A Concise Synthetic Method for Constructing 3-Substituted Piperazine-2-Acetic Acid Esters from 1,2-Diamines.

We report a short synthetic route for synthesizing 2,3-substituted piperazine acetic acid esters. Optically pure amino acids were efficiently converted into 1,2-diamines that could be utilized to deliver the title 2,3-substituted piperazines in five steps with a high enantiomeric purity. The novel route facilitated, for the first time, the synthesis of 3-phenyl substituted-2-piperazine acetic acid esters that were difficult to achieve using other methods; however, in this case, the products underwent racemization.

Design and Construction of a Focused DNA-Encoded Library for Multivalent Chromatin Reader Proteins.

Chromatin structure and function, and consequently cellular phenotype, is regulated in part by a network of chromatin-modifying enzymes that place post-translational modifications (PTMs) on histone tails. These marks serve as recruitment sites for other chromatin regulatory complexes that 'read' these PTMs. High-quality chemical probes that can block reader functions of proteins involved in chromatin regulation are important tools to improve our understanding of pathways involved in chromatin dynamics.

Synthesis of Enantiomerically Pure 3-Substituted Piperazine-2-acetic Acid Esters as Intermediates for Library Production.

The piperazine heterocycle is broadly exploited in FDA-approved drugs and biologically active compounds, but its chemical diversity is usually limited to ring nitrogen substitutions, leaving the four carbon atoms underutilized. Using an efficient six-step synthesis, chiral amino acids were transformed into 3-substituted piperazine-2-acetic acid esters as diastereomeric mixtures whose cis and trans products (dr 0.56 → 2.

Synthesis and biological evaluation of rapamycin-derived, next generation small molecules.

Over the years, rapamycin has attracted serious attention due to its remarkable biological properties and as a potent inhibitor of the mammalian target of rapamycin (mTOR) protein through its binding with FKBP-12. Several efficient strategies that utilize synthetic and biosynthetic approaches have been utilized to develop small molecule rapamycin analogs or for synthesizing hybrid compounds containing a partial rapamycin structure to improve pharmacokinetic properties. Herein, we report selected case studies related to the synthesis of rapamycin-derived compounds and hybrid molecules to explore their biological properties.

Synthesis of Enantiomerically Pure 6-Substituted-Piperazine-2-Acetic Acid Esters as Intermediates for Library Production.

The piperazine heterocycle is broadly exploited in FDA-approved drugs and biologically active compounds, but its chemical diversity is usually limited to ring nitrogen substitutions, leaving the four carbon atoms underutilized. Using an efficient four-step synthesis, chiral amino acids were transformed into 6-substituted piperazine-2-acetic acid esters as diastereomeric mixtures whose cis and trans products could be chromatographically separated. From six amino acids (both antipodes), a complete matrix of 24 monoprotected chiral 2,6-disubstituted piperazines was obtained, each as a single absolute stereoisomer in multigram quantities.

A novel medium size lactam ring analoges as antibacterial agents: Synthesis, biological evaluation and molecular docking studies.

A novel series of medium size (S)-3-alkyl-3,4,6,7-tetrahydro-1H-benzo[e][1,4]diazonine-2,5-dione analogues were synthesized from (E)-3-(2-nitrophenyl)acrylicacid reacting with various amino acid esters using Di-isopropyl Carbodiimide as a coupling agent. The final cyclization is carried out by using reagent 1-Ethyl-3(3-dimethylaminopropyl) Carbodiimide Hydrochloride. The synthesized compounds have been supported by Mass, H-NMR and C-NMR.

Stereoselective synthesis of rapamycin fragment to build a macrocyclic toolbox.

A stereoselective synthesis of a rapamycin fragment is developed and further utilized toward building a macrocyclic chemical toolbox. The amino alcohol moiety embedded in the 22-membered macrocyclic ring allowed for the addition of a variation in the chiral side chain. The key reactions leading to the synthesis of the rapamycin-derived pyran fragment include the following: (i) Paterson aldol, (ii) stereoselective β-OH carbonyl reduction, and (iii) regio- and stereoselective intramolecular oxy-Michael reaction.

Practical stereoselective synthesis of eribulin fragment toward building a hybrid macrocyclic toolbox.

A practical stereoselective synthesis to obtain the substituted furan ring as the substructure of eribulin is developed. An asymmetric syn-aldol and intramolecular oxy-Michael were two key steps in our approach. The functionalized furan derivatives were then utilized further to build the 14- and 12-membered macrocyclic diversity as trans- and cis-fused (C-29 and C-30) compounds.

Tetrahydroquinoline-derived macrocyclic toolbox: the discovery of antiangiogenesis agents in zebrafish assay.

A novel approach to incorporate the macrocyclic rings onto the privileged substructure, i.e., tetrahydroquinoline scaffold, is developed.