JPH01168653A - N,n-dialkylpolyhydroxy acid amide - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R1 is 6-18C alkyl or alkenyl; R2 is 1-4C alkyl, alkenyl or hydroryalkyl; n is 3-5). USE:A nonionic surfactant utilizable as a detergent, emulsifying aud dispersing agent, solubilizing agent, etc., and useful as a biochemical surfactant, such as membrane protein solubilizing agent. PREPARATION:YA secondary amine expressed by formula II is reacted with a lactone, e.g., D-ribono-gamma-lactone, D-glucono-delta-lactone or D-gluconoheptono-gamma- lactone, at 60-70 deg.C temperature to provide an N,N-dialkylhydroxy acid amide expressed by formula I. In the process, the secondary amine may be present in a somewhat large amount than that of the lactone; however, both are preferably reacted in stiochiometric amounts. Methanol, etc., are preferably used as the solvent. The above-mentioned method can be readily carried out in high yield and the compound expressed by formula I exhibits excellent performance as follows. Stably preservable without hygroscopicity, etc.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention is directed to a novel nonionic surfactant that can be used as a detergent, an emulsifier/dispersant, a solubilizer, etc., particularly a membrane protein solubilizer, etc. The present invention relates to a novel N,N-dialkyl polyhydroxy acid amide that can be used as a biochemical surfactant.

[Prior art]

Various surfactants have been developed so far, but in general, surfactants are substances that significantly lower the interfacial tension when added in small amounts, and essentially contain hydrophobic and hydrophilic groups in the molecule. It is essential to have both. In general, hydrocarbons and fluorine hydrocarbons are used as hydrophobic groups, and anionic dissociative groups such as sulfonates, sulfate ester salts, phosphate ester salts, and carboxylates, quaternary ammonium salts, It is a known fact that cationic dissociative groups such as benzalkonium salts are used. In addition, betaine-type surfactants that have both anionic and cationic dissociative groups as hydrophilic groups, or nonionic surfactants that have ethylene oxide groups or polyols that are easily hydrated with water molecules, although the hydrophilic groups are not dissociative. Many surfactants are also known.

Among these, nonionic surfactants are surfactants with extremely weak irritation, such as Triton X-10.
It has been revealed that it can be used as a membrane protein solubilizer, such as 0.

However, many nonionic surfactants such as Triton X-100 have a problem in that cmc is small and it is difficult to remove the surfactant by dialysis. On the other hand, many anionic or cationic surfactants denature proteins and inhibit their functions, so they can only be used as solubilizers in extremely limited cases. Furthermore, betaine type surfactants have a small effect of denaturing proteins.

On the other hand, recently, Baron (C) and Thompson (T, E) reported that octyl glucoside (OG), a nonionic surfactant, can be used as a membrane protein solubilizer. There is (Bio
chim, Biophys, Acta, 382,276
-285 (1975)).

The OG has a high cmc, excellent light transmittance in the ultraviolet region, and can be easily removed as a surfactant by dialysis. Furthermore, Hildreth (J.E., Hildreth) is -
It has been reported that nonionic surfactants with maximum (II) are excellent as membrane protein solubilizers (Biochem).

J., 207.363-366 (1982)).

(In the formula, R is a heptyl, octyl, or nonyl group.) However, the above-mentioned nonionic surfactants have a complicated synthesis route, have poor crystallinity and are difficult to purify, and are highly hygroscopic. Therefore, special consideration is required for preservation, which poses problems when mass-produced or used in large quantities.

Also, Meltretter et al.
ERetal, ) synthesized N-alkyl gluconamides as intermediates in obtaining certain surfactants (J, Am, OiI Chem, Soc, 29.20
2-207 (1952)) - This compound corresponds to the compound in which R2 is hydrogen in the general formula (1) described below, but this compound does not dissolve in water and does not exhibit sufficient surfactant ability. Ta.

[Problem that the invention seeks to solve]

Therefore, an object of the present invention is to provide a novel compound having surface activity that has a wide range of uses and can be used as a membrane protein solubilizer.

[Means for solving problems]

The present invention was made based on the knowledge that a new compound can be obtained by reacting a specific dialkylamine with a lactone, and that this compound has excellent surfactant ability.

That is, the present invention provides -maximum [■] :mu□ (wherein, R3 is an alkyl group or alkenyl group having 6 to 18 carbon atoms, and R2 is an alkyl group, alkenyl group, or hydroxyalkyl group having 1 to 4 carbon atoms. and n represents 3 to 5).

