scholarly journals A Reliable Enantioselective Route to Mono-Protected N1-Cbz Piperazic Acid Building Block

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5939
Author(s):  
Evanthia Papadaki ◽  
Dimitris Georgiadis ◽  
Michail Tsakos
Keyword(s):  
Natural Products ◽  
Amino Acid ◽  
Total Synthesis ◽  
Building Block ◽  
Optical Purity ◽  
Protecting Group ◽  
High Optical Purity

The chiral N1-Cbz, N2-H derivative of the piperazic acid monomer is a valuable building block in the total synthesis of natural products, comprising this nonproteinogenic amino acid. In that context, we wish to report an improved synthetic protocol for the synthesis of both (3R)- and (3S)-piperazic acids bearing the carboxybenzyl protecting group (Cbz) selectively at the N1 position. Our method builds on previously reported protocols, circumventing their potential shortcomings, and optimizing the ultimate selective deprotection at the N2 position, thus, offering an efficient and reproducible pathway to suitably modified piperazates in high optical purity.

Total synthesis and establishment of the absolute stereochemistry of (+)-mostueine. Addition of chiral nucleophiles to 3,4-dihydro-2-methyl-9-(p-toluenesulfonyl)-β-carbolinium iodide

1992 ◽  
Vol 70 (12) ◽  
pp. 2922-2928 ◽  
Author(s):  
Allan W. Rey ◽  
Walter A. Szarek ◽  
David B. MacLean
Keyword(s):  
Total Synthesis ◽  
Indole Alkaloid ◽  
Optical Purity ◽  
Ring System ◽  
Asymmetric Induction ◽  
Iminium Salt ◽  
High Optical Purity ◽  
The Absolute ◽  
Absolute Stereochemistry ◽  
Mediated Reduction

A highly convergent synthesis of the pentacyclic indole alkaloid (+)-mostueine (1) is described. The key step involved the coupling of the dianion derived from (1′S)-3-(1′-hydroxyethyl)-4-methylpyridine (4) with the iminium salt 3,4-dihydro-2-methyl-9-(p-toluenesulfonyl)-β-carbolinium iodide (3). Low asymmetric induction (15% de) at the C-1 position of the β-carboline ring system (C-3 of mostueine) was obtained. The nonfermenting baker's yeast-mediated reduction of 3-acetyl-4-methylpyridine provided the hydroxyethylpyridine component in acceptable yield (67%) and high optical purity (99.0% ee). This synthesis of 1 has established that the absolute stereochemistry of mostueine is (3S, 19R).

Advances in catalytic and protecting-group-free total synthesis of natural products: a recent update

2020 ◽  
Vol 56 (61) ◽  
pp. 8569-8590 ◽  
Author(s):  
Rodney A. Fernandes ◽  
Praveen Kumar ◽  
Priyanka Choudhary
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Protecting Group ◽  
Feature Article ◽  
Total Syntheses

This feature article highlights the recently achieved efficient total syntheses of many natural products based on catalytic steps and protecting-group-free strategies, leading to overall economy and efficiency in synthesis.

Synthesis of Azido Acids and Their Application in the Preparation of Complex Peptides

Synthesis ◽  
2020 ◽  
Author(s):  
Ryan Moreira ◽  
Michael Noden ◽  
Scott D. Taylor
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Total Synthesis ◽  
Cyclic Peptides ◽  
Protecting Groups ◽  
Side Chain ◽  
Coupling Reactions ◽  
Protecting Group

AbstractAzido acids are important synthons for the synthesis of complex peptides. As a protecting group, the azide moiety is atom-efficient, easy to install and can be reduced in the presence of many other protecting groups, making it ideal for the synthesis of branched and/or cyclic peptides. α-Azido acids are less bulky than urethane-protected counterparts and react more effectively in coupling reactions of difficult-to-form peptide and ester bonds. Azido acids can also be used to form azoles on complex intermediates. This review covers the synthesis of azido acids and their application to the total synthesis of complex peptide natural products.1 Introduction2 Synthesis of α-Azido Acids2.1 From α-Amino Acids or Esters2.2 Via α-Substitution2.3 Via Electrophilic Azidation2.4 Via Condensation of N-2-Azidoacetyl-4-Phenylthiazolidin- 2-Thi one Enolates with Aldehydes and Acetals2.5 Synthesis of α,β-Unsaturated α-Azido Acids and Esters3 Synthesis of β-Azido Acids3.1 Preparation of Azidoalanine and 3-Azido-2-aminobutanoic Acids3.2 General Approaches to Preparing β-Azido Acids Other Than Azi doalanine­ and AABA4 Azido Acids in Total Synthesis4.1 α-Azido Acids4.2 β-Azido Acids and Azido Acids Containing an Azide on the Side Chain5 Conclusions

