14618-77-0Relevant academic research and scientific papers
β2-Homo-amino acid scan of μ-selective opioid tetrapeptide TAPP
Kosson, Piotr,Lipiński, Piotr F. J.,Misicka, Aleksandra,Tymecka, Dagmara
, (2020/08/11)
TAPP (H-Tyr-d-Ala-Phe-Phe-NH2) is a potent, μ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β2-Homo-amino acid (β2hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for μ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β2-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β2hPhe4 turned out to bind μOR with affinities equal to that of the parent. β2hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. β2-Homologation in the second position gave derivatives with very poor μOR binding. According to molecular modelling, the presented α/β-peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high μOR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound.
Palladium-catalyzed synthesis of monofluoroalkenes from 3,3-difluoropropenes using dimethylmalonate and derivatives as nucleophiles
Drouin, Myriam,Tremblay, Sébastien,Paquin, Jean-Fran?ois
supporting information, p. 2376 - 2384 (2017/03/20)
The synthesis of monofluoroalkenes bearing a malonate or its derivatives at the β position is presented. The reaction can be performed with various 3,3-difluoropropenes. A preliminary result for an enantioselective variant is also reported. Further synthetic transformations of a monofluoroalkene were also accomplished.
Palladium-Catalyzed Direct Arylation of C(sp3)-H Bonds of α-Cyano Aliphatic Amides
Reddy, M. Damoder,Watkins, E. Blake
, p. 11447 - 11459 (2015/12/05)
Pd(OAc)2-catalyzed arylation of C(sp3)-H bonds in α-cyano-α-methyl aliphatic amides is achieved in the presence of 8-aminoquinoline, as a removable directing group, using Mn(OAc)2 and Na2CO3. The current strategy enables the placement of an aryl/heteroaryl group at the β-position of α-cyano aliphatic acids for the first time. Wide functional group tolerance and easily accessible starting materials provide an efficient protocol for the synthesis of arylated α-cyano amides. Furthermore, the synthetic utility of the products has been demonstrated by their efficient conversions to medicinally important α,α-dialkylated acid and β-amino acid derivatives.
Asymmetric Michael reaction of α-cyano carboxylates catalyzed by a rhodium complex with trans-chelating chiral diphosphine PhTRAP
Sawamura, Masaya,Hamashima, Hitoshi,Ito, Yoshihiko
, p. 4439 - 4454 (2007/10/02)
Asymmetric Michael reaction of 2-cyanopropionates with vinyl ketones or acrolein in the presence of 0.1-1 mol% of a rhodium catalyst prepared in situ from RhH(CO)(PPh3)3 and a trans-chelating chiral diphosphine ligand (S,S)- (R,R)-PhTRAP in benzene at 3-5 °C gave optically active Michael adducts with high enantiomeric excesses (83-93% ee) in high yields. The reaction of 2- cyanopropionate with methacrolein and crotonaldehyde proceeded somewhat slowly, giving diastereomer mixtures in moderate enantioselectivities but in low diastereoselectivities. The reaction of 2-cyanobutyrate and 2-cyano-3- methylbutyrate with acrolein gave corresponding Michael adducts with much lower enantiomeric excesses than that of 2-cyanopropionates. The Michael addition product from acrolein was converted into an optically active α- methyl-α-amino acid.
Cephalosporin compounds
-
, (2008/06/13)
The present invention relates to new cephalosporin compounds of the formula(I), pharmaceutically acceptable non-toxic salts thereof, and physiologically hydrolyzable esters and solvates thereof, which have potent and broad antibacterial activities STR1 wherein R1 is a C1?4 alkyl, C3?4 alkenyl, C3?4 alkynyl group, or --C(Ra)(Rb)CO2 H1 wherein Ra and Rb are the same or different, and each is a hydrogen atom or a C1?4 alkyl group, or Ra and Rb form a C3?7 cycloalkyl group with the carbon atom to which they are linked; R2 is a C1?4 alkyl, C3?4 alkenyl or C3?4 cycloalkyl group, a substituted or unsubstituted amino group, or a substituted or unsubstituted phenyl group; R3 is hydrogen or a C1?4 alkyl group; and Q is N or CH. The invention further relates to a process for preparing said compounds, and to pharamaceutical compositions containing said compounds.
