CHCl3 to 15% MeOH in CHCl3 afforded the
free C-ribonucleosides 7k–o.
624.3930, found 624.3931. IR (CCl ): ν = 3463, 3351, 3069, 3021,
˜
4
2956, 2897, 1663, 1676, 1603, 1580, 1552, 1513, 1483, 1472, 1463,
1412, 1390, 1362, 1280, 1257, 1154, 1126, 1105, 1088, 1005, 940,
883, 838, 680 cm–1.
2,3,5-Tri-O-(tert-butyldimethylsilyl)-1-deoxy-1β-[2-(N,N-dimethyl-
carbamoyl)benzyl]-D-ribofuranose (4n): Compound 4n was prepared
1β-(2-Carboxybenzyl)-1-deoxy-D-ribofuranose (7k): Compound 7k
from 4k (180 mg, 0.30 mmol) and dimethylamine hydrochloride
(50 mg, 0.60 mmol) according to the general procedure for amide
synthesis in 88 % yield as a colorless oil. 1H NMR (500 MHz,
[D6]DMSO): δ = –0.09, –0.04, 0.06, 0.07 and 0.09 (6ϫ s, 6 ϫ 3 H,
CH3Si); 0.84, 0.87 and 0.90 [3ϫ s, 3 ϫ 9 H, (CH3)3C]; 2.50–2.75
was prepared from 4k (250 mg, 0.41 mmol) according to the gene-
ral procedure (method B) in 79% yield as a white solid. H NMR
(500 MHz, CD3OD): δ = 3.21 (dd, Jgem = 13.9, JCH2a,1Ј = 7.5 Hz,
1 H, CH2a); 3.39 (dd, Jgem = 13.8, JCH2b,1Ј = 5.0 Hz, 1 H, CH2b);
3.53 (dd, Jgem = 12.0, J5Јa,4Ј = 4.9 Hz, 1 H, 5Ј-Ha); 3.62 (dd, Jgem
1
(m, 2 H, CH2); 2.72 and2.98 [2s, 2ϫ 3 H, (CH3)2N]; 3.58 (dd, Jgem = 12.0, J5Јb,4Ј = 3.6 Hz, 1 H, 5Ј-Hb); 3.76 (td, J4Ј,5Јa = J4Ј,3Ј = 5.1,
= 11.3, J5Јa,4Ј = 3.5 Hz, 1 H, 5Ј-Ha); 3.65 (dd, Jgem = 11.3, J5Јb,4Ј J4Ј,5Јb = 3.7 Hz, 1 H, 4Ј-H); 3.77 (t, J2Ј,3Ј = J2Ј,1Ј = 5.4 Hz, 1 H, 2Ј-
3.6 Hz, 1 H, 5Ј-Hb); 3.72 (dt, J4Ј,3Ј = 4.7, J4Ј,5Јa = J4Ј,5Јb = 3.5 Hz, H); 3. 89 (t, J3Ј,4Ј = J3Ј,2Ј = 5.4 Hz, 1 H, 3Ј-H); 4.04 (dt, J1Ј,CH2a
1 H, 4Ј-H); 3.87 (m, 1 H, 1Ј-H); 3.91 (br. t, J2Ј,1Ј = J2Ј,3Ј = 4.3 Hz, 7.5, J1Ј,2Ј = J1Ј,CH2b = 5.2 Hz, 1 H, 1Ј-H); 7.28 (ddd, J4,3 = 7.8, J4,5
=
=
1 H, 2Ј-H); 4.03 (br. t, J3Ј,4Ј = J3Ј,2Ј = 4.3 Hz, 1 H, 3Ј-H); 7.15 (br.
dd, J3,5 = 7.5, J3,5 = 1.5 Hz, 1 H, 3-H); 7.26 (td, J4,5 = J4,3 = 7.5,
= 7.1, J4,6 = 1.6 Hz, 1 H, 4-H); 7.40 (br. dd, J6,5 = 7.7, J6,4
=
1.6 Hz, 1 H, 6-H); 7.43 (ddd, J5,6 = 7.7, J5,4 = 7.1, J5,3 = 1.5 Hz, 1
J4,6 = 1.5 Hz, 1 H, 4-H); 7.32 (td, J5,6 = J5,4 = 7.4, J5,3 = 1.5 Hz, H, 5-H); 7.83 (dd, J3,4 = 7.8, J3,5 = 1.5 Hz, 1 H, 3-H) ppm. 13C
1 H, 5-H); 7.36 (dd, J6,5 = 7.7, J6,4 = 1.5 Hz, 1 H, 6-H) ppm. 13C
NMR (125.7 MHz, [D6]DMSO): δ = –5.5, –5.4, –4.84, –4.76, –4.6
NMR (125.7 MHz, CD3OD): δ = 38.4 (CH2); 63.6 (CH2-5Ј); 72.7
(CH-3Ј); 75.7 (CH-2Ј); 84.8 (CH-1Ј); 85.3 (CH-4Ј); 127.3 (CH-4);
and –4.5 (CH3Si); 17.6, 17.7 and 18.0 [(CH3)3C]; 25.75, 25.77 and 131.3 (CH-3); 132.4 (CH-5); 133.0 (CH-6); 133.2 (C-2); 140.4 (C-
25.8 [(CH3)3C]; 34.0 and 38.1 [(CH3)2N]; 36.8 (CH2); 62.5 (CH2- 1); 172.2 (CO) ppm. HRMS (ESI) for C13H16O6: [M – H]– calcd.
