One-pot synthesis of novel 2′-deoxyuridine derivatives containing α-aminophosphonate moieties

Article abstract of DOI:10.1002/hc.20288

A series of α-aminophosphonate derivatives of 2′-deoxyuridine (8a-k) have been prepared from 5′-O-tert-butyldimethylsilyl-3′- amino-2′, 3′-dideoxyuridine in good yields. The structures of all the products were confirmed by ¹H NMR, ³¹

Full text of DOI:10.1002/hc.20288

Heteroatom Chemistry
Volume 18, Number 3, 2007
ꢀ
One-Pot Synthesis of Novel 2 -Deoxyuridine
Derivatives Containing α-Aminophosphonate
Moieties
Zhi-Qiang Shang, Ru-Yu Chen, and You Huang
State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry,
Nankai University, Tianjin 300071, People’s Republic of China
Received 25 October 2005; revised 30 March 2006
titumor agents [6], or enzyme inhibitors [7], with a
ABSTRACT: A series of α-aminophosphonate deriva-
broad application in many areas of agriculture and
medicine [8]. Their synthesis has therefore been the
subject of much interest. A variety of methods are
tives of 2ꢀ-deoxyuridine (8a–k) have been pre-
pared from 5ꢀ-O-tert-butyldimethylsilyl-3ꢀ-amino-2ꢀ,
3ꢀ-dideoxyuridine in good yields. The structures of all
available, but the nucleophilic addition reaction of
the products were confirmed by H NMR, 31P NMR,
phosphites with imines is the most direct and effi-
31C NMR, and IR spectroscopy, and mass spectrom-
cient one among them.
1
ꢁ
C
etry and elemental analyses.
2007 Wiley Periodicals,
To search for novel anticancer drugs, a series of
α-aminophosphonate derivatives of 2ꢀ-deoxyuridine
were synthesized by the addition reactions of phos-
phite and imines, which were produced from 3ꢀ-
amino-2ꢀ,3ꢀ-dideoxyuridine and aromatic aldehydes.
Inc. Heteroatom Chem 18:230–235, 2007; Published on-
line in Wiley InterScience (www.interscience.wiley.com).
DOI 10.1002/hc.20288
INTRODUCTION
RESULTS AND DISCUSSION
Nucleoside analogues have figured prominently in
the search for effective antiviral agents despite con-
cerns over the toxicity generally associated with this
class of compounds [1]. To date, a number of mod-
ifications of the sugar moiety in nucleosides have
been carried out. Especially, various attempts have
been made to synthesize the 2ꢀ- and 3ꢀ-sites of nu-
cleosides in connection with AZT, a potent anti-HIV
agent [2]. On the other hand, α-amino phosphonic
acid and phosphonate esters have attracted atten-
tion because not only are they biologically attractive
peptide mimics of α-amino acid but they also ex-
hibit intriguing biological activities [3]. They have
been employed as antibiotics [4], herbicides [5], an-
The individual steps are summarized in Schemes 1
and 2. 2ꢀ-Deoxyuridine (1) was first converted into
Correspondence to: Ru-Yu Chen; e-mail: shangren5504@mail.
nankai.edu.cn.
2007 Wiley Periodicals, Inc.
c
ꢀ
SCHEME 1
230

One-Pot Synthesis of Novel 2ꢀ-Deoxyuridine Derivatives Containing α-Aminophosphonate Moieties 231
α-aminophosphonates. A variety of metal halides
such as TiCl4 [13], SnCl4 [14], and ZnCl2 [15] have
been used as Lewis catalysts in methylene chlo-
ride or other organic solvents to promote this addi-
tion. However, organic solvents, particularly chlori-
nated hydrocarbons, are high on the list of damaging
chemicals because of their volatile nature, consider-
able toxicity, and their use in large quantities for a
reaction. On the other hand, the metal halides uti-
lized as catalysts in these procedures are not all eco-
friendly, and often entail severe environmental pol-
lution during the waste disposal process. To avoid
these disadvantages, imines 6 with dimethyl phos-
phite were heated at 80◦C in neat without any solvent
and in the presence of a catalyst to give the corre-
sponding α-aminophosphonates 7. Deprotection of
5ꢀ-TBDMS group with ammonium fluoride at 50◦C
in MeOH provided the title compounds 8 in good
yields [16]. The results are summarized in Table 1.
The configurations of the three chiral carbon
atoms of 5 are known, but the newly formed chi-
ral carbon atom resulting from the addition reac-
tion might have two configurations. The phospho-
rus atom may attack the carbon atom from the back
(mode A) or the front (mode B) of the imine. Accord-
ingly, the configuration of the chiral carbon atom
formed by the reaction is either R or S (Scheme 3).
