CN101595120B - The poltpeptide polymer and the synthetic method of the same - Google Patents

The poltpeptide polymer and the synthetic method of the same Download PDF

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CN101595120B
CN101595120B CN200780044854.8A CN200780044854A CN101595120B CN 101595120 B CN101595120 B CN 101595120B CN 200780044854 A CN200780044854 A CN 200780044854A CN 101595120 B CN101595120 B CN 101595120B
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polypeptide
replacing
replacement
unsubstituted
general formula
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CN101595120A (en
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孙怀林
张坚
刘秋华
于蕾
赵江瑜
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Nankai University
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Abstract

The present invention provides a synthetic method of polypeptides and the polypeptides made by the method. The polypeptides have a general formula of (I), wherein R1 and R2 are substituted or unsubstituted alkyl, substituted or unsubstituted aryl, respectively, and wherein n is a natural number of equal to or more than 2. The synthetic method of the polypeptides is characterized in that an imine having general formula of (II) and a carbon monoxide are used as monomers in alternating copolymerization, in the presence of cobalt catalyst, to produce the polypeptides of a general formula (I) directly. By the method of the present invention, complex steps in those conventional methods can be avoided, the synthetic processes of polypeptides can be simplified considerably, and some polypeptides can be obtained, which are unobtainable by the methods of prior art.

Description

Poltpeptides and synthetic method thereof
Technical field:
The present invention relates to a kind of new polypeptide synthesis method, particularly relate to a kind of method of synthesizing polypeptide of reacting by metal catalytic imines and CO-copolymerization.The method is made raw material without amino acid, but take imines and carbon monoxide as monomer, at transition metal-catalyzed lower generation alternating copolymerization, directly generates polypeptide.This copolyreaction is a kind of brand-new polyreaction type, also is a kind of method of very succinct synthetic polypeptide newly.Can obtain by this method on nitrogen-atoms that a class can not obtain with existing method and the carbon atom while with substituent polypeptide.This class polypeptide has water-insoluble and unique degradation property, will have important purposes at aspects such as biomedical materials.
Background technology:
Polypeptide is a kind of important compound, is not only the carrier of life entity inner structure and function, and has extensive use at catalysis, material and field of medicaments.The synthetic of polypeptide all carries out take amino acid as raw material traditionally, thereby such method need to use special reagent that high stability carboxyl is activated the generation peptide bond.This synthesizing is to be finished by the catalysis of rrna and relevant enzyme in vivo, can synthesize the polypeptide with specific amino acid sequence by genetically engineered by this method, makes raw material but basically be only limited to natural amino acid.Utilize the synthetic polypeptide of chemical process not have the raw material restriction.For example liquid phase and solid phase coupling technology are the common methods of synthetic small peptide, but relate to numerous and diverse step and higher cost, and are not suitable for synthetic macromolecule amount polypeptide.
Concerning synthetic high molecular weight polypeptide, the simplest method is the ring-opening polymerization method of amino acid-N-carboxylic acid (NCA).But the method still relates to higher cost, hinders scale operation and the application of polypeptide.In addition, the ring-opening polymerization method is only applicable to the synthetic of polypeptide that general non-N-substituted amino acid consists of.For the N-substituted amino acid, because sterically hindered relation, so that this ring-opening polymerization difficult (Ballard, D.G.H.et al.J.Chem.Soc.1958,355).At present, the polymkeric substance that only has proline(Pro) and sarkosine that can access, and the short chain polymer of N-methylalanine (Cosani, A.et al.Macromolecules 1978,11,1041).
The polypeptide that natural non-N-substituted amino acid consists of has water-soluble usually, is not suitable for directly as biomedical materials such as artificial organs materials.And on the nitrogen-atoms with substituent polypeptide, effective synthetic method and be difficult to obtain for want of always.In order to solve the composition problem of these polypeptide, the most attracting may scheme be to synthesize polypeptide by the copolymerization of imines and carbon monoxide.But unfortunately this reaction is difficult to realize always, and reason is to lack suitable catalyzer.
