32675-71-1Relevant academic research and scientific papers
Convergent Synthesis of Calcium-Dependent Antibiotic CDA3a and Analogues with Improved Antibacterial Activity via Late-Stage Serine Ligation
Blasco, Pilar,Chen, Delin,Chen, Sheng,Li, Xuechen,Po, Kathy Hiu Laam
supporting information, (2020/06/29)
A convergent synthesis via the late-stage serine ligation of naturally occurring calcium-dependent antibiotic CDA3a and its analogues has been developed, which allowed us to readily synthesize the analogues with the variation on the lipid tail. Some analogues were found to show 100-500-fold higher antimicrobial activity than the natural compound CDA3a against drug resistant bacteria. This study will enhance our understanding of CDA3a and provide valuable antibacterial lead candidates for further development.
Chiral sensors for determining the absolute configurations of α-amino acid derivatives
Chen, Zhongxiang,Fan, Hongjun,Yang, Shiwei,Bian, Guangling,Song, Ling
, p. 6933 - 6939 (2018/10/02)
A simple strategy for configurational assignments of alpha-amino acids has been developed by comparison of the proton NMR chemical shift values of the alpha hydrogens of N-phthaloyl protected alpha-amino acids in the presence of (R)-CSA 1 and (S)-CSA 1, respectively. Highly resolved NMR spectra can be obtained directly on the mixed solution of the chiral solvating agents with N-phthaloyl protected alpha-amino acids in NMR tubes, giving well distinguishable proton signals without interference which dramatically improve the accuracy of assignment and hasten the assigning procedure. The strategy is widely applicable for varied natural and non-natural amino acids.
Studies on Aculeines: Synthetic Strategy to the Fully Protected Protoaculeine B, the N-Terminal Amino Acid of Aculeine B
Shiozaki, Hiroki,Miyahara, Masayoshi,Otsuka, Kazunori,Miyako, Kei,Honda, Akito,Takasaki, Yuichi,Takamizawa, Satoshi,Tukada, Hideyuki,Ishikawa, Yuichi,Sakai, Ryuichi,Oikawa, Masato
supporting information, p. 3403 - 3407 (2018/06/11)
A synthetic strategy for accessing protoaculeine B (1), the N-terminal amino acid of the highly modified peptide toxin aculeine, was developed via the synthesis of the fully protected natural homologue of 1 with a 12-mer poly(propanediamine). The synthesis of mono(propanediamine) analog 2, as well as core amino acid 3, was demonstrated by this strategy. New amino acid 3 induced convulsions in mice; however, compound 2 showed no such activity.
Phthaloyl amino acids as anti-inflammatory and immunomodulatory prototypes
Leite, Ana Cristina Lima,Barbosa, Fabio Fernandes,Cardoso, Marcos Verissimo De Oliveira,Moreira, Diogo R. M.,Coelho, Lucas Cunha D.,Da Silva, Elany Barbosa,Filho, Gevanio Bezerra De Oliveira,De Souza, Valdenia Maria Oliveira,Pereira, Valeria Rego A.,Reis, Luiza De C.,Ferreira, Paulo Michel Pinheiro,Pessoa, Claudia,Wanderley, Almir Goncalves,Mota, Fernanda Virginia B.,Da Silva, Teresinha G.
, p. 1701 - 1708 (2014/05/06)
A series of phthalimide analogs were synthesized by derivatization of phthalic anhydride, a highly toxic substance, using a "one pot" condensation reaction to α-amino acids. All phthaloyl amino acid derivatives presented anti-oral inflammatory activity, but compounds 2e and 2g were found to possess the best activities comparable to thalidomide.Most of the compounds effectively suppressed nitric oxide production inmurine cells stimulatedwith lipopolysaccharide. N-phthaloyl amino acids did not exhibit any significant cytotoxicity in vitro when tested against tumor cells as well as a spleen cell culture of BALB/c mice. Compounds 2a, 2g, and 2h were able to inhibit TNF-α and IL-1β production by macrophages. At the same concentration, thalidomide did not exhibit significant inhibitory activity. Springer Science+Business Media 2013.