Thus, there may be a mixture of diastereoisomers for
compound 8. In the 1H, 31P, and 13C NMR spectra of
compound 8, two diastereoisomers were clearly ob-
served, because some of H, P, and C atoms of 8 gave
two sets of signals. Moreover, the H and C atoms in
CHP exhibit “dd” peaks due to the phosphorus cou-
pling 2 JPH = 18.0–22.0 Hz and 1 JPC = 155.1–163.0 Hz,
respectively. The product obtained in each synthesis
was a mixture of two diastereomers in roughly 2:3 ra-
tio (determined from 1H NMR spectra). The attempts
SCHEME 2
its 5ꢀ -O-tert-butyldimethylsilyl derivative 2 in 68%
yield by treatment with tert-butyldimethylsilyl chlo-
ride (TBDMSCl) and imidazole in DMF below −10◦C
[9]. When 2 was treated with triphenylphosphine-
diisopropyl azodicarboxylate at room temperature,
a cyclonucleoside derivative 3 is obtained in 68%
yield [10]. Conversion of 3 into the AzddUrd 4 in
87% yield was attempted by a nucleophilic open-
ing reaction with sodium azide in DMF at 120◦C
[11]. The P N ylide obtained by the Staudinger re-
action was treated with 25% ammonia solution at
50◦C to give the key intermediate 5 in 75% yield
[12]. When the amino nucleoside 5 was heated
under reflux with aromatic aldehydes in EtOH,
imines 6 were obtained. The nucleophilic addition
of phosphites to imines catalyzed by a base or an
acid is the most convenient method to synthesize
TABLE 1 Physical and Chemical Data of Compounds 8
Analysis Found (Calculated)
Compound
R
Yielda (%)
Formula
C
H
N
8a
8b
8c
8d
8e
8f
8g
8h
8i
H
2,4-Cl
4-CH3
4-Cl
70
61
65
68
66
60
70
62
55
63
65
C18H24N3O7P
C18H22Cl2N3O7P
C19H26N3O7P
50.58 (50.82)
43.92 (43.74)
51.86 (51.94)
46.91 (47.02)
48.73 (48.76)
45.72 (45.96)
49.90 (50.11)
48.56 (48.62)
46.02 (45.96)
46.92 (47.02)
47.04 (47.02)
5.46 (5.69)
4.67 (4.49)
5.90 (5.96)
5.31 (5.04)
5.32 (5.23)
5.09 (4.93)
5.66 (5.75)
5.22 (5.15)
5.07 (4.93)
5.20 (5.04)
5.24 (5.04)
10.02 (9.88)
8.63 (8.50)
9.30 (9.56)
8.91 (9.14)
9.27 (9.48)
11.86 (11.91)
9.30 (9.23)
8.81 (8.95)
11.87 (11.91)
9.14 (9.14)
9.10 (9.14)
C
18H23ClN3O7P
4-F
C18H23FN3O7P
4-NO2
4-OCH3
3,4-OCH2O
3-NO2
2-Cl
C18H23N4O9P
C19H26N3O8P
C19H24N4O9P
C18H23N4O9P
8j
8k
C
18H23ClN3O7P
3-Cl
C18H23ClN3O7P
aIsolated yield on the basis of compound 5 in three steps.
Heteroatom Chemistry DOI 10.1002/hc

232 Shang, Chen, and Huang
were purchased from commercial sources and used
without further purification unless specified. All sol-
vents were dried and distilled according to standard
1
procedures. In H NMR analysis, J1 and J2 repre-
sent coupling constants of each diastereomer, re-
spectively. In 13C NMR analysis: A, value for one
diastereomer; B, value for two diastereomers.
General Procedure for the Synthesis of 8a–k
Aromatic aldehyde (1 mmol) was added to a solution
of 5 (1 mmol) in ethanol (10 mL), and then heated
under reflux for 4 h. The solvent was removed un-
der reduced pressure, and then dimethyl phosphite
(4 mmol) was added. The mixture was stirred for 2 h
at 80◦C, and then 10 mL of methanol and ammonium
fluoride (10 mmol) were added. The solution was
heated at 50◦C for 2 h, and then the solvent was evap-
orated in vacuo. The crude residue was dissolved in
CHCl3 and extracted with water (3 × 15mL). The or-
ganic layer was dried with Na2SO4, filtered off, and
the solvent was removed under reduced pressure.
The crude was purified by chromatography column
(7% MeOH/CH3Cl), affording a white foamy solid
after vacuum drying.
SCHEME 3
to obtain single diastereomer using fractional crys-
tallization and column chromatography also failed.
