engleski

Synthesis of (±)‐trans‐3‐amino‐β‐lactam and its enantioseparation on the new polysaccharide‐based chiral stationary phase by HPLC and SFC

β‐Lactams, or azetidin‐2‐ones, are of utmost importance in medicine owing to their broad range of bioactivities [1]. They are the key structural component in the most widely used class of antibiotics, β-lactam antibiotics, such as penicillin, cephalosporin, carbapenem, etc [2]. Apart from their pharmacological purposes, β‐lactams are also valuable from a synthetic point of view as they can function as building blocks for the synthesis of numerous biologically active and natural compounds [1]. Some of the example include non-natural amino acid, peptides and peptidomimetics, anti-cancer drug paclitaxel and other taxis and anti-tumor antibiotics lankacidin [3]. β-lactam can easily rearranged into five-membered, six-membered, medium-size rings, which is in focus of our current research [4] In conducted research the (±)-trans-3-amino-β-lactam 3 was prepared by Staudinger reaction, [2+2] ketene-imine cycloaddition. Reaction of imine 1 with N-phthaloylglycine in the presence of base triethylamine and 2-chloro-N-methylpyridinium iodide in dry dichloromethane afforded a mixture of (±)-cis 2a and (±)-trans-3-phthalimido-β-lactam 2b in a ratio 1:5 (Scheme 1). In the next step, deprotection of the phthalimido group was carried out by converting the (±)-trans-2b to 3-amino-β-lactam 3 with ethylene diamine in dry ethanol (Scheme 2). The stereochemistry of β-lactams has already been determined and remains unchanged during this conversion [4]. Enantioseparation of 3 was studied using HPLC and SFC on the new chiral stationary phase based on a very unique polysaccharide, and also on the "golden four" polysaccharide type chiral stationary phases. The obtained results showed that the enantioseparation of 3 achieved by SFC is superior in terms of high resolution and short analysis time than using conventional HPLC.

β‐Lactami ; SFC ; HPLC

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