Synthesis of solanesyl phosphonate

Article abstract of DOI:10.1080/10426500701795043

Three solanesyl phosphonates were synthesized using standard Arbuzov reaction, and their structures were determined by ESI-MS, NMR, and IR. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500701795043

Phosphorus, Sulfur, and Silicon, 183:631–635, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701795043
Synthesis of Solanesyl Phosphonate
Qu Lingbo,1 Shi Xiaona, Chen Xiaolan, and Fan Libo
,2
2
2
2
1
Henan University of Technology, Henan Province, Zhengzhou,
P. R. China;
2
Department of Chemistry, Zhengzhou University, Zhengzhou,
P. R. China
Three solanesyl phosphonates were synthesized using standard Arbuzov reaction,
and their structures were determined by ESI-MS, NMR, and IR.
Keywords Anti-cancer drug; arbuzov reaction; phosphonates; solanesyl phosphonate
INTRODUCTION
Solanesol, a long-chain terpenoid alcohol mainly existing in tobacco
leaves, is the starting material for many high-value biochemicals, in-
cluding Vitamin K analogues and co-enzyme Q10 which is useful in the
treatment of heart diseases, cancers and ulcers. Solanesol itself can be
used as cardiac stimulant, lipid antioxidant and antibiotics, and clinical
1
trials are also developing the use of solanesol as an anti-cancer drug.
Phosphonates have important applications in flame retardancy, or-
2
ganic synthesis, and biological applications. Phosphate esters play an
important role in a wide variety of structurally diverse natural and bio-
3
logically active compounds, from glycolipids to nucleic acids. Introduc-
tion of a phosphate group essentially changes the physical and chem-
ical properties of the parent molecule, resulting in changes to the po-
larization and intermolecular bonding characteristics of that molecule.
Within the pharmaceutical industry, phosphate esters are often used
as pro-drugs to increase the water solubility and hence bio-availability
4
of the agent, such as the antiinflammatory agents dexamethasone and
oxyphenbutazone.5 The toxicity of phosphonates to aquatic organisms
The authors thank the Chinese National Science Foundation (No. 20472076 and
2
0175026) and Henan Academic Foundation of Science and Technology for their financial
support.
Address correspondence to Chen Xiao-lan, Department of Chemistry, Zhengzhou Uni-
versity, Zhengzhou 450052, P. R. China. E-mail: chenxl@zzu.edu.cn
631

6
32
Q. Lingbo et al.
is low. Human toxicity is also low which can be seen in the fact that phos-
phonates are used to treat various diseases. Phosphonates are similar
to phosphates except that they have a C P bond in place of the C O P
linkage. Due to their structural similarity to phosphate esters, phospho-
nates often act as inhibitors of enzymes due in part to the high stability
of the C P bond.
The Michaelis-Arbuzov reaction is a chemical reaction for the for-
mation of phosphonates from trialkyl phosphites and alkyl halides. In
the work described in this paper, three solanesyl phosphonates were
6
synthesized using standard Arbuzov reaction (Scheme 1), and their
structures were determined by ESI-MS, NMR, and IR.
SCHEME 1 Synthesis of solanesyl phosphonates.
EXPERIMENTAL
IR spectra were recorded on a Shimadazuir-408. H-NMR and 31P-NMR
1
spectra were on a Bruker-DTX-400, chemical shifts were expressed in
1
parts per million positive values downfield from internal TMS ( H) and
31
external 85% H3PO4 ( P), coupling constants were expressed in Hertz.
MS was recorded on Bruker Esquire-3000 and Micromiss Q-Tof. Melt-
ing point was recorded on a microscopical determinator XT4 A (the
thermometer was not adjusted).
Synthesis of Solanesyl Bromide 27
Solanesol 1 10.0 g was dissolved in 70 ml petroleum ether in a 250 ml
three-necked flask. Then 14 ml pyridine was added into the flask, and
◦
the temperature was maintained at −5 C using an ice/salt bath. A so-
lution of 2.2 g phosphorus tribromide in 15 ml of petroleum ether was
added dropwise to the mixture over 1 h. Then the mixture was stirred
◦
and the temperature was maintained at −5 C for 3 h. The disappear-
ance of the solanesol in the reaction solution was checked using TLC

