176896-73-4Relevant academic research and scientific papers
Synthesis of Enantiopure Unnatural Amino Acids by Metallaphotoredox Catalysis
Faraggi, Tomer M.,Rouget-Virbel, Caroline,Rincón, Juan A.,Barberis, Mario,Mateos, Carlos,García-Cerrada, Susana,Agejas, Javier,De Frutos, Oscar,Macmillan, David W. C.
, p. 1966 - 1973 (2021/08/18)
We describe herein a two-step process for the conversion of serine to a wide array of optically pure unnatural amino acids. This method utilizes a photocatalytic cross-electrophile coupling between a bromoalkyl intermediate and a diverse set of aryl halides to produce artificial analogues of phenylalanine, tryptophan, and histidine. The reaction is tolerant of a broad range of functionalities and can be leveraged toward the scalable synthesis of valuable pharmaceutical scaffolds via flow technology.
Nickel-Catalyzed Reductive Cross-Coupling of Aryl Triflates and Nonaflates with Alkyl Iodides
Sumida, Yuto,Sumida, Tomoe,Hosoya, Takamitsu
, p. 3590 - 3601 (2017/08/16)
A nickel-catalyzed cross-electrophile coupling of aryl triflates and nonaflates with alkyl iodides using manganese(0) as a reductant is described. The method is applicable to the reductive alkylation of various aryl sulfonates, including o -borylaryl triflate, which enabled efficient construction of diverse alkylated arenes under mild conditions.
Much improved conditions for the Negishi cross-coupling of iodoalanine derived zinc reagents with aryl halides
Ross, Andrew J.,Lang, Hannah L.,Jackson, Richard F. W.
supporting information; experimental part, p. 245 - 248 (2010/04/06)
(Chemical Equation Presented) A combination of Pd2(dba) 3 and SPhos (1:2 molar ratio) is an excellent precatalyst for the Negishi cross-coupling of the serine-derived organozinc reagent 2 with aryl halides, including previously difficult ortho-substituted examples. In the case of meta- and para-substituted aryl halides, Pd-loadings of 0.5 mol % give satisfactory results. Use of 2-iodoaniline as substrate gives the lactam 12 in good yield. 2009 American Chemical Society.
Access to enantioenriched α-amino esters via rhodium-catalyzed 1,4-addition/enantioselective protonation
Navarre, Laure,Martinez, Remi,Genet, Jean-Pierre,Darses, Sylvain
, p. 6159 - 6169 (2008/12/20)
Conjugate addition of potassium trifluoro(organo)borates 2 to dehydroalanine derivatives 1, mediated by a chiral rhodium catalyst and in situ enantioselective protonation, afforded straightforward access to a variety of protected α-amino esters 3 with high yields and enantiomeric excesses up to 95%. Among the tested chiral ligands and proton sources, Binap, in combination with guaiacol (2-methoxyphenol), an inexpensive and nontoxic phenol, afforded the highest asymmetric inductions. Organostannanes have also shown to participate in this reaction. By a fine-tuning of the ester moiety, and using Difluorophos as chiral ligand, increased levels of enantioselectivity, generally close to 95%, were achieved. Deuterium labeling experiments revealed, and DFT calculation supported, an unusual mechanism involving a hydride transfer from the amido substituent to the α carbon explaining the high levels of enantioselectivity attained in controlling this α chiral center.
Negishi cross-coupling reactions of α-amino acid-derived organozinc reagents and aromatic bromides
Oswald, Claire L.,Carrillo-Márquez, Tomás,Caggiano, Lorenzo,Jackson, Richard F.W.
, p. 681 - 687 (2008/09/16)
The Negishi cross-coupling reaction of organozinc iodides derived from α-amino acids with aromatic bromides to give substituted phenylalanine derivatives is described, using either Pd(OAc)2 or Pd2(dba)3 in combination with P(o-Tol)3 as catalyst in DMF at 50 °C. Similar results are obtained using Pd[PtBu3]2 as catalyst. The difference in reactivity displayed between aryl iodides and bromides (ArI>ArBr) has been utilised in a short synthesis of an unsymmetrical, orthogonally protected para-phenylene bis-alanine derivative.