5Ј); 71.9 (CH-3Ј); 75.3 (CH-2Ј); 82.4 (CH-1Ј); 83.2 (CH-4Ј); 125.8
267.0874, found 267.0874. IR (KBr): ν = 3419, 3392, 3335, 3280,
˜
(CH-3); 126.2 (CH-4); 128.3 (CH-5); 130.4 (CH-6); 134.9 (C-1); 3240, 3079, 2660, 2573, 2542, 2521, 1728, 1600, 1578, 1498, 1445,
137.0 (C-2), 169.9 (CO) ppm. HRMS (ESI) for C33H63NO5Si3: [M 1435, 1314, 1304, 1117, 1076, 1051, 1039, 918, 783 cm–1.
10
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
Carba Analogues of Phosphoribosylanthranilate
1β-(2-Carbamoylbenzyl)-1-deoxy- -ribofuranose (7l): Compound 7l
D
ing to the general procedure (method B) in 76% yield as a white
was prepared from 4l (275 mg, 0.45 mmol) according to the general
solid. 1H NMR (500 MHz, [D6]DMSO): δ = 2.82 (dd, Jgem = 14.1,
procedure (method B) in 74 % yield as a white solid. 1H NMR
JCH2a,1Ј = 8.5 Hz, 1 H, CH2a); 3.03 (dd, Jgem = 14.1, JCH2b,1Ј =
(500 MHz, [D6]DMSO): δ = 2.85 (dd, Jgem = 14.1, JCH2a,1Ј
=
4.5 Hz, 1 H, CH2b); 3.31 (br. ddd, Jgem = 11.5, J5Јa,OH = 5.7, J5Јa,4Ј
= 5.2 Hz, 1 H, 5Ј-Ha); 3.39 (ddd, Jgem = 11.5, J5Јb,OH = 5.5, J5Јb,4Ј
= 4.1 Hz, 1 H, 5Ј-Hb); 3.57 (br. q, J2Ј,1Ј = J2Ј,3Ј = J2Ј,OH = 5.8 Hz,
1 H, 2Ј-H); 3.58 (m, 1 H, 4Ј-H); 3.73 (br. q, J3Ј,2Ј = J3Ј,4Ј = J3Ј,OH
8.3 Hz, 1 H, CH2a); 3.05 (dd, Jgem = 14.1, JCH2b,1Ј = 4.6 Hz, 1 H,
CH2b); 3.33 (ddd, Jgem = 11.6, J5Јa,OH = 6.0, J5Јa,4Ј = 5.1 Hz, 1 H,
5Ј-Ha); 3.40 (ddd, Jgem = 11.6, J5Јb,OH = 5.5, J5Јb,4Ј = 4.2 Hz, 1 H,
5Ј-Hb); 3.59 (br. q, J4Ј,3Ј = J4Ј,5Јa = J4Ј,5Јb = 4.6 Hz, 1 H, 4Ј-H); 3.61 = 5.1 Hz, 1 H, 3Ј-H); 3.86 (ddd, J1Ј,CH2a = 8.4, J1Ј,2Ј = 6.0, J1Ј,CH2b
(br. q, J2Ј,1Ј = J2Ј,3Ј = J2Ј,OH = 5.7 Hz, 1 H, 2Ј-H); 3.75 (br. q, J3Ј,2Ј = 4.5 Hz, 1 H, 1Ј-H); 4.44 (d, JCH2,NH = 6.1 Hz, 2 H, CH2-Ph);
= J3Ј,4Ј = J3Ј,OH = 5.2 Hz, 1 H, 3Ј-H); 3.87 (ddd, J1Ј,CH2a = 8.3,
J1Ј,2Ј = 5.9, J1Ј,CH2b = 4.6 Hz, 1 H, 1Ј-H); 4.59 (t, JOH,5Јa = JOH,5Јb
4.62 (t, JOH,5Јa = JOH,5Јb = 5.6 Hz, 1 H, O5Ј-H); 4.72 (d, JOH,3Ј
5.4 Hz, 1 H, O3Ј-H); 4.73 (d, JOH,2Ј = 5.9 Hz, 1 H, O2Ј-H); 7.22–
=
= 5.7 Hz, 1 H, O5Ј-H); 4.71 (d, JOH,3Ј = 5.4 Hz, 1 H, O3Ј-H); 4.74 7.29 (m, 2 H, 4-H, H-p-Ph); 7.32–7.39 (m, 3 H,3,5,6-H); 8.77 (t,
(d, JOH,2Ј = 5.8 Hz, 1 H, O2Ј-H); 7.23 (m, 1 H, 4-H); 7.30–7.36 JNH,CH2 = 6.1 Hz, 1 H, NH) ppm. 13C NMR (125.7 MHz,
(m, 4 H,3,5,6-H, NH2a); 7.72 (br. s, 1 H, NH2b) ppm. 13C NMR
(125.7 MHz, [D6]DMSO): δ = 36.6 (CH2); 62.2 (CH2-5Ј); 71.2 (CH-
3Ј); 74.4 (CH-2Ј); 82.7 (CH-1Ј); 84.4 (CH-4Ј); 125.9 (CH-4); 127.4
[D6]DMSO): δ = 36.5 (CH2); 42.6 (CH2-Ph); 62.1 (CH2-5Ј); 71.1