Glyoxylic acid derivatives in asymmetric synthesis

2000 ◽  
Vol 72 (9) ◽  
pp. 1589-1596 ◽  
Author(s):  
Janusz Jurczak ◽  
Tomasz Bauer
Keyword(s):  
Natural Products ◽  
Asymmetric Synthesis ◽  
Glyoxylic Acid ◽  
Optical Purity ◽  
Organic Syntheses ◽  
High Optical Purity ◽  
Derivatives Of

Synthesis of chiral derivatives of glyoxylic acid with special emphasis on N-glyoxyloyl-(2R)-bornane-10,2-sultam is presented. Investigation of glyoxylic acid chiral derivatives in various stereocontrolled organic syntheses showed their excellent ability to provide products of high optical purity. Application of our methodology to the synthesis of natural products and their analogs is presented.

Organocatalytic Allylic Amination of Morita–Baylis–Hillman Carbonates­

Synthesis ◽  
2018 ◽  
Vol 51 (04) ◽  
pp. 907-920 ◽  
Author(s):  
Jan Veselý ◽  
Bedřich Formánek ◽  
Michal Šimek ◽  
Martin Kamlar ◽  
Ivana Císařová
Keyword(s):  
Building Block ◽  
Aromatic Amines ◽  
Optical Purity ◽  
Optically Active ◽  
Allylic Amines ◽  
Allylic Amination ◽  
Cholesterol Lowering ◽  
High Optical Purity ◽  
Efficient Route ◽  
Lowering Drug

An organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates with aromatic amines in the presence of β-isocupreidine is described. Chiral allylic amines were obtained in almost quantitative yields (90–96%) with moderate enantioselectivity. Recrystallization afforded products in good yields (45–73%) and high optical purity (82–99% ee). This method provides a facile and efficient route to obtain optically active β-lactams, including the building block of the cholesterol-lowering drug Ezetimibe.

ChemInform Abstract: An Efficient Synthesis of N-Hydroxy-α-amino Acid Derivatives of High Optical Purity.

ChemInform ◽  
1987 ◽  
Vol 18 (35) ◽  
Author(s):  
R. W. FEENSTRA ◽  
E. H. M. STOKKINGREEF ◽  
R. J. F. NIVARD ◽  
H. C. J. OTTENHEIJM
Keyword(s):  
Amino Acid ◽  
Optical Purity ◽  
Amino Acid Derivatives ◽  
Efficient Synthesis ◽  
High Optical Purity ◽  
Derivatives Of

An efficient synthesis of N-hydroxy-α-amino acid derivatives of high optical purity

1987 ◽  
Vol 28 (11) ◽  
pp. 1215-1218 ◽  
Author(s):  
R.W Feenstra ◽  
E.H.M Stokkingreef ◽  
R.J.F Nivard ◽  
H.C.J Ottenheijm
Keyword(s):  
Amino Acid ◽  
Optical Purity ◽  
Amino Acid Derivatives ◽  
Efficient Synthesis ◽  
High Optical Purity ◽  
Derivatives Of

scholarly journals Synthesis of the Enantiomers of Thioridazine

SynOpen ◽  
2020 ◽  
Vol 04 (01) ◽  
pp. 12-16 ◽  
Author(s):  
Simen Antonsen ◽  
Erling B. Monsen ◽  
Kirill Ovchinnikov ◽  
Jens M. J. Nolsøe ◽  
Dag Ekeberg ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Optical Purity ◽  
Scaling Up ◽  
Racemic Mixture ◽  
Bacterial Strains ◽  
Beneficial Effects ◽  
High Optical Purity ◽  
Primary Indication ◽  
Optically Pure

Thioridazine, a well-known antipsychotic drug, has shown promising effects on several bacterial strains (including Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus). Suppressive effects towards selected cancer cell-lines have also been reported. However, due to adverse effects, the compound is no longer in use for the primary indication. More recent research has demonstrated that these side effects are limited to one of the two enantiomers, (+)-thioridazine. The question arises to whether the beneficial effects of thioridazine are limited to one enantiomer, or if (–)-thioridazine can prove itself to be useful in its pure enantiomeric state. The published procedures on the synthesis of the optically pure enantiomers of thioridazine were found to be unsatisfactory, either due to low optical purity, high cost, or problems scaling up. Herein, we have used an auxiliary-based strategy for the total synthesis of both enantiomers in high optical purity and good overall yield. The strategy can easily be scaled up. Both enantiomers were tested against several bacteria. Comparison of the racemic mixture, (–)-thioridazine and its (+)-antipode revealed that they have the same antimicrobial effects. Thus, the non-toxic enantiomer, (–)-thioridazine, can prove useful in this role and should be investigated further.

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