Synthesis of O,O-diphenyl [substituted (2-selenomorpholin-4-yl-acetyl amino)] alkyl phosphonates

Article abstract of DOI:10.1080/10426500490459687

A series of O,O-diphenyl [substituted (2-selenomorpholin-4-yl-acetyl amino)] alkyl phosphonates were synthesized by the reactions of selenomorpholine with O,O-diphenyl 2-chloro- acetylamino alkyl phosphonates. The structures of all new compounds have been

Full text of DOI:10.1080/10426500490459687

This article was downloaded by: [University of California, San Diego]
On: 07 October 2014, At: 07:04
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the Related
Elements
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gpss20
SYNTHESIS OF O,O-DIPHENYL [SUBSTITUTED (2-
SELENOMORPHOLIN-4-YL-ACETYL AMINO)] ALKYL
PHOSPHONATES
Liming Hu a , Zhiyuan Chen b , Shengmei Lu b , Xueshu Li b , Zhaojie Liu b & Hansheng Xu c
a Xiamen University , Xiamen, Fujian, China
b Central China Normal University , Wuhan, Hubei, China
c Wuhan University , Wuhan, Hubei, China
Published online: 16 Aug 2010.
To cite this article: Liming Hu , Zhiyuan Chen , Shengmei Lu , Xueshu Li , Zhaojie Liu & Hansheng Xu (2004) SYNTHESIS OF
O,O-DIPHENYL [SUBSTITUTED (2-SELENOMORPHOLIN-4-YL-ACETYL AMINO)] ALKYL PHOSPHONATES, Phosphorus, Sulfur, and
Silicon and the Related Elements, 179:6, 1065-1073, DOI: 10.1080/10426500490459687
To link to this article: http://dx.doi.org/10.1080/10426500490459687
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 179:1065–1073, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490459687
SYNTHESIS OF O,O-DIPHENYL [SUBSTITUTED
(2-SELENOMORPHOLIN-4-YL-ACETYL AMINO)]
ALKYL PHOSPHONATES
Liming Hu,a,b Zhiyuan Chen,b Shengmei Lu,b Xueshu Li,b
Zhaojie Liu,b and Hansheng Xuc
Xiamen University, Xiamen, Fujian, China;a Central China
Normal University, Wuhan, Hubei, China;b
and Wuhan University, Wuhan, Hubei, Chinac
(Received December 30, 2002; accepted October 8, 2003)
A series of O,O-diphenyl [substituted (2-selenomorpholin-4-yl-acetyl
amino)] alkyl phosphonates were synthesized by the reactions of se-
lenomorpholine with O,O-diphenyl 2-chloro- acetylamino alkyl phos-
phonates. The structures of all new compounds have been confirmed by
1H NMR, 31P NMR, IR spectroscopy, Mass spectroscopy and elemental
analyses.
Keywords: Glutathione peroxidase; phosphorylation; selenium; se-
lenomorpholine
Since selenium was found to be an active center of glutathione
peroxidase (GSH-Px), which can catalyze and decompose liquid hy-
droperoxide or hydrogen peroxide, the bioactivity of selenium has
developed rapidly.1−2 Selenoorganic compound Ebselen (2-phenyl-1,2-
benzisoselenazolone) was found the function against biological damage
caused in vivo by reactive hydroperoxides.3−7 This increased a striking
interest in developing new selenoorganic compound for therapy. They
have been potentially used in a variety of fields varying from medicinal
to agriculture application.8−11 Recently, the antibiotic activity and plant
systemic activity of selenomorpholine derivatives were studied.12−14
In our previous articles, a number of amino acid ester derivatives of
benzisoselenazolone were synthesized, and these compounds exhib-
ited excellent pharmacological effect.15−16 2-Amino alkylphosphonats
show varied biological activity, such as antibacterial, antitumor, her-
bicidal activity, and inhibitory to enzymes,17−20 however, no attempt
has been made to synthesize 2-amino alkyl phosphonates containing
Address correspondence to L. M. Hu, Department of Chemistry, Xiamen University,
PO Box 849, Xiamen, Fujian 361005, China. E-mail: huliming2813@sohu.com
1065

