rexresearch.com
Gilberto CHIERICE
PhosphoEthanolamine vs Cancer
http://www.sciencemag.org/news/2016/04/brazil-president-signs-law-legalizing-renegade-cancer-pill
Brazil president signs law legalizing
renegade cancer pill
By Herton Escobar
Responding to political pressure and popular demand for a largely
untested cancer drug, Brazilian President Dilma Rousseff signed
into law today a measure that allows the renegade
compound—synthetic phosphoethanolamine—to be produced and sold
legally as a cancer therapy in Brazil.
Scientists poured scorn on the decision, contending it puts
patients at risk and undermines the authority of the Brazilian
Health Surveillance Agency (the equivalent of the U.S. Food and
Drug Administration) to regulate research and approval of new
drugs based on internationally accepted safety and efficacy
protocols. This was a “political decision inspired by a messianic
surge of pseudoscience,” says Gustavo Fernandes, president of the
Brazilian Society of Clinical Oncology in Brasília. “It was the
worst possible way of dealing with this problem.”
The “cancer pill” sparked a national debate last year after
Brazilian media carried testimonials of patients claiming that it
relieved symptoms or even cured their cancer. The compound was
developed in the early 1990s by Gilberto Chierice, an analytical
chemist at the University of São Paulo whose lab distributed it to
patients free of charge for several years, without any regulatory
approval or clinical oversight.
Apart from a few studies in mouse models and in cell lines, there
is no laboratory evidence that synthetic phosphoethanolamine works
as a cancer drug. The university tried to shut down Chierice’s
operation in June 2014, but since then more than 15,000 people
sued the university, forcing it to continue providing them with
the pills. Advocacy groups, meanwhile, pressured politicians and
health authorities to legalize use of the compound as a cancer
drug. Brazil’s congress passed a bill to do just that last month.
Officials in the ministries of health, industry, and science
advised Rousseff to veto the bill, according to O Estado de S.
Paulo newspaper. But with Rousseff fighting for her political
life—the congress is attempting to impeach her over allegations of
fiscal improprieties—her executive office recommended signing the
bill, sources say.
The law authorizes production, prescription, and consumption of
synthetic phosphoethanolamine as a cancer therapy “independently”
of registration with the Brazilian Health Surveillance Agency. To
acquire the pills, consumers must show medical proof that they
have a malignant tumor and sign a consent form.
Under the new law, the substance can only be produced and
distributed by “licensed agents.” On 1 April, the University of
São Paulo closed Chierice’s former research lab, which had until
then been producing the pills under court orders. The only place
the compound is currently being produced is a private lab
contracted by the São Paulo state government to supply it for an
upcoming clinical trial. The lab is preparing the pills according
to a formula patented by Chierice and six colleagues; they claim
their preparation is different from the synthetic
phosphoethanolamine available on the international market as a
dietary supplement.
Late last year, the science ministry committed to spending nearly
$3 million on preclinical studies of synthetic
phosphoethanolamine. Initial results, made public last month, were
not promising. According to the experiments, conducted at four
academic and private labs, the pills produced by Chierice’s group
contained only 30% synthetic phosphoethanolamine, and the
substance failed to kill cancer cells. It doesn’t appear to be
toxic.
At a 5 April hearing in Brazil’s Federal Senate, Chierice charged
that the government-sponsored studies are being done in “bad
faith,” and stated that his group is obtaining clinical data from
overseas. The University of São Paulo in 2015 lodged a complaint
with the police accusing Chierice of “curandeirismo,” or illegally
dispensing unproven medical treatments. A criminal investigation
is underway, according to news reports. “Maybe [Chierice] was well
intentioned, but he did a lot of wrongs,” Fernandes says.
The new law may please desperate cancer patients, but it’s an
unfortunate move, says biochemist Luiz Fernando Lima Reis,
research director at Hospital Sírio-Libanês in São Paulo, where
high-profile politicians have been treated for cancer, including
Rousseff in 2009 and former President Luiz Inácio Lula da Silva in
2011. “Decisions like this should be based on scientific
evidence,” Reis says.
http://onlinenewsads.com/latest-news/discovery-rare-that-substance-to-cure-cancer-patients/
Phosphoethanolamine
...What substance is this? It is the combination of a very common
substance used in many hair shampoos, called monoethanolamine, and
phosphoric acid, which is a food preservative. The combination of
these two compounds produces a substance called
phosphoethanolamine, which is a marker of differentiated cells,
which are considered cancer cells.
As it acts in the body? This substance ourselves manufacture
within the long muscle cells and liver endoplasmic reticulum. So
we can not call it natural product because it is synthesized, but
your body already makes for the same purpose: to defend you at all
times of your life cells that differentiate.
In practice, this substance reinforces what we already have? How
it acts in the cancer cell? First, it passes the digestive tract
to the bloodstream, it goes to the liver and forms a reaction with
the fatty acid. What is this fatty acid? It is the substance that
is fed to the tumor. It tumor energy. And it goes along with this
substance inside the cell. When she comes in, that cell is
relatively still, ie the main organelle her, called mitochondria,
is stopped. It forces the mitochondria to work and when it forces,
it denounces to the immune system and the cell is settled, is
called apoptosis…
Is there any contraindications? The capsule has to be ingested
before the person to do chemotherapy? There is no “before” because
it does not work as an adjunct. If you blow the immune system of
the person, the results are not good because the action of
fosfoamina requires that the immune system is intact. If there is
no chemotherapy which destroys the immune system, perfect, may be
combined. You have an idea of how many people have benefited
from this substance in the last 20 years? Lately we made about
50,000 capsules per month. This equates to 60 each person, 800
people or close to a thousand people a month. Now how many people
have benefited I am not able to say because many of them, who were
terminally ill, are there, alive. So I can not say how many people
were healed. You published this study in several scientific
journals. How many in total? Today I suppose there are nine to ten
work in the best oncology journals in the world, which are
international journals, along with the staff of the [Institute]
Butantan, and explain the fosfoamina mechanism of action…
BRPI0800463
Fosfoetanolamina como precursor de fosfolipìdeo para
correção de disfunções celulares e metabólicas
Inventor(s): NETO SALVADOR CLARO; AL-ASFOUR
SANDRA VASCONCELLOS; DE ALMEIDA MARCOS VINICIUS; MENEGUELO RENATO;
CHIERICE GILBERTO ORIVALDO; REIMER ANTONIO JOSE
Que representa uma aplicação inovadora para um composto precursor
de síntese de lipídeos, denominado fosfoetanolamina, o qual possui
atividade de correção de disfunção celular e metabólica, incluindo
atividades antiproliferativas, apoptóticas, neuroprotetora e
antiepiléptica.
