Synthesis of Novel Selenapenams, Selenacephems, and Selenazepines Using a 2-(Trimethylsilyl)ethyl Protection Approach

Abstract

Selenapenams, selenacephems, and selenazepines were synthesized using a 2-(trimethylsilyl)ethyl (TSE) protection approach in an extremely simple way. TSE protection for selenium is used for the first time in the synthesis of selenium-containing beta-lactam. Novel intramolecular cycloaddition reaction of selenium with alkynes and allenes is used in the present synthesis.

Facile Synthesis of Selenium‐Containing Bicyclic β‐Lactams through Enyne Metathesis

“…Our group has demonstrated the utility of the TSE protection approach for the synthesis of variety of selenium-containing bicyclic β-lactams. [4,9] Compound 6 ( Table 2) was therefore selected as an important starting material for the insertion of the propargylseleno moiety at the C(4) position in the azetidin-2-one system. Selective removal of the TSE group of 6 and subsequent in situ alkylation of the selenolate anion was attempted for the synthesis of the key intermediates 7 having propargylseleno moieties at their C(4) positions (Table 2).…”

“…To the best of our knowledge, there are only four reports on the preparation of seven-membered selenium-containing heterocycles (that is, 1,3-selenazepines), [4,9,11] whereas there is only one report for the synthesis of eight-membered selenium heterocycles such as 1,3-selenazocine, by our group. [8] This RCEYM approach allows the synthesis of previously inaccessible selenium-containing heterocycles.…”

“…In this context, however, there are very few reports relating to the synthesis of seleniumcontaining bicyclic β-lactams available in the literature, due to the difficulties involved in their preparation. [3] We have recently reported a 2-(trimethylsilyl)ethyl (TSE) protection approach [4] for the incorporation of selenium into penam and cephem nuclei and an iodocyclization approach [5] for the synthesis of selenium-containing β-lactams with a selenium atom at the 3-or 4-position, with the aim of providing some novel compounds of potential biological significance.…”

Synthesis and characterization of novel trans-3-benzyl/(diphenyl)methyl/naphthyl seleno substituted monocyclic β-lactams: X-ray structure of trans-1-(4′-methoxyphenyl)-3-(diphenyl)methylseleno-4-(4′-methoxyphenyl)azetidin-2-one

“…Recently, the revolutionary and magical development reported by Schiesser et al [21,22] in incorporation of selenium in penam and cephalosporin nuclei provides some novel compounds of potential biological significance. Very recently, Koketsu et al [23,24] have reported 2-(trimethylsilyl)ethyl (TSE)-protection approach for the synthesis of bicyclic seleno-b-lactams, which further involves intramolecular cycloaddition reaction of selenium with alkynes and allenes. Thus, most recent trend in the b-lactam research has emerged, is the substitution of sulfur group with selenium and synthesis of this heterocycle with variety of substitutents at C-3, C-4 as well as N-1.…”

Reactions of Acid Chlorides/Ketenes with 2‐Substituted 4,5‐Dihydro‐4,4‐dimethyl‐1,3‐thiazoles: Formation of Penam Derivatives

“…Furthermore, the continuing interest in penam derivatives is shown by the elaboration of new methods for their preparation (e.g. [17]), the synthesis of analogs such as selenapenams [18], and the modifcation of known compounds, e.g., 6-aminopenicillic acid (6-APA) [19].…”