1066
L. Hu et al.
SCHEME 1
selenomorpholine. In the course of our studies on the application of
selenomorpholinyl phosphonates, we found the compounds showed dis-
tinctly antifungal activity.21
RESULTS AND DISCUSSION
Synthesis of Synthesis of O,O-Diphenyl [substituted
(2-selenomorpholin-4-yl-acetyl Amino)] Alkyl
Phosphonates
There are several reports on the synthesis of substituted selenomor-
pholine.22 However, there are few reports on the selenomorpholine.
Herein we report the reaction of selenium power, sodium borohydride
and nitrogen mustard hydrochloride to synthesize selenomorpholine
under mild conditions in 56% yield as shown in Scheme 1. The low
yield is partly because reaction of sodium selenhydrate with nitrogen
mustard hydrochloride to produce a hetero-crown ether through 2 + 2
reaction.
The title compounds 5 were synthesized by a multistep route outlined
in Scheme 2. Preparation of O, O-diphenyl 2-aminoalkyl phosphonates
SCHEME 2

Alkyl Phosphonates
1067
3 were readily accomplished in a three-step sequence (51–76% overall
yield) starting from benzyl carbamate, aldehyde and triphenyl phos-
phite. First, condensation of benzyl carbamate, aldehydes and triphenyl
phosphite form O, O-diphenyl 1-benzyloxycarbonylamino 2-substituted
alkyl phosphonates 2. Then, deproection with saturated hydrogen bro-
mide acetic acid solution produces the hydrobromide salt of 3. Using
ammonia or triethylamine as base in ether, the salt could be converted
to 2-amino alkyl phosphonate 3 in high yield. The reaction of 3 with
chloroacetic chloride was carried out in chloroform with an organic
base as an acid acceptor in 40◦C. After cooling to room temperature,
the mixture was washed with water, and extracted with chloroform,
the combined organic fractions were dried and solvent was removed
under reduced pressure. The products 4 are a light yellowish syrup;
TLC found the compounds to have high purity. The reaction of 4 with
selenomorpholine was carried out in acetone in the presence of triethy-
lamine under reflux to give the title compounds (yield 43–72%).
The Structures of the Products
1H NMR, 31P NMR, IR, MS spectroscopy, and elemental analysis con-
1
firmed the structures of the title compounds prepared. The H NMR
spectrum of all these compounds displayed a sharp multiplet at δ about
2.65 ppm and 2.75 ppm, respectively, which is characteristic for SeCH2
and NCH2 of the selenomorpholine moiety. There is a doublet at δ about
5.8 ppm, which corresponds to PCH2. The IR spectra showed peaks at
about 1680 cm−1 (C O) and about 1260 cm−1 (P O). The EI-MS spec-
tra showed the existence of weak molecular ion peak. The fragment ion
peaks were consistent with their structures; e.g., compound 5 show the
existence of weak molecular ion peak. The major MS peaks, particularly
m/z 164, 150, 136 are common to all compounds. Other peaks were con-
sistent with their structures and can be clearly assigned, because there
are two major isotopes of selenium (approximately 2:1).
EXPERIMENTAL
The melting points were determined on a hot stage apparatus and un-
corrected, 1H and 31PNMR spectra were taken with tetramethylsilane
as internal standard and 85% phosphoric acid as external standard,
respectively, on Varian XL-200 spectrometer. Mass spectra were regis-
tered on Finngam Trace MS instrument. IR spectra were recorded on
Nicolet Avatar 360. The elemental analyses were performed on a Perkin
Elmer 2400CHN element analyzer. Unless other noted, all solvents