Related :
WO2015093588
ANTI-CANCER AGENT
Inventor(s): NISHIZAKI TOMOYUKI [JP]; NAKANO
TAKASHI [JP] +
Applicant(s): KTN BIOTEC INC [JP] +
The present invention provides an anti-cancer agent containing
1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine as an active
ingredient, an agent to induce cell death, a protein phosphatase
2A activation potentiator, and a protein tyrosine phosphatase 1B
activation potentiator, and the like.
WO 2008119146
CHEMICAL COMPOSITION IN MASS OF
COMPOUND FOR THE TREATMENT OF BRONCHIAL ASTHMA..
The object of the invention is a composition for the treatment of
bronchial asthma and chronic obstructive pulmonary disease,
characterized in that the composition comprises
phosphoethanolamine and Omega-3 folly acids in pre-established
proportions. The preferred dose is 400 to 1200 mg/day, more
specifically 800 mg/day for the phosphoethanolamine and 500 to
3200 mg/day, more specifically 1000 mg/day for the
cicosapentaenoic acid 'EPA' and 350 to 2000 mg/day, more
specifically 750 mg/day for the cocosahexaenoic acid 'DHA'.
https://www.facebook.com/PhosphoethanolamineSynthetic/info?tab=page_info
Phosphoethanolamine Synthetic - The
Cancer cure
http://www.fosfo.etanolamina.com.br
USP 3644603
Method of Making 2-AminoEthylPhosphate
http://www1.folha.uol.com.br/internacional/en/scienceandhealth/2016/06/1777072-effectiveness-of-cancer-pill-disproved-in-new-test.shtml
06/01/2016
Effectiveness of 'Cancer Pill'
Disproved in New Test
REINALDO JOSÉ LOPES
The hope in the therapeutic potential of phosphoethanolamine, the
"cancer pill", suffered a new setback in tests sponsored by the
federal government.
Mice and rats with cancer that received doses of the substance had
no improvement - the tumors in the animals' organisms continued to
grow.
Posted on the website of the Ministry of Science, Technology,
Innovation and Communications (MCTIC, in its Portuguese acronym),
the results add to other evidence that "phospho", as it is called,
may not have a good performance against cancer.
Until now, the only positive result was the indication that
phosphoethanolamine would not be toxic even when ingested at
relatively high concentrations.
The data have been challenged by researchers who work with the
substance, led by chemist Gilberto Chierice, a retired professor
at the University of São Paulo.
Chierice and colleagues as Durvanei Augusto Maria, of Butantan
Institute, argued that the concentration of "phospho" used in the
in vitro tests were much lower than those employed in their own
studies, and that the individual's metabolism as a whole (and not
single cells) would be necessary for the pill to work.
The team published some studies showing anti-tumor effects of
"phospho", both in vitro and in vivo (in live animals), involving
different types of tumor.
Folha tried to speak to the researchers that vouch for the
benefits of phospho, but they did not answer until the conclusion
of this edition.
https://www.mpbio.com/product.php?pid=05217802&country=223
05217802 MP BIOMEDICALS
o-PHOSPHOETHANOLAMINE
White Crystalline Powder
Synonyms O-Phosphorylethanolamine, 2-Aminoethyl dihydrogen
phosphate, O-Phosphocolamine, Colaminephosphoric acid
CAS Number 1071-23-4
Molecular Formula C2H8NO4P
Molecular Weight 141.06
Beilstein Registry Number 1758916
EC Number 213-988-5
MDL Number MFCD00008178
Properties
Keywords Glycerolipid Metabolism, Lipid,
Lipid Library, Lipids and Related Products, Metabolic Libraries,
Metabolic Pathways, Metabolomics, Research Essentials
Product Type Biochemicals
Biochemical Category Organophosphorus
Chemical Class Organophosphorus
Melting Point 245 °C(Lit.)
http://www.sciencemadness.org/talk/viewthread.php?tid=64374
Phosphoethanolamine
Hi anyone have any information on the simple synthesis of
phosphoethanolamine, because here in Brazil is much talked about
for its anticancer properties.
View user's profile View All Posts By User
It should be pretty easy to make. It's just the phosphoric acid
mono-ester of monoethanolamine.
I'd say reflux monoethanolamine with a large excess of phosphoric
acid for a couple hours, basify with sodium carbonate, then see
what can be distilled off under vacuum. Or, extract it with some
inorganic solvent.
Not sure though. Sigma calls for -20C as a storage temp. Could be
unstable.
Boiling with phosphoric acid will not give any product. You need a
specialized phosphorylating agent such as, for example,
dibenzyphopshoryl chloride. There is a huge literature on this
subject (phosphorylation reactions and reagents) and it is
relatively easy to find and learn from.
Hi, i find the simple way, i see various syntheses with complex
molecules, gold chloride, barium, etc. Already the largest
university researchers have invented a process by the reaction of
the two compounds(mea and phosphoric acid) in an alcoholic medium,
washinhg with ethanol and heating at 190 degrees to transform
phosphate in phospho and neutralization with calcium and magnesium
carbonates with yeld of 90%. the problem is the details, here
patents has no free access. [*] posted on 18-11-2015 at 05:28
Well, phooey. For some reason I assumed phosphates were like
borates. It does seem pretty straightforward with the right
reagents though. All the preps in Brauer use POCl3 so they're kind
of prohibitive for amateur use.
This paper has an interesting route:
http://www.sciencedirect.com/science/article/pii/S0040403908...
