- NaBH4 - A novel method for the deprotection of Nω-nitro-arginine
-
The selective deprotection of Nω-nitro-arginine derivatives represents a major preparative challenge. This problem can be circumvented by the use of catalytic hydrogenation, but often high pressure, elevated temperature, and/or long reaction times are needed. In certain cases hydrogenation is not suitable, for example, small-scale reactions, parallel synthesis, or due to selectivity issues. Herein, we demonstrate for the first time, the use of NaBH4 in the presence of a metal ion catalyst for the removal of the Nω-nitro moiety under simple, 'open-vessel' conditions. This process using NaBH4 does not remove the benzyloxycarbonyl-protecting group; thus the method is orthogonal for this protecting scheme.
- Sebestyén, Mónika,Kóczán, Gy?rgy,Csámpai, Antal,Hudecz, Ferenc
-
-
Read Online
- Direct guanylation of amino groups by cyanamide in water: Catalytic generation and activation of unsubstituted carbodiimide by scandium(iii) triflate
-
Guanylation proceeded efficiently upon treatment of the various amines with cyanamide in the presence of catalytic amounts of scandium(III) triflate under mild conditions. The method did not require the guanylation reagents to be preactivated, and the reaction proceeded efficiently in water. The method, therefore, has practical utility for substrates that dissolve only in aqueous solutions, for example, peptides or pharmacologically important compounds. Georg Thieme Verlag Stuttgart New York.
- Tsubokura, Kazuki,Iwata, Takayuki,Taichi, Misako,Kurbangalieva, Almira,Fukase, Koichi,Nakao, Yoichi,Tanaka, Katsunori
-
p. 1302 - 1306
(2014/06/10)
-
- Papain-catalyzed peptide bond formation: Enzyme-specific activation with guanidinophenyl esters
-
The substrate mimetics approach is a versatile method for small-scale enzymatic peptide-bond synthesis in aqueous systems. The protease-recognized amino acid side chain is incorporated in an ester leaving group, the substrate mimetic. This shift of the specific moiety enables the acceptance of amino acids and peptide sequences that are normally not recognized by the enzyme. The guanidinophenyl group (OGp), a known substrate mimetic for the serine proteases trypsin and chymotrypsin, has now been applied for the first time in combination with papain, a cheap and commercially available cysteine protease. To provide insight in the binding mode of various Z-XAA-OGp esters, computational docking studies were performed. The results strongly point at enzyme-specific activation of the OGp esters in papain through a novel mode of action, rather than their functioning as mimetics. Furthermore, the scope of a model dipeptide synthesis was investigated with respect to both the amino acid donor and the nucleophile. Molecular dynamics simulations were carried out to prioritize 22 natural and unnatural amino acid donors for synthesis. Experimental results correlate well with the predicted ranking and show that nearly all amino acids are accepted by papain.
- de Beer, Roseri J.A.C.,Zarzycka, Barbara,Amatdjais-Groenen, Helene I.V.,Jans, Sander C.B.,Nuijens, Timo,Quaedflieg, Peter J.L.M.,van Delft, Floris L.,Nabuurs, Sander B.,Rutjes, Floris P.J.T.
-
experimental part
p. 2201 - 2207
(2012/05/05)
-
- The total large-scale synthesis of argiopine
-
The total large-scale synthesis of a natural toxin argiopine, a polymethylenepolyamine derivative, was developed. It consisted of 26 stages and included three key block schemes. Most of the stages proceeded quantitatively, which excluded the necessity of using the chromatographic separation of intermediates.
- Formanovsky,Popova,Mikhura
-
experimental part
p. 752 - 758
(2010/07/15)
-
- Solvent-free synthesis of azole carboximidamides
-
A one-pot procedure is described for the preparation of azole carboximidamides 2, 3 and guanidinylation of amines with 3. The X-ray crystal structure of 3b, has been determined. A one-pot procedure is described for the preparation of 1H-pyrazole-carboximidamides 2, 1H-benzotriazole-carboximidamides 3 and guanidinylation of amines with 3. The X-ray crystal structure of N,N-dimethyl-1H-benzotriazole-1-carboximidamide 3b, has been determined.
- Zahariev, Sotir,Guarnaccia, Corrado,Lamba, Doriano,?ema?ar, Ma?a,Pongor, Sándor
-
p. 9423 - 9426
(2007/10/03)
-
- Improved selective protections of L-arginine
-
Reliable procedures for the selective introduction of carbobenzyloxy and phthalimido groups onto the α-amino position, and of carboethoxy groups onto the δ- and ω-guanidino positions of L-arginine are described.
- Moynihan, Humphrey A.,Yu, Weiping
-
-
- Two New Protecting Groups for the Guanidino Function of Arginine
-
Two new synthons, Fmoc-L-Arg(biphenyl-4-sulphonyl)-OH (8) and Fmoc-Arg(4-methoxy-3-t-butylbenzenesulphonyl)-OH (14), are prepared for the synthesis of arginine-containing peptides.These groups are cleaved by commonly employed trifluoroacetic acid and methanesulphonic acid.Kinetic studies reveal that extended bicyclic aromatic conjugation, as in biphenyl, slightly improves the acid lability compared to the electron-donating t-butyl group.
