193148-58-2Relevant academic research and scientific papers
Efficient and direct solid phase synthesis of ketomethylenimino and ketomethylenamino peptides
Bernard, Elise,Vanderesse, Régis
, p. 8603 - 8606 (2004)
The reaction between the free amino terminus of a solid-supported peptide and a glyoxal leads to two families of pseudopeptides, the ketomethylenimino and the ketomethylenamino peptides. The aim of this study is the synthesis of pseudopeptides on solid supports, in order to quickly obtain modified peptides. We report a convenient step-by-step synthesis of ketomethylenimino ψ[CO-CH=N] and ketomethylenamino ψ[CO-CH2-NH] peptides. The key is the reaction between the free amino terminus of the supported peptide and a glyoxal-modified amino acid, leading to a ketomethylenimino bond, which can be reduced to a ketomethylenamino bond.
Tubulysin Synthesis Featuring Stereoselective Catalysis and Highly Convergent Multicomponent Assembly
Vishwanatha, Thimmalapura M.,Giepmans, Ben,Goda, Sayed K.,D?mling, Alexander
supporting information, p. 5396 - 5400 (2020/07/08)
A concise and modular total synthesis of the highly potent N14-desacetoxytubulysin H (1) has been accomplished in 18 steps in an overall yield of up to 30percent. Our work highlights the complexity-augmenting and route-shortening power of diastereoselective multicomponent reaction (MCR) as well as the role of bulky ligands to perfectly control both the regioselective and diastereoselective synthesis of tubuphenylalanine in just two steps. The total synthesis not only provides an operationally simple and step economy but will also stimulate major advances in the development of new tubulysin analogues.
TUBULYSIN DERIVATIVES AND METHODS FOR PREPARING THE SAME
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Page/Page column 21, (2020/02/16)
The invention relates to novel means and methods for the synthesis of tubulysin and derivatives thereof, which find their use e.g. as cytotoxic agents in targeted drug delivery. Provided is a method for preparing a tubulysin derivative, comprising reacting compounds A, B and C in a 3- component Passerini reaction, wherein compound A is a carboxylic acid according to the general formula (A); wherein compound B is an aldehyde according to the general formula (B); and wherein compound C is an isocyanide according to the general formula (C).
A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
Siciliano, Carlo,De Marco, Rosaria,Guidi, Ludovica Evelin,Spinella, Mariagiovanna,Liguori, Angelo
, p. 10575 - 10582 (2013/02/22)
The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.
Applying small molecule microarrays and resulting affinity probe cocktails for proteome profiling of mammalian cell lysates
Shi, Haibin,Uttamchandani, Mahesh,Yao, Shao Q.
supporting information; experimental part, p. 2803 - 2815 (2012/07/14)
Small molecule microarrays (SMMs) are proving to be increasingly important tools for assessing protein-ligand interactions, as well as in screening for enzyme substrates and inhibitors, in a high-throughput manner. We previously described an SMM-facilitated screening strategy for the rapid identification of probes against γ-secretase, an aspartic protease. In this article, we extend upon this work with an expanded library of hydroxyethylamine-derived inhibitors which non-exclusively target aspartic proteases. Our library is diversified across P2, P1, P1 ′, and P2′ positions. Accordingly, 86 new inhibitors are synthesized using a combinatorial, solid-phase synthetic approach, bringing the total library size to 284-biotinylated compounds, which were arrayed onto avidin slides. In order to elucidate enzymatic activity and profiles within complex biological samples, screening is performed using fluorescently-labeled mammalian cell lysates. This yielded reproducible profiles or binding fingerprints that correspond with interactions from aspartic proteases or accessory proteins as well as other interacting targets that were present in the sample. The brightest microarray hits were converted to affinity-based probes (AfBPs) using convenient, 1-step "click" chemistry with benzophenone from the relevant building blocks. Pull-down/mass spectrometric analysis with these probes (individuals or cocktail) yielded putative protein targets that include well-known aspartic proteases, such as cathepsinD which is a clear marker for breast cancer cell lines, T47D. Many other hits were also identified, which may be secondary or tertiary interactors of aspartic proteases, or yet unreported off-targets of the hydroxyethylamine pharmacophore. Our work herein thus provides a candidate list of biomarkers for further investigations. Taken together, this SMM-facilitated strategy for the discovery of new AfBPs should provide a useful tool for high-throughput development of novel small molecule probes and the identification of new aspartic proteases as well as related biomarkers in the future.
Ultrasound mediated synthesis of 2-amino-1,3-selenazoles derived from Fmoc/Boc/Z-α-amino acids
Lalithamba, Haraluru S.,Narendra,Naik, Shankar A.,Sureshbabu, Vommina V.
experimental part, p. 77 - 90 (2010/12/19)
A simple and efficient one-pot synthesis of Fmoc/Boc/Z-amino acid derived 2-amino-1,3-selenazoles by the condensation of Nα-urethane protected amino acid derived bromomethyl ketones with selenourea under the influence of ultrasound has been described. Insertion of 2-amino-1,3-selenazole moiety in the side chains of Asp and Glu has also been achieved following the similar protocol. ARKAT USA, Inc.
A novel synthesis of N-but-3-enyl-α- and β-amino acids
Van Nguyen,Brownlee, Robert T. C.,Hughes, Andrew B.
experimental part, p. 1991 - 1998 (2010/03/24)
N-But-3-enyl-α- and β-amino acids can be prepared by cleaving 1,3-oxazolidin-5-ones and 1,3-oxazinan-6-ones in the presence of allylsilanes and boron trifluoride etherate at room temperature in good to excellent yields. Georg Thieme Verlag Stuttgart.
Hexahydropyridazine-3-carboxylic acid derivatives, pharmaceutical compositions containing same and methods of preparation
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Page/Page column 11, (2010/02/13)
The present invention discloses and claims compounds of formula (I) as inhibitors of proteases and kinases, method using said compounds of formula (I) for the prevention or treatment of certain cardiovascular, central nervous system, inflammatory, and bon
Homologation of α-amino acids to β-amino acids: 9-Fluorenylmethyl chloroformate as a carboxyl group activating agent for the synthesis of Nα-protected aminoacyldiazomethanes
Kantharaju,Suresh Babu, Vommina V.
, p. 2152 - 2158 (2007/10/03)
An efficient and stereospecific homologation of urethane-protected α-amino acids to β-amino acids by Arndt-Eistert approach using an equimolar mixture of Fmoc-/Boc-/Z-α-amino acid and 9-fluorenylmethyl chloroformate for the acylation of diazomethane synth
Synthesis of β-amino acids: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (TBTU) for activation of Fmoc-/Boc-/Z-α-amino acids
Patil, Basanagoud S.,Vasanthakumar, Ganga-Ramu,Suresh Babu
, p. 3089 - 3096 (2007/10/03)
A new and efficient method for the homologation of urethane protected α-amino acids to its β-homomers by the Arndt-Eistert method using TBTU as a coupling agent is described. Several Fmoc-/Boc-/Z-protected α-amino diazoketone derivatives have been obtaine
