JPS59164331A - Compound of structure similar to that of phospholipid and its polymer and production thereof - Google Patents

Abstract

PURPOSE:To produce in good efficiency a polymer having a main chain constituted of phospholipid, which easily forms a membrane stronger than that obtained from natural phospholipid and is useful in a wide variety of fields of humidity sensors, ion-permeable membranes, artificial organs, etc. CONSTITUTION:A compound of formula III is obtained by reacting compounds of formulas I and II [wherein R'' is substituent selected from the group consisting of -(CH2CH2O)nCH2CH2-, -(CH2)n-, etc., and X is a halogen] in the presence of an organic base such as triethylamine or pyridine in a solvent (e.g., tetrahydrofuran). The compound of formula III is reacted with a compound of formula IV[wherein R is H or -CnH2n+1, and R' is (CH2)n- or the like] in a solvent to obtain the desired polymer of formula V (wherein R, R', and R'' are as defined above, and m, n, and p are integers).

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.

(Prior Art) It has been revealed that living bodies 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 cell membranes, are closely related to the metabolic processes of living organisms, are energy sources for other layered tissues, transport and absorb fat, coagulate blood, and perceive the taste of food. It also plays an important role.

Since phospholipids have many functions in supporting the life of living organisms, many attempts have been made to apply them to various artificial organs, cell fusion, enzyme immobilization, artificial cultivation, biosensors, etc.

However, the phospholipid u commonly used in these attempts
, lecithin, phosphatidylethanolamine, phosphatitulserine, etc. are all natural products extracted from living organisms themselves and have low molecular weights, making it extremely difficult to obtain a uniform and strong membrane.

Therefore, in order to be used in the above-mentioned fields such as humidity sensors, gas sensors, ion-permeable membranes, artificial organs, cell fusion, enzyme immobilization, biosensors, and artificial cultivation, these must be obtained from relatively high polymers and must be strong. There is an extremely high demand for these materials to be able to be formed into films and to be highly economical.

(Objective of the Invention) In order to eliminate these problems and meet the above-mentioned demands, the object of the present invention is to provide a polymer in which phospholipid constitutes the main chain, and to provide a method for efficiently producing the polymer. It is something.

(Structure of the Invention) That is, the present invention is based on the general formula:
O) nCIF((CH3)C)Tl! -1(CH2C
H2CH2CH20)y)CT(2CI(20H2CH
2-1 (represents a substituent selected from the group consisting of CHJH-1, m.

n and P represent integers) It is a polymer represented by

The present invention will be explained in detail below.

(Structure and Examples of the Invention) First, for example, literature (Makromol, Chem, .
Rapid Commun, 3,457-459 (191
32) Or PolymerPreprints,
Japan, pages 2735-2738,
vol, 31 +Nn1O), 2-chloro-1,3,2- as shown in the following formulas (6) and (7)
Dioxyphosphorane (x)- was synthesized.

(1) Next, tetraethylene glycoxy (HO-(CH1CH
20).

-H) 0.1 mol'e200i of tetrahydrofuran (
THF) and triethylamine (TEA)
After adding and dissolving 0.2 mol, the mixture was cooled to -20°C.

To this mixed solution, 0.2 mol of the above compound (I) was gradually added dropwise while stirring so that the temperature of the contents did not exceed 110°C. After the dropwise addition was completed, the temperature of the solution was gradually raised over about 1 hour and maintained at 5°C. After removing the precipitate formed in the solution by filtration, the solution was concentrated, and the precipitate deposited was again filtered and removed. After repeating the same operation two more times, the solvent in the ν liquid was evaporated, and a solid product was obtained with a yield of about 80%.

The results of elemental analysis and infrared absorption analysis of the obtained product show that the product has absorption in a specific structure as shown in Table 1 and Figure 1, and these analyzes indicate that the product undergoes the reaction of the following formula (8). (2-okine-1.3.2-sooxaphosphoryl)tetraethyleneglycoxy-2-oxo-1 produced by
, 3,2-dioxaphosphorane (compound 1[') was confirmed.

Table 1 (■') Similar results were obtained when ethyl ether was used as the solvent instead of THF.

Also, substantially similar results were obtained when an organic base such as trimethylamine or pyridine was used instead of TEA.

Furthermore, in place of tetraethylene glycol, ethylene glycol (HO(CH2), OH), propylene glycol (HO-CH(C'Hs)CH2-OH), polypropylene glycol (HO-(C1((CHs)
CH2O)n H), polytetramethylene glycol (
HO (CH2CI(2CH2CH2O)n H), trimethylene glycol (HO(CH2)30H), 1,4
-Butanol (HO(CH2)40H), 1.5-
Pentanesol (HO-(CH2)5-OH), 1
,6-hexanesool (HO-(CH2), -OH
), 1,7-hebutanesool (HOCCH2) 70H
), 1,8-octanediol-(ethylene glycol) ajitaku-toji (neopentyl glycol) assopate NOF ``K-Flex'' (product name) NOF 1-ester diol 204'' (product name) Polycaprolactone The reaction was carried out in the same manner as above using any one of all-trimethylpentanediol 1,2-polybutatsuene glycol Parikabinol HE (trade name) manufactured by NOF Co., Ltd., and the product was identified in the same manner. iL expressed by equation (2)
It was confirmed that a compound (II) similar to the above-mentioned compound (II) was obtained.