KETENIMINE-NITRILE REARRANGEMENTS OF N-ALKOXYKETENIMINES UNDER THEIR GENERATION CONDITIONS
Shustov, G. V.,Kachanov, A. V.,Kostyanovskii, R. G.
, p. 2039 - 2045 (2007/10/02)
C,C-Substituted N-ethoxyketenimines are extremely unstable even under their generation conditions (dehydrochlorination of N-ethoxyimidoyl chlorides, dehalogenation of α-bromo-N-ethoxyimidoyl halides, the reaction of methylmethoxycarbonylketene with N-etho
Reaction of lithium trimethylsilyldiazomethanide with ketenimines bearing electron-withdrawing groups
Aoyama,Nakano,Marumo,Uno,Shioiri
, p. 1163 - 1167 (2007/10/02)
Ketenimines bearing electron-withdrawing groups (X in 1) at the C2-position react with lithium trimethylsilyldiazomethanide [diazo(lithio)trimethylsilylmethane] to give 4-amino-3-trimethylsilylpyrazoles 4 or 5 mainly; in some cases 4-trimethylsilyl-1,2,3-triazole derivatives 3 were formed as the major products.
C-H Bond Activation by Ruthenium(0) Complexes. Isolation of an Active Intermediate in the Ruthenium Catalyzed Aldol and Michael Reactions
Mizuho, Yuji,Kasuga, Noriko,Komiya, Sanshiro
, p. 2127 - 2130 (2007/10/02)
Carbon-hydrogen bond oxidative addition of alkyl cyanoacetate to Ru(C2H4)(PPh3)3 in benzene at room temperature gives mer-RuH(NCCHCOOR)(NCCH2COOR)(PPh3)3 (R=Me, Et) accompanied by the liberation of ethylene.X-Ray structure analysis of the THF adduct (R=Me) reveals that NCCHCOOMe group bonds to ruthenium not through the methine carbon but the cyano group.These complexes react with benzaldehyde and methyl iodide to give alkyl (E)-1-cyanocinnamate and alkyl-2-cyanopropionate, respectively.
Resonanzstabilisierung von Alkylradikalen durch zwei geminale Cyangruppen
Pakusch, Joachim,Beckhaus, Hans-Dieter,Ruechardt, Christoph
, p. 1191 - 1198 (2007/10/02)
Effects of Substituents on the Strength of C-C bonds, 10. - Resonance Stabilization of Alkyl Radicals by Two Geminal Cyano groups The activation parameters of the homolytic cleavage of the Cq-Cq bonds of several dialkylated malonodinitriles (2-5) and of 1,1,2,2-tetracyanoethane (7) and the heat of dissociation of 6 in solution have been determined.Together with the ground state strain of the radical precursor (obtained from the heats of combustion or EFF calculations) the steric influence on the dissociation process has been determined.The resonancestabilization energy of α,α'-dicyanoalkyl radicals then calculated was (12.4 +/- 0.9) kcal/mol.This result is discussed within the concept of capto-dative stabilization.The destabilizing interaction of two geminal cyano groups is apparently the same in the ground state of 2-7 and the radicals generated from them.
Ruthenium-catalyzed Reductive Alkylation of Active Methylene Compounds with Aldehydes under Synthesis Gas
Abe, Fujio,Hayashi, Teruyuki,Tanaka, Masato
, p. 765 - 768 (2007/10/02)
Active methylene compounds undergo reductive alkylation with aldehydes when heated at 135-230 deg C under synthesis gas of 100 atm in the presence of ruthenium carbonyl.
