CN108727209A - With N, the compound and preparation method thereof of N- dialkyl group leucine structures - Google Patents
With N, the compound and preparation method thereof of N- dialkyl group leucine structures Download PDFInfo
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- CN108727209A CN108727209A CN201810634997.4A CN201810634997A CN108727209A CN 108727209 A CN108727209 A CN 108727209A CN 201810634997 A CN201810634997 A CN 201810634997A CN 108727209 A CN108727209 A CN 108727209A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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Abstract
The invention belongs to chemical biology technical fields, specially have N, the Leucine compound and preparation method thereof of N- dialkyl structures.The present invention, with sodium cyanoborohydride and corresponding aldehyde solution reaction in sodium-acetate buffer, obtains a kind of with N, the Leucine compound of N- dialkyl structures using leucine as raw material；Or using leucine as raw material, with potassium carbonate and acetonitrile, react under reflux conditions；It is finally redissolved and is recrystallized with acetonitrile, what is purified has N, the Leucine compound of N- dialkyl structures.Preparation method of the present invention is simple, and efficiency of pcr product is high, and product purity is high.
Description
Technical field
The invention belongs to chemical biology technical fields, and in particular to the compound of a kind of N, N- dialkyl group leucine structure
And preparation method thereof.
Background technology
Leucine is a kind of amino acid in organism.It can aoxidize and be converted into ketone acid faster, metabolism generates grape
Sugar can effectively prevent muscle loss.In addition, leucine can promote the healing of bone, skin and injured muscle tissue, therefore
Study leucine and its derivative has extensive and important meaning in biochemistry.N, N- dialkyl group leucine have enhanced sensitivity
A variety of potential application prospects such as probe mass spectral analysis, there is presently no N, N- diethyl to cetyl Leucine compound,
N, N- diethyl are to cetyl leucine product and its report of synthetic method.
Invention content
The object of the present invention is to provide a kind of N, the compounds and preparation method thereof of N- dialkyl group leucine structures.
The compound of one kind N, N- dialkyl group leucine structure provided by the invention, structure is as shown in following formula I：
Wherein, the integer that n is 1 to 16（Saturated alkane chain）, R can be H, alkyl, alkoxy, phenyl ring, substituted benzene ring, miscellaneous
Ring.
The compound of above-mentioned N, N- dialkyl group leucine structure, including two kinds of isomers leucines of L and D types and its mixing
Object：II（It is denoted as L-Leu）And III（It is denoted as D-Leu）：
The compound of the N, N- dialkyl group leucine structure, structure include free structure type, organic salt or inorganic salts
Structure type.
Further, in such compound, n is preferably 1-6.
Further, in such compound, the preferred H of R, alkyl.
Further, the preferred L- or D- types leucine structure of such compound.
Further, such compound preferably its free structure, inorganic salts, organic salt.
Further, in one embodiment of the present of invention, when it is H that n, which is 1, R, correspondence compound of the invention in this way is just
As N, N- diethyl leucines（That is N, N-diethyl Leucine or 2-Diethylamino-4-methyl-
pentanoic acid）.
The present invention also provides above-mentioned N, the preparation method of N- dialkyl group Leucine compounds, it is specific there are two types of：
（a）Method 1：It takes leucine to be added in the sodium-acetate buffer of pH=5, after stirring and dissolving, sodium cyanoborohydride is added, then
Corresponding aldehyde compound solution is added dropwise, is reacted 20-28 hours in 30-40 DEG C, certain density hydrochloric acid solution is added and terminates instead
It answers；Revolving removes organic reagent, and freeze-drying using reversed phase column chromatography mode purified product, obtains dialkyl group leucine；
（b）Method 2：It takes and is dissolved in acetonitrile in leucine round-bottomed flask, halogenated alkane, potassium carbonate is added, reacts under reflux conditions
20-28 hours；Filtering, revolving remove solvent；Crude product is added diethyl ether and refilters, and precipitation is washed repeatedly with ether, finally uses acetonitrile
Recrystallization is redissolved, what is purified has N, the Leucine compound of N- dialkyl structures.
Further, in method 1, preferable reaction temperature is 37 DEG C.
Further, in method 1, the corresponding aldehyde compound for participating in reaction is the saturated aldehyde from acetaldehyde to hexadecanoyl；It is excellent
It is selected as acetaldehyde.