(CH-3Ј); 74.4 (CH-2Ј); 82.8 (CH-1Ј); 84.4 (CH-4Ј); 126.0 (CH-4);
126.9 (CH-p-Ph); 127.4 (CH-o-Ph); 127.5 (CH-3); 128.5 (CH-m-
(CH-3); 129.2 (CH-5); 130.7 (CH-6); 136.4 (C-1); 137.7 (C-2); 171.4 Ph); 129.3 (CH-5); 130.60 (CH-6); 136.59 (C-1); 137.5 (C-2); 139.8
(CO) ppm. HRMS (ESI) for C13H17NO5: [M + Na]+ calcd.
(C-i-Ph); 169.4 (CO) ppm. HRMS (ESI) for C20H23NO5: [M +
290.0999, found 290.0999. IR (KBr): ν = 3396, 3278, 3221, 3074,
Na]+ calcd 380.1468, found 380.1467. IR (KBr): ν = 3450, 3283,
˜
˜
3030, 1652, 1608, 1574, 1492, 1450, 1422, 1099, 1045, 761, 630,
3087, 3064, 3061, 1640, 1629, 1597, 1578, 1541, 1496, 1487, 1453,
599 cm–1.
1284, 1209, 1105, 1030, 762, 698, 596 cm–1.
1-Deoxy-1β-[2-(N-methylcarbamoyl)benzyl]-
D
-ribofuranose (7m):
General Procedure for the Synthesis of 5Ј-Monophosphates: Starting
C-ribonucleoside (56 mg, 0.19 mmol) was placed in an argon-
purged flask and dried at 80 °C for 2 h. Then PO(OMe)3 (0.5 mL)
and POCl3 (27 μL, 0.28 mmol) were added successively at 0°C. The
Compound 7m was prepared from 4m (253 mg, 0.41 mmol) accord-
ing to the general procedure (method B) in 79% yield as a white
solid. 1H NMR (500 MHz, CD3OD): δ = 2.87 and 3.11 [2ϫ s, 2 ϫ
3 H, (CH3)2N]; 2.60–3.10 (m, 2 H, CH2); 3.52 (dd, Jgem = 11.9, reaction mixture was stirred at 0 °C for 3 h and then quenched by
J5Јa,4Ј = 4.7 Hz, 1 H, 5Ј-Ha); 3.63 (dd, Jgem = 11.9, J5Јb,4Ј = 3.7 Hz,
1 H, 5Ј-Hb); 3.71 (t, J2Ј,1Ј = J2Ј,3Ј = 5.9 Hz, 1 H, 2Ј-H); 3.75 (td,
addition of aqueous TEAB (triethylammonium bicarbonate, 2 m,
2 mL). The solvents were evaporated, and the residue was co-dis-
tilled with water several times. The product was isolated on a
J4Ј,5Јa = J4Ј,3Ј = 4.7, J4Ј,5Јb = 3.7 Hz, 1 H, 4Ј-H); 3.90 (dd, J3Ј,2Ј
=
5.7, J3Ј,4Ј = 4.7 Hz, 1 H, 3Ј-H); 3.94 (br. q, J1Ј,CH2a = J1Ј,2Ј = J1Ј,CH2b DEAE Sephadex column (300 mL) eluting with a gradient of 0–
= 6.3 Hz, 1 H, 1Ј-H); 7.19 (dd, J3,4 = 7.6, J3,5 = 1.6 Hz, 1 H, 3-H); 1.2 m TEAB, concentrated, co-distilled with water several times,
7.29 (td, J4,3 = J4,5 = 7.5, J4,6 = 1.3 Hz, 1 H, 4-H); 7.37 (td, J5,6
=
converted into salt form (Dowex 50WX8 in Na+ cycle) and lyophi-
J5,4 = 7.6, J5,3 = 1.5 Hz, 1 H, 5-H); 7.46 (br. d, J6,5 = 7.8 Hz, 1 H,
6-H) ppm. 13C NMR (125.7 MHz, CD3OD): δ = 35.1 and 39.5
[(CH3)2N]; 37.7 (CH2); 63.5 (CH2-5Ј); 72.6 (CH-3Ј); 76.0 (CH-2Ј);
84.4 (CH-1Ј); 85.9 (CH-4Ј); 127.2 (CH-3); 127.6 (CH-4); 130.3
(CH-5); 131.9 (CH-6); 136.8 (C-1); 137.8 (C-2); 173.9 (CO) ppm.