1998, Sen and Arndtsen studied respectively the insertion reaction of imines to acyl group palladium key, although the polypeptide in not obtaining envisioning, success obtained acid amides (Kacker, S.et al.Angew.Chem.Int.Ed.1998,37,1251; Dghaym, R.D.et al.Organometallics 1998,17,4).This is first example that imines successfully inserts the transition metal carbon bond.The people such as Arndtsen have also attempted realizing with the carbonyl compound of nickel and manganese the insertion of imines.But up to now, people getable best result be single imines and carbon monoxide to the insertion of metal carbon bond, generate an amino acid whose structural unit.And towards aspect the synthetic effort of polypeptide, even the simplest dipeptides synthetic, also never must be successfully (Davis, J.L.et al.Organometallics 2000,19,4657; Lafrance, D.et al.Organometallics 2001,20,1128).
Notice that cobalt metal is a kind of important carbonylation reaction catalyst, can be used for the copolymerization (Jia, L.et al.J.Am.Chem.Soc.2002,24,7282) of catalysis ethylenimine and carbon monoxide.Yet Sen etc. attempt to synthesize polypeptide with the copolymerization of this class catalyst imines and carbon monoxide, and the result but fails, but have obtained N-alkyl phthalimidine (Funk, J.K.et al.Helv.Chim.Acta 2006,89,1687).
Summary of the invention:
The invention provides a kind of new polypeptide synthesis method, relate to particularly a kind of method of synthesizing polypeptide by the alternating copolymerization of transition metal-catalyzed lower imines and carbon monoxide.This synthetic method can overcome the limitation of traditional method (such as the ring-opening polymerization method), and the while is with substituent polypeptide on the nitrogen-atoms that can not obtain before obtaining and the carbon atom.This peptide species loses the ability that generates hydrogen bond because the hydrogen on the nitrogen-atoms is substituted, has fundamentally changed the water-soluble of polypeptide, and will have important purposes in field of biomedical materials.
Polypeptide provided by the present invention has the structure of general formula (I):
Figure G54244852150138000D000031
R wherein 1And R 2Be respectively and replace or unsubstituted alkyl, replacement or unsubstituted aryl; N is the natural number more than or equal to 2.
The represented polypeptide of general formula (I) can comprise following compound:
(1) the represented polypeptide of general formula (I), wherein R 1For replacing or unsubstituted alkyl; R 2For replacing or unsubstituted alkyl, replacement or unsubstituted aryl; Condition is R 1=R 2In the situation of=methyl is not included in.
(2) the represented polypeptide of general formula (I), wherein, R 1For replacing or unsubstituted alkyl; R 2For replacing or unsubstituted alkyl, replacement or unsubstituted aryl.
(3) the represented polypeptide of general formula (I), wherein, R 1Be methyl; R 2For replacing or unsubstituted alkyl, replacement or unsubstituted aryl.
(4) the represented poltpeptides of general formula (I), wherein, R 1Be methyl; R 2For replacing or unsubstituted phenyl.
(5) the represented polypeptide of general formula (I), wherein, R 1Be methyl; R 2Be the tertiary butyl or tert-pentyl.
Described raw material imines has the structure of general formula (II):
R 1N＝CHR 2
(II)
R wherein 1And R 2Have and top same implication.
Described polymerization process can represent with following equation:
Figure G54244852150138000D000032
Catalyzer for above-mentioned polyreaction of the present invention is positive monovalence acyl group cobalt compound, and its structure can be used general formula (III) expression:
R wherein 3For replacing or unsubstituted alkyl, replacement or unsubstituted aryl, replacement or unsubstituting alkoxy, replacement or unsubstituted aryloxy, amido; L is carbonyl ligands, phosphorus part, nitrogen ligand or isonitrile part.
The represented acyl group cobalt compound of general formula (III) can comprise following compound:
(1) the represented acyl group cobalt compound of general formula (III), wherein R 3For replacing or unsubstituted alkyl, replacement or unsubstituted aryl, replacement or unsubstituting alkoxy, replacement or unsubstituted aryloxy, amido; L is carbonyl ligands.
(2) the represented acyl group cobalt compound of general formula (III), wherein R 3For replacing or unsubstituted alkyl, replacement or unsubstituted aryl, replacement or unsubstituting alkoxy, replacement or unsubstituted aryloxy, amido; L is carbonyl ligands.