Synthesis and evaluation of analogues of N-phthaloyl-l-tryptophan (RG108) as inhibitors of DNA methyltransferase 1
Asgatay, Saa?dia,Champion, Christine,Marloie, Ga?l,Drujon, Thierry,Senamaud-Beaufort, Catherine,Ceccaldi, Alexandre,Erdmann, Alexandre,Rajavelu, Arumugam,Schambel, Philippe,Jeltsch, Albert,Lequin, Olivier,Karoyan, Philippe,Arimondo, Paola B.,Guianvarc'H, Dominique
, p. 421 - 434 (2014/02/14)
DNA methyltransferases (DNMT) are promising drug targets in cancer provided that new, more specific, and chemically stable inhibitors are discovered. Among the non-nucleoside DNMT inhibitors, N-phthaloyl-l-tryptophan 1 (RG108) was first identified as inhibitor of DNMT1. Here, 1 analogues were synthesized to understand its interaction with DNMT. The indole, carboxylate, and phthalimide moieties were modified. Homologated and conformationally constrained analogues were prepared. The latter were synthesized from prolinohomotryptophan derivatives through a methodology based amino-zinc-ene-enolate cyclization. All compounds were tested for their ability to inhibit DNMT1 in vitro. Among them, constrained compounds 16-18 and NPys derivatives 10-11 were found to be at least 10-fold more potent than the reference compound. The cytotoxicity on the tumor DU145 cell line of the most potent inhibitors was correlated to their inhibitory potency. Finally, docking studies were conducted in order to understand their binding mode. This study provides insights for the design of the next-generation of DNMT inhibitors.
Synthesis and biological evaluation of 18F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging
Chiotellis, Aristeidis,Mu, Linjing,Müller, Adrienne,Selivanova, Svetlana V.,Keller, Claudia,Schibli, Roger,Kr?mer, Stefanie D.,Ametamey, Simon M.
, p. 768 - 780 (2013/12/04)
In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[18F]fluoropropyl)-dl- tryptophan ([18F]2-FPTRP) and 5-(3-[18F]fluoro-propyl)-dl- tryptophan ([18F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [18F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [ 18F]2-FPTRP comparable to the well established tyrosine analog O-(2-[18F]fluroethyl)-l-tyrosine ([18F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation.
Stereoselective synthesis of brevianamide e
Zhao, Liang,May, Jonathan P.,Huang, Jack,Perrin, David M.
supporting information; experimental part, p. 90 - 93 (2012/02/15)
The hydroxypyrroloindolenine (Hpi) motif forms the fundamental core of the pentacyclic natural product, brevianamide E, the concise stereoselective synthesis of which, via oxidative cyclization, is described.
Photoinduced electron-transfer chemistry of the bielectrophoric N-phthaloyl derivatives of the amino acids tyrosine: Histidine and tryptophan
Griesbeck, Axel G.,Neudoerfl, Joerg,Kiff, Alan De
experimental part, p. 518 - 524 (2011/06/28)
The photochemistry of phthalimide derivatives of the electron-rich amino acids tyrosine, histidine and tryptophan 8-10 was studied with respect to photoinduced electron-transfer (PET)induced decarboxylation and Norrish II bond cleavage. Whereas exclusive photodecarboxylation of the tyrosine substrate 8 was observed, the histidine compound 9 resulted in a mixture of histamine and preferential Norrish cleavage. The tryptophan derivative 10 is photochemically inert and shows preferential decarboxylation only when induced by intermolecular PET.
Synthesis and characterization of bioactive molecules grafted on poly(e{open}-caprolactone) by " click" chemistry
Suksiriworapong, Jiraphong,Sripha, Kittisak,Junyaprasert, Varaporn Buraphacheep
experimental part, p. 2286 - 2295 (2011/10/05)
A facile and efficient strategy to graft bioactive molecules (nicotinic acid, p-aminobenzoic acid, and phthaloyltryptophan) onto poly(e{open}-caprolactone) (P(e{open}CL)) was achieved by copper-catalyzed Huisgen's 1,3-dipolar cycloaddition known as click reaction. P(αCle{open}CL), with 10, 20, and 30% of α-chloro-e{open}-caprolactone (αCle{open}CL) units were copolymerized by ring opening polymerization using e{open}CL and αCle{open}CL as starting materials in the presence of 1,4-butanediol and Sn(Oct)2. Subsequently, the chloride pendent was converted to azide followed by cycloaddition with terminal alkyne derivatives of the aforementioned bioactive molecules. The complete addition was accomplished at all ratios. The characteristic molecular features of these copolymers were evaluated by FTIR, NMR, and GPC. Thermal analysis data indicated that the grafted compounds led to polymorphic alteration and different pattern of thermal degradation depending on the molecular structure and the size of the grafted compounds. They are the basis for further development of grafted copolymer as drug delivery carriers.
PHTHALAMIDES, SUCCINIMIDES AND RELATED COMPOUNDS AND THEIR USE AS PHARMACEUTICALS
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Page/Page column 48; 53, (2008/06/13)
The present invention relates to certain phthalamides, succinimides and related compounds and their use as pharmaceuticals. In particular, the present invention relates to these compounds, pharmaceutical compositions comprising these compounds, and use of these compounds, for example, to inhibit DNA methylation in cells, particularly tumour cells.
