31 research outputs found
Green Strategies for the Preparation of Enantiomeric 5–8-Membered Carbocyclic β-Amino Acid Derivatives through CALB-Catalyzed Hydrolysis
The synthesis of pharmacologically important oxindoles via the asymmetric aldol reaction of isatin and the investigation of the organocatalytic activity of new alicyclic β-amino acid derivatives
This work involves the synthesis and subsequent development of a number of novel organocatalysts generated from β-amino acids bearing diendo and diexo norbornene skeletons to improve their catalytic characteristics
Ring closure reactions of bicyclic prolinol and prolin ester enantiomers
Starting from the of bicyclic proline ester, ethyl
exo-2-azabicyclo[2.2.1]heptane-3-carboxylate (+)-5 several hydantoines
and thiohydantoines were prepared by acidic ring closure of the
corresponding urea or thiourea derivatives. Enantiomer (-)-5 was
reduced to 2-azanorbornylmethanol 12, which was transformed to
5,8-methanooxazolo- and thiazolo[3,4-a] pyridine derivatives. The
structures, stereochemistry and relative configurations of the
synthesized compounds were proved by NMR
Angular Regioselective Synthesis of Varied Functionalized Hexahydro-1,2,4-triazolo[4,3-a]quinazolin-9-ones and Their Antiproliferative Action
New 2-thioxopyrimidin-4-ones capable of participating in regioselective reactions with functionally diverse hydrazonoyl chlorides towards angular regioisomers, rather than linear ones, were designed and synthesized to form stereoisomeric cis- and trans-hexahydro [1,2,4]triazolo[4,3-a]quinazolin-9-ones to be tested as antitumor candidates. The angular regiochemistry of the products was verified through crystallographic experiments and NMR studies. In addition, the regioselectivity of the reaction was found to be independent of the stereochemistry of the used 2-thioxopyrimidin-4-one. Only compound 4c demonstrated satisfactory growth inhibition against all the cancer cells used among all the produced drugs
Novel High Affinity Sigma-1 Receptor Ligands from Minimal Ensemble Docking-Based Virtual Screening
Sigma-1 receptor (S1R) is an intracellular, multi-functional, ligand operated protein that also acts as a chaperone. It is considered as a pluripotent drug target in several pathologies. The publication of agonist and antagonist bound receptor structures has paved the way for receptor-based in silico drug design. However, recent studies on this subject payed no attention to the structural differences of agonist and antagonist binding. In this work, we have developed a new ensemble docking-based virtual screening protocol utilizing both agonist and antagonist bound S1R structures. This protocol was used to screen our in-house compound library. The S1R binding affinities of the 40 highest ranked compounds were measured in competitive radioligand binding assays and the sigma-2 receptor (S2R) affinities of the best S1R binders were also determined. This way three novel high affinity S1R ligands were identified and one of them exhibited a notable S1R/S2R selectivity
Synthesis and Transformations of di-endo-3-Aminobicyclo-[2.2.2]oct-5-ene-2-carboxylic Acid Derivatives
all-endo-3-amino-5-hydroxybicyclo[2.2.2]octane-2-carboxylic acid (13) and all-endo-5-amino-6-(hydroxymethyl)bicyclo[2.2.2]octan-2-ol (10) were prepared via dihydro-1,3-oxazine or g-lactone intermediates by the stereoselective functionalization of an N-protected derivative of endo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid (2). Ring closure of b-amino ester 4 resulted in tricyclic pyrimidinones 15 and 16. The structures, stereochemistry and relative configurations of the synthesized compounds were determined by IR and NMR
Green Strategies for the Preparation of Enantiomeric 5–8-Membered Carbocyclic β-Amino Acid Derivatives through CALB-Catalyzed Hydrolysis
Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5–8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino esters were performed in tBuOMe at 65 °C. The unreacted β-amino ester enantiomers (1R,2S) and product β-amino acid enantiomers (1S,2R) were obtained with modest to excellent enantiomeric excess (ee) values (ees > 62% and eep > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H2O extraction
Synthesis of Pyrrolo[1,2-a]pyrimidine Enantiomers via Domino Ring-Closure followed by Retro Diels-Alder Protocol
From 2-aminonorbornene hydroxamic acids, a simple and efficient method for the
preparation of pyrrolo[1,2-a]pyrimidine enantiomers is reported. The synthesis is based on domino
ring-closure followed by microwave-induced retro Diels-Alder (RDA) protocols, where the chirality
of the desired products is transferred from norbornene derivatives. The stereochemistry of the
synthesized compounds was proven by X-ray crystallography. The absolute configuration of the
product is determined by the configuration of the starting amino hydroxamic acid.peerReviewe
Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives
The syntheses of various pyrimidinones as potentially bioactive products by means of the highly controlled continuous-flow retro-Diels–Alder reaction of condensed pyrimidinone derivatives are presented. Noteworthy, the use of this approach allowed us to rapidly screen a selection of conditions and quickly confirm the viability of preparing the desired pyrimidinones in short reaction times. Yields typically higher than those published earlier using conventional batch or microwave processes were achieved