Facile synthesis of simple mono-alkyl phosphates.png - 8kB
The only difficult thing to get here is the pyridine.
http://www.tandfonline.com/doi/abs/10.3109/01485019708994876
Archives of Andrology: Journal of Reproductive Systems,
Volume 38, Issue 3, 1997
DOI: 10.3109/01485019708994876
Synthesis of Ether Lipids and
Phosphatidylethanolamine by Ejaculated Human Spermatozoa
E. Jones
Abstract
Ether lipids are the 1-O-alkyl derivatives of phospholipids. In
contrast to nongerminal tissues where the plasma membrane content
of ether lipids is low, over 40% of the phospholipids present in
sperm plasma membranes are ether lipids. This study was undertaken
to determine whether ejaculated human sperm could synthesize ether
lipids either through reacylation of
l-alkyl-jn-2-lysophos-phatidylcholine or through direct
incorporation of 1-hexadecanol into diacyl phosphatidylcholine or
diacyl phosphatidylethanolamine. The ability of sperm to reacylate
l-acyl-jn-2-lysophosphatidyl-ethanolamine was also assessed. In
these experiments, freshly ejaculated sperm were unable to
reacylate a phosphocholine lyso ether lipid with either palmitic
(16:0) or docosahexaenoic (22:6) acids. In contrast, sperm readily
incorporated both 16:0 and 22:6 into 1-acyl
lysophosphatidylethanolamine. Similarly, sperm freely incorporated
1-hexadecanol into diacyl phosphatidylethanolamine thus forming a
1-alkyl phosphoethanolamine ether lipid. Diacyl
phosphatidylcholine could not serve as a substrate in this
reaction. It is apparent, based on these data, that human
spermatozoa can directly synthesize phosphoethanolamine ether
lipids that may subsequently undergo exhaustive methylation to
form phosphocholine ether lipids.
https://www.wikigenes.org/e/chem/e/1015.html
2-aminoethoxyphosphonic
acid
Chemical Compound Review
CHEMBL146972 2-aminoethoxyphosphonic
acid
Synonyms: CHEBI:17553, P0503_SIGMA, HMDB00224, ANW-43177,
GEO-00129, ...
Pessi, G. et al., Bottazzi, B. et al., Menon, A.K. et al.,
Kennedy, E.P. et al., Fedde, K.N. et al., et al.
Table of contents
Disease relevance of ethanolamine phosphate
Psychiatry related information on
ethanolamine phosphate
High impact information on ethanolamine
phosphate
Chemical compound and disease context of
ethanolamine phosphate
Biological context of ethanolamine
phosphate
Anatomical context of ethanolamine
phosphate
Associations of ethanolamine phosphate
with other chemical compounds
Gene context of ethanolamine phosphate
Analytical, diagnostic and therapeutic
context of ethanolamine phosphate
Disease relevance of ethanolamine phosphate
Alkaline phosphatase (tissue-nonspecific
isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate
ectophosphatase: normal and hypophosphatasia fibroblast study [1].
Unique modifications with phosphocholine and
phosphoethanolamine define alternate antigenic forms of Neisseria
gonorrhoeae type IV pili [2].
The human lymphoma cell line MOLT-4 was also
found to contain high levels of phosphocholine and
phosphoethanolamine [3].
Identification of sn-glycero-1-phosphate and
phosphoethanolamine residues linked to the membrane-derived
Oligosaccharides of Escherichia coli [4].
Lipid A modifications in polymyxin-resistant
Salmonella typhimurium: PMRA-dependent
4-amino-4-deoxy-L-arabinose, and phosphoethanolamine incorporation
[5].
Psychiatry related information on ethanolamine phosphate
Ethanolamine and phosphoethanolamine inhibit
mitochondrial function in vitro: implications for mitochondrial
dysfunction hypothesis in depression and bipolar disorder [6].
Phosphoethanolamine (PE) is a metabolite of the
phospholipid metabolism which is decreased in Alzheimer's disease
brain [7].
High impact information on ethanolamine phosphate
We show that trypanosome GPIs can be labelled
via CDP-[3H]ethanolamine or [beta-32P]CDP-ethanolamine in a
cell-free system, indicating that phosphoethanolamine is acquired
en bloc [8].
GPI anchors are synthesized in the endoplasmic
reticulum by stepwise glycosylation of phosphatidylinositol (via
UDP-GlcNAc and dolichol-P-mannose) followed by the addition of
phosphoethanolamine [8].
(ii) The phosphoethanolamine and the
phosphocholine head group conformation were found to be remarkably
similar in pure lipid bilayers and in intact L-M cell membranes
with the head group dipoles being oriented parallel to the
membrane surface [9].
S-Adenosyl-L-methionine:phosphoethanolamine
N-methyltransferase (PEAMT; EC 2.1.1.103) catalyzes the key step
in choline (Cho) biosynthesis, the N-methylation of
phosphoethanolamine [10].
Here, we describe in P. falciparum a plant-like
S-adenosyl-l-methionine-dependent three-step methylation reaction
that converts phosphoethanolamine into phosphocholine, a precursor
for the synthesis of phosphatidylcholine [11].
Chemical compound and disease context of ethanolamine phosphate
Ca2+-induced phosphoethanolamine transfer to
the outer 3-deoxy-D-manno-octulosonic acid moiety of Escherichia
coli lipopolysaccharide. A novel membrane enzyme dependent upon
phosphatidylethanolamine [12].
Pig-o knockout F9 embryonal carcinoma cells
expressed very little GPI-anchored proteins and accumulated the
same major GPI intermediate as the mouse class F mutant cell,
which is defective in transferring phosphoethanolamine to the
third mannose due to mutant Pig-f gene [13].
Identification of a gene (lpt-3) required for
the addition of phosphoethanolamine to the lipopolysaccharide
inner core of Neisseria meningitidis and its role in mediating
susceptibility to bactericidal killing and opsonophagocytosis
[14].
The increase of the 3.2 ppm peak in the glioma
was found to result from the increase of taurine and
phosphoethanolamine contents [15].
We conclude that a dysfunction of the BBB, of a
degree known to induce brain edema (10 mg of protamine sulfate),
significantly increases the extracellular concentration of
excitatory amino acids, GABA, taurine, and phosphoethanolamine in
the extracellular space [16].
Biological context of ethanolamine phosphate
A pathway for phosphatidylcholine biosynthesis
in Plasmodium falciparum involving phosphoethanolamine methylation
[11].