HRMS (ESI) for C14H19NO5: [M + Na]+ calcd. 304.1155, found
lized to give monophosphates 8e,f,l,n,p.
1β-(2-Aminobenzyl)-1-deoxy-D-ribofuranose Monophosphate (8e):
Compound 8e was prepared from 7e (80 mg, 0.33 mmol) according
to the general procedure for 5Ј-monophosphate synthesis in 46%
1
yield as a white powder. H NMR (500 MHz, D2O): δ = 2.83 (dd,
Jgem = 14.7, JCH2a,1Ј = 8.2 Hz, 1 H, CH2a); 2.94 (dd, Jgem = 14.7,
JCH2b,1Ј = 4.1 Hz, 1 H, CH2b); 3.84 (m, 2 H, 5Ј-H); 3.99 (br. q,
J4Ј,3Ј = J4Ј,5Јa = J4Ј,5Јb = 4.4 Hz, 1 H, 4Ј-H); 4.05 (br. t, J2Ј,1Ј = J2Ј,3Ј
= 5.6 Hz, 1 H, 2Ј-H); 4.11 (ddd, J1Ј,CH2a = 8.2, J1Ј,2Ј = 5.8, J1Ј,CH2b
304.1155. IR (KBr): ν = 3421, 3280, 3100, 3070, 3030, 1631, 1601,
˜
1575, 1558, 1487, 1460, 1115, 1106, 1050, 763, 603 cm–1.
1-Deoxy-1β-[2-(N,N-dimethylcarbamoyl)benzyl]-D-ribofuranose
(7n): Compound 7n was prepared from 4n (270 mg, 0.42 mmol) = 4.1 Hz, 1 H, 1Ј-H); 4.12 (br. t, J3Ј,2Ј = J3Ј,4Ј = 5.1 Hz, 1 H, 3Ј-
according to the general procedure (method B) in 76% yield as a H); 7.88–6.93 (m, 2 H, 5,3-H); 7.16 (br. td, J4,3 = J4,5 = 7.7, J4,6
=
1
white solid. H NMR (500 MHz, CD3OD): δ = 2.87 and 3.11 [2ϫ
1.6 Hz, 1 H, 4-H); 7.22 (br. dd, J6,5 = 7.9, J6,4 = 1.6 Hz, 1 H, 6-
s, 2 ϫ 3 H, (CH3)2N]; 2.60–3.10 (m, 2 H, CH2); 3.52 (dd, Jgem
11.9, J5Јa,4Ј = 4.7 Hz, 1 H, 5Ј-Ha); 3.63 (dd, Jgem = 11.9, J5Јb,4Ј
=
=
H) ppm. 13C NMR (125.7 MHz, D2O): δ = 37.1 (CH2); 66.8 [d,
J(C,P) = 4.8 Hz, CH2-5Ј]; 73.9 (CH-3Ј); 76.8 (CH-2Ј); 85.3 (d, JC,P
3.7 Hz, 1 H, 5Ј-Hb); 3.71 (t, J2Ј,1Ј = J2Ј,3Ј = 5.9 Hz, 1 H, 2Ј-H); 3.75 = 8.5 Hz, CH-4Ј); 86.0 (CH-1Ј); 120.4 (CH-3); 123.1 (CH-5); 127.5
(td, J4Ј,5Јa = J4Ј,3Ј = 4.7, J4Ј,5Јb = 3.7 Hz, 1 H, 4Ј-H); 3.90 (dd, J3Ј,2Ј (C-1); 130.7 (CH-4); 133.7 (CH-6); 146.8 (C-2) ppm. 31P NMR
= 5.7, J3Ј,4Ј = 4.7 Hz, 1 H, 3Ј-H); 3.94 (br. q, J1Ј,CH2a = J1Ј,2Ј
=
( 2 0 2 . 3 M H z , D 2 O ) : δ = 3 . 3 3 p p m . H R M S ( E S I ) f o r
J1Ј,CH2b = 6.3 Hz, 1 H, 1Ј-H); 7.19 (dd, J3,4 = 7.6, J3,5 = 1.6 Hz, 1 C12H17NNaO7P: [M – Na]– calcd. 318.0748, found 318.0750. IR
H, 3-H); 7.29 (td, J4,3 = J4,5 = 7.5, J4,6 = 1.3 Hz, 1 H, 4-H); 7.37
(td, J5,6 = J5,4 = 7.6, J5,3 = 1.5 Hz, 1 H, 5-H); 7.46 (br. d, J6,5
(KBr): ν = 3430, 3252, 2707, 1628, 1603, 1586, 1498, 1458, 1137,
˜
=
1107, 1072, 1046, 978, 916, 831, 753 cm–1.
