RHODIUM(I)-CATALYZED CYCLOISOMERIZATION OF NITROGEN TETHERED ENE-ALLENES: FORMATION OF TETRAHYDROAZEPINES

Abstract: A novel cycloisomerization process involving nitrogen-tethered 1,6-ene-allenes has been realized. Subjecting ene-allene 9 to rhodium biscarbonyl chloride dimer produces tetrahydroazepine 10 in moderate to high yields. Substituting the allene moiety with the bulky tert-butyl-group (R4 = t-Bu), while employing a trans-alkene tether, afforded the corresponding azepines in the highest yields. This formal Alder-ene transformation tolerated not only a variety of alkyl-substituents on both the alkene and allene portions but also silyl-[R2 = SiMe3, SiMe2Bn; R4 = Si(i-Pr)3] and phenyl-(R2 = Ph, R4 = Ph) substituents. A deuterium labeling study aided in the postulation of two possible mechanisms for this cycloisomerization. During the course of this investigation, a novel carbon monoxide insertion reaction was observed. Our findings to date are reported and discussed herein

Enantioselective Aldehyde α-Nitroalkylation via Oxidative Organocatalysis

Enantioselective Aldehyde α-Nitroalkylation via Oxidative Organocatalysi

Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228

Metallo-β-lactamases (MBLs), such as New Delhi metallo-β-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of β-lactam antibiotics, with the exception of monobactams, which are intrinsically stable to MBLs. However, existing first generation monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine β-lactamases (SBLs), which are often co-expressed in clinical isolates. Here, we optimized novel monobactams for stability against SBLs, which led to the identification of LYS228 (compound 31). LYS228 is potent in the presence of all classes of β-lactamases and shows potent activity against carbapenem-resistant isolates of Enterobacteriaceae (CRE)