Despite substantial ALP activity, in cell
homogenates, toward the artificial substrate 4-methyl-umbelliferyl
phosphate (4-MUP), there was a marked deficiency in ALP activity
toward the natural substrates pyridoxal 5'-phosphate (PLP) and
phosphoethanolamine (PEA), indicating altered substrate
specificity [17].
ATP analogs such as ADP and AMP exerted marked
inhibitory effects on both [gamma-32P]ATP hydrolysis and
ATP-initiated calcification by intact MVs, whereas
phosphomonoesters such as beta-glycerophosphate or
phosphoethanolamine had no effect [18].
The N-methylation of phosphoethanolamine is the
committing step in choline biogenesis in plants and is catalyzed
by S-adenosyl-L-methionine:phosphoethanolamine N-methyltransferase
(PEAMT, EC ) [19].
The changes in gene expression were not due to
a direct effect of beta-GP itself, because similar gene changes
occurred in the presence of phosphoethanolamine, another agent
which induces mineralization [20].
Anatomical context of ethanolamine phosphate
Phosphoethanolamine as a growth factor of a
mammary carcinoma cell line of rat [21].
A possible role of phosphoethanolamine in the
growth of mammary tumor cells as well as of normal mammary
epithelial cells and other tissues is discussed [21].
Phosphoethanolamine contents were significantly
reduced at autopsy in frontal and occipital cortex, and in the
substantia innominata [22].
Both patients had subnormal serum alkaline
phosphatase activity, absence of leukocyte alkaline phosphatase,
increased amounts of urinary phosphoethanolamine, and normal
levels of immunoreactive calcitonin and parathyroid hormone [23].
Phosphocholine is synthesized in the cytosol by
three successive S-adenosyl-Met-dependent N-methylations of
phosphoethanolamine [24].
Associations of ethanolamine phosphate with other chemical
compounds
Serine, which is actively transported by
Plasmodium from human serum and readily available in the parasite,
is subsequently converted into phosphoethanolamine [11].
After the higher doses the relative
concentrations (in percentage of total phosphate as visible in the
nuclear magnetic resonance spectrum) of phosphomonoesters (mainly
phosphoethanolamine) and phosphocreatine also decreased in favor
of Pi [25].
Although the formation of CDP-ethanolamine is
regarded as the rate-limiting step for phosphatidylethanolamine
biosynthesis, choline was found to inhibit ethanolamine kinase,
but did not have any effect on phosphoethanolamine
cytidylyltransferase [26].
The phosphoethanolamine residues are linked to
position 6 of glucose units, as proved by the isolation of glucose
6-phosphate as a product of partial acid hydrolysis [4].
Matrix-assisted laser desorption
ionization/time of flight mass spectrometry of purified EV1 to EV6
indicated that these compounds were lipid A species substituted
singly or in combination with palmitoyl, phosphoethanolamine,
and/or aminodeoxypentose residues [27].
Gene context of ethanolamine phosphate
Pig-n, a mammalian homologue of yeast Mcd4p, is
involved in transferring phosphoethanolamine to the first mannose
of the glycosylphosphatidylinositol [28].
Glycosylphosphatidylinositol biosynthesis
defects in Gpi11p- and Gpi13p-deficient yeast suggest a branched
pathway and implicate gpi13p in phosphoethanolamine transfer to
the third mannose [29].
Unlike the classical pentraxins CRP and SAP,
PTX3 did not bind phosphoethanolamine, phosphocholine, or high
pyruvate agarose [30].
Isolation and characterization of ECT1 gene
encoding CTP: phosphoethanolamine cytidylyltransferase of
Saccharomyces cerevisiae [31].
On the other hand, low-molecular-mass
(monomeric or dimeric) AQN-3 and AWN-1 were the only spermadhesins
retained in a phosphorylethanolamine affinity column [32].
Analytical, diagnostic and therapeutic context of ethanolamine
phosphate
Electrospray ionization-mass spectrometry
analysis of the O-deacylated LOS oligosaccharide indicated a
modification of the core structure characterized in part by a net
loss in phosphoethanolamine [33].
Using in vitro pH titration data to calculate
intracellular pH, it was found that pH values from the
phosphoethanolamine peak (pH 6.84 to 6.80) were lower than pH
estimates from the inorganic phosphate peak (pH 7.22 to 6.99)
[34].
Superfusate aspartate, glutamate,
phosphoethanolamine, taurine, and GABA were significantly elevated
by cerebral ischemia, then declined during reperfusion [35].
Significant perturbations in tissue
phosphoethanolamine (3.84 delta resonance) content were evident at
various time points during ischemia and postischemic recovery,
which varied according to the perfusion conditions [36].
L3,7,9 phosphoethanolamine (PEA)
group-containing oligosaccharide-tetanus toxoid conjugates evoked
high immunoglobulin G (IgG) antibody levels in rabbits which were
detected by an L2-, L3,7,9-, and, depending on the antiserum,
L1-specific enzyme-linked immunosorbent assay (ELISA) [37].
References
Alkaline phosphatase (tissue-nonspecific
isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate
ectophosphatase: normal and hypophosphatasia fibroblast study.
Fedde, K.N., Whyte, M.P. Am. J. Hum. Genet. (1990)
Unique modifications with phosphocholine and
phosphoethanolamine define alternate antigenic forms of Neisseria
gonorrhoeae type IV pili. Hegge, F.T., Hitchen, P.G., Aas, F.E.,
Kristiansen, H., Løvold, C., Egge-Jacobsen, W., Panico, M., Leong,
W.Y., Bull, V., Virji, M., Morris, H.R., Dell, A., Koomey, M.