7.8 Hz, 1 H, 6-H) ppm. 13C NMR (125.7 MHz, CD3OD): δ = 35.1
and 39.5 [(CH3)2N]; 37.7 (CH2); 63.5 (CH2-5Ј); 72.6 (CH-3Ј); 76.0
(CH-2Ј); 84.4 (CH-1Ј); 85.9 (CH-4Ј); 127.2 (CH-3); 127.6 (CH-4);
130.3 (CH-5); 131.9 (CH-6); 136.8 (C-1); 137.8 (C-2); 173.9
(CO) ppm. HRMS (ESI) for C15H21NO5: [M + Na]+ calcd.
1β-[2-(Dimethylamino)benzyl]-1-deoxy-D-ribofuranose Monophos-
phate (8f): Compound 8f was prepared from 7f (39 mg, 0.15 mmol)
according to the general procedure for 5Ј-monophosphate synthesis
in 33% yield as a white powder. 1H NMR (500 MHz, D2O): δ =
2.85 [s, 6 H, (CH3)2N]; 3.04 (dd, Jgem = 14.9, JCH2a,1Ј = 8.8 Hz, 1
H, CH2a); 3.10 (dd, Jgem = 14.9, JCH2b,1Ј = 4.3 Hz, 1 H, CH2b);
3.86 (m, 2 H, 5Ј-H); 3.99 (q, J4Ј,3Ј = J4Ј,5Јa = J4Ј,5Јb = 4.4 Hz, 1 H,
4Ј-H); 4.08 (br. t, J2Ј,1Ј = J2Ј,3Ј = 5.8 Hz, 1 H, 2Ј-H); 4.15 (ddd,
J1Ј,CH2a = 8.8, J1Ј,2Ј = 6.1, J1Ј,CH2b = 4.3 Hz, 1 H, 1Ј-H); 4.23 (br.
t, J3Ј,2Ј = J3Ј,4Ј = 5.1 Hz, 1 H, 3Ј-H); 7.27 (td, J5,4 = J5,6 = 7.4, J5,3
318.1312, found 318.1311. IR (KBr): ν = 3431, 3072, 3025, 2923,
˜
2869, 2860, 1624, 1600, 1580, 1509, 1482, 1458, 1444, 1400, 1120,
1101, 1045, 765, 597 cm–1.
1β-[2-(N-Benzylcarbamoyl)benzyl]-1-deoxy-
D-ribofuranose (7o):
Compound 7o was prepared from 4o (303 mg, 0.43 mmol) accord-
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
11

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
T. Kubelka, L. Slaveˇtínská, M. Hocek
132.5 (CH-5); 134.1 (CH-6); 137.1 (C-1); 138.4 (C-2); 175.9
FULL PAPER
= 1.4 Hz, 1 H, 5-H); 7.39 (br. ddd, J4,3 = 8.2, J4,5 = 7.3, J4,6
=
1.7 Hz, 1 H, 4-H); 7.44 (dd, J3,4 = 8.2, J3,5 = 1.3 Hz, 1 H, 3-H); (CO) ppm. 31P NMR (202 MHz, D2O): δ = 2.51 ppm. HRMS
7.46 (dd, J6,5 = 7.6, J6,4 = 1.7 Hz, 1 H, 6-H) ppm. 13C NMR (ESI) for C15H21NaO8P: [M – Na]– calcd. 374.1010, found
(125.7 MHz, D2O): δ = 36.8 (CH2); 48.2 [(CH3)2N]; 66.4 (d, JC,P
=
374.1010. IR (KBr): ν = 3432, 3264, 3069, 1629, 1600, 1578, 1510,
˜
4.6 Hz, CH2-5Ј); 73.9 (CH-3Ј); 77.1 (CH-2Ј); 85.6 (CH-1Ј); 85.8 (d, 1483, 1445, 1400, 1193, 1118, 1102, 1073, 1046, 978, 919 cm–1.
