Synthesis of 2-aziridinyl phosphonates by modified Gabriel–Cromwell reaction and their antibacterial activities

Doğan, Özdemir; Babiz, Hakan; Gözen, Ayşe Gül; Budak, Songül

doi:10.1016/j.ejmech.2011.03.037

Cited by 26 publications

(26 citation statements)

References 29 publications

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“…In such circumstances, the elimination option was reconsidered, but ammonia was replaced by Et 3 N (the first stage) and subsequently by a benzylamine derivative (the second step) [23]. The use of benzyl or α-methylbenzylamine gave N-substituted aziridinephosphones 9 in a reasonable yield (Scheme 1, pathway C ).…”

Section: Resultsmentioning

confidence: 99%

A structural insight into the P1 S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases

Węglarz-Tomczak

Berlicki

Pawełczak

et al. 2016

European Journal of Medicinal Chemistry

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N'-substituted 1,2-diaminoethylphosphonic acids and 1,2-diaminoethylphosphinic dipeptides were explored to unveil the structural context of the unexpected selectivity of these inhibitors of M1 alanine aminopeptidases (APNs) versus M17 leucine aminopeptidase (LAP). The diaminophosphonic acids were obtained via aziridines in an improved synthetic procedure that was further expanded for the phosphinic pseudodipeptide system. The inhibitory activity, measured for three M1 and one M17 metalloaminopeptidases of different sources (bacterial, human and porcine), revealed several potent compounds (e.g., Ki = 65 nM of 1u for HsAPN). Two structures of an M1 representative (APN from Neisseria meningitidis) in complex with N-benzyl-1,2-diaminoethylphosphonic acid and N-cyclohexyl-1,2-diaminoethylphosphonic acid were determined by the X-ray crystallography. The analysis of these structures and the models of the phosphonic acid complexes of the human ortholog provided an insight into the role of the additional amino group and the hydrophobic substituents of the ligands within the S1 active site region.

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Section: Resultsmentioning

confidence: 99%

A structural insight into the P1 S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases

Węglarz-Tomczak

Berlicki

Pawełczak

et al. 2016

European Journal of Medicinal Chemistry

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“…ATR data were reported in cm −1 . N ‐alkyl substituted aziridine‐2‐phosphonates were prepared according to a published procedure …”

Section: Methodsmentioning

confidence: 99%

“…Although the literature have many examples to ring opening reactions of aziridine‐2‐carboxylates, the same reaction studied with the aziridine‐2‐phosphonates are limited . Our group is also involved in this field and reported the synthesis of racemic and chiral aziridine‐2‐phosphonates by modified Gabriel–Cromwell reaction and the results of their antibacterial activities . Our efforts in related chemistry continued with the ring opening reaction of aziridine‐2‐phosphonates by HCl which resulted in the formation of β ‐chloro‐ α ‐amino phosphonates .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Functionalized Novel α‐Amino‐β‐alkoxyphosphonates through Regioselective Ring Opening of Aziridine‐2‐phosphonates

Polat-Çakır

Beksultanova

Doğan

2019

Helvetica Chimica Acta

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Aziridines are highly useful compounds as building blocks for the synthesis of important organic compounds. Amino acid synthesis by aziridine ring opening reaction is a good example to the use of aziridines. Although this reaction is studied by many groups, the synthesis of amino phosphonic acids is less explored. In this study, we have carried out the ring opening reaction of aziridinyl phosphonates with a variety of alcohols including the more functional propargylic and allylic alcohols. These reactions provided functionalized α‐amino‐β‐alkoxyphosphonates in 40–91 % yield.

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“…Aziridine 2-phosphonates 1a-1i were prepared by the modified GabrielÀ Cromwell reaction starting from vinyl phosphonate or α-tosylvinyl phosphonate as reported by our group. [21,22] For the conversion of phosphonates to phosphonic acid derivatives, different hydrolysis conditions were examined. First, aziridine 2-diethylphosphonates were heated with KOH at 100°C then passed through a Dowex column.…”

Section: Resultsmentioning

confidence: 99%

“…TLC plate was stained with phosphomolybdic acid solution in ethanol. All the aziridine‐2‐phosphonates 1a – 1i were prepared as reported in the literature …”

Section: Methodsmentioning

confidence: 99%

Synthesis, Characterization and Evaluation of Cytotoxic Activities of Novel Aziridinyl Phosphonic Acid Derivatives

Khan

Ulusan

Banerjee

et al. 2019

Chemistry & Biodiversity

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New aziridine 2‐phosphonic acids were prepared by monohydrolysis of the aziridine 2‐phosphonates that were obtained by the modified Gabriel−Cromwell reaction of vinyl phosphonate or α‐tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT‐116 colorectal cancer cell lines and the CCD‐18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)‐1‐[(1S)‐1‐(naphthalen‐2‐yl)ethyl]aziridin‐2‐yl}phosphonate), 2h (ethyl hydrogen (1‐benzylaziridin‐2‐yl)phosphonate), and 2i (ethyl hydrogen (1‐cyclohexylaziridin‐2‐yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well‐known apoptosis inducing agent.

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Synthesis of 2-aziridinyl phosphonates by modified Gabriel–Cromwell reaction and their antibacterial activities

Cited by 26 publications

References 29 publications

A structural insight into the P1 S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases

A structural insight into the P1 S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases

Synthesis of Functionalized Novel α‐Amino‐β‐alkoxyphosphonates through Regioselective Ring Opening of Aziridine‐2‐phosphonates

Synthesis, Characterization and Evaluation of Cytotoxic Activities of Novel Aziridinyl Phosphonic Acid Derivatives

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