Owing to the overlap of peaks, H-5 proton signal of
all compounds and H on the carbon connecting to
phosphorus signal of 8a appear as a triplet. The IR
spectra of compounds 8 show normal stretching ab-
sorption bands, indicating the existence of groups
N H (∼3400 cm−1), C O (1670–1708 cm−1), P O
(1264–1272 cm−1), and P O C (1021–1055 cm−1).
In summary, we provide a new synthetic
method of 2-deoxyuridine derivatives containing α-
aminophosphonate moieties at the 3-position of the
deoxyribose ring. It is also important to mention
that hydrophosphonylation of imines with dimethyl
phosphite without any solvent and in the presence of
a catalyst is a simple and green method to cater the
need of academia as well as industries. Further stud-
ies on the separation and application of title prod-
ucts are in progress.
1 H, 31 P, 13C NMR, and IR Spectra and Mass
Spectrometry of Compounds 8a–k. Compound 8a
(diastereoisomers): IR vmax (KBr)/cm−1 3628, 3388,
3162, 1697, 1464, 1397, 1272, 1052; 31P NMR (CDCl3)
1
δ = 25.54 and 25.60 ppm; H NMR (CDCl3) δ = 8.97
and 8.93 (s each, 1H together, NH), 7.80 and 7.60
(d each, J1 = J2 = 8.0 Hz, 1H together, H-6,), 7.36–
7.41 (m, 5H, ArH), 6.20 and 6.11 (t each, J1 =
J2 = 5.20 Hz, 1H together, H-1ꢀ), 5.67 (t, 1H, H-5),
4.09–4.19 (t, 1H, CHP), 3.40–3.93 (m, 10H, H-3ꢀ, 4ꢀ,
5ꢀ, POCH ), 2.05–2.32 (m, 3H, H-2ꢀ, OH,); 13C NMR
3
(CDCl3) δ = 164.51 (C-4, A), 164.45 (C-4, A), 150.83
(C-2, B), 140.97 (C-6, A), 140.82 (C-6, A), 136.14
(ArC, B), 135.10 (ArC, B), 128.96 (ArC, B), 128.57
(ArC, B), 102.35 (C-5, A), 102.23 (C-5, A), 85.87 (A),
85.78 (A), 85.66 (A), 85.50 (C-1ꢀ, 4ꢀ, A), 62.12 (C-5ꢀ,
EXPERIMENTAL
1
Melting points were determined with a model
YANACO MP-500 apparatus, and are uncorrected.
IR spectra were recorded on a Bruker Equinox
55 spectrometer. Elemental analyses were carried
on a Yanaco CHN Corder MT-3 apparatus. 1H,
31P, and 13C NMR spectra were measured by using
Varian 400 Mercury plus spectrometer (400 MHz
for 1H, 100 MHz for 13C, and 162 MHz for 31P)
with TMS and 85% H3PO4 as the internal and ex-
ternal references, respectively, and with CDCl3 as
the solvent. Mass spectra were obtained using a
Bruker ESQUIRE∼LCTM ESI ion trap spectrometry
equipped with a gas nebulizer probe. All reagents
A), 61.94 (C-5ꢀ, A), 59.47 (d, JPC = 158.1 Hz, CHP,
1
A), 58.78 (d, JPC = 155.1 Hz, CHP, A), 56.54 (d,
2
2 JPC = 15.0 Hz, POCH3, B), 55.49 (d, JPC = 13.9 Hz,
3
POCH3, B), 54.19 (d, JPC = 5.4 Hz, C-3ꢀ, A), 53.98
3
(d, JPC = 6.1 Hz, C-3ꢀ, A), 39.74 (C-2ꢀ, A), 38.25 (C-
2ꢀ, A); ESI-MS (positive) m/z 426 (M + H)+, m/z 448
(M + Na)+; (negative) m/z 424 (M − H)−.