JC,P = 8.1 Hz, CH-4Ј); 122.69 (CH-3); 128.8 (CH-5); 130.9 (CH-4);
Supporting Information (see footnote on the first page of this arti-
cle): Copies of all NMR spectra.
133.7 (CH-6); 134.7 (C-1); 152.2 (C-2) ppm. 31P NMR (202 MHz,
D2O): δ = 4.43 ppm. HRMS (ESI) for C14H21NNaO7P: [M –
Na]– calcd. 346.1061, found 346.1060. IR (KBr): ν = 3435, 3060,
˜
3000, 2824, 1782, 1695, 1599, 1579, 1570, 1494, 1453, 1305, 1188,
1134, 1099, 1050, 978, 945, 915, 767 cm–1.
Acknowledgments
1β-(2-Carbamoylbenzyl)-1-deoxy-D-ribofuranose Monophosphate
(8l): Compound 8l was prepared from 7l (56 mg, 0.21 mmol) ac-
cording to the general procedure for 5Ј-monophosphate synthesis
in 33% yield as a white powder, accompanied by 8p in 12% yield
This work was supported by the Academy of Sciences of the Czech
Republic (ASCR) (RVO 61388963), the Czech Science Foundation
(P207/11/0344 to M. H.), the Grant Agency of the ASCR
(IAA400550902 to T. K.) and the Gilead Sciences, Inc.. The inhibi-
tion of PriA isomerase was studied by Dr. Jana Tatur and Prof. M.
Wilmanns (EMBL Hamburg). The contribution of these scientists
is gratefully appreciated.
1
as a white powder. H NMR (500 MHz, D2O): δ = 3.08 (dd, Jgem
= 14.2, JCH2a,1Ј = 9.0 Hz, 1 H, CH2a); 3.20 (dd, Jgem = 14.2, JCH2b,1Ј
= 4.3 Hz, 1 H, CH2b); 3.78 (m, 2 H, 5Ј-H); 3.95 (q, J4Ј,3Ј = J4Ј,5Јa
= J4Ј,5Јb = 4.7 Hz, 1 H, 4Ј-H); 4.03 (br. t, J2Ј,1Ј = J2Ј,3Ј = 5.8 Hz, 1
H, 2Ј-H); 4.09 (ddd, J1Ј,CH2a = 9.0, J1Ј,2Ј = 6.1, J1Ј,CH2b = 4.3 Hz,
1 H, 1Ј-H); 4.15 (br. dd, J3Ј,2Ј = 5.3, J3Ј,4Ј = 4.9 Hz, 1 H, 3Ј-H);
7.38 (m, 1 H, 4-H); 7.46 (m, 1 H, 6-H); 7.49–7.54 (m, 2 H, 3,5-
H) ppm. 13C NMR (125.7 MHz, D2O): δ = 38.7 (CH2); 66.6 (d,
[1] a) U. Hommel, M. Eberhard, K. Kirschner, Biochemistry 1995,
34, 5429–5439; b) W. M. Patrick, J. M. Blackburn, FEBS J.
2005, 272, 3684–3697.
JC,P = 4.5 Hz, CH2-5Ј); 74.2 (CH-3Ј); 76.8 (CH-2Ј); 85.7 (d, JC,P
8.5 Hz, CH-4Ј); 86.0 (CH-1Ј); 129.6 (CH-4); 130.3 (CH-3); 133.5
and 138.1 (CH-5, 6); 137.8 (C-1); 138.1 (C-2); 178.2 (CO) ppm. 31
=
[2] a) M. Hann-Sax, R. Thoma, S. Schmidt, M. Hennig, K.
Kirschner, R. Sterner, Biochemistry 2002, 41, 12032–12042; b)
J. Kuper, C. Doenges, M. Wilmanns, EMBO Rep. 2005, 6, 134–
139; c) F. List, R. Sterner, M. Wilmanns, ChemBioChem 2011,
12, 1487–1494.
P
NMR (202 MHz, D2 O): δ = 4.61 ppm. HRMS (ESI) for
C13H17NNaO8P: [M – Na]– calcd. 346.0697, found 346.0697. IR
(KBr): ν = 3428, 3197, 3067, 2690, 2580, 1663, 1617, 1573, 1493,
˜
1452, 1397, 1301, 1130, 1098, 1046, 977, 916, 830, 764 cm–1.
ˇ
[3] Reviews: a) J. Stambaský, M. Hocek, P. Kocˇovský, Chem. Rev.
2009, 109, 6729–6764; b) M. F. A. Adamo, R. Pergoli, Curr.
Org. Chem. 2008, 12, 1544–1569; c) Q. P. Wu, C. Simons, Syn-
thesis 2004, 1533–1553.
