289658-75-9Relevant academic research and scientific papers
A new synthesis of protected phosphonodipeptides with an N-terminal amino acid
Sikora, Dorota,Gajda, Tadeusz
, p. 3755 - 3761 (2007/10/03)
A new simple protocol for the direct synthesis of phosphonodipeptides from N-protected amino acids, diethyl 1-azidoalkylphosphonates and tertiary alkyl phosphine (Bu3P, Me3P) was developed. The method is general and the coupling occurred with good yield (42-97%). Depending on the phosphine used and/or mechanism operating during the condensation, the reaction can be accomplished at room temperature, or on heating in toluene. (C) 2000 Elsevier Science Ltd.
Electrochemical Decarboxylation of L-Threonine and Oligopeptide Derivatives with Formation of N-Acyl-N,O-acetals: Preparation of Oligopeptides with Amide or Phosphonate C-Terminus
Seebach, Dieter,Charczuk, Roland,Gerber, Christian,Renaud, Philippe,Berner, Heinz,Schneider, Helmut
, p. 401 - 425 (2007/10/02)
Derivatives of α-amino acids with two stereogenic centers (cf.L-threonine) and di-, tri- and tetrapeptides are electrolyzed in MeOH or AcOH, with formation of N-acyl-N,O-acetals (1b - 15b, 20b), in an anodic oxidative substitution of the COOH by an OR group.The amine ends of the oligopeptides may be benzyloxycarbonyl(Z)- or (tert-butoxy)carbonyl(Boc)-protected.With unprotected dipeptides, an electrolytic decarboxylative cyclization to imidazolidinones (18c, 19c) may also occur (in H2O/NH4OAc).The electrolyses are carried out in simple flasks with cooling jackets ('undivided cell'), using constant current conditions and anodes of Pt or glassy C.The electrolyte is generated in situ by adding 10 - 20 mol-percent of a tertiary amine.Mild acidic hydrolysis of electrolysis products thus obtained may lead to amino-acid amides or peptide amides (10c, 11c, 12c, 17c) with one amino acid less than the starting material.The N,O-acetals from L-threonine and the oligopeptides also react with organometallic nucleophiles such as Grignard compounds (->21 - 26, 29), with formation of products in which the original COOH group has been replaced by alkyl or allyl (sometimes even with moderate stereoselectivity).By treatment of the peptide-derived (open-chain) N,O-acetals with trialkyl or triaryl phosphites/TiCl4, the RO group is replaced by a phosphodiester group in a (non-diastereoselective) Michaelis-Arbuzov-type reaction (1d, 1e, 2d - 9d, 5e).Thus, the two-step sequence of electrolysis and phosphonation converts an oligopeptide derivative to an analogue with a phosphonic-acid end group.The diastereoisomeric N-protected dimethyl and diethyl dipeptidephosphonates (also prepared from the corresponding diaryl esters by Ti(OR)4-mediated transesterification) could be separated by preparative HPLC (SiO2, Lichrosorb Si 60, 10 μm); the dextrorotatory isomers of 1d - 3d were assigned L,D-, the laevorotatory ones L,L-configuration by hydrolysis to and identification of the known amino and aminophosphonic acids.The results described demonstrate a new simple route leading, from a give oligopeptide, to pure peptide analogues of known configuration.
CONVERSION OF AMINO ACIDS AND DIPEPTIDES INTO THEIR PHOSPHONIC ANALOGS; Aminoalkylphosphonic acids and peptides II.
Oesapay, George,Szilagyi, Ildiko,Seres, Jenoe
, p. 2977 - 2984 (2007/10/02)
Acylamino carboxylic acids were degradated by the Hunsdiecker-reaction; the bromo-derivatives were reacted with NaPO(OC2H5)2.Aminophosphonic acids were obtained by acidic hydrolysis, and half-blocked derivatives by the selective removal of masking substituents.Two phosphonopeptides were also prepared by this route.
Phosphonodipeptides: synthesis and separation of diastereoisomers
Kafarski, Pawel,Lejczak, Barbara,Mastalerz, Przemslaw,Szewczyk, Jerzy,Wasielewski, Czeslaw
, p. 3081 - 3084 (2007/10/02)
Diastereoisomeric mixtures of phosphonodipeptides, prepared from racemic dialkyl 1-aminoalkanephosphonates, were separated by ion-exchange column chromatography.Phosphonodipeptides were found to be much more readily available from dialkyl 1-aminoalkanephosphonates than from the corresponding free acids and the mixed carboxylic-carbonic anhydride method was found to be the most effective one.
STUDIES ON THE SYNTHESIS OF CHEMOTHERAPEUTICS. PART XI. SYNTHESIS AND ANTIBACTERIAL ACTIVITIES OF PHOSPHONOPEPTIDES
Kametani, Tetsuji,Kigasawa, Kazuo,Hiiragi, Mineharu,Wakisaka, Kikuo,Haga, Seiji,et al.
, p. 1205 - 1242 (2007/10/02)
A variety of phosphonopeptides, shown in 2 as a general formula, containg natural and/or unnatural amino acids were synthesized, and their in vitro antibacterial activities were examined.N-Protected amino acids were condensed with 1-amino-ethylphosphonic acid or its ester followed by deprotection and hydrolysis to give the requisite phosphonopeptides.Several compounds showed higher levels of activity against certain members of Gram-negative bacteria than those of Alafosfalin (1) as the standard phosphonopeptide.A brief discussion on structure-activity relationships is also described.
