- The photoredox-catalyzed hydrosulfamoylation of styrenes and its application in the novel synthesis of naratriptan
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The hydrosulfamoylation of diverse aryl olefins provides facile access to alkylsulfonamides. Here we report a novel protocol utilizing radical-mediated addition and a thiol-assisted strategy to achieve the hydrosulfamoylation of diverse styrenes in modest to excellent yields under mild and economic reaction conditions. The methodology was found to provide an efficient and convenient approach for the synthesis of the anti-migraine drug naratriptan and it also can be used for the late-stage functionalization of natural products or medicines.
- Zhang, Mingjun,Chen, Miaomiao,Ding, Xin,Kang, Jin,Gao, Yongyue,He, Xingxing,Wang, Ziwen,Lu, Aidang,Wang, Qingmin
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p. 9140 - 9143
(2021/09/14)
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- Method of producing peptide
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The present invention is related to a method of producing a peptide, characterized in contacting a reaction mixture with a base after a condensation reaction to hydrolyze while a basic condition is maintained until a ratio of a remaining unreacted active
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- Amino-protecting groups subject to deblocking under conditions of nucleophilic addition to a Michael acceptor. Structure-Reactivity studies and use of the 2-(tert-Butylsulfonyl)-2-propenyloxycarbonyl (Bspoc) group
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A new type of amino-protecting group is described in which a Michael acceptor is incorporated into the protectant so that treatment with a nucleophile will trigger deblocking. Comparison of various Michael acceptors showed that for several key electron-withdrawing groups, the order of reactivity was C6H5SO2 > Me3CSO2 > COOEt > C6H5SO > C6H4NO2-p. The reactivity of the nucleophile (e.g., primary and secondary aliphatic amines) followed an order related to both intrinsic basicity and steric effects. β- Substituents in the Michael acceptor caused significant retardation of the deblocking process. The Bspoc function was chosen for initial elaboration into a practical system for use in peptide synthesis. Bspoc amino acid chlorides were used as coupling agents and silica-tethered secondary amines as deblocking agents. With the latter, deblocking occurs cleanly and no byproducts remain in the organic solvent in which the deblocking is executed.
- Carpino, Louis A.,Philbin, Michael
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p. 4315 - 4323
(2007/10/03)
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- Synthesis of [Leu5]enkephalin using Fmoc-Amino Acid Chlorides/KOAt
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The coupling of Fmoc-amino acid chlorides can be mediated by the potassium salt of 1-hydroxy-7-azabenzotriazole. Thus the synthesis of [Leu5]enkephalin has been accomplished in good yield and purity.
- Gopi,Suresh Babu
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p. 511 - 513
(2007/10/03)
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- Synthesis and application of N,N-bis-(1-adamantyloxycarbonyl) amino acids.
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The preparation of novel bis-(1-adamantyloxycarbonyl) amino acid derivatives has been undertaken and their properties studied. Among them, the p-nitrophenyl esters were subsequently applied to the stepwise synthesis of Leu-enkephalin. In the last coupling step, some hydantoin formation was encountered but it could be nearly completely overcome by working with more concentrated solution. The preparation of a tyrosine derivative presented special problems owing to the existence of the phenolic group in the precursor. The relative stability of 1-adamantyloxycarbonyl as N- and O-protecting groups was also studied.
