Ring closure reactions of bicyclic prolinol and prolin ester enantiomers

Abstract

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.

Molecular Simulation Investigation of Prolyl Oligopeptidase from Pyrobaculum Calidifontis and In Silico Docking With Substrates and Inhibitors

“…The docking study has shown that Ser431 formed a strong covalent bond with the inhibitor [59]. The similar nature of modification has also been reported earlier [60]. It's docking with the PC-POP, as shown in Figure 10, revealed that the sulfur and carbonyl groups of inhibitor formed bonds with the catalytic Ser431 and the two active glycines, Gly430 and Gly353.…”

Chemistry of α-Oxoesters: A Powerful Tool for the Synthesis of Heterocycles

“…First, the aza-Diels−Alder (DA) reaction between α-imino ester, in situ derived from ethyl glyoxalate and enantiopure 1-phenylethylamine, and cyclopentadiene was carried out in the presence of TFA and BF 3 • OEt 2 in DCM at −78 °C for 8 h. The DA adduct 352 then was hydrogenated over Pd(OH) 2 /C (5%) in absolute EtOH for 3 days, to give amino ester 353, which was transformed into tricyclic 2-thioxo-imidazolidinone 354, when treated with isothiocyanate in toluene at room temperature overnight, followed by refluxing in the presence of dry HCl in EtOH for 5 h. The yields for the last step are 52−73% (Scheme 100). 171 Imidazo The reaction of 2-amino-1,3,4-thiadiazoles with ethyl bromopyruvate was developed to prepare imidazothiadiazole-6-carboxylates 370. Reactions were conducted in dry EtOH under reflux conditions, for 6 h, and gave 370 in 35−48% yields, which were converted to [1,3,4]thiadiazole[2′,3′:2,3]imidazo [4,5-d]pyridazin-8(7H)-ones 371, when reacted with hydrazine hydrate in EtOH under reflux conditions, followed by treatment with Vilsmeier reagent (Scheme 104).…”

“…The synthesis of 2-thioxoimidazolidinone 354 was reported starting from ethyl glyoxalate. First, the aza-Diels–Alder (DA) reaction between α-imino ester, in situ derived from ethyl glyoxalate and enantiopure 1-phenylethylamine, and cyclopentadiene was carried out in the presence of TFA and BF 3 ·OEt 2 in DCM at −78 °C for 8 h. The DA adduct 352 then was hydrogenated over Pd­(OH) 2 /C (5%) in absolute EtOH for 3 days, to give amino ester 353 , which was transformed into tricyclic 2-thioxo-imidazolidinone 354 , when treated with isothiocyanate in toluene at room temperature overnight, followed by refluxing in the presence of dry HCl in EtOH for 5 h. The yields for the last step are 52–73% (Scheme ) …”

P(III)‐Mediated Cascade C‐N/C‐S Bond Formation: A Protocol towards the Synthesis of N,S‐Heterocycles and Spiro Compounds

“…Likewise, the synthesis of pyrrolo[1,2‐ c ]thiazoles was realized by the cyclization of prolinol derivatives with isothiocyanates in presence of conc. HCl [5f,6a,c] . In contrast, structurally enthralling 3‐thia‐1‐azaspiro compounds are barely explored, albeit their medicinal importance [7] .…”