Ales Krbavcic

A convenient synthesis of 4-aminomethyl-4,5,6,7-tetrahydro-1,3-benzothiazole arginine side-chain mimetics

Abstract A convenient synthesis of novel 4-aminomethyl-4,5,6,7-tetrahydro-1,3-benzothiazole arginine side-chain mimetics designed for incorporation into thrombin inhibitors is reported.

Preparation of diastereomerically pure immunologically active carbocyclic nor-muramyldipeptide analogues

Abstract The preparation of diastereomerically pure immunologically active carbocyclic nor-muramyldipeptide analogues (1′R,2′R)-/(1′S,2′S)-N-[2-(2′-acetylamino-cyclohexyloxy)acetyl]-L-alanyl-D-isoglutamine and (1′R,2′R)-/(1′S,2′S)-N-]2-(2′-acetylaminocyclohexyloxy)acetyl]-L-alanyl-D-glutamic acid is described. The title compounds were synthesized using two independent synthetic routes from racemic trans-2-azidocyclohexanol and (1R,2R)-/(1S,2S)-2-aminocyclohexanol, respectively.

Synthesis and Structure Investigations of Potential Sedative and Anticonvulsant Hydroxy- and Acetoxy-N-(3-oxobutyl)-pyrido[2,3-d]pyridazinonesa

Summary. Novel N-(3-oxobutyl)-hydroxy- and acetoxypyrido[2,3-d]pyridazinones were synthesized and tested in vivo for their sedative and anticonvulsant activity. The Michael-type reaction of quinolinic acid hydrazide and methyl vinyl ketone afforded a mixture of two isomers, 5-hydroxy-N7-(3-oxobutyl)-pyrido[2,3-d]pyridazin-8(7H)-one and 8-hydroxy-N6-(3-oxobutyl)-pyrido[2,3,-d]pyridazin-5-(6H)-one, in a ratio of 2:1 which were separated by crystallization. Subsequent acetylation of both isomers yielded the corresponding 5- and 8-acetoxy compounds. The structures of the compounds were proven and completely assigned on the basis of 1H, 13C, 15N NMR, and 1D NOE difference spectra as well as 2D C,H-correlation experiments. Preliminary pharmacological tests showed low acute toxicity with a LD50 > 1000 mg/kg in the mouse and sedative activity for the title compounds. 5-Acetoxy-N7- (3-oxobutyl)-pyrido[2,3-d]pyridazin-8(7H)-one displayed a borderline anticonvulsant activity in the metrazole test model.

Synthesis and functionalization oftrans-2-(2′-aminocyclohexyloxy)-andtrans-2-(2′-azidocyclohexyloxy)acetic acid

SummarySynthesis of the hydrochloride oftrans-2-(2′-aminocyclohexyloxy)acetic acid (4) fromtrans-2-(2′-azidocyclohexyloxy)acetic acid (1) is described.4 was acylated at the amino group to give compounds5–8.1 was converted into acid chloride (9) and amides10–13.ZusammenfassungDie Synthese destrans-2-(2′-Aminocyclohexyloxy)essigsäurehydrochlorids (4), ausgehend vontrans-2-(2′-Azidocyclohexyloxy)essigsäure (1), wird beschrieben.4 wurde durch Acylierung der Aminogruppe in die Verbindungen5–8 übergeführt.1 wurde in das Säurechlorid9 und die Carbonsäureamide10–13 umgewandelt.