15028-41-8Relevant articles and documents
Expected and unforeseen reactions of 2,3,3-trimethyl-1λ6-isothiazolidine-1,1,4-trione and their spiro derivative
Popova, Maria V.,Dobrydnev, Alexey V.,Dyakonenko, Viktoriya V.,Konovalova, Irina S.,Shishkina, Svitlana V.,Volovenko, Yulian M.
, p. 1231 - 1245 (2019)
Herein, we present a full account of our studies with respect to the reactivity of insufficiently explored 1λ6-isothiazolidine-1,1,4-triones (so-called β-keto-γ-sultams). This heterocyclic system possesses two reaction centers: the EWG-activate
Preparation and NMR spectra of substituted 2-(4-nitrophenyl)imidazolinones
Sedlak, Milos,Halama, Ales,Kavalek, Jaromir,Machacek, Vladimir,Mitas, Petr,Sterba, Vojeslav
, p. 910 - 920 (1996)
A series of 11 substituted 2-(4-nitrophenyl)imidazolinones have been prepared by base catalyzed cyclizations of substituted 2-(4-nitrobenzoylamino)alkanamides. At higher methoxide concentrations the cyclization can be accompanied by reduction of nitro group to azoxy group. All the substances prepared have been identified by 1H and 13C NMR spectra.
Stapling of a 310-helix with click chemistry
Jacobsen, yvind,Maekawa, Hiroaki,Ge, Nien-Hui,Goerbitz, Carl Henrik,Rongved, Pal,Ottersen, Ole Petter,Amiry-Moghaddam, Mahmood,Klaveness, Jo
, p. 1228 - 1238 (2011)
Short peptides are important as lead compounds and molecular probes in drug discovery and chemical biology, but their well-known drawbacks, such as high conformational flexibility, protease lability, poor bioavailability and short half-lives in vivo, have prevented their potential from being fully realized. Side chain-to-side chain cyclization, e.g., by ring-closing olefin metathesis, known as stapling, is one approach to increase the biological activity of short peptides that has shown promise when applied to 310-and α-helical peptides. However, atomic resolution structural information on the effect of side chain-to-side chain cyclization in 310-helical peptides is scarce, and reported data suggest that there is significant potential for improvement of existing methodologies. Here, we report a novel stapling methodology for 310-helical peptides using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction in a model aminoisobutyric acid (Aib) rich peptide and examine the structural effect of side chain-to-side chain cyclization by NMR, X-ray diffraction, linear IR and femtosecond 2D IR spectroscopy. Our data show that the resulting cyclic peptide represents a more ideal 310-helix than its acyclic precursor and other stapled 310-helical peptides reported to date. Side chain-to-side chain stapling by CuAAC should prove useful when applied to 3 10-helical peptides and protein segments of interest in biomedicine.(Figure Presented)
Influence of the C-terminal substituent on the crystal-state conformation of Adm peptides
Mir, Fatemeh M.,Crisma, Marco,Toniolo, Claudio,Lubell, William D.
, (2020)
The bis-functionalized diamondoid α-amino acid 2-aminoadamantane-2-carboxylic acid (Adm) has been used as the building block of four Nα-formyl homo-dipeptide alkylamide sequences via a solution-phase Ugi multicomponent reaction approach. The conformers of these peptides have been determined in the crystalline state by X-ray diffraction to distinguish the influences of the C-terminal substituent. One of the Adm peptides folds into an open and a hydrogen-bonded γ-turn geometry. Moreover, 3D-structures have been observed featuring two consecutive γ-turns in an incipient γ-helical structure, a significantly distorted nonhelical β-turn, as well as an S-shaped conformation with opposite helical screw senses. A significant topological variety is thus exhibited by the -Adm-Adm- sequences contingent on their C-terminal substituents, illustrating both the broad conformational potential and the need for further characterization of this sterically bulky residue in explorations of its ?, ψ space.
Conformation-specific spectroscopy of capped, gas-phase Aib oligomers: Tests of the Aib residue as a 310-helix former
Gord, Joseph R.,Hewett, Daniel M.,Hernandez-Castillo, Alicia O.,Blodgett, Karl N.,Rotondaro, Matthew C.,Varuolo, Adalgisa,Kubasik, Matthew A.,Zwier, Timothy S.
, p. 25512 - 25527 (2016)
The conformational preferences of a series of capped peptides containing the helicogenic amino acid aminoisobutyric acid (Aib) (Z-Aib-OH, Z-(Aib)2-OMe, and Z-(Aib)4-OMe) are studied in the gas phase under expansion-cooled conditions. Aib oligomers are known to form 310-helical secondary structures in solution and in the solid phase. However, in the gas phase, accumulation of a macrodipole as the helix grows could inhibit helix stabilization. Implementing single-conformation IR spectroscopy in the NH stretch region, Z-Aib-OH and Z-(Aib)2-OMe are both observed to have minor conformations that exhibit dihedral angles consistent with the 310-helical portion of the Ramachandran map (φ, ψ = -57°, -30°), even though they lack sufficient backbone length to form 10-membered rings which are a hallmark of the developed 310-helix. For Z-(Aib)4-OMe three conformers are observed in the gas phase. Single-conformation infrared spectroscopy in both the NH stretch (Amide A) and CO stretch (Amide I) regions identifies the main conformer as an incipient 310-helix, having two free NH groups and two C10 H-bonded NH groups, labeled an F-F-10-10 structure, with a calculated dipole moment of 13.7 D. A second minor conformer has an infrared spectrum characteristic of an F-F-10-7 structure in which the third and fourth Aib residues have φ, ψ = 75°, -74° and -52°, 143°, Ramachandran angles which fall outside of the typical range for 310-helices, and a dipole moment that shrinks to 5.4 D. These results show Aib to be a 310-helix former in the gas phase at the earliest stages of oligomer growth.