Further, in method 1, the chemical equation of N, the compound of N- dialkyl group leucine structures are as follows：
。
Further, in method 2, the halogenated hydrocarbons for participating in reaction is chlorohydrocarbon, bromo-hydrocarbons, iodine of the ethyl group to cetyl
For hydrocarbon, preferably alkane iodide.
Further, in method 2, the chemical equation of N, the compound of N- dialkyl group leucine structures are as follows：
。
Preparation method of the present invention is simple, and efficiency of pcr product is high, and product purity is high.
Specific implementation mode
Embodiment：The specific synthesis of N, N- diethyl leucine
One, experiment material and instrument
1 experiment material source of table
。
Laboratory apparatus
The moulds such as Agilent 1290 UHPLC systems, including DAD detectors, autosampler, binary gradient pump, temperature conditioning unit
Block.The chromatographic column of outfit is ACQUITY UPLC HSS T3 C18 reverse-phase chromatographic columns（1.8 μm, the mm of 2.1 mm × 100）
Bruker microTOF-Q Ш MS
Bruker AVIII 600 MHz NMR
Peace section N-1001D-OSB2100 Rotary Evaporators
Christ ALPHA 1-2 LD plus freeze driers.
Two, experimentation：
N, N- diethyl leucine synthetic method 1
Weigh leucine powder（800 mg, 6 mmol）In 100 mL round-bottomed flasks, 40 mL sodium-acetate buffers are added（0.2
M, pH=5）, in 37 DEG C of stirring and dissolvings, sodium cyanoborohydride powder is added（1.6 g, 24 mmol）After acetaldehyde solution is added dropwise（3.4
ML, 60 mmol）, reaction mixture 37 DEG C of stir abouts for 24 hours, be added 6 M HCl solutions（4 mL, 24 mmol）It is stirred at 37 DEG C
10 min terminate reaction, and revolving removes organic reagent, and freeze-drying obtains about 4 g white powder crude products.It is pure using reversed phase column chromatography mode
Change crude product, weigh about 25 g reverse phase filler methanol soaked overnights, prepares eluting solvent：2% methanol water mixed solvent and 100%
Methanol solvate（Contain 0.1% trifluoroacetic acid）, 1g or so crude products 4 mL, 2% methanol water mixed solvents（Containing 0.1% trifluoro second
Acid）Dissolving, 2% methanol water mixed solvent（Containing 0.1% trifluoroacetic acid）Elute three column volumes（Remove impurity）, 100% methanol solvate
（Containing 0.1% trifluoroacetic acid）Six column volumes are eluted, merging obtains purified product, is concentrated to give colorless viscous grease, identified
It is diethyl leucine.Yield：89-98%；1H NMR（600 MHz, D2O）：δ0.97（Dd, 6H）, 1.30（T, 6H）, 1.65（M,
2H）, 1.76（M, 1H）, 3.25（M, 4H）, 3.67（Dd, 1H）；MS（TOF）m/z 188.1645.
N, N- diethyl leucine synthetic method 2
Weigh leucine powder（800 mg, 6 mmol）In 100 mL round-bottomed flasks, the potassium carbonate powder after grinding is added
（4.8 g, 6 mmol）And 40 mL acetonitriles, solution of iodine oxide is added dropwise under stirring condition（9.6 mL,120 mmol）It flows back at 90 DEG C
Under the conditions of react 24 hours.It is filtered to remove excessive potassium carbonate, revolving removes solvent.Diethyl ether filtering is added in crude product, and precipitation is used
Ether is washed repeatedly, is finally recrystallized to give purified product with acetonitrile redissolution.
Claims (7)
1. having N, the compound of N- dialkyl group leucine structures, its structural features are as follows shown in Formulas I：
Wherein, n is integer, is the saturated carbon atom of 1-16, and R is selected from H, alkyl, alkoxy, phenyl ring, substituted benzene ring, heterocycle.
2. according to claim 1 have N, the compound of N- dialkyl group leucine structures, which is characterized in that including II
The isomers and its mixture of two kinds of Leu derivatives of L and D types shown in formula and formula III：
Wherein, II formulas compound is denoted as L-Leu structure, and formula III compound is denoted as D-Leu structure.