0 111 (1) That is, it was found that the above compound (1) reacts with the above compound having an OH group at both ends to give a shaving compound (It).

0.1 mol of compound (n) obtained as above and hexamethylenetetramethylsamine ((CHs)2N
-(CH2)6-N(CHs)2) 0, 1 mole is 3
0 Oct! The mixture was dissolved in acetonitrile, placed in a pressure bottle, and stirred at 50 to 70°C for 10 hours with shaking.

After the reaction was completed, the acetonate (IJ) in the solution was distilled off under reduced pressure, the residue was poured into a large excess of acetone, the solution was allowed to stand still, the supernatant liquid was discarded, and the residue was collected. After repeating the same operation three times, the residue was vacuum dried. After dissolving the dried residue in methanol, it was filtered using absorbent cotton, the p solution was added dropwise to a large excess of acetone with stirring, the supernatant liquid was left to stand, the supernatant liquid was discarded, and the product was vacuum-dried and then weighed. The yield was about 70 inches.

The results of molecular weight measurement, elemental analysis, and red light absorption analysis of this product showed that it had absorption in a specific structure as shown in Table 2 and Figure 2. was confirmed to be a polymer (1) produced by the following reaction formula (9).

Table 2 Acetonitrile NCCL)2 (■')...
...(9) Also, the same results as above were obtained when any one of methanol, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or a mixture of methanol and DMF was used as a solvent instead of acetonitrile. It was done. In addition, when the temperature of the reaction solution is 25°C, 10
Similar results were obtained when the reaction was carried out for 0 hours.

Next, instead of hexamethylene lenti I/ramethyl diamine,
Ethylenesoamine (H, N-(C mountain), -NH-ri, ethylenetetramethylcyamine (((j(s)tN-(C-X)z N(C-X)2), N, N'-ethylene Nomethylsoamine (C-(C)).

-NHCHs), ethylenetetraethylcysoamine ((C crystal)tN-(CH2)-r-N(C crystal)2), N
, N'-ethylenesoethyldiamine (C2H8N1
-I- (C Junmei-Kanaki), tetramethylenetetramethylsoami/((CHs)2N(CL)4N(C'Hs)
2), p-phinidinetetramethylsoamine ((CH
3) When the reaction was carried out in the same manner as above using 2N- and the product was identified, it was confirmed that a polymer similar to the above polymer (■') was obtained. Furthermore, when a series of compounds according to the above formula (any one of the former and any one of the above diamines were completely reacted, the yield was slightly different, but in each case, a polymer similar to the polymer (m') was obtained. was gotten.

That is, it is clear that the compound (n) represented by the general formula (2) reacts with diamines as shown in the following formula (10) to produce the polymer (In) represented by the general formula (1). Became.

0 (111) 1f of the polymer produced as above is mixed with 10d of water
and drop it onto a glass substrate with a force of 1000~3
After rotating at 000 rpm and drying at room temperature for a day and night, a uniform, strong, and transparent film was obtained.

For comparison, we attempted to form a film using the same method as above using the naturally occurring phospholipids phos-7atysolethanolamine and phosphatidylcholine, but a uniform film could not be obtained and the strength of the film was poor. It was extremely weak.

(Effects of the Invention) As is clear from the above explanation, according to the present invention, the entire polymer whose main chain is composed of phospholipid passes through an intermediate, which can also be considered a precursor, as shown in the cutting allowance. y) It can be easily synthesized in a few reaction steps with high yield and reactivity, and can be produced economically and inexpensively on an industrial scale.

In general, the properties of polymers are controlled by the properties of the monomer units that make up the main chain, but the polymer according to the present invention has a main chain with a structure similar to phospholipids, so it is different from conventional natural phospholipids. In other words, because it is a polymer, it is extremely easy to form a membrane, and the resulting membrane is much stronger than that of natural phospholipids.

becomes. Therefore, it can be used in a wide range of fields such as the above-mentioned humidity sensors, waste sensors, ion-permeable membranes, artificial organs, cell fusion, fermentation fixation, biosensors, and artificial cultivation, and its industrial value is extremely large.

