JPS60179408A - Compound having phospholipid-like structure and its polymer and production thereof - Google Patents

Abstract

PURPOSE:To obtain the titled compound excellent in film properties and useful for artificial organs, gas sensors, etc., by reacting two specified compounds in a polar solvent. CONSTITUTION:A compound having a phospholipid-like structure of formula Vis obtained by reacting a compound of formula I (wherein R is -CmH2m-1, -CmH2m-3, formula II, formula III, or the like, R'' is -H, -CH3, or -Cl, X is -H, -Cl, -Br, -CmH2m+1, or -O-CmH2m+1 and m is an integer) with a compound of formula IV (wherein R' is -H, or -CmH2m+1, and n is an integer) in a polar solvent in the temperature range of 0 deg.C- b.p. of the solvent. This compound is dissolved in a solvent and then polymerized in the presence of a reaction initiator by heating or irradiation to obtain a polymer of formula VI (wherein Z is a degree of polymerization).

Description

DETAILED DESCRIPTION OF THE INVENTION (Technical Field) The present invention relates to compounds and polymers having structures similar to phospholipids, and methods for producing the same.

(Technical background) It has been revealed that living organisms contain many types of phospholipids, and these phospholipids play an important role in maintaining the life of living organisms.

For example, phospholipids are components of cytoplasm such as n4 old it, + membranes, and are closely related to the divine metabolic processes of living organisms.
In addition, it plays a very important role in the energy source of the brain tissue, the transport and absorption of fat, blood coagulation, and the perception of food taste.

As described above, since phospholipids have many functions in supporting overall life, many attempts have been made to apply them to various artificial organs, cell fusion, enzyme immobilization, artificial cultivation, biosensors, etc.

However, the phospholipids generally used in these attempts, such as lecithin, phosphatidylethanolamine, and phosphatidylserine, are all natural products extracted from living organisms, and their low molecular weight makes it extremely difficult to obtain a uniform and strong membrane. Have difficulty.

Therefore, in order to be used in the fields of humidity sensors, gas sensors, ion permeable membranes, artificial organs, cell fusion, enzyme immobilization, biosensors, artificial cultivation, etc. mentioned above, it is necessary to obtain these in relatively simple molecules and The situation is such that the requirements for JI7, such as being able to form a strong film and having high therapeutic properties, are extremely high.

(Objective of the Invention) In order to eliminate the above-mentioned problems and meet the above-mentioned demands, an object of the present invention is to provide a compound with a phospholipid-like structure and a method for effectively producing the same.

(Summary of the invention) 1! II. The present invention is based on the following general formula (R in the formula C is -CH* 'm"2m-13' -CmH2m-5
'2m-1 -CInH2□-7°OR" 1l -OH0H-0-0-0=OH,.

+12 R' is -H or -GmH2m+1 'R'' is -H,
-0H8t'take-CI.

m and n are integers.

or -H, -ON, -01l, -Br +-C
The present invention relates to a compound having a phospholipid-like structure expressed by mH1m+1 or 100 mHzm+1, a polymer thereof, and a method for producing a compound having a phospholipid-like structure.

The compound represented by the above formula (I) of the present invention is prepared by adding a compound represented by the following general formula (R in the formula is the same as that of the above formula (I)) in a suitable polar solvent at 0°C. The following general formula (R' in the formula,
When the compound is reacted with a compound represented by the formula (R" is the same as that of formula (I)), it can be easily produced by reacting as shown in the following reaction formula (1).

0 (CH2)nNR,' (II) (III) ■(''r■) The compound of the above formula (II) can be produced as follows.

For example, in the literature (Makromol, Ohem, .
Rapid Oommun, vow, B, 45
7-459 (1982) or Polymer P
reprint, s, Japan, page
2785 '278t'l * vol, Bl, A1
According to the method described in 0), the following reaction formula (2),
2-chloro-1,12-dioxyphosphorane (TV) is synthesized as shown in (8).

(■) The above compound (1■) produced and oleyl alcohol (O
Using H(Off)OH=GH(OH2)80H),
According to the method described in the same document, 2-oxo-2-oleloxy-1,1+'l 12-dioxophosphorane (compound V) is synthesized as shown in the following reaction formula (4).

HO(OH2)80f(=CH(C1(,)7Gl(8
""""""""Allyl alcohol (0H2=OHOH,OH), crotonyl alcohol (0H8CH=OHOH20H), lylyl alcohol (0H8(OH2), CH=OHGH2) in place of the above-mentioned oleyl alcohol
CH=GH(OH2)80H), lilunylalj J
u (OHa OH20H” 0HOHs OH”=
GH (EH20H”0H(OH,)80H), arachitonyl alcohol (0H8(GH2) 40H=OHO
H20H=OHCH20H=CHOH20H20H(O
H2)40B).