1β-(2-Cyanobenzyl)-1-deoxy-
D-ribofuranose Monophosphate (8p):
1H NMR (500 MHz, D2O): δ = 3.12 (dd, Jgem = 14.2, JCH2a,1Ј
=
[4] Examples: a) D. Malyshev, Y. J. Seo, P. Ordoukhanian, F. E.
Romesberg, J. Am. Chem. Soc. 2009, 131, 14620–14621; b)
D. A. Malyshev, D. A. Pfaff, S. I. Ippoliti, G. T. Hwang, T. J.
Dwyer, F. E. Romesberg, Chem. Eur. J. 2010, 16, 12650–12659;
c) Y. J. Seo, D. A. Malyshev, T. Lavergne, P. Ordoukhanian,
F. E. Romesberg, J. Am. Chem. Soc. 2011, 133, 19878–19888.
[5] a) M. Urban, N. Joubert, M. Hocek, R. E. Alexander, R. D.
Kuchta, Biochemistry 2009, 48, 10866–10881; b) M. Urban, N.
Joubert, B. Purse, M. Hocek, R. Kuchta, Biochemistry 2010,
49, 727–735; c) T. Lund, N. Cavanaugh, N. Joubert, M. Urban,
J. Patro, M. Hocek, R. D. Kuchta, Biochemistry 2011, 50,
7243–7250.
8.3 Hz, 1 H, CH2a); 3.25 (dd, Jgem = 14.2, JCH2b,1Ј = 4.8 Hz, 1 H,
CH2b); 3.81 (m, 2 H, 5Ј-H); 4.00 (q, J4Ј,3Ј = J4Ј,5Јa = J4Ј,5Јb = 4.8 Hz,
1 H, 4Ј-H); 4.09 (br. t, J2Ј,1Ј = J2Ј,3Ј = 5.7 Hz, 1 H, 2Ј-H); 4.14 (ddd,
J1Ј,CH2a = 8.3, J1Ј,2Ј = 6.0, J1Ј,CH2b = 4.8 Hz, 1 H, 1Ј-H); 4.19 (br.
t, J3Ј,2Ј = J3Ј,4Ј = 5.0 Hz, 1 H, 3Ј-H); 7.45 (td, J4,3 = J4,5 = 7.7, J4,6
= 1.1 Hz, 1 H, 4-H); 7.58 (br. d, J6,5 = 7.8 Hz, 1 H, 6-H); 7.68 (td,
J5,4 = J5,6 = 7.7, J5,3 = 1.4 Hz, 1 H, 5-H); 7.78 (dd, J3,4 = 7.8, J3,5
= 1.3 Hz, 1 H, 3-H) ppm. 13C NMR (125.7 MHz, D2O): δ = 40.4
(CH2); 66.7 (d, JC,P = 4.8 Hz, CH2-5Ј); 74.3 (CH-3Ј); 76.8 (CH-2Ј);
84.8 (CH-1Ј); 85.8 (d, JC,P = 8.3 Hz, CH-4Ј); 114.3 (C-2); 121.7
(CN); 130.1 (CH-4); 133.5 (CH-6); 135.9 (CH-3); 136.3 (CH-5);
144.4 (C-1) ppm. 31P NMR (202 MHz, D2O): δ = 4.62 ppm.
HRMS (ESI) for C13H15NNaO7P: [M – Na]– calcd. 328.0592,
[6] a) M. Hocek, R. Pohl, B. Klepetárˇová, Eur. J. Org. Chem. 2005,
4525–4528; b) M. Urban, R. Pohl, B. Klepetárˇová, M. Hocek,
J. Org. Chem. 2006, 71, 7322–7328; c) N. Joubert, R. Pohl, B.
Klepetárˇová, M. Hocek, J. Org. Chem. 2007, 72, 6797–6805; d)
found 328.0591. IR (KBr): ν = 3435, 3072, 2800, 2700, 2570, 2226,
˜
1602, 1578, 1489, 1450, 1303, 1213, 1180, 1136, 1097, 1046, 978,
ˇ
M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek, Eur. J. Org.
916, 830, 761, 559 cm–1.