Solanesyl Phosphonate
633
(
CHCl3:CH3OH = 1:1). 60 ml ice water was added to the reaction solu-
tion afterwards, and then extracted by 3 × 45 mL petroleum ether. The
organic layer was washed with saturated sodium chloride solution and
dried with anhydrous sodium sulphate. The crude solanesyl bromide 2
(
6.7 g), a light-yellow liquid was finally obtained and then used in the
next reaction without further purification.
Synthesis of Title Compound 3 through Arbuzov Reaction
5.0 g crude solanesyl bromide 2, 35 ml toluene and 5.4 g trialkylphos-
phate were added to a 100 ml flask. The mixture was refluxed for 12
◦
h. and then evaporated in vacuo below 50 to remove toluene and part
of trialkylphosphate. The title compound 3, a light-yellow liquid was
obtained after being purified by column chromatography (petroleum
ether: CH3COOCH2CH3 = 1:1).
Compound 3a (C H O P)
4
7
79
3
1
H NMR (CDCl3 400 MHz) δ: 1.60∼1.68 (30H, CH3), 2.04∼2.08
(
m, 32H, CH2), 2.52∼2.59 (dd, J = 22.0, 7.6 Hz, 2H, CH2-
P), 4.09∼4.14 (m, 6H, OCH3), 5.08∼5.13 (m, 9H, CH); ESI-
+
+
+
+
MS/MS, m/z: 723 [M+H] ,746 [M+Na] , 432 [M-C17H31O3P+Na] ,
+
3
64 [M-C22H39O3P+Na] , 296 [M-C27H47O3P +Na] , 228[M-
+
C32H55O3P+Na] . A detail ESI-MS/MS fragmentation pathway
of sodium adduct of compound 3a was shown in Scheme 2. A molecular
SCHEME 2 ESI-MS/MS fragmentation pathway of sodium adduct of com-
pound 3a.

6
34
Q. Lingbo et al.
formula of C47H79O3P was determined from the molecular ion peak at
+
m/z 723.5801 [M+H] (calcd. for C47H79O3P 722.5767) obtained by
ESIQ-TOF.
Compound 3b (C H O P)
4
9
83
3
1
H NMR (CDCl3 400 MHz) δ: 1.29∼1.33 (t, 6H, -CH2CH3), 1.60∼1.68
(
30H, CH3), 2.04∼2.08 (m, 32H, CH2), 2.53∼2.61 (dd, J = 22.0, 7.6
Hz, 2H, CH2-P), 4.08∼4.15 (m, 4H, OCH2CH3), 5.10∼5.11 (m, 9H, -
+
CH); ESI-MS, m/z: 751 [M+H] . A molecular formula of 49H83O3P was
+
determined from the molecular ion peak at m/z 751.6086 [M+H] (calcd.
for 49H83O3P 750.6080) obtained by ESIQ-TOF.
Compound 3c (C H O P)
5
1
87
3
1
H NMR (CDCl3 400 MHz) δ: 1.30∼1.35 (m, 12H, -CH3), 1.60∼1.68
(
30H, CH3), 2.05∼2.08 (m, 32H, 16-CH2), 2.51∼2.57 (dd, J = 21.9, 7.6
Hz, 2H, CH2-P), 4.60∼4.70 (m, 2H, CH), 5.10∼5.13 (m, 9H, CH);
+
ESI-MS, m/z: 779 [M+H] . A molecular formula of C51H87O3P was de-
+
termined from the molecular ion peak at m/z779.6389 [M+H] (calcd.
for C51H87O3P 778.6393) obtained by ESIQ-TOF.
The products described above were characterized by H, 13C, and
1
3
1
P NMR. An additional splitting of proton resonance of -CH2-P group
was observed. The signal from the two equivalent hydrogen atoms of
the -CH2-P group is split into dd peaks by adjacent hydrogen of the =
CH- group and adjacent phosphorus atom. The spectra of phosphorus-
containing compounds frequently show additional splitting of proton
resonances due to 31P- H coupling.
1
CONCLUSION
Three new solanesyl phosphonates were synthesized using standard
6
Arbuzov reaction. Their structures were determined by ESI-MS, NMR,
and IR.
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