Studies on the Development of New Reaction Modes for the Synthesis of New Drugs

我们已经扩展了对新反应模式用于synthesis的发展seed and lead compounds of new drugs by utilizing the latent active species. Recently，我们已经分开了两个新的反应，作为追随者。3'- (phenylphosphoryl) -bis (1,3-thiazolidine-2-thione) was exploited for intramoleculardehydration of various beta-amino acids to give the coreresponding beta-lactamswhich be useful for the monobactam antibiotics. New beta-lactamase inhibitors，thienamonobactams were successfully synthesized by utilizing the latent [2+2] cycloaddition反应diketene with an imine derivative. A unique heterocyclic compound，mercaptobicyclotriazolium chloride as the pendant molecule of a一1 beta-methylcarbapenemantibiotic " biapenem ",was efficiently synthesized the reaction cascade employing a pyrazolidine derivative and ethylformimidate hydrochloride. New angiotensin II (Ag II) receptor antagonists，acylimino thiadiazolines were synthesized by exploiting the latent regioselective activation ofthe nitrogen atom in the heterocyclic moiety of 2- transportroatamido -1,3,4-thiadiazoles. 1,5-Typeintramolecular nonbonding S O interaction was clarified by X-ray crystallographic analyzes andabinito MO calculation of the Ag II receptor antagonists and their simple model compounds. We havealso developed several new reactions useful for the rug syntheses such as a chemoselectivedieckman -type reaction mode toward the enantiodivergent processthe Horner-Wadsworth-Emmons reaction of aryl alkyl ketones using tin (II) -triflate andn - ethylpiperidine,and syntheses of new strained [6] and [7] metacyclophanes utilizing the latent conjugated allenylketone systems。

We are extensively carrying out the development of new reaction modes useful for the synthesis of seed and lead compounds of new drugs by utilizing the latent active species. Recently, we have disclosed several new reactions as follows. A new reagent, 3,3'- (phenylphosphoryl) -bis (1,3-thiazolidine-2-thione) was exploited for intramolecular dehydration of various beta-amino acids to give the coreresponding beta-lactams, which could be useful for the monobactam antibiotics. New beta-lactamase inhibitors, thienamonobactams were successfully synthesized by utilizing the latent [2+2] cycloaddition reaction of diketene with an imine derivative. A unique heterocyclic compound, mercaptobicyclotriazolium chloride as the pendant molecule of a remarkable 1beta-methylcarbapenem antibiotic "biapenem", was efficiently synthesized via the reaction cascade employing a pyrazolidine derivative and ethyl formimidate hydrochloride. New angiotensin II (Ag II) receptor antagonists, (acylimino) thiadiazolines were synthesized by exploiting the latent regioselective activation of the nitrogen atom in the heterocyclic moiety of 2-trifluoroacetamido-1,3,4-thiadiazoles. 1,5-Type intramolecular nonbonding S・・・O interaction was clarified by X-ray crystallographic analyzes and abinito MO calculation of the Ag II receptor antagonists and their simple model compounds. We have also developed several new reactions useful for the drug syntheses such as a chemoselective Dieckmann-type reaction mode toward the enantiodivergent process, the Horner-Wadsworth-Emmons reaction of aryl alkyl ketones using tin (II) -triflate and N-ethylpiperidine, and syntheses of new strained [6] and [7] metacyclophanes utilizing the latent conjugated allenyl ketone systems.