Chem. 2008, 1689–1704; e) N. Joubert, M. Urban, R. Pohl,
M. Hocek, Synthesis 2008, 1918–1932; f) J. Bárta, R. Pohl, B.
Klepetárˇová, N. P. Ernsting, M. Hocek, J. Org. Chem. 2008,
73, 3798–3806; g) T. Kubelka, L. Slaveˇtínská, B. Klepetárˇová,
1-Deoxy-1β-[2-(N,N-dimethylcarbamoyl)benzyl]-D-ribofuranose Mo-
nophosphate (8n): Compound 8n was prepared from 7n (56 mg,
0.19 mmol) according to the general procedure for 5Ј-monophos-
phate synthesis in 49 % yield as a white powder. 1H NMR
(500 MHz, D2O): δ = 2.83 (br. m, 1 H, CH2a), 2.93 [s, 3 H,
(CH3)2N]; 3.05 (m, 1 H, CH2b); 3.15 [s, 3 H, (CH3)2N]; 3.88 (m, 2
H, 5Ј-H); 3.98 (br. q, J4Ј,5Јa = J4Ј,3Ј = J4Ј,5Јb = 4.4 Hz, 1 H, 4Ј-H);
3.99 (t, J2Ј,1Ј = J2Ј,3Ј = 5.7 Hz, 1 H, 2Ј-H); 4.09 (br. m, 1 H, 1Ј-H);
4.18 (t, J3Ј,4Ј = J3Ј,2Ј = 4.9 Hz, 1 H, 3Ј-H); 7.28 (dd, J3,4 = 7.6, J3,5
= 1.4 Hz, 1 H, 3-H); 7.39 (td, J4,3 = J4,5 = 7.4, J4,6 = 1.5 Hz, 1 H,
ˇ
M. Hocek, Eur. J. Org. Chem. 2010, 2666–2669; h) M. Stefko,
L. Slaveˇtínská, B. Klepetárˇová, M. Hocek, J. Org. Chem. 2010,
75, 442–449; i) J. Bárta, L. Slaveˇtínská, B. Klepetárˇová, M.
ˇ
Hocek, Eur. J. Org. Chem. 2010, 5432–5443; j) M. Stefko, L.
Slaveˇtínská, B. Klepetárˇová, M. Hocek, J. Org. Chem. 2011, 76,
6619–6635; k) T. Kubelka, L. Slaveˇtínská, M. Hocek, Synthesis
2012, 44, 953–965; l) H. Chapuis, N. Joubert, T. Kubelka, R.
Pohl, M. Hocek, Eur. J. Org. Chem. 2012, 1759–1767.
[7] L. F. Bonnac, G.-Y. Gao, L. Chen, S. E. Patterson, H. N. Jaya-
ram, K. W. Pankiewicz, Nucleosides, Nucleotides Nucleic Acids
2007, 26, 1249–1253.
4-H); 7.48 (br. t, J5,6 = J5,4 = 7.5 Hz, 1 H, 5-H); 7.52 (br. d, J6,5
=
7.5 Hz, 1 H, 6-H) ppm. 13C NMR (125.7 MHz, D2O): δ = 37.5
[(CH3)2N]; 39.0 (CH2); 41.8 [(CH3)2N]; 67.3 (CH2-5Ј); 74.0 (CH-
3Ј); 77.1 (CH-2Ј); 85.3 (CH-1Ј,4Ј); 128.8 (CH-3); 129.7 (CH-4);
[8] A. G. M. Barrett, H. B. Broughton, S. V. Attwood, A. A. L.
Gunatilaka, J. Org. Chem. 1986, 51, 495–503.
12
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
Carba Analogues of Phosphoribosylanthranilate
ˇ
[9] J. P. Wolfe, H. Tomori, J. P. Sadighi, J. Yin, S. L. Buchwald, J.
Org. Chem. 2000, 65, 1158–1174.
[10] X. Huang, S. L. Buchwald, Org. Lett. 2001, 3, 3417–3419.
[11] B. H. Yang, S. L. Buchwald, J. Organomet. Chem. 1999, 576,
125–146.
[13] P. Capek, R. Pohl, M. Hocek, J. Org. Chem. 2005, 70, 8001–
8008.
ˇ
[14] M. Stefko, R. Pohl, M. Hocek, Tetrahedron 2009, 65, 4471–
4483.
[15] A. V. Due, J. Kuper, A. Geerlof, J. P. von Kries, M. Wilmanns,
Proc. Natl. Acad. Sci. USA 2011, 108, 3554–3559.
Received: June 19, 2012
[12] a) K. W. Anderson, T. Ikawa, R. E. Tundel, S. L. Buchwald, J.
ˇ
Am. Chem. Soc. 2006, 128, 10694–10695; b) M. Stefko, M. Ho-
cek, Synthesis 2010, 4199–4206.
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
13

Job/Unit: O20819
/KAP1
Date: 25-07-12 16:27:09
Pages: 14
T. Kubelka, L. Slaveˇtínská, M. Hocek
FULL PAPER
C-Nucleosides
ˇ
Novel benzyl C-nucleosides were designed
and prepared as carba analogues of phos-
phoribosylanthranilate, an important inter-
mediate in the biosynthesis of tryptophan.
T. Kubelka, L. Slavetínská,
M. Hocek* ...................................... 1–14
Synthesis of Substituted Benzyl Homo-C-
Ribonucleosides and -Nucleotides as
Carba Analogues of Phosphoribosyl-
anthranilate
Keywords: Nucleosides
/ Nucleotides /
Cross-coupling / Phosphoribosylanthranil-
ate / Amides
14
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