(3) the represented acyl group cobalt compound of general formula (III), wherein R 3For replacing or unsubstituted alkyl; L is carbonyl ligands.
Because the represented acyl group cobalt compound of general formula (III); under solution state, be actually the mixture of the represented cobalt metal compound (being the Alkyl-cobalt compound) of itself and general formula (IV); and between the two mutual conversion can occur; there is following balance, and has inseparable relation:
Figure G54244852150138000D000042
Therefore, in fact the catalyzer of described polyreaction comprises the precursor compound (IV) that can be converted into compound (III).Under polymeric reaction condition, this precursor compound (IV) can be converted into compound (III), serves as the catalyzer of polyreaction.
Compound (IV) as acyl group cobalt catalyst presoma can comprise following compound:
R 3-Co(CO) 3L
(IV)
(1) general formula is the cobalt metal compound of (IV), wherein R 3For replacing or unsubstituted alkyl, replacement or unsubstituted aryl, replacement or unsubstituting alkoxy, replacement or unsubstituted aryloxy, amido; L is carbonyl ligands, phosphorus part, nitrogen ligand or isonitrile part.
(2) general formula is the cobalt metal compound of (IV), wherein R 3For replacing or unsubstituted alkyl, replacement or unsubstituted aryl, replacement or unsubstituting alkoxy, replacement or unsubstituted aryloxy, amido; L is carbonyl ligands.
(3) general formula is the cobalt metal compound of (IV), wherein R 3For replacing or unsubstituted alkyl; L is carbonyl ligands.
Described copolyreaction can be carried out in inert organic solvents, and solvent for use namely can be that polarity also can be nonpolar.
Reaction can carried out in the carbon monoxide pressure scope very widely, be preferably more than or equal and carry out under the 0.1013MPa (i.e. 1 normal atmosphere), more preferably carry out to 5.52MPa (being roughly equal to 55 normal atmosphere) at 4.14MPa (being roughly equal to 41 normal atmosphere).
Reaction also can be carried out in very wide temperature range.Consider the reason of catalyst stability, temperature of reaction can not be higher than 200 ℃, is preferably at 20 ℃ to 100 ℃, more preferably at 40 ℃ to 60 ℃.
More particularly, acyl group cobalt catalyst of the present invention can have following structure:
Figure G54244852150138000D000051
Wherein R is alkyl, phenyl or substituted-phenyl.The structure of the imines that adopts can for:
MeN＝CHR′
Wherein, R ' is phenyl, substituted-phenyl or alkyl.The structure of the polypeptide that generates can for:
Figure G54244852150138000D000052
Wherein, R ' is phenyl, substituted-phenyl or alkyl; N is the natural number more than or equal to 2.
Polypeptide synthesis method of the present invention can comprise the steps:
1) in the autoclave that is full of CO gas, adds dry inert solvent; It is 0.1mM～1M that adding acyl group cobalt catalyst makes its concentration, is preferably 1～100mM.Increase the pressure of carbon monoxide extremely greater than 0.1013
MPa is preferably in 4.14～5.52MPa; Leave standstill, make the acyl group cobalt catalyst by the form that partly loses carbonyl, all be converted into the form of above-mentioned acyl group cobalt, the time is 0.5～24 hour, is preferably 6～12h.
2) after the release, add imines and valve-off; Be forced into carbon monoxide pressure for greater than 0.1013MPa, be preferably 4.14～5.52MPa; The oil bath heating is stirred, and temperature of reaction is 20～100 ℃, is preferably 40～60 ℃.
3) reaction complete after, the cooling, still is driven in pressure release, the liquid that obtains again vacuum is taken out desolventizing, obtains the crude product of aforementioned polypeptides.
