2304-96-3Relevant articles and documents
PYRROLOBENZODIAZEPINE DIMER PRECURSOR AND LIGAND-LINKER CONJUGATE COMPOUND THEREOF
-
Paragraph 0251; 0252, (2020/02/18)
The present invention relates to a pyrrolobenzodiazepine dimer prodrug and a ligand-linker conjugate compound thereof, a composition containing these, and therapeutic use thereof particularly as an anticancer drug. The stability of the compounds themselves and the stability thereof in plasma are excellent and the compounds are advantageous in terms of manifestation of toxicity, and thus the compounds are industrially useful in that it is possible to target proliferative diseases such as cancer, to perform a specific treatment, to maximize the drug efficacy, and to minimize the occurrence of side effects.
Method for synthesizing chiral 4-(N-carbobenzoxy) pyrrolidone
-
Paragraph 0021-0024, (2019/10/01)
The invention provides a method for synthesizing chiral 4-(N-carbobenzoxy) pyrrolidone. L-asparaginate is adopted as an initial raw material, through four steps of reactions of amino protection, diazo-reactions, carbonyl reduction and cyclization, chiral 4-(N-carbobenzoxy) pyrrolidone is prepared, raw materials are low in price and easy to obtain, chiral resolution is not needed in the reaction process, the yield is high, the reaction speed is rapid, a small amount of byproducts are generated, and the method is very applicable to industrial application.
Phosphate bioisostere containing amphiphiles: A novel class of squaramide-based lipids
Saha, Abhishek,Panda, Subhankar,Paul, Saurav,Manna, Debasis
supporting information, p. 9438 - 9441 (2016/07/29)
We describe a novel class of amphiphiles with squaramide moiety as a phosphate bioisostere. Most synthesized squaramide-based amphiphiles have the favorable physicochemical properties of lipids, such as: formation of stable liposomes or giant unilamellar vesicles in aqueous solution, high phase-transition temperature, low vesicle leakage and phospholipase resistance properties.
Synthesis of a series of ω-dimethylaminoalkyl substituted ethylenediamine ligands for use in enantioselective catalysis
Ghosh, Subrata K.,Ganzmann, Carola,Gladysz, John A.
, p. 1273 - 1280 (2015/11/09)
The title compounds H2NCH((CH2)nNMe2)CH2NH2 L1-L4 (n = 1-4) are efficiently synthesized in enantiopure form. The commercial starting materials, l-asparagine, (S)-5-hydroxymethyl-2-pyrrolidinone, and (S)-6-(((benzyloxy)carbonyl)-amino)-2-((tert-butoxycarbonyl)amino)hexanoic acid, are elaborated in 6-9 standard steps to give L1 (18% overall), L2 (13%), L3 (36%) and L4 (38%) or the corresponding tris(hydrochloric acid) salts [H3NCH((CH2)nNHMe2)CH2NH3]3+ 3Cl-, which are preferable for long term storage. The sequences make use of isobutyl carbamate, Cbz, and Boc protecting groups and Hofmann type rearrangements; the dimethylamino groups are introduced at late stages, either via reductive dimethylations or nucleophilic displacements involving mesylates and HNMe2. L1-L4 chelate to [Co(en)2]3+ fragments to give octahedral complexes that catalyze numerous enantioselective reactions.
Solution phase synthetic approach to fellutamide B
Yadav, Jhillu Singh,Dachavaram, Soma Shekar,Grée, René,Das, Saibal
supporting information, p. 3999 - 4001 (2015/06/08)
Abstract A convenient solution phase approach for the synthesis of fellutamide B with efficient purification techniques has been demonstrated on the molecule for the first time. The strategy involves the use of natural amino acids as starting materials and classical peptide coupling reactions. The synthesis has been achieved in 10 steps with overall yield of 26.7% making the synthesis facile.
Total Synthesis of cis-Clavicipitic Acid from Asparagine via Ir-Catalyzed C-H bond Activation as a Key Step
Tahara, Yu-Ki,Ito, Mamoru,Kanyiva, Kyalo Stephen,Shibata, Takanori
, p. 11340 - 11343 (2015/08/03)
4-Substituted tryptophan derivatives and the total synthesis of cis-clavicipitic acid were achieved in reactions in which Ir-catalyzed C-H bond activation was a key step. The starting material for these reactions is asparagine, which is a cheap natural amino acid. The reductive amination step from the 4-substituted tryptophan derivative gave cis-clavicipitic acid with perfect diastereoselectivity.
Sulfate Encapsulation in Supramolecular Structures from L -Asparagine-Derived 2,5-Diketopiperazine Scaffolds: Anion Binding
Naini, Santhosh Reddy,Lalancette, Roger A.,Gorlova, Olga,Ramakrishna, Kallaganti V. S.,Yadav, Jhillu Singh,Ranganathan, Subramania
, p. 7015 - 7022 (2016/02/19)
We report a new sulfate receptor, anchored onto 2,5-diketopiperazine units, which results in the formation of two types of supramolecules; one in which the sulfate ion guest fits snugly into extended cavities and the other in which the guest is sandwiched between layers. In each case, the anion is held by six hydrogen bonds from the host. 1H NMR spectroscopic solution studies enabled the construction of Job plots, and calculation of stoichiometry and association constants. These findings are of possible significance in drug design and for construction of combinatorial libraries.
Papain-catalyzed peptide bond formation: Enzyme-specific activation with guanidinophenyl esters
de Beer, Roseri J.A.C.,Zarzycka, Barbara,Amatdjais-Groenen, Helene I.V.,Jans, Sander C.B.,Nuijens, Timo,Quaedflieg, Peter J.L.M.,van Delft, Floris L.,Nabuurs, Sander B.,Rutjes, Floris P.J.T.
experimental part, p. 2201 - 2207 (2012/05/05)
The substrate mimetics approach is a versatile method for small-scale enzymatic peptide-bond synthesis in aqueous systems. The protease-recognized amino acid side chain is incorporated in an ester leaving group, the substrate mimetic. This shift of the specific moiety enables the acceptance of amino acids and peptide sequences that are normally not recognized by the enzyme. The guanidinophenyl group (OGp), a known substrate mimetic for the serine proteases trypsin and chymotrypsin, has now been applied for the first time in combination with papain, a cheap and commercially available cysteine protease. To provide insight in the binding mode of various Z-XAA-OGp esters, computational docking studies were performed. The results strongly point at enzyme-specific activation of the OGp esters in papain through a novel mode of action, rather than their functioning as mimetics. Furthermore, the scope of a model dipeptide synthesis was investigated with respect to both the amino acid donor and the nucleophile. Molecular dynamics simulations were carried out to prioritize 22 natural and unnatural amino acid donors for synthesis. Experimental results correlate well with the predicted ranking and show that nearly all amino acids are accepted by papain.
An improved large scale procedure for the preparation of N-Cbz amino acids
Pehere, Ashok D.,Abell, Andrew D.
experimental part, p. 1493 - 1494 (2011/05/16)
A simple and scalable method for the preparation of N-Cbz protected amino acids is presented which uses a mixture of aqueous sodium carbonate and sodium bicarbonate to maintain the appropriate pH during the addition of benzyl chloroformate. The method has been extended to other N-protections and is amenable to large scale preparation of an intermediate toward Zofenopril, an ACE inhibitor.
Chemo-enzymatic preparation of chiral 3-aminopyrrolidine derivatives
Iding, Hans,Wirz, Beat,Rogers-Evans, Mark
, p. 647 - 653 (2007/10/03)
A new simple method for the enantioselective enzymatic hydrolysis of N-protected D-asparagine esters suitable for the use on the preparative scale is presented. Due to major obstacles observed under conventional reaction conditions - racemization of the retained ester and a strong enzyme inactivation - a comparatively low pH together with an organic co-solvent had to be employed. Under these conditions, nearly all tested proteases demonstrated good activity and excellent enantioselectivity giving access to the corresponding D-esters and L-asparagines in high optical purities (>95% ee) and good chemical yields (>40%). From the unnatural D-asparagine derivative, sequential cyclization, selective deprotection and reduction yielded efficiently benzyl protected (R)-3-aminopyrrolidine, a homo-chiral building block utilized in numerous drug candidates.
