69729-07-3Relevant articles and documents
Method of producing peptide
-
, (2014/05/20)
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
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
Carpino, Louis A.,Philbin, Michael
, p. 4315 - 4323 (2007/10/03)
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.
Synthesis of [Leu5]enkephalin using Fmoc-Amino Acid Chlorides/KOAt
Gopi,Suresh Babu
, p. 511 - 513 (2007/10/03)
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.
Synthesis and application of N,N-bis-(1-adamantyloxycarbonyl) amino acids.
Nyasse,Ragnarsson
, p. 374 - 379 (2007/10/02)
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.
Preparation and Properties of Nα-Di-tert-Butoxycarbonyl Amino Acids. Applicability in the Synthesis of Leu-Enkephalin
Gunnarsson, Kerstin,Ragnarsson, Ulf
, p. 944 - 951 (2007/10/02)
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
The 2-Chloro-3-indenylmethyloxycarbonyl and Benzinden-3-ylmethyloxycarbonyl Base-Sensitive Amino-Protecting Groups. Application to an Inverse Merrifield Approach to Peptide Synthesis
Carpino, Louis A.,Cohen, Beri J.,Lin, Yao-Zhong,Stephens, Kenton E.,Triolo, Salvatore
, p. 251 - 259 (2007/10/02)
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
Use of Dimethylformamide-Sulphur Trioxide Complex as a Sulphating Agent of Tyrosine
Futaki, Shiroh,Taike, Takashi,Yagami, Takeshi,Ogawa, Toyoko,Akita, Tadashi,Kitagawa, Kouki
, p. 1739 - 1744 (2007/10/02)
Dimethylformamide-sulphur trioxide (DMF-SO3) complex was found to be more suitable for tyrosine sulphation than pyridine-sulphur trioxide (Pyr-SO3) complex, the most commonly used sulphur trioxide complex for sulphation.The work-up after sulphation using