1068
L. Hu et al.
were dried over Na2SO4 or MgSO4, and the solvent was removed in
a rotary evaporator under reduce pressure, chromatography was per-
formed on silica gel.
Selenomorpholine 1
Sodium borohydride (4.3 g, 0.11 mmol) was added to the mixture of
power selenium (7.9 g, 0.10 mmol) and absolute ethanol (100 mL) as
−5◦C under argon with stirring until a colorless solution was formed,
then sodium hydride (4.4 g, 0.11 mmol) was added and stirred vigor-
ously for 20 min. The ethanol solution of nitrogen mustard hydrochlo-
ride (17.8 g, 0.10 mmol) was added dropwise, after being refluxed for
4 h. The mixture was filtered, concentrated, and a colorless oil 1 was
obtained by distillation under reduced pressure, b.p. 54◦C/1.33kP, yield
56%. 1H NMR (δ, ppm) 1.62 (s, 1H, NH), 2.61 (m, 4H SeCH2), 3.22 (m,
4H, NCH2); MS (m/z, %): 151 (M+, 74.0)
Compounds 2 and 3 were prepared according to literature.23
O,O-Diphenyl 2-Chloroacetylaminoalkyl Phosphonates 4
To a stirred solution of O,O-diphenyl 2-aminoalkyl phosphonates
(10 mmol), triethylamine (11 mmol) and 15 mL solvent chloroform
at 5◦C, a mixture of chloroacetyl chloride (10 mmol) and 5 mL chlo-
roform was added dropwise, then the mixture was stirred at 40◦C
for 2 h. The resulting mixture was quenched with water and the or-
ganic layer was dried by sodium sulfate. The solvent was removed
under reduced pressure to give a light yellowish syrup, TLC found
the compound have high purity, yield: 76–92%. Typical compound 4a:
yield: 89%, 1H NMR (δ, ppm) 3.69 (s, 2H, CH2CO), 4.90 (dd, 1H, PCH,
2
3JHH = 10.0Hz, JPH = 20.0Hz), 6.73–7.14 (m, 15H, Ph), 8.05 (d, 1H,
3
NH, JHH = 10.0Hz); IR (cm−1) 1637 (νC O), 1259 (νP O), 935 (δP C),
MS (EI, 70eV) m/z: 384.5 (M+, 9.5), 302.5(15.7), 164(100), 292(56.8),
77(100), 31PNMR δ, ppm: 10.52.
O,O-Diphenyl [substituted-(2-selenomorpholin-4-yl-
acetylamino)methyl] Phosphonates 5
O,O-diphenyl 2-chloroacetylaminoalkyl phosphonate (10 mmol), se-
lenomorpholine (11 mmol), triethylamine (11 mmol) and 15 mL solvent
acetone were added into a 50 mL reaction flask. The mixture was then
stirred at reflux for 2–3 h. The resulting mixture was quenched with
water and the solvent was removed under reduced pressure, the residue
was dissolved in choloroform, and organic layer was washed with H2O

Alkyl Phosphonates
1069
(60 mL), dried by sodium sulfate, and evaporated to give a crude oil.
Chromatography on silica gel using petromeum ether and acetone (5:1)
as eluent gave product 5.
O,O-Diphenyl [Phenyl-(2-selenomorpholin-4-yl-
acetylamino)methyl] Phosphonate (5a)
Yield: 63%, m.p. 134–137◦C.
1H NMR (δ, ppm): 2.60∼2.67 (m, 4H SeCH2), 2.72∼2.76 (m, 4H,
NCH2), 2.92 (s, 2H, CH2CO), 5.90 (dd, 1H, PCH, 3JHH = 10.0Hz, 2JPH
=
20.0Hz), 6.80–7.45 (m, 15H, Ph), 8.23 (d, 1H, NH, 3JHH = 10.0 Hz)
IR (cm−1) 1673 (νC O), 1264 (νP O), 937 (δP
)
C
MS (EI, 70eV) m/z: 530 (M+, 0.15), 182 (6.38), 164 (100), 150 (27.70),
136 (53.42), 108 (18.24), 93 (50.86)
31PNMR (δ, ppm): 13.83
Anal. Calcd for C25H27N2O4PSe (530): C, 56.72; H, 5.14; N, 5.29;
found, C, 56.48; H, 5.38; N, 5.41
O,O-Diphenyl [2-Chlorophenylphenyl-(2-selenomorpholin-
4-yl-acetylamino)methyl] Phosphonate (5b)
Yield: 45%, m.p. 113–115◦C.
1H NMR (δ, ppm): 2.62∼2.84 (m, 8H SeCH2, NCH2), 2.94 (s, 2H,
CH2CO), 6.45 (dd, 1H, PCH, 3JHH = 10.0Hz, 2JPH = 22.0Hz), 6.80–7.53
(m, 14H, Ph), 8.25 (d, 1H, NH, 3JHH = 10.0Hz)
IR (cm−1) 1684 (νC O), 1269 (νP=O), 937 (δP
)
C
MS (EI,70eV) m/z: 565 (M+,1.12), 164 (100), 150 (36.70), 136 (40.74),
94 (60.54)
31PNMR (δ, ppm): 12.97
Anal. Calcd for C25H26ClN2O4PSe (564.5): C, 53.26; H, 4.65; N, 4.97;
found, C, 52.93; H, 4.49; N, 5.04
O,O-Diphenyl [3-Chlorophenyl-(2-selenomorpholin-4-yl-
acetylamino)methyl] Phosphonate (5c)
Yield: 49%, m.p. 122–123◦C
1H NMR (δ, ppm): 2.59∼2.69 (m, 4H SeCH2), 2.74∼2.86 (m, 4H,
NCH2), 2.96 (s, 2H, CH2CO), 5.85 (dd, 1H, PCH, 3JHH = 10.0Hz, 2JPH
=
20.0Hz), 6.86–7.41 (m, 14H, Ph), 8.13 (d, 1H, NH, 3JHH = 10.0Hz)
IR (cm−1) 1688 (νC O), 1271 (νP O), 937 (δP
)
C
MS (El, 70eV) m/z: 565 (M+, 0.23), 164 (100), 150 (27.67), 136 (42.94),
93 (37.96)
31PNMR (δ, ppm): 13.21
Anal. Calcd for C25H26ClN2O4PSe (564.5): C, 53.26; H, 4.65; N, 4.97;
found, C, 53.04; H, 4.72; N, 4.83.