- Ali, Syed Safdar,Khan, Khalid Mohammed,Echner, Hartmut,Voelter, Wolfgang,Hasan, Mashooda,Atta-ur-Rahman
-
-
- Factors Influencing the Acid Lability of Substituted Arylsulphonyl Arginine Protecting Groups
-
The kinetics of hydrolysis of new, NG-protected 2,4,6-triisopropylbenzene-sulphonyl (6), 4-methoxy-3,5-di-tert-butylbenzenesulphonyl (12) and phenanthrene-3-sulphonyl (17) Fmoc derivatives of L-arginine (1) in comparison with commercially available Fmoc-Arg(Mtr)-OH (Mtr = 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (2)) are studied.The acid lability of the arylsulphonyl group is decreasing as follows Mtr > Tip > Mtbs > Phen.The effect of electron-donating alkyl groups as substituents in increasing the acid lability of the arylsulphonyl residue seems to be in the order of methyl > isopropyl > tert-butyl, while the effect of extended delocalization does not appreciably increase the acid lability. - Keywords: 2,4,6-Triisopropylbenzenesulphonyl (Tip), 4-methoxy-3,5-di-tert-butylbenzenesulphonyl (Mtbs), Phenanthrene-3-sulphonyl (Phen) Residues
- Ali, Syed Safdar,Echner, Hartmut,Khan, Khalid Mohammed,Schroeder, Christoph,Hasan, Mashooda,et al.
-
p. 1425 - 1433
(2007/10/02)
-
- An approach toward the total synthesis of cyclotheonamides; preparation of a C(1) to N(14) segment
-
The C(1) to N(14) segment of the potent thrombin inhibitor cyclotheonamide A was prepared from L-arginine, L-proline, and L-asparagine. The arginine backbone was extended via a cyanohydrin, and the usual diaminopropanoic acid residue was obtained from hypervalent iodine oxidation of the asparagine side chain.
- Wipf, Peter,Kim, Hong-Yong
-
p. 4275 - 4278
(2007/10/02)
-
- Enzymes in organic synthesis: Use of subtilisin and a highly stable mutant derived from multiple site-specific mutations
-
A subtilisin mutant (subtilisin 8350) derived from subtilisin BPN' via six-specific mutations (Met50Phe, Gly169Ala, Asn76Asp, Gln206Cys, Tyr217Lys, and Asn218Ser) was found to be 100 times more stable than the wild-type enzyme in aqueous solution at room temperature and 50 times more stable than the wild type in anhydrous dimethylformamide. Kinetic studies using ester, thio ester, and amide substrates, and the transition-state analogue inhibitor Boc-Ala-Val-Phe-CF3, indicate the both the wild-type and the mutant enzymes have very similar specificities and catalytic properties. The inhibition constant (K(i)) = 5.0 μM) for the wild-type enzyme is approximately 5 times that of the mutant enzyme (K(i)) = 1.1 μM), suggesting that the mutant enzyme binds the reaction transition state more strongly than the wild-type enzyme. This result is consistent with the observed rate constants for the corresponding ester and amide substrates; i.e. the k(cat)/k(m) values for the mutant are larger than those for hhe wild-type enzyme. Application of the mutant enzyme and the wild-type enzyme to organic synthesis has been demonstrated in the regioselective acylation of nucleosides in anhydrous dimethylformamide (with 65-100% regioselectivity at the 5'-position), in the enantioselective hydrolysis of N-protected and unprotected common and uncommon amino acid esters in water (with 85-98% enantioselectivity for the L-isomer), and in the synthesis of di- and oligopeptides via aminolysis of N-protected amino acid and peptide esters. The enzymatic peptide synthesis was carried out under high concentrations of DMF (~50%) to improve substrate solubility and to minimize enzymatic peptide cleavage. Low enantioselectivity was observed in the enzymatic transformation of non-amino acid alcohols and acids.
- Wong,Chen,Hennen,Bibbs,Wang,L iu,Pantoliano,Whitlow,Bryan
-
p. 945 - 953
(2007/10/02)
-
- INTRAMOLECULAR CATALYTIC MECHANISMS INVOLVED IN THE ALKALINE HYDROLYSIS OF p-NITROPHENYL ESTERS OF α-CARBOBENZOXY AMINO ACIDS
-
A study on the alkaline hydrolysis of p-nitrophenyl esters of α-carbobenzoxy amino acids, in the presence and absence of free amino acids as catalysts, are reported.The effect of free amino acids represents an interesting model for the study of the cataly
- Ascenzi, Paolo,Sleiter, Giancarlo,Antonini, Eraldo
-
p. 307 - 318
(2007/10/02)
-