[Brief explanation of the drawing]

FIGS. 1 and 2 are diagrams showing the results of infrared spectroscopic analysis of compounds in the present invention, respectively. Patent Applicant Okitonke Kogyo Co., Ltd. (2 others) Continued from page 10 Inventor Tadao Nakaya 4-2-29 Kitakasugaoka, Ibaraki City Inventor Minoru Imoto 3-46 Okaminamachi, Hirakata City Applicant: Tadao Nakaya 4-2-29 Kitakasugaoka, Ibaraki City 0 Applicant: Minoru Imoto 3-46 Okanami-cho, Hirakata City Procedural amendment September 1999 - 911 Commissioner of the Japan Patent Office Kazuo Wakasugi 1. Case description Showa 1958 Patent Application No. 36649 Polymer and its manufacturing method 3, Relationship with the case of the person making the amendment Patent Applicant (029) Oki Electric Industry Co., Ltd. 4, Agent 5, Date of amendment order Showa year, month, day ( Voluntary) 6. As per the column for detailed description of the invention subject to amendment, drawing 7, and content of the amendment attached (]) Chemical formula (2) on page 13 of the specification is corrected as follows: O 111 (2) Delete "and reactivity" on page 18, line 12. (3) Figures 1 and 2 are revised by 9 in the attached figure. Procedural Amendment June-6, 1981 Kazu Wakasugi, Commissioner of the Japan Patent Office Husband 1, Indication of the incident 1982 Patent Application No. 36649 2.
No name Compounds and polymers with phospholipid-like structure and their manufacturing method 3, Relationship with the case of the person making the amendment Patent Applicant (029) Oki Electric Industry Co., Ltd. (2 others) 4, Agent 5, Amendment order Date: Showa Year, Month, Day (voluntary) 6, Claims to be amended, Column 7 for detailed description of the invention, Contents of amendment 1- (1) Claims as attached, 'NT, +j
do. (2) Page 7 of the specification, line 1 r-〇M2()-cru,'' followed by [-(Cru)2CONHCH2NHCO(CH2)z
- Add 5J. (3) Add the following in the middle section of page 8 before "Selected from a large group." Note 1) 1 (in the formula, R" is -CnQ2n+>) or -CnH2n-x
. CnH4n-B, -CnI (representing a substituent selected from 2n-5)" (4) Add the following in the middle of page 13 before "using any one of the following.""Bis(4-hydroxyphenyl)sulfonyl distearate, ((HOCl(2)2C(CH
200CC, 7H35)2). Pentaerythritol silyroot-) ((HOCH2)tC(CH200C+a H31)2
), pentaerythritol simiristate ((HO
CH2) 2C(CH200C13H2□)2). Pentaerythritol tsucapronate ((HOCH2)2C(CH200CoH+o)2)
, pesotaerinurritol dilyrunate ((HOCH2)
zC(CH200Ct7I(2o)2). Pentaerythritol silylate ((HOCH2)2C(CH200CI7H-31)
, pentaerythritol silylate ((HOCH2
)2C(CH,0OCI7H33)2)J(5) Add the following between lines 18 and 19 on page 16. [,N,N'-y'tyrenebis(3-dimethylaminepropionylamide((Cl)2N(CH2)2
CONH-CH2NHCO(CI(2)zN(Cxin)2
, Claim 1, General formula (wherein R is -H, -CnH(2n+1), H is -(
CH2)n-. NHCO(CH2) 2-2R" is -(CH2CH20
) nCH, CI(2+-. (CH(CH9)CI(20)nCH(CHs)CH2
-1(CI(2CI(2CHZ CH20)n, :H2
CruC&CFbr (CHJn +0M. -CH2CH,0-C-(C匍.-C-OCH2CHt
-2111 0 CH! C Exit I - C Ru C - C 艮ρ - C - C - CH2-111 CH30C . 1 (in the formula, R'/ is -CnI (2n+1) or -CnHs
H-1, CnHsl-a. represents a substituent selected from the group consisting of -CnH2n-5), and m. n and p represent integers. ). j? IJ Mama-2, a compound having the general formula (wherein R" represents a substituent selected from the same group of substituents as R" in formula (1)). 3. A compound represented by the general formula (wherein R" represents a substituent selected from the same group of substituents as R" in formula (1), and X represents a halokene atom) can be used as triethylamine, pyridine, etc. A method for producing a compound represented by the general formula 0 111 12 , which comprises reacting in a solvent in the presence of an organic base. 4. A compound represented by the general formula, and the general formula, R,NR'-NR2... (5) (wherein, R,, R' is , represents a substituent selected from the same group of substituents as R') A polymer represented by the general formula, characterized in that a compound represented by t'1. manufacturing method.

Claims (1)

[Claims] 1. General formula % formula % (1) (wherein R is -H, -CnH(21-H), R' is -
(CH,)n-. -(C)l(CH,)CseedC)I(Cru)Cru. -((Jl, CI(2cLcru0)ncLcLc&cH
2,(,CL)n-. Replacement fund representation selected from the group consisting of: m. n and p represent integers. ) is a polymer represented by 2. A compound represented by the general formula (in the formula, Rf/ represents a substituent selected from the same group of substituents as R" in formula (1)). 3. A compound represented by the general formula (in the formula, R" is a substituent selected from the same substituent group as R in the formula ('', ). A method for producing a compound represented by the general formula OO 111 , which comprises reacting in the presence of a solvent. 4. A compound represented by the general formula 0 0 111 and the general formula R2H-R' NR2 (5) (wherein R, R' are R in formula (1) , representing a substituent selected from the same group of substituents as R') is reacted in a solvent.