Compound 8b (diastereoisomers): IR vmax
(KBr)/cm−1 3624, 3306, 3147, 1681, 1466, 1396,
1272, 1038; 31P NMR (CDCl3) δ = 25.11 and 25.17
1
ppm; H NMR (CDCl3) δ = 9.82 and 9.72 (s, 1H to-
gether, NH), 7.74 and 7.28–7.64 (d and m, J1 = 8.40
Hz, 4H together, H-6 and ArH), 6.16–6.22 (m, 1H,
Heteroatom Chemistry DOI 10.1002/hc

One-Pot Synthesis of Novel 2ꢀ-Deoxyuridine Derivatives Containing α-Aminophosphonate Moieties 233
H-1ꢀ), 5.68 (t, 1H, H-5), 4.71 and 4.68 (d each,
1
1ꢀ, 4ꢀ, A), 62.00 (C-5ꢀ, B), 58.80 (d, JPC = 155.7 Hz,
2
2 JPH1 = 22.0 Hz JPH2 = 21.6 Hz, 1H together, CHP),
CHP, A), 58.13 (d, 1 JPC = 156.5 Hz, CHP, A), 56.75 (d,
3
3.68–3.91 (m, 3H, H-5ꢀ, 4ꢀ), 3.85 (d, JPH = 10.4 Hz,
2 JPC = 15.2 Hz, POCH3, B), 55.46 (d, JPC = 16.3 Hz,
2
3
POCH3, B), 54.28 (d, JPC = 4.8 Hz, C-3ꢀ, A), 54.00
3
3H, POCH ), 3.57 (d, JPH = 10.8 Hz, 3H, POCH ),
3
3
3.25–3.39 (m, 1H, H-3ꢀ), 3.19 (bs, 1H, NH, B), 1.98–
2.32 (m, 1H, H-2ꢀ); 13C NMR (CDCl3) δ = 164.45 (C-
4, A), 164.36 (C-4, A), 150.89 (C-2, B), 140.94 (C-6,
A), 140.79 (C-6, A), 135.16 (ArC, B), 134.77 (ArC,
B), 133.10 (ArC, B), 130.76 (ArC, B), 129.57 (ArC,
B), 128.11 (ArC, B), 102.50 (C-5, A), 102.41 (C-5,
A), 85.81 (A), 85.63 (A), 85.47 (C-1ꢀ, 4ꢀ, A), 62.45
(d, JPC = 6.7 Hz, C-3ꢀ, A), 39.69 (C-2ꢀ, A), 38.21 (C-
3
2ꢀ, A); ESI-MS (positive) m/z 460 (M + H)+, m/z 482
(M + Na)+; (negative) m/z 458 (M − H)−.
Compound 8e (diastereoisomers): IR vmax
(KBr)/cm−1 3610, 3349, 3133, 1695, 1465, 1398, 1227,
1055; 31P NMR (CDCl3) δ = 25.43 ppm; 1H NMR
(CDCl3) δ = 9.38 (bs, 1H, NH), 7.78 and 7.60 (d
each, J1 = 8.4 Hz and J2 = 8.0 Hz, 1H together, H-
6), 7.36–7.39 (t, 2H, ArH), 7.04–7.08 (t, 2H, ArH),
6.21 and 6.12 (t each, J1 = 6.2 Hz and J2 = 6.0 Hz,
1H together, H-1ꢀ), 5.67 (t, 1H, H-5), 4.14 and 4.11
(C-5ꢀ, A), 62.18 (C-5ꢀ, A), 59.47 (d, JPC = 158.1 Hz,
1
1
CHP, A), 58.78 (d, JPC = 155.1 Hz, CHP, A), 56.54
2
2
(d, JPC = 15.0 Hz, POCH3, B), 55.49 (d, JPC = 13.9
Hz, POCH3, B), 54.19 (d, 3 JPC = 5.4 Hz, C-3ꢀ, A), 53.98
(d, JPC = 6.1 Hz, C-3ꢀ, A), 39.74 (C-2ꢀ, A), 38.25 (C-
3
2
2
(d each, JPH1 = 19.2 Hz and JPH2 = 18.0 Hz, 1H to-
2ꢀ, A); ESI-MS (positive) m/z 494 (M + H)+, m/z 516
(M + Na)+; (negative) m/z 492 (M − H)−.