Proc. Natl. Acad. Sci. U.S.A. (2004)
Regulation of the cytidine phospholipid
pathways in human cancer cells and effects of
1-beta-D-arabinofuranosylcytosine: a noninvasive 31P nuclear
magnetic resonance study. Daly, P.F., Zugmaier, G., Sandler, D.,
Carpen, M., Myers, C.E., Cohen, J.S. Cancer Res. (1990)
Identification of sn-glycero-1-phosphate and
phosphoethanolamine residues linked to the membrane-derived
Oligosaccharides of Escherichia coli. Kennedy, E.P., Rumley, M.K.,
Schulman, H., Van Golde, L.M. J. Biol. Chem. (1976)
Lipid A modifications in polymyxin-resistant
Salmonella typhimurium: PMRA-dependent
4-amino-4-deoxy-L-arabinose, and phosphoethanolamine
incorporation. Zhou, Z., Ribeiro, A.A., Lin, S., Cotter, R.J.,
Miller, S.I., Raetz, C.R. J. Biol. Chem. (2001)
Ethanolamine and phosphoethanolamine inhibit
mitochondrial function in vitro: implications for mitochondrial
dysfunction hypothesis in depression and bipolar disorder.
Modica-Napolitano, J.S., Renshaw, P.F. Biol. Psychiatry (2004)
Inactivity of phosphoethanolamine, an
endogenous GABA analog decreased in Alzheimer's disease, at GABA
binding sites. Klunk, W.E., Debnath, M.L., McClure, R.J.,
Pettegrew, J.W. Life Sci. (1995)
Phosphatidylethanolamine is the donor of the
terminal phosphoethanolamine group in trypanosome
glycosylphosphatidylinositols. Menon, A.K., Eppinger, M., Mayor,
S., Schwarz, R.T. EMBO J. (1993)
Structure and dynamics of the
phosphatidylcholine and the phosphatidylethanolamine head group in
L-M fibroblasts as studied by deuterium nuclear magnetic
resonance. Scherer, P.G., Seelig, J. EMBO J. (1987)
Silencing of phosphoethanolamine
N-methyltransferase results in temperature-sensitive male
sterility and salt hypersensitivity in Arabidopsis. Mou, Z., Wang,
X., Fu, Z., Dai, Y., Han, C., Ouyang, J., Bao, F., Hu, Y., Li, J.
Plant Cell (2002)
A pathway for phosphatidylcholine biosynthesis
in Plasmodium falciparum involving phosphoethanolamine
methylation. Pessi, G., Kociubinski, G., Mamoun, C.B. Proc. Natl.
Acad. Sci. U.S.A. (2004)
Ca2+-induced phosphoethanolamine transfer to
the outer 3-deoxy-D-manno-octulosonic acid moiety of Escherichia
coli lipopolysaccharide. A novel membrane enzyme dependent upon
phosphatidylethanolamine. Kanipes, M.I., Lin, S., Cotter, R.J.,
Raetz, C.R. J. Biol. Chem. (2001)
Requirement of PIG-F and PIG-O for transferring
phosphoethanolamine to the third mannose in
glycosylphosphatidylinositol. Hong, Y., Maeda, Y., Watanabe, R.,
Inoue, N., Ohishi, K., Kinoshita, T. J. Biol. Chem. (2000)
Identification of a gene (lpt-3) required for
the addition of phosphoethanolamine to the lipopolysaccharide
inner core of Neisseria meningitidis and its role in mediating
susceptibility to bactericidal killing and opsonophagocytosis.
Mackinnon, F.G., Cox, A.D., Plested, J.S., Tang, C.M., Makepeace,
K., Coull, P.A., Wright, J.C., Chalmers, R., Hood, D.W., Richards,
J.C., Moxon, E.R. Mol. Microbiol. (2002)
In vivo, ex vivo, and in vitro one- and
two-dimensional nuclear magnetic resonance spectroscopy of an
intracerebral glioma in rat brain: assignment of resonances. Rémy,
C., Arús, C., Ziegler, A., Lai, E.S., Moreno, A., Le Fur, Y.,
Décorps, M. J. Neurochem. (1994)
Concentrations of amino acids in extracellular
fluid after opening of the blood-brain barrier by intracarotid
infusion of protamine sulfate. Westergren, I., Nyström, B.,
Hamberger, A., Nordborg, C., Johansson, B.B. J. Neurochem. (1994)
Pseudohypophosphatasia: aberrant localization
and substrate specificity of alkaline phosphatase in cultured skin
fibroblasts. Fedde, K.N., Cole, D.E., Whyte, M.P. Am. J. Hum.
Genet. (1990)
Evidence of the presence of a specific ATPase
responsible for ATP-initiated calcification by matrix vesicles
isolated from cartilage and bone. Hsu, H.H., Anderson, H.C. J.
Biol. Chem. (1996)
cDNA cloning of phosphoethanolamine
N-methyltransferase from spinach by complementation in
Schizosaccharomyces pombe and characterization of the recombinant
enzyme. Nuccio, M.L., Ziemak, M.J., Henry, S.A., Weretilnyk, E.A.,
Hanson, A.D. J. Biol. Chem. (2000)
Deep zone articular chondrocytes in vitro
express genes that show specific changes with mineralization. Sun,
Y., Kandel, R. J. Bone Miner. Res. (1999)
Phosphoethanolamine as a growth factor of a
mammary carcinoma cell line of rat. Kano-Sueoka, T., Cohen, D.M.,
Yamaizumi, Z., Nishimura, S., Mori, M., Fujiki, H. Proc. Natl.
Acad. Sci. U.S.A. (1979)
Amino acids, glutathione, and glutathione
transferase activity in the brains of patients with Alzheimer's
disease. Perry, T.L., Yong, V.W., Bergeron, C., Hansen, S., Jones,
K. Ann. Neurol. (1987)
Heterogeneity of adult hypophosphatasia. Report
of severe and mild cases. Weinstein, R.S., Whyte, M.P. Arch.
Intern. Med. (1981)
Maintaining methylation activities during salt
stress. The involvement of adenosine kinase. Weretilnyk, E.A.,
Alexander, K.J., Drebenstedt, M., Snider, J.D., Summers, P.S.,
Moffatt, B.A. Plant Physiol. (2001)
Murine mammary tumor response to hyperthermia
and radiotherapy evaluated by in vivo 31P-nuclear magnetic
resonance spectroscopy. Sijens, P.E., Bovée, W.M., Seijkens, D.,
Koole, P., Los, G., van Rijssel, R.H. Cancer Res. (1987)
Choline regulates phosphatidylethanolamine
biosynthesis in isolated hamster heart. Zelinski, T.A., Choy, P.C.
J. Biol. Chem. (1982)
Lipid A modifications characteristic of
Salmonella typhimurium are induced by NH4VO3 in Escherichia coli
K12. Detection of 4-amino-4-deoxy-L-arabinose, phosphoethanolamine
and palmitate. Zhou, Z., Lin, S., Cotter, R.J., Raetz, C.R. J.
Biol. Chem. (1999)
Pig-n, a mammalian homologue of yeast Mcd4p, is
involved in transferring phosphoethanolamine to the first mannose
of the glycosylphosphatidylinositol. Hong, Y., Maeda, Y.,
Watanabe, R., Ohishi, K., Mishkind, M., Riezman, H., Kinoshita, T.
J. Biol. Chem. (1999)
Glycosylphosphatidylinositol biosynthesis
defects in Gpi11p- and Gpi13p-deficient yeast suggest a branched
pathway and implicate gpi13p in phosphoethanolamine transfer to
the third mannose. Taron, C.H., Wiedman, J.M., Grimme, S.J.,
Orlean, P. Mol. Biol. Cell (2000)
Multimer formation and ligand recognition by
the long pentraxin PTX3. Similarities and differences with the
short pentraxins C-reactive protein and serum amyloid P component.
Bottazzi, B., Vouret-Craviari, V., Bastone, A., De Gioia, L.,
Matteucci, C., Peri, G., Spreafico, F., Pausa, M., D'Ettorre, C.,
Gianazza, E., Tagliabue, A., Salmona, M., Tedesco, F., Introna,
M., Mantovani, A. J. Biol. Chem. (1997)
Isolation and characterization of ECT1 gene
encoding CTP: phosphoethanolamine cytidylyltransferase of
Saccharomyces cerevisiae. Min-Seok, R., Kawamata, Y., Nakamura,
H., Ohta, A., Takagi, M. J. Biochem. (1996)
Interaction of non-aggregated boar AWN-1 and
AQN-3 with phospholipid matrices. A model for coating of
spermadhesins to the sperm surface. Dostàlovà, Z., Calvete, J.J.,
Töpfer-Petersen, E. Biol. Chem. Hoppe-Seyler (1995)
Mutation of the htrB locus of Haemophilus
influenzae nontypable strain 2019 is associated with modifications
of lipid A and phosphorylation of the lipo-oligosaccharide. Lee,
N.G., Sunshine, M.G., Engstrom, J.J., Gibson, B.W., Apicella, M.A.
J. Biol. Chem. (1995)
The use of the chemical shift of the
phosphomonoester P-31 magnetic resonance peak for the
determination of intracellular pH in the brains of neonates.
Corbett, R.J., Laptook, A.R., Nunnally, R.L. Neurology (1987)
Studies on the effects of lactate transport
inhibition, pyruvate, glucose and glutamine on amino acid, lactate
and glucose release from the ischemic rat cerebral cortex.
Phillis, J.W., Ren, J., O'Regan, M.H. J. Neurochem. (2001)
P-31 nuclear magnetic resonance analysis of
brain: II. Effects of oxygen deprivation on isolated perfused and
nonperfused rat brain. Kopp, S.J., Krieglstein, J., Freidank, A.,
Rachman, A., Seibert, A., Cohen, M.M. J. Neurochem. (1984)
Minimal oligosaccharide structures required for
induction of immune responses against meningococcal immunotype L1,
L2, and L3,7,9 lipopolysaccharides determined by using synthetic
oligosaccharide-protein conjugates. Verheul, A.F., Boons, G.J.,
Van der Marel, G.A., Van Boom, J.H., Jennings, H.J., Snippe, H.,
Verhoef, J., Hoogerhout, P., Poolman, J.T. Infect. Immun. (1991)
BRPI0800460
nova metodologia de sìntese da fosfoetanolamina na forma
sólida com cálcio, magnésio e zinco e na forma de solução com
monoetanolamina
Inventor(s): NETO SALVADOR CLARO; CHIERICE
GILBERTO ORIVALDO; REIMER ANTONIO JOSE; AL-ASFOUR SANDRA
VASCONCELLOS; RIBEIRO OTAVIANO MENDONCA JR; MENEGUELO RENATO; DE
ALMEIDA MARCOS VINICIUS +
NEW METHODOLOGY synthesis phosphoethanolamine in solid form with
calcium, magnesium and zinc SOLUTION AND HOW TO MONOETHANOLAMINE.
Using espeetroscopia vibrational techniques in the infrared and
elemental analysis, and has a final yield of 90% being added to
the pure crystal, calcium carbonate, magnesium and zinc, for
complete neutralization of phosphoethanolamine in solid form, and
where adding monoethanolamine for neutralization can be a strategy
for obtaining a buffer may be used in cellular and metabolic
disorders.
CN101974029
Method for preparing phosphorylethanolamine compound
Inventor(s): HAIYAN HU; YUCHUAN LI; JINGLING
CHANG +
The invention relates to a method for preparing a
phosphorylethanolamine compound, which belongs to the technical
field of biochemistry. The method comprises the following steps
of: adding ethanolamine or ethanolamine solution into one of
phosphorus pentoxide, the solution of phosphoric acid, phosphorus
oxychloride or the solution of phosphorus oxychloride at a certain
reaction temperature to form a reaction mixture; heating the
reaction mixture for vacuum-drying by using a direct program to
form phosphorylethanolamine or phosphorylethanolamine
hydrochloride; and dissolving the reaction product into water in a
certain amount and then adding ethanolamine or the ethanolamine
solution, wherein the mass ratio of the reaction product to the
water in the certain amount is 1:1-100.; As the water serves as a
solvent, the method of the invention ensures high yield, vast raw
material sources, low production cost, simple, safe and rational
process, short production cycle and high purity of the prepared
product, and avoids wastewater, waste gases and waste residues.
The present invention relates to a process for preparing the
compound phosphoethanolamine, belonging to the technical field of
biochemistry. At a certain temperature the reaction solution was
added to ethanolamine or ethanolamine pentoxide, phosphoric acid,
phosphorus oxychloride or phosphorus oxychloride in a solution to
obtain a reaction mixture; and the reaction mixture was dried
under vacuum through direct temperature program after the
ethanolamine obtained ethanolamine phosphate or phosphoric acid
chloride; the reaction can be first dissolved in a certain amount
of water was then added a solution of ethanolamine or
ethanolamine; the reaction mass with an amount of water in the
ratio of 1 to 100. The present invention is a solvent with water,
which has high yield, wide source of raw materials, low production
cost, no waste, the process is simple and safe and reasonable,
short production cycle, high purity of the product prepared.