1070
L. Hu et al.
O,O-Diphenyl [4-Chlorophenyl-(2-selenomorpholin-4-yl-
acetylamino)methyl] Phosphonate (5d)
Yield: 56%, m.p. 89–93◦C
1H NMR (δ, ppm): 2.63∼2.68 (m, 4H SeCH2), 2.74∼2.78 (m, 4H,
NCH2), 2.97 (s, 2H, CH2 CO), 5.84 (dd, 1H, PCH, 3JHH = 10.0Hz, 2JPH
22.0Hz), 6.84–7.43 (m, 14H, Ph), 8.15 (d, 1H, NH, 3JHH = 10.0Hz)
=
IR (cm−1) 1654 (νC O), 1278 (νP=O), 932 (δP
)
C
MS (El, 70eV)m/z: 565 (M+, 0.63), 164 (100), 150 (18.62), 136 (32.97),
93 (42.50)
31PNMR (δ, ppm): 13.28
Anal. Calcd for C25H26ClN2O4PSe (564.5): C, 53.26; H, 4.65; N, 4.97;
found, C, 53.12; H, 4.53; N, 4.89.
O,O-Diphenyl [3,4-Dichlorophenyl-(2-selenomorpholin-4-
yl-acetylamino)methyl] Phosphonate (5e)
Yield: 54%, m.p. 105–107◦C
1H NMR (δ, ppm): 2.64∼2.68 (m, 4H, SeCH2), 2.75∼2.78 (m, 4H,
NCH2), 2.98 (s, 2H, CH2CO), 5.81 (dd, 1H, PCH, 3JHH = 10.0Hz, 2JPH
=
20.0Hz), 6.75∼7.51 (m, 13H, Ph), 8.17 (d, 1H, NH, 3JHH = 10.0Hz)
IR (cm−1) 1669 (νC O), 1275 (νP=O), 932 (δP
)
C
MS (El, 70eV)m/z: 599 (M+, 0.24), 164 (100), 150 (24.76), 136 (42.35),
93 (54.62)
31PNMR (δ, ppm): 12.67
Anal. Calcd for C25H25Cl2N2O4PSe (599): C, 50.19; H, 4.21; N, 4.68;
found, C, 51.07; H, 4.13; N, 4.56.
O,O-Diphenyl [4-Methoxyphenyl-(2-selenomorpholin-4-yl-
acetylamino)methyl] Phosphonate (5f )
Yield: 76%, m.p. 81–83◦C
1H NMR (δ, ppm): 2.59∼2.66 (m, 4H SeCH2), 2.71∼2.79 (m, 4H,
NCH2), 2.94 (s, 2H, CH2CO), 3.76 (s, 3H, CH3O), 5.86 (dd, 1H, PCH,
3JHH = 10.0Hz, 2JPH = 20.0Hz)
IR (cm−1) 1682 (νC O), 1267 (νP=O), 940 (δP
)
C
MS (El,70eV) m/z: 599 (M+, 0.24), 164 (100), 150 (24.76), 136 (42.35),
93 (54.62)
31P NMR (δ, ppm): 12.67
Anal. Calcd for C26H29N2O5PSe (560): C, 55.83; H, 5.23; N, 5.01;
found, C, 55.68; H, 5.18; N, 4.89.
O,O-Diphenyl [1,3-Dihydro-isobenzofuran-5-yl)-
(2-selenomorpholin-4-yl-acetylamino)methyl]
Phosphonate (5g)
Yield: 72%, m.p. 81–83◦C

