Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

Abstract

Herein, we present an efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates. Each step of the synthesis was optimized to provide excellent yields. Moreover, the absolute configuration of the obtained compounds was determined by X-ray analysis, which proved the stereochemistry that was proposed based on NMR studies.

Application of α-Amino-β-fluorophosphonates in Construction of their Dipeptide Analogues

“…Compounds 1 were prepared on 8 mmol scale according to previously reported procedure. 22 The NMR data for 1a-e were in good agreement. 16,21…”

“…7,9,12,18 One such example may be utilization of 2HF•Et 3 N during the XtalFluor-E nucleophilic deoxyfluorination reaction. 7,19 In a continuation of our research on the synthesis and application of fluorinated aminophosphonates, 16,17,[20][21][22] herein we report our progress on the development and improvement of deoxyfluorination reaction of amino alcohols for the construction of dipeptide analogues.…”

“…Compounds (1R,2S)-1a-e were obtained from the corresponding amino acids in a four-step procedure. 22 In addition, during purification of leucine derivative, (1S,2S)-1f diastereoisomer was isolated as well. Amino alcohols 1 were next subjected to regioselective fluorination using XtalFluor-E (1.5 equiv) ( Table 1).…”

Design and Synthesis of New α-hydroxy β-fluoro/β-trifluoromethyl and Unsaturated Phosphonates from Carbohydrate-Derived Building Blocks via Pudovik and Horner–Wadsworth–Emmons Reactions

“…, dried over MgSO 4 or Na 2 SO 4 , filtrated and concentrated under reduced pressure. The residue was purified using column chromatography (chloroform/methanol 100:0 100:0.5) [ 26 ].…”

“…In the literature, there are many examples of various properties and biological activities of phosphonic acid derivatives containing a hydroxyl group [ 19 , 20 ] and/or fluorine atom in α position to a phosphonate group [ 21 , 22 , 23 , 24 , 25 , 26 ]. These compounds are also isosteric analogues of natural products [ 27 ] and enzyme inhibitors ( Figure 2 ) [ 19 , 28 ].…”