TECHNICAL FIELD
The present invention relates to a process for preparing the
compound phosphoethanolamine, belonging to the technical field of
biochemistry.
Background technique
Phosphoethanolamine structured into ethanolamine phosphate (CAS:
1071-23-4), phosphoric acid diethanolamine (CAS: 6094-81-1) and
triethanolamine phosphate (CAS: 29901-63-1). Wherein
monoethanolamine phosphate dihydrogen phosphate, also known as
2-aminoethanol, 2-aminoethanol phosphate, amine phosphates, o-
phosphoethanolamine, phosphoric acid, 2-ethyl-aminoethanol
phosphate, phosphoric acid, cholestyramine, 2-aminoxy ethyl
dihydrogen phosphate, phosphoric acid, cholestyramine, 2-
hydroxyethylamine and phosphoric acid.
Ethanolamine phosphate compounds are widely used in the fields of
biotechnology, medicine, etc., can also be used as feed additives,
special lubricants. Synthetic methods and technology related
ethanolamine phosphate compounds have been disclosed mainly
phosphoric acid and ethanolamine, the first two were prepared with
a solvent solution of a certain concentration, the two mixed in
the reaction solvent and filtered to give ethanolamine phosphate
Finally, in an organic solvent and then dehydrated to obtain a
high temperature phosphoethanolamine; or phosphoric acid and
ethanolamine in an aromatic hydrocarbon (e.g. benzene, toluene,
xylene, etc.), bicyclic hydrocarbons, halogenated hydrocarbons and
high-boiling ethers and ketones and other organic solvents, then
azeotropic, in addition to the high temperature process water,
etc. to obtain purified phosphoethanolamine, e.g. US 2,730,542;
Tetrahedron Letters, (24), 1913-1916,1975; PL 196501, which
reaction formula (1) below. The resulting presence of a single raw
material, process complex, multi-step, long cycle, low yields (44%
-80%), by-products, low purity, high cost, serious waste problems
such above method.
[Image] formula (1)
In the two step reaction phosphoethanolamine large amount of
solvent is required in both: the first reaction, ethanolamine
phosphate precipitated in an organic solvent, while the reaction
system in the lead, heavy metals such as inorganic ions are
precipitated together with, resulting in impurities rich product,
these impurities followed them into the subsequent reaction, and
can not be directly removed in the second step reaction, the
product quality decline, to improve the quality of the need to
adopt further purification treatment such as activated carbon,
increasing the cost and the amount of waste, while reducing the
yield; the second reaction used in organic solvent impurities also
enrichment in the final product, so that product quality to
decline further. In addition, due to the production uses a lot of
organic solvent, resulting in the production environment is poor,
waste, high costs.
SUMMARY
Object of the present invention is to overcome the disadvantages
of the prior art, a method for preparing a compound of
ethanolamine phosphate, which has high yield, wide source of raw
materials, low production cost, no waste, the process is simple
and safe and reasonable, short production cycle, the the product
prepared in high purity.
Object of the present invention is achieved by the following
technical solutions.
A process for preparing ethanolamine phosphate compound of the
present invention, wherein (2) the compound of formula
phosphoethanolamine formula:
[Image]
Wherein, R1 is H or H2N-CH2-CH2, R2 is H or H2N-CH2-CH2, x is 1, 2
or 3;
Specific steps of the method are:
1) At a certain reaction temperature Ethanolamine (HOCH2CH2NH2) or
ethanolamine was added to the reaction to obtain a reaction
mixture;
2) The reaction mixture was temperature-programmed directly
through vacuum dried to obtain ethanolamine or ethanolamine
phosphate, phosphoric acid chloride;
Step 1) The reaction may be first dissolved in a certain amount of
water was then added ethanolamine (HOCH2CH2NH2) or ethanolamine
solution; the reaction mass with an amount of water in the ratio
of 1 to 100;
Step a) of the reactants phosphorus pentoxide (the P2O5),
phosphoric acid (of H3PO4) solution of phosphorus oxychloride (a
POCl3) or phosphorus oxychloride (a POCl3) in a solution;
Solvent solution phosphoric acid (of H3PO4) or a high-boiling
solvent is water, high-boiling solvent is preferably a ketone;
phosphoric acid concentration (of H3PO4) solution of 1% to 85%;
Phosphorus oxychloride (a POCl3) solution, the solvent is an
aromatic hydrocarbon, bicyclic hydrocarbon, a halogenated
hydrocarbon of carbon atoms between 1 and 4, high-boiling ethers,
high boiling ketones or carbon atoms in the ester of between 1 to
7, or a mixture thereof; wherein the aromatic hydrocarbon is
preferably benzene, toluene or xylene; phosphorus oxychloride (a
POCl3) solution concentration of 1% to 99%;
Step 1) ethanolamine in the solution, the solvent is an aromatic
hydrocarbon, bicyclic hydrocarbon, a halogenated hydrocarbon of
carbon atoms between 1 and 4, high-boiling ethers, high boiling
ketones, carbon atoms between 1 and 7 carbon atoms, or an ester in
an alcohol having 1 to 7 in between or a mixture thereof; wherein
the aromatic hydrocarbon is preferably benzene, toluene or xylene;
ethanolamine solution concentration of from 1% to 99%;
Step 1) The reaction is phosphorus pentoxide (the P2O5) when added
phosphorus pentoxide (the P2O5) ethanolamine 1:2.0 to 6.0 molar
ratio;
When step 1) is phosphoric acid reactant (of H3PO4) solution, the
molar ratio of the added phosphoric acid (of H3PO4) ethanolamine
is 1:1.0 to 3.0;
Step 1) as reactants in phosphorous oxychloride (a POCl3) or
phosphorus oxychloride (a POCl3) solution, the molar ratio of
phosphorus oxychloride was added (a POCl3) ethanolamine is 1:1.0
to 3.0;
Step 1) in a certain reaction temperature is -20 ~ 100 ° C;
Step 1) was added to the time of 5min to 72h;
Step 2) The temperature program in the range of -20 ~ 250 ° C, the
heating time is 0.5 ~ 72h;
Step 2) the degree of vacuum dried in vacuo 0 ~ 101.18 * 10
<5> KPa.
