CN1049220C - Preparation of pentacoordinate phosphinylidyne-amino-acid mixed anhydride and its method for synthetizing polypeptide - Google Patents
Preparation of pentacoordinate phosphinylidyne-amino-acid mixed anhydride and its method for synthetizing polypeptide Download PDFInfo
- Publication number
- CN1049220C CN1049220C CN96114152A CN96114152A CN1049220C CN 1049220 C CN1049220 C CN 1049220C CN 96114152 A CN96114152 A CN 96114152A CN 96114152 A CN96114152 A CN 96114152A CN 1049220 C CN1049220 C CN 1049220C
- Authority
- CN
- China
- Prior art keywords
- amino
- pentacoordinate
- phosphinylidyne
- mixed anhydride
- amino acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The present invention relates to a preparation method of penta-coordinate phosphoryl-amino acid mixed anhydride and a method for using penta-coordinate phosphoryl-amino acid mixed anhydride to synthesize polypeptides. In the preparation method, circle phosphorus oxychloride and N, O-bi(trimethylsilyl)amino acids react in organic solvents for 5 to 24 hours at reaction temperature of 0 to 50 DEG C.In the method for using penta-coordinate phosphoryl-amino acid mixed anhydride to synthesize polypeptides, when one kind or various N, O-bi(trimethylsilyl)amino acids are added to circle phosphorus oxychloride, self-assembly uniform or non-uniform polypeptides can be obtained; if an N, O-bi(trimethylsilyl)amino acid comprising side chain function groups (such as hydroxyl) exists, polypeptides comprising O-seryl phosphate can be obtained; all of the self-assembly reactions firstly generate penta-coordinate phosphoryl-amino acid mixed anhydride which can be used for preparing penta-coordinate phosphoryl-amino acids as synthons for liquid phase and solid phase directional polypeptide synthesis.
Description
The present invention relates to the novel pentacoordinate phosphinylidyne-amino-acid mixed anhydride of a class, them as polypeptide synthetic synthon, may be used on the polypeptide of liquid phase, solid phase synthetic in, belong to the preparation field of bio-organic compounds.
Traditional polypeptide is synthetic to be to be that the basis is protected amino acid whose amino and carboxyl with the carbon geochemistry, utilizes coupling reagent to make it to be condensed into peptide then, because troublesome is usually protected and gone to protect to the relative stability of carbon geochemistry.Polypeptide synthetic chemistry men adopted the method for non-equal monoamino-acid-amino-acid mixed anhydride to synthesize polypeptide, owing to there is not selectivity often to cause some by products.After F.Lipamann1941 proposed to contain the hypothesis of the mixed acid anhydride of phosphoric acid-carboxylic acid in proteinic biosynthesizing, the chemiluminescent polypeptide man had produced very big interest to organophosphorus reagent.They have adopted three-fold coordination phosphorous acid-amino-acid mixed anhydride, and because of its reactive behavior is very high, racemization is more serious, and the easy oxidation by air of three-fold coordination phosphorous acid.Also useful four-coordination phosphoryl chloride and amino acid ester reaction generate N-phosphinylidyne amino acid ester, and alkaline hydrolysis gets N-phosphinylidyne amino acid then, gets the N-phosphoramidon with the condensation of DCC coupling reagent again, and acidolysis can get dipeptides.This method is only quite protected amino acid whose amino, carboxyl is not activated.Above method and biosynthesizing differ greatly.
The objective of the invention is to develop a class pentacoordinate phosphinylidyne-amino-acid mixed anhydride.This compounds had both been protected amino, had simultaneously activated carboxyl again, and reactive behavior is very high, selectivity and optical activity is good, productive rate is also higher.It is synthetic that this compounds not only can be used for the liquid phase polypeptide, and it is synthetic to can be used for solid-phase polypeptide.It is synthetic that this method is only applicable to contain the polypeptide of a-amino acid residue, is similar to proteinic biosynthesizing.It is applied in the combinatorial chemistry field vast potential for future development.
Content of the present invention:
The reaction formula for preparing novel pentacoordinate phosphinylidyne-amino-acid mixed anhydride is as follows:
Be R
1-CH-CH-R
2Or R
1-C=C-R
2Be alkyl and the aromatic base that contains non-nucleophilic group, R1, R2 are respectively that carbon atom is 0～10 alkyl, aromatic base.R1、
3; the method of the synthetic polypeptide of a kind of usefulness pentacoordinate phosphinylidyne-amino-acid mixed anhydride as claimed in claim 1; it is characterized in that described polypeptide is the O-phospho-peptide; its building-up process is: under room temperature (25 ℃); cyclic phosphorochloridate and excessive 50% side chain have the amino acid trimethyl silicane radical derivative of hydroxyl to react in aprotic solvent 24～48 hours; form pentacoordinate phosphinylidyne-amino-acid mixed anhydride; second N then; O; the carbonyl of the amino acid whose amino nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride of O '-three (trimethyl silicon based) forms dipeptides; the amino of the dipeptides carbonyl of nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride again forms tripeptides; repeat to obtain polypeptide like this; wherein there is a phosphoryl to be retained on the side chain of an amino acid hydroxyl; when with trifluoroacetic acid (TFA) acidolysis, obtain the O-polypeptide phosphate.
4; the method of the synthetic polypeptide of a kind of usefulness pentacoordinate phosphinylidyne-amino-acid mixed anhydride as claimed in claim 1; it is characterized in that containing on the described polypeptide chain two or more amino-acid residue; its building-up process is: under room temperature (25 ℃); as cyclic phosphorochloridate and two or more N of excessive 50%; O-two (trimethyl silicon based) amino acid reacted in aprotic solvent 24～72 hours; form pentacoordinate phosphinylidyne-amino-acid mixed anhydride; second N then; the carbonyl of the amino acid whose amino nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride of O-two (trimethyl silicon based) forms dipeptides; the amino of the dipeptides carbonyl of nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride again forms tripeptides; repeat to obtain different aminoacids residue combination polypeptide; when existing side chain that the amino acid trimethyl silicane radical derivative of hydroxyl is arranged in the reaction system; have a phosphoryl be retained in an amino acid hydroxyl on; when with trifluoroacetic acid (TFA) acidolysis, obtain the O-polypeptide phosphate.
5, the method for the synthetic polypeptide of a kind of usefulness pentacoordinate phosphinylidyne-amino-acid mixed anhydride as claimed in claim 1, it is characterized in that described synthetic method is: under room temperature (25 ℃), use two volumetrys with equimolar cyclic phosphorochloridate solution and N earlier, O-two (trimethyl silicon based) amino acid solution (solvent is an aprotic solvent) splashes in the there-necked flask simultaneously, stir while dripping, after all dripping off, use
31P NMR follows the tracks of, when treating that cyclic phosphorochloridate all is converted into pentacoordinate phosphinylidyne-amino-acid mixed anhydride (5 minutes～24 hours), wait mole N with second kind, O-two (trimethyl silicon based) amino acid solution slowly splashes in above-mentioned pentacoordinate phosphinylidyne-amino-acid mixed anhydride, stir while dripping, react and promptly obtained dipeptides in 6～24 hours, during resultant dipeptides and second kind of pentacoordinate phosphinylidyne-amino-acid mixed anhydride reactant, obtain tripeptides, repeat to obtain desired sequences polypeptide.
6, the method for the synthetic polypeptide of a kind of usefulness pentacoordinate phosphinylidyne-amino-acid mixed anhydride as claimed in claim 1, it is characterized in that described synthetic method is: under room temperature (25 ℃), use two volumetrys with equimolar cyclic phosphorochloridate solution and N earlier, O-two (trimethyl silicon based) amino acid solution (solvent is an aprotic solvent) splashes in the there-necked flask simultaneously, stir while dripping, after all dripping off, use
31P NMR follows the tracks of; (5 minutes～24 hours) can use when treating that cyclic phosphorochloridate all is converted into pentacoordinate phosphinylidyne-amino-acid mixed anhydride; pentacoordinate phosphinylidyne-amino-acid mixed anhydride and the polymer solid phase carrier that has functional group (for crosslinked methylol polystyrene resin or silica gel) reaction with preparation; use mineral acid (hydrochloric acid) to remove phosphoryl again; can repeat to obtain being with high molecular polypeptide like this; use trifluoroacetic acid (TFA) or Hydrogen bromide (HBr) that polypeptide is scaled off from polymer at last, promptly obtain target polypeptides with high performance liquid chromatography (HPLC) purifying for preparing.
Under room temperature (25 ℃), cyclic phosphorochloridate and excessive 50% N, when O-two (trimethyl silicon based) amino acid reacts 24-48 hour in aprotic solvent (as benzene or tetracol phenixin), at first form pentacoordinate phosphinylidyne-amino-acid mixed anhydride, second N then, the carbonyl of the amino acid whose amino nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride of O-two (trimethyl silicon based) forms dipeptides, the amino of the dipeptides carbonyl of nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride again forms tripeptides, can repeat to obtain polypeptide like this.
2. contain the amino acid whose peptide self-assembly of side chain functionalities
Under room temperature (25 ℃), cyclic phosphorochloridate and excessive 50% contain side chain N, when O-two (trimethyl silicon based) amino acid (as Serine) reacts 24～48 hours in aprotic solvent (as benzene or tetracol phenixin), at first form pentacoordinate phosphinylidyne-amino-acid mixed anhydride, second N then, the carbonyl of the amino acid whose amino nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride of O-two (trimethyl silicon based) forms dipeptides, the amino of the dipeptides carbonyl of nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride again forms tripeptides, can repeat to obtain polypeptide like this.But there is a phosphoryl to be retained on the side chain of an amino acid hydroxyl.When with trifluoroacetic acid (TFA) acidolysis, can obtain (as O-phosphoric acid seryl) polypeptide.
3. two or more amino acid whose peptide self-assembly
Under room temperature (25 ℃), as cyclic phosphorochloridate and two or more N of excessive 50%, when O-two (trimethyl silicon based) amino acid reacts 24～72 hours in aprotic solvent (as benzene or tetracol phenixin), at first form pentacoordinate phosphinylidyne-amino-acid mixed anhydride, second N then, the carbonyl of the amino acid whose amino nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride of O-two (trimethyl silicon based) forms dipeptides, the amino of the dipeptides carbonyl of nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride again forms tripeptides, can repeat to obtain polypeptide like this.Can obtain different aminoacids residue combination polypeptide.If the side chain of containing N is arranged, during O-three (trimethyl silicon based) amino acid (as Serine) reaction, there is a phosphoryl to be retained on the side chain of an amino acid hydroxyl.When with trifluoroacetic acid (TFA) acidolysis, can obtain (O-phosphoric acid seryl) polypeptide.
4. utilizing pentacoordinate phosphinylidyne-amino-acid mixed anhydride to carry out orientation synthesizes
Under room temperature (25 ℃), use two volumetrys with equimolar cyclic phosphorochloridate solution and N earlier, the amino acid whose aprotic solvent of O-two (trimethyl silicon based) (as benzene or tetracol phenixin) solution splashes in the there-necked flask simultaneously, stirs while dripping.After all dripping off, use
31P NMR follows the tracks of, when treating that cyclic phosphorochloridate all is converted into pentacoordinate phosphinylidyne-amino-acid mixed anhydride (about 5 minutes～24 hours), wait mole N with second kind, O-two (trimethyl silicon based) amino acid solution slowly splashes in above-mentioned pentacoordinate phosphinylidyne-amino-acid mixed anhydride, stir while dripping, react and to obtain dipeptides in 6～24 hours.During with resultant dipeptides and second kind of pentacoordinate phosphinylidyne-amino-acid mixed anhydride reactant, can obtain tripeptides.Repeat like this to obtain desired sequences polypeptide.
5. utilize pentacoordinate phosphinylidyne-amino-acid mixed anhydride to carry out solid phase synthesis
Under room temperature (25 ℃), use two volumetrys with equimolar cyclic phosphorochloridate solution and N earlier, the amino acid whose aprotic solvent of O-two (trimethyl silicon based) (as benzene or tetracol phenixin) solution splashes in the there-necked flask simultaneously, stirs while dripping.After all dripping off, use
31P NMR follows the tracks of, and (about 5 minutes～24 hours) can use when treating that cyclic phosphorochloridate all is converted into pentacoordinate phosphinylidyne-amino-acid mixed anhydride.With the pentacoordinate phosphinylidyne-amino-acid mixed anhydride and polymer solid phase carrier (as crosslinked methylol polystyrene resin, the silica gel) reaction that has functional group of preparation, use mineral acid (example hydrochloric acid) to remove phosphoryl again.Can repeat to obtain being with high molecular polypeptide like this, use trifluoroacetic acid (TFA) or Hydrogen bromide (HBr) that polypeptide is scaled off from polymer at last.High performance liquid chromatography (HPLC) purifying with preparation can obtain target polypeptides.
Below be embodiments of the invention:
Example 1: pentacoordinate (O-phenylene) phosphinylidyne-leucine mixes the synthetic of acid anhydride
Under nitrogen protection; be dissolved in the benzene of 10ml at the inferior benzene phosphoryl chloride of O-of room temperature (25 ℃) 5mmol (0.953 gram); with the N of 5mmol (1.375 gram), O-two (trimethyl silicon based) leucine is dissolved in the benzene of 10ml, these two kinds of solution is respectively charged in two drop-burettes again.Adopt two volumetrys that these two kinds of solution are splashed in the there-necked flask simultaneously, stir while dripping.After titration is intact, use
31P NMR follows the tracks of, and treats that the inferior benzene phosphoryl chloride of O-is converted into pentacoordinate phosphinylidyne-leucine fully and mixes stopped reaction (about 20 minutes) behind the acid anhydride.Rotary distillation can be that the pentacoordinate phosphinylidyne-leucine more than 95% mixes acid anhydride except that desolvating and other low volatility materials, can obtaining purity.
Example 2: pentacoordinate (O-phenylene) phosphinylidyne-phenylalanine mixes the synthetic of acid anhydride
Under nitrogen protection; be dissolved in the benzene of 10ml at the inferior benzene phosphoryl chloride of O-of room temperature (25 ℃) 5mmol (0.953 gram); N with 5mmol (1.545 gram); O-two (trimethyl silicon based) phenylalanine is dissolved in the benzene of 10ml, by the reaction of the method for example 1 and handle that can to obtain purity be the mixed acid anhydride of pentacoordinate phosphinylidyne-phenylalanine 95% or more.
Example 3:N, the peptide self-assembly of O-two (trimethyl silicon based) phenylalanine
Under nitrogen protection, with 10ml 7.5mmol (2.32 gram) N, O-two (trimethyl silicon based) phenylalanine benzole soln splashes in the inferior benzene phosphoryl chloride of the O-benzole soln of 10ml 5mmol (0.953 gram) at leisure, stirs while dripping in room temperature (25 ℃).Continue about 24 hours of reaction after titration is intact again, rotary distillation can remove and desolvate and other low volatility materials, acidolysis then.Ethyl acetate extraction with 3 * 10ml goes out by product, and lyophilize then can obtain dipeptides～decapeptide series product with preparation HPLC at last.Becoming the peptide productive rate is 81%.
Example 4:N, the leucic peptide self-assembly of O-two (trimethyl silicon based)
Under nitrogen protection; in room temperature (25 ℃) with 10ml 7.5mmol (2.06 gram) N; O-two (trimethyl silicon based) phenylalanine benzole soln splashes in the inferior benzene phosphoryl chloride of the O-benzole soln of 10ml 5mmol (0.953 gram) at leisure, by the method reaction of example 3 and handle that can to obtain into the peptide productive rate be 84% dipeptides～octapeptide series product
Example 5:N, O-two (trimethyl silicon based) phenylalanine and N, the leucic self-assembly of O-two (trimethyl silicon based)
Under nitrogen protection; in room temperature (25 ℃) with 4mmol (1.24 gram) N; O-two (trimethyl silicon based) phenylalanine and 4mmol (1.10 gram) N; O-two (trimethyl silicon based) leucine 10ml benzole soln splashes in the inferior benzene phosphoryl chloride of the O-benzole soln of 10ml 5mmol (0.953 gram) at leisure, stirs while dripping.Continue about 48 hours of reaction after titration is intact again, rotary distillation can remove and desolvate and other low volatility materials, acidolysis then.Ethyl acetate extraction with 3 * 10ml goes out by product, and lyophilize then can obtain various combination dipeptides～six peptide series products with preparation HPLC at last.Becoming the peptide productive rate is 64%.
Example 6:N, O-three (trimethyl silicon based) Serine and N, the leucic self-assembly of O-two (trimethyl silicon based)
Under nitrogen protection; in room temperature (25 ℃) with 4mmol (1.284 gram) N; O-two (trimethyl silicon based) Serine and 4mmol (1.10 gram) N; O-two (trimethyl silicon based) leucine 10ml benzole soln splashes in the inferior benzene phosphoryl chloride of the O-benzole soln of 10ml 5mmol (0.953 gram) at leisure, stirs while dripping.Press the method reaction of example 5, add trifluoroacetic acid then, the alkoxyl group of O-alcoxyl phosphoryl is removed on the serine residue side chain, can obtain various combination (O-phosphoric acid seryl) dipeptides～six peptide series products with preparation HPLC at last.Becoming the peptide productive rate is 50%.
Example 7: utilize pentacoordinate phosphinylidyne-amino-acid mixed anhydride liquid phase to synthesize Ile-Phe Leu-Phe
Under nitrogen protection; in room temperature (25 ℃) with 10ml 6mmol (1.854 gram) N; O-two (trimethyl silicon based) phenylalanine benzole soln splashes at leisure by synthetic 5mmol pentacoordinate (O-phenylene) phosphinylidyne-leucine of the method for example 1 and mixes in the acid anhydride, stirs while dripping.Continue about 28 hours of reaction after titration is intact again, rotary distillation can remove and desolvate and other low volatility materials, acidolysis then.Ethyl acetate extraction with 3 * 10ml goes out by product, and lyophilize then can obtain two peptide prods with preparation HPLC at last.Becoming the peptide productive rate is 88%.
Example 8: utilize pentacoordinate phosphinylidyne-amino-acid mixed anhydride liquid phase to synthesize leucine-L-Ala Leu-Ala
Under nitrogen protection; in room temperature (25 ℃) with 10ml 6mmol (1.41 gram) N; O-two (trimethyl silicon based) phenylalanine benzole soln splashes at leisure by synthetic 5mmol pentacoordinate (O-phenylene) phosphinylidyne-leucine of the method for example 1 and mixes in the acid anhydride, reacts and handle by the method for example 7 to obtain two peptide prods.Becoming the peptide productive rate is 81%.
Example 9: utilize pentacoordinate phosphinylidyne-amino-acid mixed anhydride solid phase synthesis Ile-Phe Leu-Phe mix acid anhydride 20mmol 20ml benzole soln and 0.5 gram polystyrene hydroxymethyl resin room temperature (25 ℃) reaction 12 hours by method 1 synthetic pentacoordinate (O-phenylene) phosphinylidyne-leucine, the elimination mother liquor, the salt acid elution is in the alkali and after drying.With the benzene washing for several times, add pentacoordinate (O-phenylene) phosphinylidyne-phenylalanine again and mix acid anhydride 20mmol 20ml benzole soln, room temperature (25 ℃) reaction 12 hours.Post-processing step is the same.The resin that obtains reacted 4 hours with 20% trifluoroacetic acid, filtered this solution, the alkali neutralization, and the desalination of Rik-Sep post, lyophilize can obtain pure LeuPhe dipeptides with the separation of HPLC preparative column.Reaction process is as follows:
Example 10: utilize pentacoordinate phosphinylidyne-amino-acid mixed anhydride solid phase synthesis phenylalanine-L-Ala Phe-Ala
Mixing acid anhydride 20mmol20ml benzole soln and 0.5 gram polystyrene hydroxymethyl resin room temperature (25 ℃) reaction 12 hours by method 2 synthetic pentacoordinates (O-phenylene) phosphinylidyne-phenylalanine, by the method reaction of example 3 and handle and to obtain two peptide prods.Becoming the peptide productive rate is 84%.
Claims (2)
1, the method for pentacoordinate phosphinylidyne-amino-acid mixed anhydride of a kind of preparation formula I, it is characterized in that, N by formula II cyclic phosphorochloridate and formula III, O-two (trimethyl silicon based) amino acid stirred 5 minutes to 24 hours in 0 ℃～50 ℃ in the presence of the organic solvent that is selected from benzene, toluene, tetracol phenixin and pyridine.The preparation feedback formula is:
Among formula I, the III
Be R
1-CH-CH-R
2Or R
1-C=C-R
2, R
1, R
2For H, carbon atom are 1～10 alkyl, aromatic base, R
1, R
2Identical, perhaps different, R
1, R
2Be ring-type, straight chain, side chain, perhaps both are interconnected to ring.
2, a kind of usefulness is the method for the synthetic polypeptide of pentacoordinate phosphinylidyne-amino-acid mixed anhydride according to claim 1, it is characterized in that having only on the described polypeptide chain side chain is the amino-acid residue of alkyl and aromatic base, its building-up process is: under room temperature (25 ℃), cyclic phosphorochloridate and excessive 50% N, O-two (trimethyl silicon based) amino acid reacted in aprotic solvent 24～48 hours, form pentacoordinate phosphinylidyne-amino-acid mixed anhydride, second N then, the carbonyl of the amino acid whose amino nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride of O-two (trimethyl silicon based) forms dipeptides, the amino of the dipeptides carbonyl of nucleophilic attack pentacoordinate phosphinylidyne-amino-acid mixed anhydride again forms tripeptides, repeat to obtain polypeptide like this, reaction process is:
R2 can be identical, also can be different.R1, R2 can be ring-type, straight or branched, also can be interconnected to ring.Can be methyl, ethyl, phenyl etc. as R1, R2.R
3Be various a-amino acid side chains.The preparation method of cyclic phosphorochloridate is: by phosphorus pentachloride and adjacent glycols or the reaction of adjacent diphenols compound, at first generate pentacoordinate trichlorine two phosphine oxide pentamethylene, add diacetyl oxide then and can obtain cyclic phosphorochloridate.N, the amino acid whose preparation method of O-two (trimethyl silicon based) is: amino acid and hexamethyldisilazane were refluxed in benzole soln 2～5 hours, and underpressure distillation can obtain N then, O-two (trimethyl silicon based) amino acid.Organic solvent can adopt and anyly can dissolve this class cyclic phosphorochloridate and N, and the amino acid whose aprotic solvent of O-two (trimethyl silicon based) is as benzene, toluene, tetracol phenixin, pyridine etc.Temperature of reaction can stir 5 minutes～24 hours down at 0 ℃-50 ℃.The productive rate of pentacoordinate phosphinylidyne-amino-acid mixed anhydride can reach more than 95%.
It is the self-assembly of polypeptide that the pentacoordinate phosphinylidyne-amino-acid mixed anhydride of the present invention's preparation can be used for synthetic polypeptide, is applied to the combinatorial chemistry field, and can select some has bioactive polypeptide and kinases.
1. do not contain the amino acid whose peptide self-assembly of side chain functionalities
Reaction equation is as follows:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96114152A CN1049220C (en) | 1996-12-27 | 1996-12-27 | Preparation of pentacoordinate phosphinylidyne-amino-acid mixed anhydride and its method for synthetizing polypeptide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96114152A CN1049220C (en) | 1996-12-27 | 1996-12-27 | Preparation of pentacoordinate phosphinylidyne-amino-acid mixed anhydride and its method for synthetizing polypeptide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1157289A CN1157289A (en) | 1997-08-20 |
| CN1049220C true CN1049220C (en) | 2000-02-09 |
Family
ID=5121967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN96114152A Expired - Fee Related CN1049220C (en) | 1996-12-27 | 1996-12-27 | Preparation of pentacoordinate phosphinylidyne-amino-acid mixed anhydride and its method for synthetizing polypeptide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1049220C (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1079473A (en) * | 1993-01-14 | 1993-12-15 | 清华大学 | The N-phosphinylidyne small peptide |
| CN1079726A (en) * | 1993-04-09 | 1993-12-22 | 清华大学 | N-phosphorylated thing and synthetic new method thereof |
| CN1093368A (en) * | 1993-12-24 | 1994-10-12 | 清华大学 | The method of amine synthetic N-phosphorylated thing of direct phosphorylated in aqueous systems |
-
1996
- 1996-12-27 CN CN96114152A patent/CN1049220C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1079473A (en) * | 1993-01-14 | 1993-12-15 | 清华大学 | The N-phosphinylidyne small peptide |
| CN1079726A (en) * | 1993-04-09 | 1993-12-22 | 清华大学 | N-phosphorylated thing and synthetic new method thereof |
| CN1093368A (en) * | 1993-12-24 | 1994-10-12 | 清华大学 | The method of amine synthetic N-phosphorylated thing of direct phosphorylated in aqueous systems |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1157289A (en) | 1997-08-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1864989B1 (en) | Method for producing l-2-amino-4-(hydroxymethylphosphinyl)- butanoic acid | |
| Soloshonok et al. | Asymmetric synthesis of novel highly sterically constrained (2S, 3S)-3-methyl-3-trifluoromethyl-and (2S, 3S, 4R)-3-trifluoromethyl-4-methylpyroglutamic acids | |
| Imperiali et al. | Stereoselective synthesis and peptide incorporation of (S)-. alpha.-amino-(2, 2'-bipyridine)-6-propanoic acid | |
| Tamiaki et al. | A novel protecting group for constructing combinatorial peptide libraries | |
| KR102479601B1 (en) | System and method for solution phase gap peptide synthesis | |
| WO2021085635A1 (en) | Reaction agent for amide reaction and method for producing amide compound using same | |
| EP0098865A4 (en) | Peptide synthesis and amino acid blocking agents. | |
| CN1049220C (en) | Preparation of pentacoordinate phosphinylidyne-amino-acid mixed anhydride and its method for synthetizing polypeptide | |
| Kayser et al. | Benzene‐Bridged Hexaalkynylphenylalanines and First‐Generation Dendrimers Thereof | |
| KR930004053B1 (en) | Process for producing n-protected-(alpha)-l-aspartyl-l-phenyallanine methyl ester | |
| Iwakura et al. | Stepwise synthesis of oligopeptides with N‐carboxy α‐amino acid anhydrides | |
| Chao et al. | Synthesis and application of Fmoc-O-[bis (dimethylamino) phosphono] tyrosine, a versatile protected phosphotyrosine equivalent | |
| JPS61155393A (en) | Synthesis of peptide from amino acid | |
| Zaloom et al. | A new synthesis of peptides from azides and unactivated carboxylic acids | |
| Ruddick et al. | A new method for the polymer-supported synthesis of cyclic oligoesters for potential applications in macrocyclic lactone synthesis and combinatorial chemistry | |
| US6090913A (en) | Transesterification and other conversion reactions of acid derivatives, using an amidine base | |
| EP1318142B1 (en) | T-butoxycarbonylaminoethylamine for the synthesis of pna monomer units, amino acid derivatives, intermediates thereof, and processes for productions of them | |
| CA1196911A (en) | Process for the preparation of compounds containing carboxylic acid amide groups, in particular of peptides | |
| CN110183513B (en) | Cyclopeptide compound simulating structure of natural product and preparation method thereof | |
| Hulst et al. | Catalytic enantioselective addition of hydrogen cyanide to benzaldehyde and p-methoxybenzaldehyde using cyclo-His-(α-Me) Phe as catalyst | |
| JP3493934B2 (en) | Method for producing N, N-bis (trimethylsilyl) allylamine | |
| Armstrong et al. | Enantioselective Synthesis of α-Aminophosphonates via Organocatalytic Sulfenylation and [2, 3]-Sigmatropic Sulfimide Rearrangement | |
| Ueda et al. | 3, 3'-(Phenylphosphinylidene) bis (2 (3H)-benzoxazolone) and 3, 3'-(phenylphosphinylidene) bis (2 (3H)-benzothiazolone). New activating agents. | |
| CA2619098A1 (en) | Novel coupling agent and uses thereof | |
| Bleicher et al. | New phenylfluorenyl based linkers for solid phase synthesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |