scholarly journals Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

2014 ◽  
Vol 10 ◽  
pp. 1135-1142 ◽  
Author(s):  
Oliver Ries ◽  
Martin Büschleb ◽  
Markus Granitzka ◽  
Dietmar Stalke ◽  
Christian Ducho
Keyword(s):  
Natural Products ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Building Blocks ◽  
Synthetic Approach ◽  
Protecting Group ◽  
Nucleoside Antibiotics ◽  
Bioactive Natural Products ◽  
Sar Studies ◽  
Derivatives Of

(2S,3S)-3-Hydroxyleucine can be found in an increasing number of bioactive natural products. Within the context of our work regarding the total synthesis of muraymycin nucleoside antibiotics, we have developed a synthetic approach towards (2S,3S)-3-hydroxyleucine building blocks. Application of different protecting group patterns led to building blocks suitable for C- or N-terminal derivatization as well as for solid-phase peptide synthesis. With respect to according motifs occurring in natural products, we have converted these building blocks into 3-O-acylated structures. Utilizing an esterification and cross-metathesis protocol, (2S,3S)-3-hydroxyleucine derivatives were synthesized, thus opening up an excellent approach for the synthesis of bioactive natural products and derivatives thereof for structure activity relationship (SAR) studies.

Improved Fmoc Solid-Phase Peptide Synthesis of Oxytocin with High Bioactivity

Synlett ◽  
2017 ◽  
Vol 28 (14) ◽  
pp. 1780-1784 ◽  
Author(s):  
Pengcheng Sun ◽  
Wenli Tang ◽  
Yu Huang ◽  
Bi-Huang Hu
Keyword(s):  
Peptide Synthesis ◽  
Disulfide Bond ◽  
High Purity ◽  
Large Scale ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Building Blocks ◽  
Side Chain ◽  
Protecting Group ◽  
Coupling Reagent

We described here the synthesis of oxytocin by an improved Fmoc solid-phase peptide synthesis (SPPS) method with a Rink-Amide resin as the solid support, HBTU as the coupling reagent, Fmoc-protected amino acids as the building blocks, and piperazine for Fmoc removal as a substitute for the standard reagent piperidine. Unlike previously reported syntheses, the removal of the S-Acm protecting group of Cys and cyclization forming the disulfide bond were carried out by using iodine on the resin with the fully protected peptide chains. Finally, a crude oxytocin with a purity of 92% was obtained by simultaneous cleavage of the peptide chains from the resin and removal of all side-chain protecting groups with trifluoroacetic acid containing the scavengers (yield 85%). The crude peptide was purified by using preparative RP-HPLC to obtain oxytocin (high purity 99.3%) with a bioactivity of 588 IU/mg, the highest reported so far in the literature. This investigation provides a contribution in efforts for the large-scale synthesis of oxytocin in high purity under mild conditions with iodine for on-resin disulfide bond formation and a substitute for the standard Fmoc-deprotecting reagent piperidine, a controlled substance.

Synthetic Approach to Argpyrimidine as a Tool for Investigating Nonenzymatic Posttranslational Modification of Proteins

Synlett ◽  
2017 ◽  
Vol 28 (15) ◽  
pp. 1950-1955
Author(s):  
Christian Becker ◽  
Maria Matveenko
Keyword(s):  
Posttranslational Modifications ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Synthetic Approach ◽  
Protecting Group ◽  
Age Related ◽  
Arginine Residues ◽  
One Step ◽  
Expanded Genetic Code ◽  
Noncanonical Amino Acid

Nonenzymatic posttranslational modifications (nPTMs) of proteins are involved in age-related, metabolic and other diseases and need to be investigated at the molecular level. Here, we describe how we used organic synthesis to enable the study of the effect of argpyrimidine (Apy), an nPTM that forms at arginine residues, on one of its target proteins. We developed an efficient approach to Apy as a universal building block for Fmoc-based solid-phase peptide synthesis that allows for the construction of peptides containing this nPTM in predetermined positions. Moreover, a straightforward one-step synthesis of protecting-group-free Apy was achieved, which enabled the preparation of gram-quantities of this noncanonical amino acid that can serve as a biomarker or a feedstock in construction of Apy-containing proteins via the expanded genetic code methods.

Formation of Carbon-Oxygen Bond Mediated by Hypervalent Iodine Reagents Under Metal-free Conditions

2020 ◽  
Vol 17 ◽  
Author(s):  
Ayesha Jalil ◽  
Yaxin O Yang ◽  
Zhendong Chen ◽  
Rongxuan Jia ◽  
Tianhao Bi ◽  
...  
Keyword(s):  
Natural Products ◽  
Bond Formation ◽  
Building Blocks ◽  
Review Article ◽  
Hypervalent Iodine ◽  
Metal Free ◽  
Bioactive Natural Products ◽  
The Past ◽  
Oxygen Bond ◽  
Privileged Scaffolds

: Hypervalent iodine reagents are a class of non-metallic oxidants have been widely used in the construction of several sorts of bond formations. This surging interest in hypervalent iodine reagents is essentially due to their very useful oxidizing properties, combined with their benign environmental character and commercial availability from the past few decades ago. Furthermore, these hypervalent iodine reagents have been used in the construction of many significant building blocks and privileged scaffolds of bioactive natural products. The purpose of writing this review article is to explore all the transformations in which carbon-oxygen bond formation occurred by using hypervalent iodine reagents under metal-free conditions

scholarly journals Reinvestigation of a Critical Reductive Amination Step Leads to an Optimized Protocol for the Synthesis of N-2-Hydroxybenzylcysteine Peptide Crypto-Thioesters

2020 ◽  
Author(s):  
Skander Abboud ◽  
Vincent AUCAGNE
Keyword(s):  
Peptide Synthesis ◽  
Reaction Mechanisms ◽  
Reductive Amination ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Building Blocks ◽  
Native Chemical Ligation ◽  
Chemical Ligation ◽  
Optimized Protocol ◽  
Depth Study

An in-depth study of the Fmoc-based solid phase peptide synthesis of N-Hnb-Cys crypto-thioester peptides, advantageous building blocks for the native chemical ligation-based synthesis of proteins, led to the identification of epimerized and imidazolidinone side products formed during a key reductive amination step. The understanding of the underlying reaction mechanisms was crucial for the developement of an automatable optimized synthetic protocol.

Electrocatalytic Difunctionalization of Olefins as a General Approach to the Synthesis of Vicinal Diamines

Synlett ◽  
2018 ◽  
Vol 29 (03) ◽  
pp. 257-265 ◽  
Author(s):  
Song Lin ◽  
Joseph Parry ◽  
Niankai Fu
Keyword(s):  
Natural Products ◽  
Building Blocks ◽  
Therapeutic Agents ◽  
Recent Contribution ◽  
Structural Motifs ◽  
Bioactive Natural Products ◽  
Methodological Approaches ◽  
Molecular Catalysts ◽  
Vicinal Diamines

Vicinal diamines are highly prevalent structural motifs in therapeutic agents, bioactive natural products, and molecular catalysts. However, there are currently few unified methodological approaches for making these pertinent synthetic building blocks. This Synpacts article provides an overview of selected landmark developments in the area of olefin diamination. In particular, we highlight our recent contribution on the electrocatalytic diazidation of olefins as a general, selective, and sustainable method for the synthesis of vicinal diamines.1 Introduction2 Background: Intermolecular Diamination of Olefins3 Background: Intermolecular Diazidation of Olefins4 Electrocatalytic Diazidation of Olefins

A Comprehensive One-Pot Synthesis of Protected Cysteine and Selenocysteine SPPS Derivatives

2014 ◽  
Vol 21 (12) ◽  
pp. 1257-1264
Author(s):  
Stevenson Flemer
Keyword(s):  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Reduction Process ◽  
Building Blocks ◽  
High Yield ◽  
One Pot ◽  
Peptide Models ◽  
Direct Use ◽  
Proof Of Principle ◽  
Subsequent Incorporation

A proof-of-principle methodology is presented in which all commercially-available cysteine (Cys) and selenocysteine (Sec) solid phase peptide synthesis (SPPS) derivatives are synthesized in high yield from easily prepared protected dichalcogenide precursors. A Zn-mediated biphasic reduction process applied to a series of four bis-Nα-protected dichalcogenide compounds allows facile conversion to their corresponding thiol and selenol intermediates followed by insitu S- or Se-alkylation with various electrophiles to directly access twenty one known Cys and Sec SPPS derivatives. Most of these derivatives were able to be precipitated in crude form out of petroleum ether in sufficient purity for direct use as peptide building blocks. Subsequent incorporation of these derivatives into peptide models nicely illustrates their viability and applicability toward SPPS.

scholarly journals Automated solid-phase peptide synthesis to obtain therapeutic peptides

2014 ◽  
Vol 10 ◽  
pp. 1197-1212 ◽  
Author(s):  
Veronika Mäde ◽  
Sylvia Els-Heindl ◽  
Annette G Beck-Sickinger
Keyword(s):  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Protecting Group ◽  
Drug Candidates ◽  
Tremendous Progress ◽  
Pharmacokinetic Properties ◽  
Critical Issues ◽  
Therapeutic Peptides ◽  
Automated Methods

The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS) offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.

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