Alkyl Phosphonates
1071
1H NMR (δ, ppm): 2.56∼2.67 (m, 4H SeCH2), 2.72∼2.84 (m, 4H,
NCH2), 2.93 (s, 2H, CH2CO), 5.77 (dd, 1H, PCH, 3JHH = 10.0Hz, 2JPH
=
22.0Hz), 5.92 (s, 2H, OCH2O), 6.72–7.31 (m, 13H, Ph), 8.10 (d, 1H, NH,
3JHH = 10.0Hz)
IR (cm−1) 1673 (νC O), 1263 (νP=O), 937 (δP
)
C
MS (El, 70eV) m/z: 574 (M+, 0.36), 164 (100), 150 (46.50), 136 (24.53),
93 (62.31)
31P NMR (δ, ppm): 13.62
Anal. Calcd for C26H29N2O6PSe (574): C, 54.46; H, 4.75; N, 4.89;
found, C, 54.82; H, 4.63; N, 4.92.
O,O-Diphenyl [2,4-Dichlorophenyl-(2-selenomorpholin-
4-yl-acetylamino)methyl] Phosphonate (5h)
Yield: 61%, m.p. 123–125◦C
1H NMR (δ, ppm): 2.56∼2.76 (m, 8H SeCH2, NCH2), 2.93 (s, 2H, CH2
CO), 6.37 (dd, 1H, PCH, 3JHH = 10.0Hz, 2JPH = 22.0Hz), 6.86–7.48 (m,
13H, Ph), 8.22 (d, 1H, NH, 3JHH = 10.0Hz)
IR (cm−1) 1685 (νC O), 1274 (δP O), 956 (νP
)
C
MS (EI, 70eV) m/z: 599 (M+, 0.27), 164 (100), 150 (32.62), 136 (34.75),
93 (63.72)
31P NMR (δ, ppm): 12.85
Anal. Calcd for C25H25Cl2N2O4PSe (599): C, 50.19; H, 4.21; N, 4.58;
found, C, 49.84; H, 4.36; N, 4.53.
O,O-Diphenyl [3-Bromophenyl-(2-selenomorpholin-4-yl-
acetylamino)methyl] Phosphonate (5i)
Yield: 59%, m.p. 86–89◦C
1H NMR (δ, ppm): 2.65∼2.68 (m, 4H SeCH2), 2.75∼2.77 (m, 4H
NCH2), 2.97 (s, 2H, CH2CO), 5.84 (dd, 1H, PCH, 3JHH = 10.0Hz, 2JPH
22.0Hz), 6.73–7.56 (m, 14H, Ph), 8.20 (d, 1H, NH,3JHH = 10.0Hz)
=
IR (cm−1) 1683 (δC O), 1280 (νP O), 939 (δP
)
C
MS (EI,70eV) m/z: 609 (M+, 0.15), 164 (100), 150 (57.21), 136 (43.40),
93 (48.50)
31PNMR (δ, ppm): 12.75
Anal. Calcd for C25H26BrN2O4PSe (609): C, 49.37; H, 4.31; N, 4.61;
found, C, 48.93; H, 4.26; N, 4.59.
O,O-Diphenyl [Furan-2-yl-(2-selenomorpholin-4-yl-
acetylamino)methyl] Phosphonate (5j)
Yield: 70%, m.p. 68–69◦C
1H NMR (δ, ppm): 2.60∼2.66 (m, 4H SeCH2), 2.73∼2.76 (m, 4H
3
NCH2), 2.97 (d, 2H, CH2 CO), 6.04 (dd, 1H, PCH, JHH = 10.0Hz,
2JPH = 22.0Hz), 6.34–7.37 (m, 3H, Furyl), 6.97–7.32 (m, 10H, Ph), 7.96
(d, 1H, NH, 3JHH = 10.0Hz)