- Nyasse,Ragnarsson
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p. 374 - 379
(2007/10/02)
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- The 2-Chloro-3-indenylmethyloxycarbonyl and Benzinden-3-ylmethyloxycarbonyl Base-Sensitive Amino-Protecting Groups. Application to an Inverse Merrifield Approach to Peptide Synthesis
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Two new base-labile amino-protecting groups, which are more sensitive than the FMOC function, are described: the 2-chloro-3-indenylmethyloxycarbonyl (CLIMOC) and benzinden-3-ylmethyloxycarbonyl (BIMOC) groups.The former was determined to be usable in solvents such as methylene dichloride but not in DMF, the latter in any common solvent including DMF.Key intermediate alcohols 10 and 16 were synthesized from 2-chloroindene (9) and benzindene (14).Treatment of indene with chlorine gave 8, which upon dehydrochlorination with DMF gave 9, which was then converted to 10 by standard procedure involving formylation and reduction.Benzindene was converted to its anion by means of n-butyllithium and the anion hydroxymethylated by gaseous formaldehyde.The alcohols were converted to the corresponding chloroformates and thence to succinimido ester 12 and azidoformate 18 for clean, selective protection of amino acids.Model CLIMOC- and BIMOC-amino acids were synthesized and demonstrated to be useful in carrying out a continous peptide synthesis via a two-polymer (polymeric reagents) approach.The protected amino acids were first loaded onto a phenolic polymer such as 21, and the resulting polymeric active esters were used to acylate an amino acid ester or peptide ester.The resulting protected peptide esters were deblocked via silica-based reagents 6 or 23.The acylation step was then repeated with the next amino acid, and the synthesis continued in the same way until completed.Tetrapeptide 26 and pentapeptide 27 were synthesized in this way via CLIMOC (CH2Cl2) and BIMOC (DMF) protection, respectively.These represent the first examples of clean, continous two-polymer syntheses carried out in a single solvent without the release of any low molecular weight byproducts into the solution. the fi
- Carpino, Louis A.,Cohen, Beri J.,Lin, Yao-Zhong,Stephens, Kenton E.,Triolo, Salvatore
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p. 251 - 259
(2007/10/02)
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- Preparation and Properties of Nα-Di-tert-Butoxycarbonyl Amino Acids. Applicability in the Synthesis of Leu-Enkephalin
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The synthesis of Nα-di-tert-butoxycarbonyl amino acids starting from the corresponding mono-derivatives via a three-step route is reported.The latter were converted into a suitable ester and then exhaustively t-butoxycarbonylated, after which t
- Gunnarsson, Kerstin,Ragnarsson, Ulf
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p. 944 - 951
(2007/10/02)
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- New process for preparing an octapeptide
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An octapeptide, endowed with thymic humoral activity, of the formula (A):, H-Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu-OH, and pharmaceutically acceptable salts thereof are prepared by condensing a compound of the formula (B), , X-Leu-G wherein X is an amino protecting group, Y and Y? are each optional and each independently represents a carboxy protecting group and K is a hydroxy or hydrazido group, with a compound of formula (C):, , H-Pro-L wherein W is an amino protecting group and Q represents a carboxy protecting group or a hydroxy group deprotecting the resultant compound of the formula (D), , X-Leu-G wherein X,Y,Y?,W and Q are as defined above; and, if desired, converting the resulting peptide of formula (A) into a pharmaceutically acceptable salt thereof.
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- Solution synthesis of an octapeptide
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An octapeptide, endowed with thymic humoral activity, of formula (A), H-Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu-OH (A), and pharmaceutically acceptable salts thereof are prepared by condensing a compound of the formula (B):, , X-Leu-G wherein X is an amino protecting group, Y and Y? are each optional and each independently represents a carboxy protecting group and K is a hydroxy or hydrazido group, with a compound of formula (C), , H-L wherein W is an amino protecting group and Q represents a carboxy protecting group or a hydroxy group; deprotecting the resultant compound of the formula (D), , X-Leu-G wherein X,Y,Y?,W and Q are as defined above; and, if desired, converting the resulting peptide of formula (A) into a pharmaceutically acceptable salt thereof.
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- THE USE OF PENICILLIN ACYLASE FOR SELECTIVE N-TERMINAL DEPROTECTION IN PEPTIDE SYNTHESIS
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Penicillin acylase from E. coli (EC 3.5.1.11) accepts a broad range of N-phenylacetyl-dipeptide esters as substrates.The enzyme hydrolyses the N-terminal protecting group selectively at room temp. and pH=8.1 without affecting the peptide- or the ester-bonds.Alternatively methyl-, benzyl-, tert-butyl and allyl esters can be cleaved chemically leaving the phenylacetamido moiety intact.