Advantageous Effects
The present invention is a solvent with water, which has high
yield, wide source of raw materials, low production cost, no
waste, the process is simple and safe and reasonable, short
production cycle, high purity of the product prepared.
detailed description
Below in conjunction with embodiments of the present invention is
further described, but the scope of the present invention is not
limited thereto.
Example 1
100After L autoclave, 50kg of water, heated to 80 ° C, 100% of
phosphorus pentoxide was added 14.2 kg, and 12.2 kg of
ethanolamine is added 100%, in addition to a vacuum degree of more
water -0.098kPa 2 hours, then heated to 100 ° C, 120 ° C, 140 ° C,
160 ° C, 180 ° C, 200 ° C, respectively at a vacuum degree of
vacuum than -0.098kPa 2 hours to remove water, and then pulverized
and agglomerated at 160 ° C -0.098kPa degree of vacuum dried for
more than 2 hours to give a white solid monoethanolamine phosphate
powder 27.1kg, m.p. 236.6 ~ 237.6 ° C, yield 96%, purity ≥99.3%.
Example 2
1000L reaction kettle was added 85% phosphoric acid (of H3PO4)
aqueous solution of 500kg, 100% at room temperature was added
ethanolamine 265kg (61.05), the temperature rose to 80 ° C, at a
vacuum degree of removal of water -0.098kPa than 2 hours, then
warmed to 100 ° C, 120 ° C, 140 ° C, 160 ° C, 180 ° C, 200 ° C at
a vacuum degree of vacuum to remove water -0.098kPa than 2 hours,
respectively, after crushing the agglomerates to a vacuum degree
of 160 ° C -0.098kPa dried over 2 hours, to give a white solid
monoethanolamine phosphate powder 593kg, m.p. 239.8 ~ 242 ° C, 97%
yield, 99.5% purity.
Example 3
100L reaction kettle was added 50% of a toluene solution of
phosphorus oxychloride 61.4kg, and then 12.2 kg of ethanolamine is
added 100%, the degree of vacuum at 80 ° C for 2 hours or more is
-0.098kPa, then warmed to 100 ° C, 120 ° C, 140 ° C, 160 ° C, 180
° C at a vacuum degree of -0.098kPa were maintained over two
hours, an aqueous solution of hydrogen chloride in the exhaust gas
was condensed, and then crushing the agglomerates to 160 ° C
degree of vacuum -0.098kPa dried for 2 hours to give a phosphoric
ethanolamine hydrochloride white solid powder 32.3kg, m.p. 247.5 ~
248.9 ° C, yield 91%, purity ≥99.0%.
Example 4
10After L kettle was charged with 5.0kg of water, heated to 80 °
C, added 100% of phosphorus pentoxide (P2O5) 1.42kg, stir added
100% of ethanolamine 2.44kg (61.05), 100 ° C to remove water 2
hour, then heated 120 ° C, 140 ° C, 160 ° C, 180 ° C, 200 ° C,
respectively at a vacuum degree of vacuum than -0.098kPa 2 hours
to remove water, and then pulverized and agglomerated at 160 ° C
in vacuo -0.098kPa drying degree than 2 hours, to give a white
solid diethanolamine phosphate powder 3.46kg, 94% yield, purity
≥99.3%.
Example 5
10L reaction kettle was added 85% phosphoric acid (of H3PO4)
aqueous solution of 2.3kg, was added 100% ethanolamine 2.44kg, the
temperature rose to 60 ° C, at a vacuum degree of removal of water
-0.098kPa than 2 hours, then warmed to 100 ° C , 120 ° C, 140 ° C,
160 ° C, 180 ° C, 200 ° C at a vacuum degree of vacuum to remove
water -0.098kPa than 2 hours, respectively, after crushing the
agglomerates to 160 ° C degree of vacuum of -0.098 kPa over 2
hours and dried to obtain a white solid diethanolamine phosphate
powder 3.54kg, yield 96%, purity ≥99.0%.
Example 6
10L reaction kettle was added a 50% solution of phosphorus
oxychloride in 3.07 kg of toluene, and then added ethanolamine
1.22kg 100%, the degree of vacuum at 80 ° C for 2 hours or more is
-0.098kPa, then warmed to 100 ° C, 120 ° C, 140 ° C, 160 ° C, 180
° C, 200 ° C at a vacuum degree of -0.098kPa were maintained over
two hours, an aqueous solution of hydrogen chloride in the exhaust
gas was condensed, and then crushing the agglomerates to 160 ° C
vacuum degree -0.098kPa is dried for 2 hours to obtain dicalcium
phosphate ethanol hydrochloride as a white solid powder 4.10kg,
93% yield, purity ≥98.0%.
Example 7
10After L autoclave, 4.0kg of water, heated to 80 ° C, phosphorus
pentoxide is added 1.42kg 100%, 100% and then added ethanolamine
3.66kg, in addition to a vacuum degree of -0.098kPa more water for
2 hours, was heated to 100 ° C, 120 ° C, 140 ° C, 160 ° C, 180 °
C, 200 ° C, respectively at a vacuum degree of vacuum than
-0.098kPa 2 hours to remove water to obtain phosphate
triethanolamine 4.32kg, yield 95 %, purity ≥99.3%.
Example 8
10L reaction kettle was added 85% phosphoric acid (of H3PO4)
aqueous solution of 2.50 kg, 100% at room temperature was added
3.97 kg of diethanolamine, the temperature rose to 60 ~ 80 ° C, at
a vacuum degree of removal of water -0.098kPa than 2 hours, then
warmed to 100 ° C, 120 ° C, 140 ° C, 160 ° C, 180 ° C, 200 ° C at
a vacuum degree of vacuum, respectively, in addition to the above
water -0.098kPa 2 hours to obtain a phosphate triethanolamine
4.77kg, 97% yield, purity ≥99.5%.