4-Hydroxybenzoic acid n-dodecylcinnamate Q14-human mixiphenyl (X is the same as that of formula (I)), 2-human mixethyl acrylate GH II 1 2- and droxyethyl-α-chloroacrylate formula ( ■
) could be synthesized.

Next, the compound (I) of the present invention is easily polymerized by dissolving it in a solvent and irradiating it with radiation in the presence of a reaction initiator or by heating it, and the following formula (R, R', R''
and n are the same as those in formula (■), and 2 indicates the degree of polymerization). The formation of this polymer is similar to known hydrophilic acrylic monomers, and the resulting polymer, which has a phospholipid-like structure, has properties not found in conventional natural phospholipids and can easily form membranes. or form a gel. The resulting membrane is more uniform and stronger than that of natural phospholipids (Explanation of Examples) The present invention will be explained by the following examples.

Example 1 0.1 mol of 2-oxo-2-osiloxy 1,8.2-dioxophosphorane (compound V') and N,N-dimethylaminoethyl meccrylate (Of(=O(OR,)002 (OH2)2N(OH8
), )0.1 mol was dissolved in 800 tyn8 dimethylformamide (DMF), poured into a sealable bottle, and reacted at 70-75°C with J&iQ stirring for 80 hours. After the reaction is complete, DMF in the liquid is removed under reduced pressure.
Pour the residue into a large excess of acetone, and after 16"
g', the liquid was removed and the residue was collected. After repeating the same operation 8 times, the remaining residue was transferred to a vacuum line, the dried residue was further dissolved in methyl alcohol, PIM was performed using absorbent cotton, and the furnace liquid was dropped into a large excess of acetone while stirring. After standing still, the supernatant liquid was discarded. The same operation was repeated 2 to 8 times, and the resulting product was dried in vacuum and then tested, and the yield was 70%. Elemental analysis and infrared absorption of this product 4,000 l)'1
#'41 IrFlx'ノ'A= I My /N
侭j 1 1'21 tT+ ：山 h ま'Ah From these analysis results, the product is methacroyl (oxyethylammonium) ethyl oleate [compound (■)] produced by the reaction of the following reaction formula (5). It was confirmed that

Table 1 (V) OCH8a(, N(CH3)2 C,'H8 C=O open, 0 111 OH8〇- (Vl) Hayashi 5 in which the above-mentioned DMF was reacted with acetonitrile or methyl alcohol as a solvent. In this case, the same compound (Vl) as in the above case was obtained, although there was a slight difference in the acid groups.

Next, in place of 2-oxo-2-osiloxy-1,8,2-dioxophosphorane (compound V), any one of the compounds of the formula (Tl>) and the above N,N-dimethylaminoethyl methacrylate The product obtained was identified as the compound (■) of the following reaction formula (6), which has a similar structure to the compound of formula (■).

H8 0H8=O Next, N,IJ-diethylaminoethyl methacrylate (CH2-C(CH8)CO2(CH2)2N(C2H
5) 2), N, N-di-18o-propylaminoethyl methacrylate (0H2=O(OH8)002(
OH2)2N(OH(OH8),)2),N,N
-di-n-butylaminoethyl methacrylate) (0H
2=O(OH8)Go□(OH2 note N[(OH,,)8
0H8]2), N-methylaminoethyl methacrylate (CH2=C(OH8)Go, (OH2)2NH(
OH8) ), N-ethylaminoethyl methacrylate)
(0H2=0(CI(8)Co, (OH2)2N)I
(02H5) ), N-n-butylaminoethyl methacrylate ((3H2=C((31(8)00.(OH,
,)2doH(CH2)8CH8), 2-aminoethyl methacrylate (CH2-C(CH8)C02(CH2)
2NH2), 8-amino-1-propyl methacrylate (0H2=O(OH8)002(OH2)8NH2')
, Φ-amino-1-butyl methacrylate (CH-C(
CH8)C02(OH,),NH,),6-amino-1
-hexyl methacrylate - (0H2=C(OH
8) Co2(OH2')6Nu2),'N,N
-dimethylaminoethyl acrylate (OH2=OH
OO2(Of(2) 2N(OH8) 2), N, N-
Dimethylaminoethyl α-chloroacrylate (0H2
=U(JOO□('0H2), any one of N(CH3)2''l and any one of the compounds of the above general formula (F)
When the reaction was carried out in the same manner as in the reaction formula (5) using the seed, a compound (1) having a structure similar to compound (■) or (■), that is, a compound represented by the general formula of the present invention was obtained. was gotten.

That is, it has been revealed that when compound (II) and compound (III) are reacted in the same manner as in the reaction formula (1), compound (1) is produced.

Example 2 'J! : methacroyl(oxyethylammonium)ethylolein m prepared in Example 1 a [: Compound (Vl
)] 4g and N,N'-methylenebisacrylamide 0
．． 29 was dissolved in 160 water and filtered, and this solution was degassed under reduced pressure and then spin-coded onto a glass substrate. When one layer of the obtained skin was irradiated with ultraviolet light from a mercury lamp (250 W) for 8 hours, a strong polymerized film was obtained.