3. according to claim 1 have N, the compound of N- dialkyl group leucine structures, structure feature includes free
The structure type of structure type, organic salt or inorganic salts.
4. having N, the preparation method of the compound of N- dialkyl group leucine structures special as described in one of claim 1-3
Sign is, is divided into two kinds：
（a）Method 1：It takes leucine to be added in sodium-acetate buffer, after stirring and dissolving, sodium cyanoborohydride is added, then phase is added dropwise
The aldehyde compound solution answered reacts 20-28h in 30-40 DEG C, and certain density hydrochloric acid solution is added and terminates reaction；Revolving is removed
Organic reagent, freeze-drying, using reversed phase column chromatography mode purified product, obtains N, N- dialkyl group leucines；
（b）Method 2：It takes and is dissolved in acetonitrile in leucine round-bottomed flask, excessive halogenated alkane, potassium carbonate is added, under reflux conditions
React 20-28h；Filtering, revolving remove solvent；Diethyl ether filtering is added in crude product, and precipitation is washed repeatedly with ether, finally multiple with acetonitrile
Molten recrystallization, what is purified has N, the compound of N- dialkyl group leucine structures.
5. preparation method according to claim 4, which is characterized in that in method 1, reaction temperature is 37 DEG C.
6. preparation method according to claim 4, which is characterized in that in method 1, the aldehyde compound is from acetaldehyde
To the straight chain saturated aldehyde of hexadecanoyl.
7. preparation method according to claim 4, which is characterized in that in method 2, the halogenated hydrocarbons is ethyl group to ten
Chlorohydrocarbon, bromo-hydrocarbons or the idohydrocarbon of six alkyl.
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| CN201810634997.4A CN108727209A (en) | 2018-06-20 | 2018-06-20 | With N, the compound and preparation method thereof of N- dialkyl group leucine structures |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB803778A (en) * | 1956-11-22 | 1958-10-29 | Basf Ag | Production of n-(hydrocarbon substituted) aminocarboxylic acids, their esters or salts |
| CN104136419A (en) * | 2011-10-27 | 2014-11-05 | 麻省理工学院 | Amino acid derivates functionalized on the n- terminal capable of forming drug incapsulating microspheres |
| CN107021886A (en) * | 2017-05-10 | 2017-08-08 | 中国科学院过程工程研究所 | One class quaternary amines chiral ionic liquid and preparation method thereof |
-
2018
- 2018-06-20 CN CN201810634997.4A patent/CN108727209A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB803778A (en) * | 1956-11-22 | 1958-10-29 | Basf Ag | Production of n-(hydrocarbon substituted) aminocarboxylic acids, their esters or salts |
| CN104136419A (en) * | 2011-10-27 | 2014-11-05 | 麻省理工学院 | Amino acid derivates functionalized on the n- terminal capable of forming drug incapsulating microspheres |
| CN107021886A (en) * | 2017-05-10 | 2017-08-08 | 中国科学院过程工程研究所 | One class quaternary amines chiral ionic liquid and preparation method thereof |
Non-Patent Citations (6)
| Title |
|---|
| KANAO SEIZO: "Alkylamino acids. I", 《YAKUGAKU ZASSHI》 * |
| KEVIN GUO等: "Stable-Isotope Dimethylation Labeling Combined with LC-ESI MS for Quantification of Amine-Containing Metabolites in Biological Samples", 《ANALYTICAL CHEMISTRY》 * |
| MIREILLE BOURHIS等: "Organometallic synthesis of N,N-disubstituted α-amino esters", 《JOURNAL OF ORGANOMETALLIC CHEMISTRY》 * |
| P. KARRER等: "Proteinogenous amino alcohols and cholines. III", 《HELVETICA CHIMICA ACTA》 * |
| RENE GOLSE等: "Synthesis of β,γ-dehydro-α-amino esters with a tertiary amine function", 《COMPTES RENDUS DES SEANCES DE L"ACADEMIE DES SCIENCES, SERIE C: SCIENCES CHIMIQUES》 * |
| V. NARESH CHARY等: "Characterization of N,N-dimethyl amino acids by electrospray ionization-tandem mass spectrometry", 《J. MASS SPECTROM.》 * |
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