1072
L. Hu et al.
IR (cm−1) 1669 (νC O), 1265 (νP O), 937 (δP
)
C
MS (EI,70eV) m/z: 520 (M+, 3.54), 164 (100), 150 (67.80), 136 (47.50),
93 (73.20)
31P NMR (δ, ppm): 11.05
Anal. Calcd for C23H25N2O5PSe (520): C, 53.19; H, 4.85; N, 5.39;
found, C, 52.98; H, 4.76; N, 5.43.
O,O-Diphenyl [1-(2-selenomorpholin-4-yl-acetylamino)]
Ethyl Phosphonate (5k)
Yield: 65%, m.p. 62–64◦C
1H NMR (δ, ppm): 1.53 (d, 3H, CH3), 2.64∼2.68 (m, 4H SeCH2),
2.75∼2.79 (m, 4H NCH2), 2.86 (d, 2H, CH2CO), 5.13 (m, 1H, PCH),
7.07–7.46 (m, 10H, Ph), 8.25 (d, 1H, NH,3JHH = 10.0Hz)
IR (cm−1) 1654 (νC O), 1255 (νP O), 934 (δP
)
C
MS (EI,70eV) m/z: 468 (M+, 4.80), 164 (100), 150 (46.53), 136 (61.42),
93 (53.14)
31P NMR (δ, ppm): 15.38
Anal. Calcd for C20H25N2O4PSe (468): C, 51.41; H, 5.39; N, 5.99;
found, C, 51.26; H, 5.51; N, 5.84.
O,O-Diphenyl [1-(2-selenomorpholin-4-yl-acetyl-amino)]
Propyl Phosphonate (5l)
Yield: 68%, m.p. 79–82◦C
3
1H NMR (δ, ppm): 0.97 (t, 3H, CH3, JHH = 7.6Hz), 1.63 (m, 2H,
CH2CH3), 2.67∼2.71 (m, 4H, SeCH2), 2.77∼2.83 (m, 4H NCH2), 2.89
(d, 2H, CH2CO), 5.26 (m, 1H, PCH), 7.03–7.41 (m, 10H, Ph), 8.18 (d,
1H, NH, 3JHH = 10.0Hz)
IR (cm−1) 1658 (νC O), 1250 (νP O), 937 (δP
)
C
MS (EI,70eV) m/z: 482 (M+, 3.77), 164 (100), 150 (51.53), 136 (47.39),
93 (29.61)
31P NMR (δ, ppm): 14.79
Anal. Calcd for C21H27N2O4PSe (482): C, 52.40; H, 5.65; N, 5.82;
found, C, 52.28; H, 5.51; N, 5.76.
REFERENCES
[1] J. T. Rotruk, A. L. Pope, H. E. Ganther, et al., Science, 179, 588 (1973).
[2] R. Landenstein, O. Epp, K. Bartels, et al., J. mol. Biol., 134, 199 (1979).
[3] A. Muller, E. Cadenzas, and R. Graf, Biochem. Pharmacol., 33(20), 3235 (1984).
[4] M. Maiorino, A. Roveri, and F. Ursine, Arch Biochem. Biophys., 295(2), 404 (1992).
[5] H. Sies, Methods Enzymol., 234, 476 (1994).

Alkyl Phosphonates
1073
[6] H. Sies, Methods Enzymol, 252, 341 (1995).
[7] H. Sies and G. E. Arteel, Free Radic, Biol. Med., 28(10), 1451 (2000).
[8] X. Qu, K. Husng, and L. Deng. Biol. Trace Elem. Res., 75(1–3), 119 (2000).
[9] K. W. Singletary, Cancer Lett., 49, 187 (1990).
[10] J. A. Czyrski and A. D. Inglot, Experientia, 47(1), 95 (1991).
[11] R. S. Glass, W. P. Singh, W. Jung, et al., Biochemistry, 32, 12555 (1993).
[12] X. Li, Y. Liu, J. Wu, and S. S. Qu, Thermochimica Acta, 375, 103 (2001).
[13] X. Li, Y. Liu, J. Wu, et al., Thermochimica Acta, 387, 57 (2002).
[14] J. Wu, F. J. Gong, Z. Y. Huang, et al. Plant Nutr., 23(3), 349 (2000).
[15] H. S. Xu, Y. X., Xiao, and X. F. Liu, J. Chinese Org. Chem., 15(3), 252 (1995).
[16] Y. X. Xiao, X. F. Liu, and H. S. Xu, Chinese Chem. Lett., 15(3), 252 (1995).
[17] J. E. Conde and M. S. Alaejos, Chem. Rev., 97, 1979 (1997).
[18] K. Hemmi and H. Takeno, Chem. Pharm. Bull., 30, 111 (1982).
[19] a) A. Paul, J. Amer. Chem. Soc., 106(15), 4282 (1984); b) B. Wysocka Skrzela, Pol. J.
Chem., 56, 1573 (1982).
[20] D. D. Baird, Proc. Annu. Calif. Weed Conf., 24, 94 (1972).
[21] L. M. Hu, W. X. Lei, J. H. Feng, and Z. J. Liu J. of Central China Normal Univ. (Sci.
& Tech.), 36(2), 204 (2002).
[22] Y. V. Migalina, V. I. Staninets, and V. G. Lendel, Khim. Geterotsikl. Soedin, 58 (1977).
[23] T. Oleksyszyn et al., Synth. Commun., 985 (1979).