- Waldmann, Herbert
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p. 1131 - 1134
(2007/10/02)
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- AMINO ACIDS AND PEPTIDES. VIII. A WATER - SOLUBLE ACTIVE ESTER, PHENOLSULFONIC ACID DERIVATIVE
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N-protected amino acid 4-phenolsulfonic acid derivative esters, such as 2,6-dibromo-4-sulfophenyl ester sodium salt, 2,6-dichloro-4-sulfophenyl ester potassium salt and 2-nitro-4-sulfophenyl ester sodium salt, were prepared.These esters are water - soluble active esters, and were applied for rhe synthesys of Leu-enkephalin.Keywords - water - soluble active ester; 2,6-dichloro-4-sulfophenyl ester; 2,6-dibromo-4-sulfophenyl ester; 2-nitro-4-sulfophenyl ester; peptide synthesis; Leu-enkephalin
- Kawasaki, Koichi,Tsuji, Toshiki,Maeda, Misuko,Matsumoto, Tatsuya,Hirase, Katsuhiko
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p. 1044 - 1048
(2007/10/02)
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- ((9-Fluorenylmethyl)oxy)carbonyl (Fmoc) Amino Acid Chlorides. Synthesis, Characterization, and Application to the Rapid Synthesis of Short Peptide Segments
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Fmoc amino acid chlorides are described as stable, easily synthesized coupling agents and shown to be useful in a novel method of rapid, repetitive peptide synthesis
- Carpino, Louis A.,Cohen, Beri J.,Stephens, Kenton E.,Sadat-Aalaee, S. Yahya,Tien, Jien-Heh,Langridge, Denton C.
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p. 3732 - 3734
(2007/10/02)
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- AMINO ACIDS AND PEPTIDES. VII. PREPARATION AND APPLICATION OF A WATER-SOLUBLE ACTIVE ESTER, p-TRIMETHYLAMMONIOPHENYL ESTER
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A water-soluble active ester, p-trimethylammoniophenyl ester iodide, and its nitro derivative were prepared from N-procteted amino acid and the corresponding phenol derivative by the dicyclohexylcarbodiimide method.The synthetic esters were applied to the synthesis of Leuenkephalin.Keywords--water-soluble active ester; p-trimethylammoniophenyl ester iodide; Leuenkephalin; peptide synthesis
- Tsuji, Toshiki,Okusada, Satoshi,Maeda, Mitsuko,Kawasaki, Koichi
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p. 2214 - 2217
(2007/10/02)
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- The Steric Hindrance of the Stepwise Reaction of N-Carboxy α-Amino Acid Anhydride with the α-Amino Acid Ester
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The mechanisms of the reactions of 4-alkyloxazolidinediones (1) (N-carboxy α-amino acid anhydrides(NCAs)) with α-amino acid benzyl ester p-toluenesulfonates (2) were investigated in acetonitrile containing triethylamine at low and room temperatures.Two types of reactions were observed: (1) the polymerization of NCAs was initiated with a small amount of 2 to produce polypeptides (6), and (2) the dipeptide benzyl esters (4) were produced by the stepwise reaction of NCAs with the esters.Both the polymerization and the dipeptide formation (1+2) seemed to be initiated by the nucleophilic attack of the amino group of the ester on the C-5 carbon of NCAs.The polymerization proceeded when the side chains of the amino acid esters (R2) were more bulky than those of the NCAs (R1).On the contrary, dipeptide esters were produced when the side chains of the NCAs (R1) were more bulky than those of the esters (R2).
- Oya, Masanao,Takahashi, Tomoko
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p. 2705 - 2707
(2007/10/02)
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- Some Ester Derivatives of 2-Methylalanine as Intermediates in Peptide Synthesis
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The o-nitrophenylthio derivative of-methylalanine served as the precursor of several new ester hydrochlorides, which have been investigated as intermediates for the synthesis of peptides containing this amino acid.Particular consideration is given to the effect of the steric hindrance associated with 2-methylalanine.Synthesis of 2-methylalanyl analogue of the opiate agonist leucine-enkephalin is described.
- Stewart, Frederick H.C.
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p. 121 - 129
(2007/10/02)
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