In the above-maximum (1), R particularly has 6 to 18 carbon atoms.
is preferably a hydrocarbon group, and R2 is preferably methyl, ethyl, or hydroxyethyl.

In addition, when comparing the compound represented by the above-mentioned maximum (1) with the surfactant represented by the above-mentioned maximum (n), it is found that the hydrophobic group and the hydrophilic group are the same in that they sandwich an amide bond. However, the orientation of the hydrophobic and hydrophilic groups is different. Also,
Although the hydrophilic group is a polyol, in the compounds of the present invention, the hydroxylmethyl group is directly connected to the carbonyl group of the amide, so the degree of freedom of movement of the hydrophilic group is reduced, and -maximum ( It is possible to simultaneously achieve more appropriate hydration and better crystallinity than the surfactant II).

The compound represented by the above-mentioned maximum (1) is, for example, a secondary amine represented by-maximum [■]: (wherein R8 and R2 have the same meanings as above) and a lactone, such as D-ribono T. -lactone, D-glucono-δ-lactone, and D-gluconobutono-lactone can be easily produced by reacting them at 60 to 70°C. At this time, the reaction may be performed with the secondary amine present in a slightly larger amount than the lactone, but it is preferable to react the two in stoichiometric amounts. Furthermore, it is preferable to use methanol or the like as a reaction solvent.

〔Effect of the invention〕

The N,N-dialkyl polyhydroxy acid amide of the present invention can be synthesized very easily in high yield, has no hygroscopicity, and can be stored stably. In addition, since it has extremely good crystallinity, it is easy to purify and has the basic properties as a membrane protein solubilizer, namely (i) it has the ability to solubilize oil-soluble substances, and (ii) it has the ability to solubilize proteins. (iii) cmc that does not denature;
(iv) good optical transmittance in the ultraviolet region, (v
) It has excellent performance of high purity and stability.

Next, the present invention will be explained with reference to examples.

〔Example〕

Example 1 5 equipped with stirrer, cooler, thermometer, and dropping funnel
20 g of D-glucono-δ-lactone (0,11+ao1) and 200 m of anhydrous methanol were placed in a four-piece 00d reaction flask and dissolved by stirring at 60°C. To this, 15.7 g of N-methyloctylamine was added from the dropping funnel.
(0.11n+oj was added dropwise over 0.5 hours, and after the dropwise addition was completed, the solution was further stirred at 60°C for 30 minutes, then cooled on ice,
The precipitated crystals were filtered and washed with ethanol 10011i to obtain 34 g of crystals (yield 95%).

The melting point was 109-110.6°C.

The analysis results are shown below.

'H-NMR measurement conditions: δin CD z COOD , TM
S internal standard, S knee double line, d: double line, t: triple line, m
: Multiplet (same below) 2.95(s), 3.05(s) : 3H(C
H:INco)3.4 (t): 2 H(Cdan,
NGO) 3.8-3.9(m): 5H(C and 0HS
C and 20H) 4.5(d), 4.7(d): I H
(COO and (OH)) GC-MS spectrum measurement conditions Two columns used: Ultra 2 (inner diameter 0.2R x
length 15 m), temperature 200-270 °C/min, detector injection temperature 270 °C (the same applies below).

The data after El mode measurement and trimethylsilylation treatment are shown below.

-5t (CH*)z 73 100
CHzOSi(CHz)s 103
12.8C, H1? N(CH3)C0-17024,2
CaH+J(CHs)COCHO5i(CHa)s+H
27379,1yt9-15 666
0.75 Molecular weight after trimethylsilylation is 6
It was 81.

The critical micelle concentration (cmc) of the compound of the present invention is 26.0
mM, and the surface tension value above that concentration is 32.
It was 3 dyne/am.

Example 2 20g of N-methyloctylamine (0,
14 mol) and D-ribono-γ-lactone 20.7 g (0
, 14 mol) in the same manner as in Example 1 to obtain 38 g of crystals. (Yield 93%) The melting point was 89-90°C.

The analysis results are shown next.

'H-NMR 2,95(s), 3.05(s): 3H(C
H3NCO)3.4 (t): 2H(C12
NC0)3.8-3.9(a+): 4H(ClO
H, Cdan 20H) 4.5(d), 4.7(d): I
H(COCH(OH))Si(CHz)s
73 100-CHzO3i (C1
h) s 103 26CsH
+J(CH3)Co 170
13CeH+J(C1h)COCHO3i(CHi)
3” 273 37M”-155640,
14 The molecular weight after trimethylsilylation was 579.

Moreover, the critical micelle concentration (cmc) of the compound of the present invention is 17
．． 5n+M, and the surface tension value above that concentration is 3
It was 0.6 dyne/ca+.