gether, CHP), 3.34–3.92 (m, 10H, H-3ꢀ, 4ꢀ, 5ꢀ, POCH ),
3
2.04–2.33 (m, 3H, H-2ꢀ, OH); 13C NMR (CDCl3)
1
Compound 8c (diastereoisomers): IR vmax
(KBr)/cm−1 3657, 3446, 3191, 1702, 1464, 1396, 1272,
1032; 31P NMR (CDCl3) δ = 26.00 and 26.14 ppm; 1H
NMR (CDCl3) δ = 9.53 and 9.50 (s each, 1H together,
NH), 7.80 and 7.60 (d each, J1 = J2 = 8.0 Hz, 1H to-
gether, H-6), 7.15–7.28 (m, 4H, ArH), 6.20 and 6.11
(t each, J1 = J2 = 6.0 Hz, 1H together, H-1ꢀ), 5.66
δ = 164.45 (C-4, B), 162.69 (d, JCF = 243.3 Hz, ArC,
B), 150.86 (C-2, B), 140.82 (C-6, B), 132.06 (ArC,
3
A), 131.00 (ArC, A), 130.33 (d, JCF = 6.1 Hz, ArC,
2
B), 105.87 (d, JCF = 21.3 Hz, ArC, B), 102.29 (C-5,
A), 102.17 (C-5, A), 85.78 (A), 85.60 (A), 85.44 (C-
1
1ꢀ, 4ꢀ, A), 61.97 (C-5ꢀ, B), 59.12 (d, JPC = 158.2 Hz,
CHP, A), 57.94 (d, 1 JPC = 155.1 Hz, CHP, A), 56.57 (d,
2
2 JPC = 15.2 Hz, POCH3, B), 55.38 (d, JPC = 15.2 Hz,
2
(t, 1H, H-5), 4.10 and 4.06 (d, JPH1= 20.4 Hz and
2 JPH2 = 17.6 Hz, 1H together, CHP), 3.53–3.91 (m,
POCH3, B), 54.24 (d, JPC = 6.1 Hz, C-3ꢀ, A), 53.93
3
10H, H-3ꢀ, 4ꢀ, 5ꢀ, POCH ), 2.33 (s, 3H, CH ), 2.00–2.16
(d, JPC = 6.1 Hz, C-3ꢀ, A), 39.68 (C-2ꢀ, A), 38.22 (C-
3
3
3
(m, 2H, H-2ꢀ); 13C NMR (100 MHz, CDCl3) δ = 164.31
(C-4, A), 164.26 (C-4, A), 150.81 (C-2, B), 140.91 (C-6,
A), 140.73 (C-6, A), 139.38 (ArC, B), 132.30 (ArC, B),
131.93 (ArC, B), 129.73 (ArC, B), 128.40 (d, 3 JPC = 8.1
Hz, ArC, B), 102.42 (C-5, A), 102.26 (C-5, A), 85.89
(A), 85.72 (A), 85.70 (A), 85.54 (C-1ꢀ, 4ꢀ, A), 62.23
2ꢀ, A); ESI-MS (positive) m/z 444 (M + H)+, m/z 466
(M + Na)+; (negative) m/z 442 (M − H)−.
Compound 8f (diastereoisomers): IR vmax
(KBr)/cm−1 3636, 3388, 3100, 1699, 1463, 1397, 1270,
1047; 31P NMR (CDCl3) δ = 24.30 and 24.32 ppm;
1H NMR (CDCl3) δ = 9.09 (bs, 1H, NH), 8.23 (d,
J = 8.4 Hz, 2H, ArH), 7.73 and 7.56–7.62 (d and m,
J = 8.0 Hz, 3H together, H-6 and ArH), 6.20 and
6.12 (t each, J1 = J2 = 6.0 Hz, 1H together, H-1ꢀ),
5.67 (t, 1H, H-5), 4.28 and 4.26 (d each, 2 JPH1 = 21.6
1
(C-5ꢀ, A), 61.93 (C-5ꢀ, A), 59.35 (d, JPC = 155.9 Hz,
CHP, A), 58.53 (d, 1 JPC = 155.0 Hz, CHP, A), 56.46 (d,
2
2 JPC = 14.9 Hz, POCH3, B), 55.37 (d, JPC = 15.6 Hz,
POCH3, B), 54.13 (d, 3 JPC = 7.7 Hz, C-3ꢀ, A), 53.98 (d,
3 JPC = 7.4 Hz, C-3ꢀ, A), 39.91 (C-2ꢀ, A), 38.32 (C-2ꢀ, A),
21.35 (CH3, B); ESI-MS (positive) m/z 440 (M + H)+,
m/z 462 (M + Na)+; (negative) m/z 438 (M − H)−.