Solvent of the present invention can be alkanes, such as Skellysolve A, normal hexane, hexanaphthene, normal heptane, octane, positive nonane, positive Gui alkane or sherwood oil; Aromatic hydrocarbons is such as benzene, toluene, p-Xylol etc., o-Xylol, m-xylene, ethylbenzene or chlorinated benzene; Ethers is such as ether, positive propyl ether, isopropyl ether, n-butyl ether, glycol dimethyl ether, ethylene glycol diethyl ether, Propylene Glycol Dimethyl Ether, Isosorbide-5-Nitrae-dioxane or methyl-phenoxide; Lipid is such as methyl acetate or ethyl acetate; Amides is such as DMF, N,N-dimethylacetamide or N-methyl ring Valerolactim; Or nitrile, such as acetonitrile or cyanophenyl.Particularly alkanes such as normal hexane, reaches ethers, such as Isosorbide-5-Nitrae-dioxane.
R of the present invention 1, R 2, and R 3Related term " replace or not substituted alkyl " means the alkyl that can replace at its one or more desired areas.The example of alkyl can comprise methyl, ethyl, methoxymethyl, methoxy ethyl, phenoxymethyl, the phenoxy group ethyl, benzyloxymethyl, the phenoxy group ethyl, face the Phthalimide ylmethyl, the fluoro methyl, the fluoro ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, amyl group, hexyl, heptyl, octyl group, nonyl, decyl, cyclopropyl, cyclobutyl, cyclopentyl, the oxyethyl group cyclopentyl, cyclohexyl, the tert.-butoxy cyclohexyl, the benzyloxy cyclohexyl, suberyl, the ring octyl group, the ring nonyl, the ring decyl, benzyl, the 2-phenylethyl, the 3-phenyl propyl, naphthyl methyl or 4-methoxy-benzyl.Particularly methyl, ethyl, the tertiary butyl, tert-pentyl or benzyl.
" replace or unsubstituted aryl " means the aryl that can replace at its one or more desired areas.The example of aryl can comprise phenyl, tolyl, p-methoxy-phenyl, ethylphenyl, ethoxyl phenenyl, propyl group phenyl, mesitylene base, naphthyl, pyridyl, furyl, pyrryl and thienyl; Particularly phenyl, tolyl or p-methoxy-phenyl.
" replace or unsubstituted alkoxyl group " means the alkoxyl group that can replace at its one or more desired areas.The example of alkoxyl group can comprise methoxyl group, oxyethyl group, n-propyl oxygen base, isopropoxy, tert.-butoxy, benzyloxy, cyclopentyloxy, cyclohexyl oxygen base, the 2-phenyl ethoxy, 3-phenyl propoxy-, the 2-methoxy ethoxy, the 3-methoxy propoxy, 2-phenoxy group oxyethyl group, 3-phenoxy group propoxy-, the fluoro oxyethyl group, heptan the oxygen base, octyloxy, the ninth of the ten Heavenly Stems oxygen base, the last of the ten Heavenly stems oxygen base, cyclopropyl oxygen base, cyclobutyl oxygen base, cyclopentyloxy, cyclohexyl oxygen base, suberyl oxygen base or ring octyl group oxygen base; Particularly methoxyl group, oxyethyl group or phenoxy group.
" replace or unsubstituted aryloxy " means the aryloxy that can replace at its one or more desired areas.The example of aryloxy can comprise phenoxy group, methylphenoxy, ethyl phenoxy group, propyl group phenoxy group, naphthyloxy, pyridyloxy, pyrroles's oxygen base, pyran oxygen base, furans oxygen base, thiophene oxy; Particularly phenoxy group or methylphenoxy.
" amido " is selected from and comprises dimethylin, diethylin, di-n-propylamine base, diisopropylamino, dibenzyl amido, cyclopentamine base, cyclohexylamino; Particularly cyclopentamine base or cyclohexylamino.
" phosphorus part " means trihydrocarbyl phosphine or trialkyl phosphite ester ligand.The example of three valent phosphors part can comprise trimethyl-phosphine, triethyl phosphine, tripropyl phosphine, tributylphosphine, thricyclohexyl base phosphine, triphenylphosphine, three (o-methyl-phenyl-) phosphine, three (aminomethyl phenyl) phosphine, three (p-methylphenyl) phosphines, trimethyl phosphite, triethyl phosphorite, tripropyl phosphorous acid ester, tributyl phosphorous acid ester, triphenyl phosphorous acid ester, triphenyl phosphorous acid ester; Particularly triphenylphosphine, three (o-methyl-phenyl-) phosphine or triphenyl phosphorous acid ester.
The example of " nitrogen ligand " can comprise Trimethylamine 99, triethylamine, tripropyl amine, Tributylamine, DMA, pyridine or quinoline; Pyridine particularly.
The example of " isonitrile part " can be methyl isonitrile, ethyl isonitrile, propyl group isonitrile, sec.-propyl isonitrile, normal-butyl isonitrile, tert-butyl isonitrile, benzyl isonitrile or phenyl isonitrile; Tert-butyl isonitrile particularly.
As everyone knows, the alternating copolymerization of metal catalytic imines and carbon monoxide is that people wish but a very difficult reaction that realizes for a long time.The acyl group cobalt catalyst of positive monovalence provided by the invention can be realized this reaction effectively, obtains polypeptide.Therefore, the present invention has opened up the synthetic new some effective of polypeptide compounds.This synthetic method can be avoided the step of numerous and diverse synthetic and activated amino acid that traditional method relates to, so that the synthetic of polypeptide simplified widely.Obtain from suitable aldehyde and amine at an easy rate owing to imines simultaneously, and carbon monoxide is a kind of cheapness and abundant raw material, so that this synthetic method consists of the approach of the synthetic polypeptide of a very economical practicality, is suitable for carrying out scale operation.
Particularly the method can be synthesized in the past on the unavailable nitrogen-atoms and carbon atom simultaneously with substituent polypeptide.These polypeptide have the characteristics of " water-insoluble ", and can be in trifluoroacetic acid the special degradation property of fast degradation, therefore aspect biomedical material, will have important use.
Embodiment:
Embodiment 1:
Figure G54244852150138000D000081
Under CO (carbon monoxide converter) gas protection, add Isosorbide-5-Nitrae-dioxane and 3ml acyl group cobalt catalyst (the III) (R of 50ml drying in the 300ml autoclave 3=PhCH 2, hexane solution (2.0M, 6mmol) L=CO).Closing valve, the pressure of rising carbon monoxide left standstill 12 hours to 5.52MPa.After laying down pressure, add 1.0g (66mol) imines IIa.Valve-off increases the pressure of carbon monoxide to 5.52MPa.50 ℃ of lower induction stirring reactions of oil bath 12 hours.Be cooled to room temperature, still is driven in pressure release, obtains brownish black liquid.Solvent removed in vacuo obtains the brownish black dope.Add a small amount of normal hexane in above-mentioned brownish black dope, fully agitator treating is removed the impurity such as unreacted monomer, obtains pressed powder.Suction filtration is collected this solid, obtains the pale powder of polypeptide Ia. 1H?NMR(400MHz，Cl 2CDCDCl 2)：δ7.17(bs，5H，Ph)，6.50(bs，1H，CH)，2.57(bs，3H，Me). 13CNMR(125MHz，Cl 2CDCDCl 2)：δ171.1(CO)，134.3(Ph)，129.5(Ph)，59.5(CH)，33.2(Me).IR(KBr)：v co?1647cm -1.
Embodiment 2:
According to example 1 similar operation steps, acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 3mmol into, obtains the pale powder of polypeptide Ia.
Embodiment 3:
According to example 1 similar operation steps, replace Isosorbide-5-Nitrae-dioxane to make thinner with normal hexane, obtain the pale powder of polypeptide Ia.
Embodiment 4:
According to example 1 similar operation steps, but catalyzer adds behind the reactor without existing greater than an atmospheric carbon monoxide and lower quietly directly adds imide monomers to processing, obtains the pale powder of polypeptide Ia.
Embodiment 5:
According to example 1 similar operation steps, with cobalt metal compound (III) (R 3=CH 3, L=PPh 3) replacement (III) (R 3=PhCH 2, L=CO) make catalyzer, obtain the pale powder of polypeptide Ia.
Embodiment 6:
According to example 1 similar operation steps, adopt cobalt metal compound (IV) (R 3=PhOCH 2, L=CO) replace (III) (R 3=PhCH 2, L=CO) make catalyzer, obtain the pale powder of polypeptide Ia.
Embodiment 7:
Figure G54244852150138000D000091
According to example 1 similar operation steps, obtained the pale powder of polypeptide Ib by imines IIb. 1H?NMR(400MHz，Cl 2CDCDCl 2)：δ6.98(bs，4H，C 6H 4)，6.48(bs，1H，CH)，2.56(bs，3H，MeN)，2.16(bs，3H，Me). 13C?NMR(125MHz，Cl 2CDCDCl 2)：δ171.2(CO)，138.9(C 6H 4)，131.2(C 6H 4)，130.1(C 6H 4)，59.1(CH)，33.1(MEN)，21.7(Me).IR(KBr)：v co?1647cm -1.
Embodiment 8:
According to example 7 similar operation stepss, wherein acyl group cobalt catalyst (IH) (R 3=PhCH 2, consumption L=CO) changes 3mmol into, obtains the pale powder of polypeptide Ib.
Embodiment 9:
Figure G54244852150138000D000101
According to example 1 similar operation steps, obtained the pale powder of polypeptide Ic by imines IIc. 1H?NMR(400MHz，Cl 2CDCDCl 2)：δ6.98(bs，2H，C 6H 4)，6.68(bs，2H，C 6H 4)，6.42(bs，1H，CH)，3.60(bs，3H，MeO)，2.54(bs，3H，MeN). 13C?NMR(125MHz，Cl 2CDCDCl 2)：δ171.3(CO)，159.9(C 6H 4)，131.0(C 6H 4)，125.9(C 6H 4)，114.9(C 6H 4)，59.2(CH)，55.9(MeO)，33.1(MeN).IR(KBr)：v co?1646cm -1.
Embodiment 10:
According to example 9 similar operation stepss, wherein acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 3mmol into, obtains the pale powder of polypeptide Ic.
Embodiment 11:
Figure G54244852150138000D000102
According to example 1 similar operation steps, by the pale powder of imines IId to polypeptide Id. 1H?NMR(400MHz，Cl 2CDCDCl 2)：δ6.69(bs，2H，C 6H 2)，6.31(bs，1H，CH)，2.85-2.33(bs，3H，MeN)，2.05(bs，3H，3Me). 13C?NMR(125MHz，Cl 2CDCDCl 2)：δ172.1(CO)，138.6(C 6H 2)，130.9(C 6H 2)，58.2(CH)，31.8(MeN)，21.4(3Me).IR(KBr)：v co?1648cm -1.
Embodiment 12:
According to example 11 similar operation stepss, wherein acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 3mmol into, obtains the pale powder of polypeptide Id.
Embodiment 13:
Under CO (carbon monoxide converter) gas protection, add Isosorbide-5-Nitrae-dioxane and 1.5ml catalyzer (the III) (R of 50ml drying in the 300ml autoclave 3=PhCH 2, hexane solution (2.0M, 3.0mmol) L=CO).Closing valve, the pressure of rising carbon monoxide left standstill 12 hours to 5.52MPa.Lay down pressure, add 1.0g (66mol) imines IIe.Valve-off increases the pressure of carbon monoxide to 5.52MPa.50 ℃ of lower induction stirring reactions of oil bath 12 hours.Be cooled to room temperature, still is driven in release, gets yellow limpid liquid, drains solvent, obtains the pale solid powder of polypeptide Ie. 1H?NMR(400MHz，Cl 2CDCDCl 2)：δ5.3
Figure G54244852150138000D000112
4.89(m，1H，CH)，2.94(bs，3H，MeN)，0.80(bs，9H，t-Bu). 13C?NMR(125MHz，Cl 2CDCDCl 2)：δ171.15(CO)，57.53(CH)，37.12(tert-C)，34.25(MeN)，28.33(3Me).IR(KBr)：v co?1641cm -1.
Embodiment 14:
According to example 13 similar operation stepss, wherein acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 1.5mmol into, obtains the pale powder of polypeptide Ie.
Embodiment 15:
According to example 13 similar operation stepss, wherein acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 1.0mmol into, obtains the pale powder of polypeptide Ie.
Embodiment 16:
According to example 13 similar operation stepss, wherein acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 0.66mmol into, obtains the pale powder of polypeptide Ie.
Embodiment 17:
Figure G54244852150138000D000121
According to example 13 similar operation stepss, obtained the pale solid powder of polypeptide If by imines IIf. 1HNMR(400MHz，Cl 2CDCDCl 2)：δ5.3
Figure G54244852150138000D000122
4.96(m，1H，CH)，2.95(bs，3H，MeN)，1.05(m，2H，CH 2)，0.82(m，6H，2Me)，0.64(bs，3H，Me). 13C?NMR(125MHz，Cl 2CDCDCl 2)：δ171.22(CO)，56.38(CH)，39.97(tert-C)，34.66(MeN)，32.75(CH 2)，24.42(2Me)，8.86(Me).IR(KBr)：v co?1640cm -1。
Embodiment 18:
According to example 17 similar operation stepss, wherein acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 1.5mmol into, obtains the pale powder of polypeptide If.
Embodiment 19:
According to example 17 similar operation stepss, wherein acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 0.82mmol into, obtains the pale powder of polypeptide If.
Embodiment 20:
According to example 17 similar operation stepss, wherein acyl group cobalt catalyst (III) (R 3=PhCH 2, consumption L=CO) changes 0.66mmol into, obtains the pale powder of polypeptide If.
The polymerization reaction experiment that above-mentioned example provides the results are shown in table 1.
The copolyreaction result of table 1. imines and CO (except situation about explicitly pointing out in footnote, it all is under 50 ℃ and 5.52MPa carbon monoxide pressure that institute responds, and carries out in the dioxane solvent)
Figure G54244852150138000D000131
[1] the reaction solvent for use is normal hexane;
[2] the reaction procatalyst is processed without the carbon monoxide precompressed, and namely catalyzer is the mixture of acyl group cobalt and Alkyl-cobalt;
[3] the reaction catalyst system therefor is (III) (R 3=CH 3, L=PPh 3);
[4] the reaction catalyst system therefor is (IV) (R 3=PhOCH 2, L=CO).
Embodiment 21:
Be M with molecular weight n=19,000 polypeptide If at room temperature is dissolved in trifluoroacetic acid.After leaving standstill 24 hours, gpc analysis shows that its molecular weight has dropped to M n=600.

Claims (9)

1. a peptide species, general formula is (I), it is characterized in that on nitrogen-atoms and the carbon atom simultaneously with substituting group, wherein R 1For replacing or unsubstituted alkyl, replacement or unsubstituted aryl R 2For replacing or unsubstituted alkyl, replacement or unsubstituted aryl, n is the natural number more than or equal to 2.
Figure FSB00000999639700011
2. polypeptide claimed in claim 1 is characterized in that R 1And R 2Be respectively replacement or unsubstituted alkyl, replacement or unsubstituted aryl, n is the natural number more than or equal to 2; Condition is R 1=R 2In the situation of=methyl is not included in.
3. claim 1 or 2 described polypeptide is characterized in that R 1For replacing or unsubstituted alkyl; R 2For replacing or unsubstituted alkyl, replacement or unsubstituted aryl.
4. claim 1 or 2 described polypeptide is characterized in that R 1Be methyl; R 2For replacing or unsubstituted alkyl, replacement or unsubstituted aryl.
5. claim 1 or 2 described polypeptide is characterized in that R 1Be methyl; R 2For replacing or unsubstituted tertiary alkyl.
6. claim 1 or 2 described polypeptide is characterized in that R 1Be methyl; R 2For replacing or unsubstituted phenyl.
7. a peptide species, general formula is (I), it is characterized in that R 1=Me; R 2=C 6H 5, p-MeC 6H 4, p-MeOC 6H 4, 2,4,6-Me 3C 6H 2, t-C 4H 9Or t-C 5H 11
8. a peptide species, general formula is (I), it is characterized in that R 1=Me; R 2=t-C 4H 9Or t-C 5H 11
9. polypeptide synthesis method is characterized in that at transition metal-catalyzed lower generation alternating copolymerization, directly obtaining polypeptide take imines and carbon monoxide as raw material; Described transition-metal catalyst is the acyl group cobalt compound of positive monovalence, has the structure shown in the general formula (III):
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PCT/CN2007/003465 WO2008067729A1 (en) 2006-12-06 2007-12-06 The poltpeptides and the synthetic method of the same
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