Example 3 20g of N-methyloctylamine (0,
14 mol) and D-glucoheptono-γ-lactone 29.
Using 1 g (0.14 mol), the reaction was carried out in the same manner as in Example 1, and the melting point was 133.8 to 133.9°C.

The analysis results are shown next.

'H-NMR 3.0(s), 3. Hs): 3H(Cl, NGO
)3.4 (t): 2H(C and tNCO)3.8
~4.0(m): 6H(CdanOH,,CHzOH
) 4.7(d), 4.8(d): IH(COCl
(OH))-St(CHi), 173 100C
IhO5i (C1,) s 103
25CsHtJ(Cl3)Co-17012CsH
+vN(CHi)COCHO3i(CHs)z+H27
34M''-157680,18 The molecular weight after trimethylsilylation was 783.

Example 4 20g of N-methyldecylamine (0,1
2 mol) and D-glucono-δ-lactone melting point is 132
The temperature was ~133°C.

'H-NMR 2,95(s), 3.05(s): 3H(C
H3NCO) 3.4 (t): 2 H(C and!
NC0)3.7-3.9(m): 5H(CHOH,
CHzOH) 4.6(d), 4.7(d): IH
(COCH(OH))Si(C113)s
73 100CHzOSi (CHx
) 3 103 27C8゜Ilz
l N (CH3) C0CHOSi (CTo)
2 ” 301 27C3°Ht+N(C
Hs)C0CHOSi(Clls)s+z 402
19C,,I□N(CHz)C0CHOSi(C
H3) s+-f 504 15M”-15694
The molecular weight after 0,4 trimethylsilylation was 709.

Example 5 20g of N-methyldecylamine (0,1
2 mol) and D-glucoheptono-γ-lactone 24.4
g (0.12 mol) and the same melting point as in Example 1 is 147
The temperature was ~148.5°C.

'H-NMR 2,95(s), 3.05(s): 3H(C
l3 NC0)3.4 (t): 2H(Cl,
NGO) 3.8-4.0 (m): 6H (ClOH,
Cdan 20H) 4.7 (d), 4.8 (d): I H
(COCl(OH))-5t(CB+)z
73 100CHZOSi(
CH3)3 103 23
C+oHztN(CHs)Co(CHOSi(CB+
)i)s 504 12C3゜Hz+N(
CII+)CO(CHOSi(CB+)+)<
606 7M''-157960,25 The molecular weight after trimethylsilylation was 811.

Example 6 20g of N-methyldodecylamine (0,
1 mol) and D-glucono-δ-lactone 17.8 g (0
, 1 mol) in the same manner as in Example 1, the melting point was 136.
The temperature was 1 to 136.7°C.

'H-NMR 2,95(s), 3.05(s): 3H(C
H3NGO)3.4 (t): 2H(Cl, NG
O) 3.7-3.9(m): 5H(CHOHSCH
zOH) 4.6(d), 4.7(d): I H(C
OCl(OH))Si(CHs)!
73 100CHzOSi (CH
3) s 103 26C
1□1IzsN(Clh)CO+ CHOSi(CB+
) x+ z 430 12C+zHzs
N(CHs)CB+CHOSi(CH3)s+-s
532 15M'''-157220,2 The molecular weight after trimethylsilylation was 737.

Example 7 20g of N-methyloccudecylamine (
0,071 mol) and D-glucono-δ-lactone 12.
Example 1 using 6 g (0,071 mol), the melting point was 1
43. The temperature was ~144.4°C.

'H-NMR 2,95(s), 3.05(s): 3H(C
12NC0)3.4 (t): 2HCCHl NC
0) 3.8-3.9(m): 5H(CHOH,CH
zOH) 4.5(d), 4.7(d): I H(C
OCH(OH))-St(CH3)!
73 100CfbO5i(CB+)s
102 26CtsH3J (C
H*)Co-(-CHOSi(CH3)s) t 5
14 15C+aH*J(CII3)CB+CH
OSi(CH:+)+) 3616 12M”
-158060,18 The molecular weight after trimethylsilylation was 821.

Claims (1)

[Claims] General formula [I]: ▲Mathematical formulas, chemical formulas, tables, etc.▼... [I] (In the formula, R_1 is an alkyl group or alkenyl group having 6 to 18 carbon atoms, and R_2 is a carbon number 1 to 4 alkyl group, alkenyl group, or hydroxyalkyl group, and n represents 3 to 5.) N,N-dialkyl polyhydroxy acid amide represented by: