Synthesis of Phosphinopeptides and Phosphinodepsipeptides

Xu, Jiaxi

doi:10.1002/ajoc.202000600

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…[100][101][102] Phosphonopeptides and phosphinopeptides have been widely applied as enzyme inhibitors and biologically active compounds due to their tetrahedral phosphorus atom. [103][104][105] Similarly, the sulfonamide structure is abundant active structural moiety in most medicines. Thus, it is reasonable to consider sulfonopeptides or peptides with certain sulfonamide moiety as potential medicinal candidates.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of sulfonopeptides

2021

Journal of Peptide Science

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Sulfonopeptides as the sulfur analogues of natural peptides have been widely used as enzyme inhibitors due to their tetrahedral sulfonamide moiety, which can mimic the transition‐state analogues of hydrolysis of the ester and amide bonds. Synthetic methods of sulfonopeptides are reviewed. The synthetic methods of sulfonopeptides include the condensation of N‐protected amino acid/peptide acids and 2‐aminoalkanesulfonic acids, coupling of N‐protected 2‐aminoalkanesulfonyl chlorides and amino acid esters/peptide esters, sulfinylation of amino acid esters/peptide esters with N‐protected 2‐aminoalkanesulfinyl chlorides and subsequent oxidation, the alkylation of taurine‐containing peptides, and the displacement of N‐aminoacyl/peptidyl 2‐aminoalkyl halides/methanesulfonates with sulfites. Hybrid sulfonophosphinopeptides are prepared through the Mannich‐type reaction of N‐protected 2‐aminoalkanesulfonamides/peptidylsulfonamides, aldehydes, and aryldichlorophosphines/phosphorus trichloride followed by the aminolysis with amino acid/peptide esters or hydrolysis. The developed synthetic methods provide diverse synthetic routes for biologically important sulfonopeptides as the candidates of medicinal agents.

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Section: Discussionmentioning

confidence: 99%

Synthesis of sulfonopeptides

2021

Journal of Peptide Science

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“…Among the plethora of bioactive scaffolds with numerous applications in drug discovery, phosphinic peptides undoubtedly hold a prominent position [1][2][3][4][5][6][7][8][9]. By acting as transition state analogues of natural peptides during proteolysis, phosphinic peptides have provided a large number of potent inhibitors of zinc and aspartyl proteases over previous decades [2,5,6].…”

Section: Introductionmentioning

confidence: 99%

Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions

et al. 2022

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In this report, a synthetic protocol for the preparation of phosphinic dipeptides of type 5 is presented. These compounds serve as valuable building blocks for the development of highly potent phosphinopeptidic inhibitors of medicinally relevant Zn-metalloproteases and aspartyl proteases. The proposed method is based on the tandem esterification of α-aminophosphinic and acrylic acids under silylating conditions in order to subsequently participate in a P-Michael reaction. The scope of the transformation was investigated by using a diverse set of readily available acrylic acids and (R)-α-aminophosphinic acids, and high yields were achieved in all cases. In most examples reported herein, the isolation of biologically relevant (R,S)-diastereoisomers became possible by simple crystallization from the crude products, thus enhancing the operational simplicity of the proposed method. Finally, functional groups corresponding to acidic or basic natural amino acids are also compatible with the reaction conditions. Based on the above, we expect that the practicality of the proposed protocol will facilitate the discovery of pharmacologically useful bioactive phosphinic peptides.

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“…Phosphinic peptides are undoubtedly one of the most interesting classes of pseudopeptides with a long record of success stories in medicinal chemistry (Scheme A) . They have been extensively used as potent inhibitors of proteases, exhibiting in several cases outstanding selectivity between closely related enzymes .…”

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Diastereoselective Synthesis of Phosphinic Dipeptide Isosteres: Domino Chirality Transfer during a Stereocontrolled P-Michael Reaction

Lelis,

Skoulikas,

Papathanasopoulou

et al. 2023

Org. Lett.

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A highly diastereoselective P-Michael addition of chiral aminophosphinic acids to achiral acrylates has been developed, leading to phosphinic dipeptide isosteres in high yields and dr of up to >50:1. The method allows for the diastereoselective preparation of target compounds without the need for chiral auxiliaries or P-chiral substrates. A possible mechanistic explanation involves a domino chirality transfer from the aminophosphinic acid to the P center, amplified by a crucial benzhydryl ester group, and then to the α-carbon.

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Synthesis of Phosphinopeptides and Phosphinodepsipeptides

Cited by 4 publications

References 40 publications

Synthesis of sulfonopeptides

Synthesis of sulfonopeptides

Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions

Diastereoselective Synthesis of Phosphinic Dipeptide Isosteres: Domino Chirality Transfer during a Stereocontrolled P-Michael Reaction

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