Compound 8d (diastereoisomers): IR vmax
(KBr)/cm−1 3577, 3388, 3155, 1692, 1473, 1399, 1272,
1047; 31P NMR (CDCl3) δ = 23.78 and 24.02 ppm;
1H NMR (CDCl3) δ = 9.27 and 9.46 (s each, 1H to-
gether, NH), 7.66–7.77 (m, 2H, H-6, ArH), 7.27–7.46
(m, 3H, ArH), 6.24 and 6.14 (t each, J1 = J2 = 6.0 Hz,
1H together, H-1ꢀ), 5.69 (t, 1H, H-5), 4.26 and 4.06
2
Hz and JPH = 19.6 Hz, 1H together, CHP), 3.35–
3.93 (m, 10H, H-3ꢀ, 4ꢀ, 5ꢀ, POCH ), 2.04–2.33 (m,
3
3H, H-2ꢀ, OH); 13C NMR (CDCl3) δ = 163.76 (C-4,
B), 150.59 (C-2, B), 147.46 (ArC, B), 144.51 (ArC,
A), 143.61 (ArC, A), 140.18 (C-6, A), 140.10 (C-
3
6, A), 129.48 (d, JCP = 5.2 Hz, ArC, A), 129.36 (d,
3 JCP = 7.4 Hz, ArC, A), 123.52 (ArC, B), 102.00 (C-
5, B), 85.47 (A), 84.88 (A), 84.82 (C-1ꢀ, 4ꢀ, A), 61.62
1
(C-5ꢀ, A), 61.37 (C-5ꢀ, A), 58.44 (d, JPC = 156.8 Hz,
CHP, A), 58.00 (d, 1 JPC = 149.0 Hz, CHP, A), 56.71 (d,
2
2
2 JPC = 16.4 Hz, POCH3, B), 55.70 (d, JPC = 15.1 Hz,
2
(d, JPH1 = 20.4 Hz and JPH2 = 18.4 Hz, 1H together,
CHP), 3.34–3.94 (m, 10H, H-3ꢀ, 4ꢀ, 5ꢀ, POCH ), 1.86–
POCH3, B), 54.39 (d, 3 JPC = 6.3 Hz, C-3ꢀ, A), 54.14 (d,
3 JPC = 6.3 Hz, C-3ꢀ, A), 39.50 (C-2ꢀ, A), 38.16 (C-2ꢀ, A);
ESI-MS (positive) m/z 493 (M + Na)+; (negative) m/z
469 (M − H)−.
3
2.27 (m, 3H, H-2ꢀ, OH); 13C NMR (CDCl3) δ = 164.40
(C-4, B), 150.86 (C-2, B), 140.88 (C-6, A), 140.79 (C-
6, A), 134.82 (ArC, B), 134.18 (ArC, B), 123.83 (ArC,
B), 128.95 (ArC, B), 129.09 (ArC, B), 102.36 (C-5,
A), 102.23 (C-5, A), 85.75 (A), 85.63 (A), 85.47 (C-
Compound 8g (diastereoisomers): IR vmax
(KBr)/cm−1 3631, 3378, 3183, 1630, 1470, 1398, 1264,
Heteroatom Chemistry DOI 10.1002/hc

234 Shang, Chen, and Huang
1027; 31P NMR (CDCl3) δ = 26.09 and 26.20 ppm;
1H NMR (CDCl3) δ = 9.49 and 9.46 (s each, 1H to-
gether, NH), 7.80 and 7.61 (d each, J1 = 8.0 Hz
and J2 = 8.4 Hz, 1H together, H-6), 7.31 (d, 2H,
ArH), 6.88 (d, 2H, ArH), 6.20 and 6.11 (t each,
J1 = J2 = 6.0 Hz, 1H together, H-1ꢀ), 5.66 (t, 1H, H-
13C NMR (CDCl3) δ = 164.05 (C-4, B), 150.77 (C-2,
B), 148.70 (ArC, B), 140.73 (C-6, B) 139.02 (ArC,
B), 138.13 (ArC, B), 134.80 (ArC, B), 129.90 (ArC,
B), 123.42 (ArC, B), 102.36 (C-5, A), 102.30 (C-5,
A), 85.83 (A), 85.76 (A), 85.62 (C-1ꢀ, 4ꢀ, A), 62.00
1
(C-5ꢀ, A), 61.82 (C-5ꢀ, A), 59.05 (d, JPC = 154.0 Hz,
5), 4.08 and 4.04 (d each, 2 JPH1 = 20.0 Hz and 2 JPH2
=
CHP, A), 58.30 (d, 1 JPC = 151.2 Hz, CHP, A), 56.79 (d,
2
17.6 Hz, 1H together, CHP), 3.35–3.88 (m, 10H, H-
3ꢀ, 4ꢀ, 5ꢀ, POCH ), 3.79 (s, 3H, OCH ), 2.00–2.28 (m,
2 JPC = 13.6 Hz, POCH3, B), 55.37 (d, JPC = 16.2 Hz,
3
POCH3, B), 54.63 (d, JPC = 5.4 Hz, C-3ꢀ, A), 54.11
3
3
3H, H-2ꢀ, OH); 13C NMR (CDCl3) δ = 164.23 (C-4, A),
164.18 (C-4, A), 159.53 (ArC, B), 150.62 (C-2, B),
140.73 (C-6, A), 140.59 (C-6, A), 129.53 (d, 3 JPC = 4.9
Hz, ArC, B), 127.74 (ArC, A), 126.65 (ArC, A), 114.21
(ArC, B), 102.12 (C-5, A), 101.99 (C-5, A), 85.68 (A),
85.57 (A), 85.46 (A), 85.30 (C-1ꢀ, 4ꢀ, A), 61.94 (C-5ꢀ,
(d, JPC = 5.3 Hz, C-3ꢀ, A), 39.67 (C-2ꢀ, A), 38.43 (C-
3
2ꢀ, A); ESI-MS (positive) m/z 471 (M + H)+, m/z 493
(M + Na)+; (negative) m/z 469 (M − H)−.