Example 8 Actual/1fIj Methacroyl (oxyethylammonium) ethyl oleate obtained in Example 1 [Compound (■)] 1
5Ji' was dissolved in 100 cm8 of methyl alcohol, 0.15, li' of 2,2'-azobisisobutyronitrile (AIBN) was added as a reaction initiator, and 70 cm
The reaction was carried out at 15°C (iI). After the reaction was completed, the solution was poured into a large excess of acetone, and the supernatant was drained and the remaining residue was collected. After repeating the same operation 8 times, the residue was collected. was dissolved in methyl alcohol and filtered using absorbent cotton, and the R solution was added dropwise to a large excess of acetone with stirring.The supernatant liquid was left to stand, and the supernatant liquid was discarded.The product was vacuum-dried. The molecular weight of this product was approximately 10,000, and as a result of infrared spectroscopy, the peak around 1620 F-1, which corresponds to the C=G bond characteristic of methacrylate, had disappeared, indicating that it was a polymer. This was confirmed.

When this Polymer 8I was dissolved in 20 degrees of water and spin-coded onto a glass substrate, it was dried at 60° C. for 2 hours, and a uniform skin pattern was obtained.

Next, the same compound (■) 2.5.9 and 0.125 g of N,N'-methylenebisacrylamide were dissolved in once-boiled pure water at room temperature, filtered, and placed in a reaction vessel to boil the pure water. The solution was diluted with water to a total volume of 50 crn''. After degassing under reduced pressure, 0.05 cm of β-dimethylaminopropionitrile and 0.0 cm of ammonium beroxoniserate were added to the solution.
．． 05,! The reaction vessel into which i' was added with gentle stirring was heated to 50°C and left for 2 hours, and a gel was formed.

Furthermore, when the same reaction as above was carried out using the compound (I) according to the above general formula, a polymerized film or gel was obtained in each case. That is, the above compound (I) according to the present invention
It was clear that it polymerized easily like known hydrophilic acrylic monomers and formed a strong film or gel.

For comparison, similar film formation was attempted using the naturally occurring phospholipids phosphatidylethanolamine and phosphatidylcholine, but a uniform film could not be obtained and the film obtained was very weak. .

(Effects of the Invention) As is clear from the above explanation, according to the present invention, a polymer having a phospholipid structure can be produced in a few reaction steps by passing through an intermediate, which can also be considered as a precursor, as shown in the curved structure. It can be synthesized simply and in a highly compact manner, and can be produced economically and inexpensively on an industrial scale.

The above-mentioned phospholipid-like structure polymer according to the present invention has properties not found in conventional natural phospholipids, that is, because it is a polymer, it is extremely easy to form a membrane.
Moreover, the resulting membrane is much stronger than that of natural phospholipids. Therefore, the humidity sensor, gas sensor,
Iontophoresis a+S, artificial organs, cell fusion, enzyme fixation,
Rated 1 for use in a wide range of fields such as biosensors and artificial cultivation.
It became a city and its industrial value is extremely large.

[Brief explanation of the drawing]

FIG. 1 is a diagram showing the results of infrared spectroscopic analysis of an example of a compound in the present invention.

Claims (1)

[Claims] L The following general formula (R in the formula is -C11]H2m-1"nlH2m-8"m"1m
-5''-C 111m-7'R' is 1 or -CmH2m+11 R'' is -H, -0H8 or -C1. m and n are integers. X is -H, -ON, -G1. -Br, -CmH1
A compound having a phospholipid-like structure represented by the following general formula (in the formula, R is -Cm) (2m-1"mH2m-8・-C1nH2)
m-5''mHgm -7・0R'' 111 -OHCH-0-0-0=OH2. 2 R' is -H and -Cm 2m+1 'R'' is -H,
, -0H8 or -CI. m and n are the number of strokes. X is -H, -ON, -C1, -Br, -CmH2m
+1 or -OOmH2o+,. 2 indicates the degree of polymerization) A polymer having a phospholipid-like structure. & The following general formula (Rke-CI11H2m-1"mH2m-8'-CmH
gm-s'-CmH2m-7・OR" 11.1 -OHOH-0-0-02CH21 2 R' is -H or -CmH2m+1 'R" is -H, -
0H8-1' or -CI. m + nld integer. X is -H+ ON +-Gll t-Br, -G
In order to produce a compound having a similar structure to the phospholipid m 2m+1 coated with H or m 2m+1 indicates -00H, the following general formula (in which R is the same as that of formula (I)) is used. ) in a polar solvent at a temperature between 0''C and the boiling point of the solvent, the compound represented by the general formula (in the formula, R' and R'' are the same as those in formula (1) 1. A method for producing a compound having a phospholipid-like structure, which comprises reacting compounds represented by the following formulas.