Compounds and compositions for treating obesity
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Page/Page column 27, (2010/11/28)
Described herein are novel and useful compounds of the general formula Compounds of this invention can advantageously exhibit melanocortin receptor agonist activity. New and useful compounds comprising such a chemical structure and methods of modulating melanocortin receptor activity in a subject (and promoting, inducing, and/or enhancing the treatment or prevention of related diseases) by administering such a compound or composition also are described.
Identification of arginine analogues as antagonists and agonists for the melanocortin-4 receptor
Nozawa, Dai,Okubo, Taketoshi,Chaki, Shigeyuki,Okuyama, Shigeru,Nakazato, Atsuro
, p. 1232 - 1239 (2008/03/11)
In the present study, conducted to explore potent and small molecular melanocortin-4 (MC4) receptor ligands, we found that tripeptide 3a, containing a D-Phe-Arg-2-Nal (Nal; naphthylalanine) sequence, exhibited a moderate affinity for the MC4 receptor. Structural optimization led to the identification of a compound with a high affinity for the MC4 receptor, namely, tripeptide 3e, which showed a 70-fold higher affinity for the MC4 receptor than the lead compound 3a. Moreover, in an effort to further reduce the peptidic characters of tripeptide 3e, we found that dipeptide 3g exhibited a relatively high affinity for the MC4 receptor. Furthermore, in these analogues, the substituted position (1′ vs. 2′) of the naphthyl ring of Nal residue at position 7 was found to be important for the differentiation of agonist and antagonist activity. The synthesis and structure-activity relationships of the arginine analogues as MC4 receptor ligands were described in this paper.
Stereoselective synthesis of 3,6-disubstituted-3,6-dihydropyridin-2-ones as potential diketopiperazine mimetics using organocopper-mediated anti-S N2′ reactions and their use in the preparation of low-molecule CXCR4 antagonists
Niida, Ayumu,Tanigaki, Hiroaki,Inokuchi, Eriko,Sasaki, Yoshikazu,Oishi, Shinya,Ohno, Hiroaki,Tamamura, Hirokazu,Wang, Zixuan,Peiper, Stephen C.,Kitaura, Kazuo,Otaka, Akira,Fujii, Nobutaka
, p. 3942 - 3951 (2007/10/03)
Organocopper-mediated anti-SN2′ reactions of γ-phosphoryloxy-α,β-unsaturated-δ-lactams were used to prepare highly functionalized diketopiperazine mimetics. The substrate phosphates 24, 32, and 47 were prepared from a-amino acid-derived allylic
Synthesis and application of phosphinoferrocenylaminophosphine ligands for asymmetric catalysis
Boaz, Neil W.,Mackenzie, Elaine B.,Debenham, Sheryl D.,Large, Shannon E.,Ponasik Jr., James A.
, p. 1872 - 1880 (2007/10/03)
(Chemical Equation Presented) A new class of bidentate ligands utilizing a phosphine-aminophosphine structure has been prepared on a ferrocenylethyl backbone in a straightforward and scalable fashion from acetylferrocene. The unique property of the α-ferrocenyl carbonium ion that allows the replacement of a variety of "leaving groups" with retention of configuration greatly facilitates the synthesis, and a number of ligands have been prepared by varying the nitrogen and phosphorus substituents on the aminophosphine. These readily prepared phosphinoferrocenylaminophosphines, known as BoPhoz ligands, show surprising hydrolytic and air stability, with no degradation after 3 years open to the air. The rhodium complexes of these ligands show exceedingly high enantioselectivities (generally > 95% ee) and activities often in excess of 50 000 catalyst turnovers per hour for the asymmetric hydrogenation of a wide variety of dehydro-α-amino acid and itaconic acid derivatives. They also show high activity and good to excellent enantioselectivity for the hydrogenation of a number of α-ketoesters.
COMPOUNDS FOR USE IN TREATING OBESITY
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Page 51, (2010/02/07)
The present invention relates to novel compounds of the general formula (I) as well as any optical or geometric isomer or tautomer form thereof, or a pharmaceutically acceptable salt thereof, as agonists of melanocortin receptors, such as agonists of the MC4 receptor. The compounds may for instance be used in the treatment of obesity.