[N-methyl-11C]MeAIB, a Tracer for System A Amino Acid Transport: Preparation from [11C]Methyl Triflate and HPLC Metabolite Analysis of Plasma Samples After Intravenous Administration in Man
Nagren, Kjell,Sutinen, Eija,Jyrkkio, Sirkku
, p. 1013 - 1021 (2000)
MeAIB, α-methylamino-isobutyric acid, is an achiral synthetic ammo acid which is a highly selective substrate for the A-type, or alanine-preferring, amino acid transport system. [N-methyl-11C]MeAIB ([11C]MeAIB) was prepared by reaction of [11C]methyl triflate with AIB methyl ester, generated in situ from its corresponding hydrochloride, followed by hydrolysis of the ester function with aqueous NaOH. After HPLC-purification, the product was obtained in a 60-70 percent decay corrected yield counted from [11C]methyl triflate. The total synthesis time was 32-37 min and the radiochemical purity of the product higher than 98 percent. HPLC analysis of plasma samples taken 5-30 min after the administration of [11C]MeAlB to man showed that more than 95 percent of the total radioactivity in the plasma consisted of unchanged [11C]MeAIB. The simple preparation and the high metabolic stability of [11C]MeAlB makes this novel tracer a potential candidate for positron emission tomography investigations for the system A amino acid transport system in vivo.
N-(tert-Butoxycarbonyl)-α-aminoisobutyryl-α-aminoisobutyric acid methyl ester: Two polymorphic forms in the space group P21/n
Gebreslasie, Hadgu Girmay,Jacobsen, yvind,Goerbitz, Carl Henrik
, p. o283-o287 (2011)
The title compound (systematic name: methyl 2-{2-[(tertbutoxycarbonyl) amino]-2-methylpropanamido}-2-methylpropanoate), C14H 26N2O5, (I), crystallizes in the monoclinic space group P21/n in two polymorphic forms, each with one molecule in the asymmetric unit. The mol-ecular conformation is essentially the same in both polymorphs, with the α-amino-isobutyric acid (Aib) residues adopting φ and ψ values characteristic of α-helical and mixed 310- and α-helical conformations. The helical handedness of the C-terminal residue (Aib2) is opposite to that of the N-terminal residue (Aib1). In contrast to (I), the closely related peptide Boc-Aib-Aib-OBn (Boc is tert-butoxycarbonyl and Bn is benzyl) adopts an αL-PII backbone conformation (or the mirror image conformation). Compound (I) forms hydrogen-bonded para-llel β-sheet-like tapes, with the carbonyl groups of Aib1 and Aib2 acting as hydrogen-bond acceptors. This seems to represent an unusual packing for a protected dipeptide containing at least one ,-disubstituted residue.
A Transannular Rearrangement Reaction of a Pyrroloindoline Diketopiperazine
Yan, Qiao,Carroll, Patrick J.,Gau, Michael R.,Winkler, Jeffrey D.,Joullié, Madeleine M.
, p. 6619 - 6623 (2019)
Oxaline, glandicoline, and meleagrin contain a unique triazaspirocyclic structure. Attracted by their biological activities, we attempted a novel strategy, mimicking a proposed biosynthetic pathway for glandicoline B in Penicillium chrysogenum and Penicil
Microwave-Assisted Ruthenium- and Rhodium-Catalyzed Couplings of α-Amino Acid Ester-Derived Phosphinamides with Alkynes
Li, Xue-Hong,Gong, Jun-Fang,Song, Mao-Ping
supporting information, (2021/12/23)
Two different types of new phosphinamide α-amino ester derivatives have been prepared in moderate to high yields via ruthenium(II) and rhodium(III)-catalyzed ortho-C?H functionalization under microwave irradiation. Specifically, the ortho-alkenylated phosphinamides were produced through coupling of phosphinamides containing an α-substituted or α,α-disubstituted α-amino ester with internal alkynes under ruthenium catalysis. In contrast, Ru and the more effective Rh-catalyzed coupling of the α-unsubstituted glycine ester phosphinamide with alkynes resulted in formation of oxidative annulation products, phosphaisoquinolin-1-ones. The developed methods feature the use of easily accessible starting materials, short reaction time, exclusive E-stereoselectivity (for ortho-alkenylation) and good functional group tolerance. The alkenylation reaction was readily scaled up to gram scale. Furthermore, the obtained alkenylated phosphinamide could be transformed into P-containing dipeptides through hydrolysis of the ester group in the catalysis product and subsequent condensation with an α-amino ester.
Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts
Kervefors, Gabriella,Kersting, Leonard,Olofsson, Berit
supporting information, p. 5790 - 5795 (2021/03/08)
A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.