Compound 8j (diastereoisomers): IR vmax
(KBr)/cm−1 3640, 3381, 3198, 1680, 1446, 1394, 1272,
1028; 31P NMR (CDCl3) δ = 25.51 ppm; 1H NMR
(CDCl3) δ = 9.27 and 9.16 (s each, 1H together, NH),
7.66–7.77 (m, 2H, H-6, ArH), 7.27–7.46 (m, 3H, ArH),
6.16 (t, J = 6.0 Hz, H-1ꢀ), 5.69 (m, 1H, H-5), 4.77 (t,
2 JPH = 21.6 Hz, 1H, CHP), 3.34–3.94 (m, 10H, H-3ꢀ,
4ꢀ, 5ꢀ, POCH ), 1.86–2.27 (m, 3H, H-2ꢀ, OH); 13C NMR
(CDCl3) δ =3164.45 (C-4, A), 164.39 (C-4, A), 150.83
(C-2, B), 140.97 (C-6, A), 140.82 (C-6, A), 134.50 (d,
2 JPC = 9.1 Hz, ArC, B), 134.21 (ArC, B), 129.82 (ArC,
B), 129.69 (ArC, B), 127.68 (ArC, B), 102.41 (C-5, A),
102.35 (C-5, A), 85.84 (A), 85.75 (A), 85.63 (A), 85.47
(C-1ꢀ, 4ꢀ, A), 62.42 (C-5ꢀ, A), 62.18 (C-5ꢀ, A), 56.95 (d,
1
A), 61.77 (C-5ꢀ, A), 58.58 (d, JPC = 157.1 Hz, CHP,
1
A), 57.82 (d, JPC = 155.6 Hz, CHP, A), 56.31 (d,
2 JPC = 15.4 Hz, POCH3, B), 55.19 (OCH3, B), 55.16
3
(POCH3, B), 53.91 (d, JPC = 7.0 Hz, C-3ꢀ, A), 53.74
3
(d, JPC = 7.1 Hz, C-3ꢀ, A), 39.58 (C-2ꢀ, A), 38.07 (C-
2ꢀ, A); ESI-MS (positive) m/z 456 (M + H)+, m/z 478
(M + Na)+.
Compound 8h (diastereoisomers): IR vmax
(KBr)/cm−1 3617, 3465, 3270, 1670, 1491, 1390, 1268,
1021; 31P NMR (CDCl3) δ = 25.79 and 25.82 ppm; 1H
NMR (CDCl3) δ = 9.27 (bs, 1H, NH), 7.80 and 7.61
(d each, J1 = 8.0 Hz and J2 = 8.4 Hz, 1H together,
H-6), 6.92 (d, J = 8.4 Hz, 1H, ArH), 6.77–6.83 (m,
2H, ArH), 6.20 and 6.12 (t each, J1 = J2 = 6.0 Hz,
1H together, H-1ꢀ), 5.98 (s, 2H, OCH O), 5.68 (t,
1H, H-5), 4.06 and 4.03 (d each, 2 JPH1 =220.0 Hz and
2 JPH2 = 21.6 Hz, 1H together, CHP), 3.38–3.92 (m,
2
2 JPC = 13.4 Hz, POCH3, B), 55.65 (d, JPC = 14.9 Hz,
POCH3, B), 54.47 (d, 1 JPC = 159.4 Hz, CHP, A), 53.79
(d, 1 JPC = 132.2 Hz, CHP, A), 54.63 (d, 3 JPC = 14.2 Hz,
3
C-3ꢀ, A), 53.80 (d, JPC = 6.2 Hz, C-3ꢀ, A), 39.61 (C-2ꢀ,
A), 38.30 (C-2ꢀ, A); ESI-MS (positive) m/z 460 (M +
H)+, m/z 482 (M + Na)+; (negative) m/z 458 (M − H)−.
