ABSTRACT
A general approach to a new generation of spirocyclic molecules - oxa-spirocycles - was developed. The key synthetic step was iodocyclization. More than 150 oxa-spirocyclic compounds were prepared. Incorporation of an oxygen atom into the spirocyclic unit dramatically improved water solubility (by up to 40 times) and lowered lipophilicity. More potent oxa-spirocyclic analogues of antihypertensive drug terazosin were synthesized and studied in vivo.
ABSTRACT
Diverse trifluoromethyl-substituted compounds were synthesized by deoxofluorination of cinnamic and (hetero)aromatic carboxylic acids with sulfur tetrafluoride. The obtained products were used as starting materials in the preparation of novel fluorinated amino acids, anilines, and aliphatic amines - valuable building blocks for medicinal chemistry and agrochemistry.
ABSTRACT
Facile synthesis of 5-fluoropyrazoles by direct fluorination of pyrazoles with N-fluorobenzenesulfonimide (NFSI) was elaborated. This approach was used to prepare the unsubstituted 5-fluoro-1 H-pyrazole, the known fungicide Penflufen, and many functionalized 5-fluoropyrazoles: building blocks for medicinal chemistry and agrochemistry.
ABSTRACT
The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps-synthesis of azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug Bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to a wide use of spirocyclic building blocks in drug discovery in the near future.
Subject(s)
Azetidines/chemical synthesis , Azetidines/pharmacology , Drug Discovery , Spiro Compounds/chemical synthesis , Spiro Compounds/pharmacology , Anesthetics/chemistry , Azetidines/chemistry , Bupivacaine/chemistry , Carboxylic Acids/chemistry , Cyclopentanes/chemistry , Proline/chemistry , Spiro Compounds/chemistryABSTRACT
The representative of P,P,P-trichloroylides-5-methyl-2-phenyl-4-(trichlorophosphoranylidene)-2,4-dihydro-3H-pyrazol-3-one-was synthesized. Its constitution was confirmed by 1H, 13C, and 31P NMR spectroscopy and by X-ray analysis. Some chemical properties were studied and compared with ones of P,P,P-trimethylylide-5-methyl-2-phenyl-4-(trimethylphosphoranylidene)-2,4-dihydro-3H-pyrazol-3-one. DFT calculations of the model molecules were carried out.
