25044-10-4Relevant academic research and scientific papers
Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions
Kokkala, Paraskevi,Voreakos, Kostas,Lelis, Angelos,Patiniotis, Konstantinos,Skoulikas, Nikolaos,Devel, Laurent,Ziotopoulou, Angeliki,Kaloumenou, Eleni,Georgiadis, Dimitris
supporting information, (2022/02/21)
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.
Investigating the phosphinic acid tripeptide mimetic DG013A as a tool compound inhibitor of the M1-aminopeptidase ERAP1
Wilding, Birgit,Pasqua, A. Elisa,E. A. Chessum, Nicola,Pierrat, Olivier A.,Hahner, Tamas,Tomlin, Kathy,Shehu, Erald,Burke, Rosemary,Richards, G. Meirion,Whitton, Bradleigh,Arwert, Esther N.,Thapaliya, Arjun,Salimraj, Ramya,van Montfort, Rob,Skawinska, Agi,Hayes, Angela,Raynaud, Florence,Chopra, Rajesh,Jones, Keith,Newton, Gary,Cheeseman, Matthew D.
supporting information, (2021/05/06)
ERAP1 is a zinc-dependent M1-aminopeptidase that trims lipophilic amino acids from the N-terminus of peptides. Owing to its importance in the processing of antigens and regulation of the adaptive immune response, dysregulation of the highly polymorphic ERAP1 has been implicated in autoimmune disease and cancer. To test this hypothesis and establish the role of ERAP1 in these disease areas, high affinity, cell permeable and selective chemical probes are essential. DG013A 1, is a phosphinic acid tripeptide mimetic inhibitor with reported low nanomolar affinity for ERAP1. However, this chemotype is a privileged structure for binding to various metal-dependent peptidases and contains a highly charged phosphinic acid moiety, so it was unclear whether it would display the high selectivity and passive permeability required for a chemical probe. Therefore, we designed a new stereoselective route to synthesize a library of DG013A 1 analogues to determine the suitability of this compound as a cellular chemical probe to validate ERAP1 as a drug discovery target.
Iodonium Ylides as Carbene Precursors in Rh(III)-Catalyzed C-H Activation
Jiang, Yuqin,Li, Pengfei,Li, Xingwei,Liu, Bingxian,Zhao, Jie
supporting information, p. 7475 - 7479 (2020/10/12)
The rhodium(III)-catalyzed coupling of C-H substrates with iodonium ylides has been realized for the efficient synthesis of diverse cyclic skeletons, where the iodonium ylides have been identified as efficient and outstanding carbene precursors. The reaction systems are applicable to both sp2 and sp3 C-H substrates under mild and redox-neutral conditions. The catalyst loading can be as low as 0.5 mol % in a gram-scale reaction. Representative products exhibit cytotoxicity toward human cancer cells at nanomolar levels.
Bridged metallocene catalysts
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Page/Page column, (2015/07/22)
A solid, particulate catalyst comprising: (i) a complex of formula (I) wherein M is zirconium or hafnium; each X is a sigma ligand; L is a divalent bridge selected from —R′2C—, —R′2C—CR′2—, —R′2Si—, —R′2Si—SiR′2—, —R′2Ge—, wherein each R′ is independently a hydrogen atom, C1-C20-hydrocarbyl, tri(C1-C20-alkyl)silyl, C6-C20-aryl, C7-C20-arylalkyl or C7-C20-alkylaryl; each R1 is a C4-C20 hydrocarbyl radical branched at the β-atom to the cyclopentadienyl ring, optionally containing one or more heteroatoms belonging to groups 14-16, or is a C3-C20 hydrocarbyl radical branched at the β-atom to the cyclopentadienyl ring where the β-atom is an Si-atom; each R18 is a C1-C20 hydrocarbyl radical optionally containing one or more heteroatoms belonging to groups 14-16; each R4 is a hydrogen atom or a C1-6-hydrocarbyl radical; each W is a 5 or 6 membered aryl or heteroaryl ring wherein each atom of said ring is optionally substituted with at least one R5 group; each R5 is the same or different and is a C1-C20 hydrocarbyl radical optionally containing one or more heteroatoms belonging to groups 14-16; and optionally two adjacent R5 groups taken together can form a further mono or multicyclic ring condensed to W optionally substituted by one or two groups R5; and each R7 is a C1-C20 hydrocarbyl radical; and (ii) a cocatalyst, preferably comprising an organometallic compound of a Group 13 metal.
A ring-closing metathesis approach for the synthesis of (±)-pregabalin
Bobade, Vivek D.,Mhaske, Pravin C.,Vadgaonkar, Kamlesh S.,Shelke, Shivaji H.
scheme or table, p. 847 - 851 (2012/08/27)
Efficient utilization of a Mannich-type reaction and the ring-closing metathesis (RCM) approach that leads to a convenient synthesis of 3-(aminomethyl)-5-methylhexanoic acid (pregabalin) is described. Springer-Verlag 2011.
Group 4 metallocenes useful as catalysts for the polymerization of olefins
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Page/Page column 22, (2012/02/04)
A complex of formula (I): wherein M is zirconium or hafnium; each X is a sigma ligand; L is a divalent bridge selected from -R'2C-, -R'2C-CR'2-, -R'2Si-, -R'2Si-SiR'2-, -R'2Ge-,
Process for olefin polymerisation using group 4 metallocene as catalysts
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Page/Page column 22, (2012/02/04)
A process for the preparation of a random propylene copolymer comprising polymerising propylene and at least one C2-10 alpha olefin (especially ethylene) in the presence of a catalyst; wherein said catalyst comprises: (i) a complex of formula (I): wherein
PROCESS FOR OLEFIN POLYMERISATION USING GROUP 4 METALLOCENE AS CATALYSTS
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Page/Page column 39, (2012/01/14)
A process for the preparation of a random propylene copolymer comprising polymerising propylene and at least one C2-10 alpha olefin (especially ethylene) in the presence of a catalyst; wherein said catalyst comprises: (i) a complex of formula (I): wherein
Stereocontrolled alkylative construction of quaternary carbon centers
Kummer, David A.,Chain, William J.,Morales, Marvin R.,Quiroga, Olga,Myers, Andrew G.
supporting information; experimental part, p. 13231 - 13233 (2009/02/06)
Protocols for the stereodefined formation of α,α-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of α,α-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine α-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the α-C-H bond with α-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common π-face of the E- and Z-enolates, proposed to be opposite the pseudoephedrine alkoxide side chain. Pseudoephedrine α-phenylbutyramides are found to undergo highly stereoselective but not stereospecific α-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that α,α-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an α-alkyl-α,β-unsaturated pseudoephedrine amide, providing α,α-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the α-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes. Copyright