Compound 8k (diastereoisomers): IR vmax
(KBr)/cm−1 3608, 3375, 3134, 1690, 1467, 1400, 1272,
10H, H-3ꢀ, 4ꢀ, 5ꢀ, POCH ), 2.09–2.30 (m, 3H, H-2ꢀ,
3
OH); 13C NMR (CDCl3) δ = 164.42 (C-4, B), 150.86
(C-2, B), 148.21 (ArC, B), 147.82 (ArC, B), 140.82
(C-6, B), 129.84 (ArC, B), 128.78 (ArC, B), 122.24
(ArC, B), 108.59 (ArC, B), 102.29 (C-5, A), 102.12
(C-5, A), 101.47 (OCH2O, B), 85.90, 85.72, 85.54 (C-
1
1051; 31P NMR (CDCl3) δ = 24.97 and 25.11ppm; H
NMR (CDCl3) δ = 9.29 (bs, 1H, NH), 7.78 and 7.62
(d each, J1 = J2 = 8.0 Hz, 1H together, H-6), 7.31–
7.39 (m, 4H, ArH), 6.21 and 6.13 (t each, J1 = 5.6 Hz
and J2 = 5.2 Hz, 1H together, H-1ꢀ), 5.68 (t, 1H, H-5),
4.12 and 4.09 (d each, 2 JPH1 = 20.8 Hz and 2 JPH2 = 18.0
Hz, 1H together, CHP), 3.36–3.89 (m, 10H, H-3ꢀ, 4ꢀ,
1
1ꢀ, 4ꢀ, A), 62.00 (C-5ꢀ, B), 59.08 (d, JPC = 158.2 Hz,
CHP, A), 58.36 (d, 1 JPC = 155.1 Hz, CHP, A), 56.45 (d,
2
2 JPC = 15.2 Hz, POCH3, B), 55.23 (d, JPC = 15.2 Hz,
3
POCH3, B), 54.22 (d, JPC = 4.5 Hz, C-3ꢀ, A), 53.95
5ꢀ, POCH ), 2.03–2.31 (m, 3H, H-2ꢀ, OH); 13C NMR
3
3
(d, JPC = 4.1 Hz, C-3ꢀ, A), 39.80 (C-2ꢀ, A), 38.25 (C-
(CDCl3) δ = 164.05 (C-4, B), 159.53 (ArC, B), 150.77
2ꢀ, A); ESI-MS (positive) m/z 470 (M + H)+, m/z 492
(M + Na)+; (negative) m/z 468 (M − H)−.
(C-2, B), 148.70 (ArC, B), 140.73 (C-6, A),139.04
3
(ArC, A), 138.12 (ArC, A), 134.78 (d, JPC = 9.5 Hz,
Compound 8i (diastereoisomers): IR vmax
(KBr)/cm−1 3630, 3363, 3178, 1691, 1468, 1399, 1273,
1050; 31P NMR (CDCl3) δ = 24.44 and 24.58 ppm;
1H NMR (CDCl3) δ = 9.09 (bs, 1H, NH), 8.23 (d,
J = 8.4 Hz, 2H, ArH), 7.73 and 7.56–7.62 (d and m,
J = 8.0 Hz, 3H together, H-6 and ArH), 6.20 and 6.12
(t each, J1 = J2 = 6.0 Hz, 1H together, H-1ꢀ), 5.67 (t,
ArC, B), 129.90 (ArC, B), 123.46 (ArC, B), 102.41
(C-5, A), 102.32 (C-5, A), 85.68 (A), 85.87 (A), 85.78
(A), 85.66 (C-1ꢀ, 4ꢀ, A), 62.03 (C-5ꢀ, A), 61.85 (C-5ꢀ,
1
A), 59.05 (d, JPC = 153.9 Hz, CHP, A), 58.30 (d,
2
1 JPC = 151.2 Hz, CHP, A), 56.79 (d, JPC = 13.6 Hz,
2
POCH3, B), 55.37 (d, JPC = 16.2 Hz, POCH3, B),
3
3
54.35 (d, JPC = 8.9 Hz, C-3ꢀ, A), 53.99 (d, JPC = 8.3
Hz, C-3ꢀ, A), 39.68 (C-2ꢀ, A), 38.22 (C-2ꢀ, A); ESI-MS
(positive) m/z 460 (M + H)+, m/z 482 (M + Na)+;
(negative) m/z 458 (M − H)−.
2
1H, H-5), 4.28 and 4.26 (d each, JPH1 = 21.6 Hz
2
and JPH = 19.6Hz, 1H, CHP), 3.35–3.93 (m, 10H,
H-3ꢀ, 4ꢀ, 5ꢀ, POCH ), 2.04–2.33 (m, 3H, H-2ꢀ, OH);
3
Heteroatom Chemistry DOI 10.1002/hc

One-Pot Synthesis of Novel 2ꢀ-Deoxyuridine Derivatives Containing α-Aminophosphonate Moieties 235
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ACKNOWLEDGMENT
The authors express their appreciation to the
National Natural Science Foundation of China
(20172027) for the financial support.
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