Month: October 2022

《Continuous process improvement in the manufacture of carfilzomib, part 2: An improved process for synthesis of the epoxyketone warhead》 was written by Beaver, Matthew G.; Shi, Xianqing; Riedel, Jan; Patel, Parth; Zeng, Alicia; Corbett, Michael T.; Robinson, Jo Anna; Parsons, Andrew T.; Cui, Sheng; Baucom, Kyle; Lovette, Mike; Icten, Elcin; Brown, Derek B.; Allian, Ayman; Flick, Tawnya G.; Chen, Wendy; Yang, Ning; Walker, Shawn D.. Application of 87694-50-6 And the article was included in Organic Process Research & Development on April 17 ,2020. The article conveys some information:

The development and kilogram-scale demonstration of an improved process for the synthesis of the epoxyketone warhead of carfilzomib is described. Critical to the success of this process was: (1) development of a scalable asym. epoxidation protocol; (2) identification of a crystalline intermediate with improved phys. properties for isolation; (3) discovery and optimization of epimerization conditions to set the target stereochem.; and (4) introduction of a seeded-bed coaddn. crystallization to facilitate isolation of the final low-melting target. The results of kilogram-scale demonstration runs are shared, including details of a continuous process for the safe execution of an exothermic Barbier-type Grignard process. The results came from multiple reactions, including the reaction of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Application of 87694-50-6)

(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) belongs to amides. Amides include many other important biological compounds, as well as many drugs like paracetamol, penicillin and LSD. Low-molecular-weight amides, such as dimethylformamide, are common solvents.Application of 87694-50-6

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

《Initiation of protein synthesis with non-canonical amino acids in vivo》 was published in Angewandte Chemie, International Edition in 2020. These research results belong to Tharp, Jeffery M.; Ad, Omer; Amikura, Kazuaki; Ward, Fred R.; Garcia, Emma M.; Cate, Jamie H. D.; Schepartz, Alanna; Soell, Dieter. Quality Control of H-Lys(Boc)-OH The article mentions the following:

By transplanting identity elements into E. coli tRNAfMet, we have engineered an orthogonal initiator tRNA (itRNATy2) that is a substrate for Methanocaldococcus jannaschii TyrRS. We demonstrate that itRNATy2 can initiate translation in vivo with aromatic non-canonical amino acids (ncAAs) bearing diverse sidechains. Although the initial system suffered from low yields, deleting redundant copies of tRNAfMet from the genome afforded an E. coli strain in which the efficiency of non-canonical initiation equals elongation. With this improved system we produced a protein containing two distinct ncAAs at the first and second positions, an initial step towards producing completely unnatural polypeptides in vivo. This work provides a valuable tool to synthetic biol. and demonstrates remarkable versatility of the E. coli translational machinery for initiation with ncAAs in vivo. The experimental process involved the reaction of H-Lys(Boc)-OH(cas: 2418-95-3Quality Control of H-Lys(Boc)-OH)

H-Lys(Boc)-OH(cas: 2418-95-3) belongs to amino acids. Amino acids are not generally considered to be electrochemically active because products of the oxidation accumulate on the electrode surface and prevent it from participating in any further electrochemical processes.Quality Control of H-Lys(Boc)-OH

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

《Pyrrolamide DNA gyrase inhibitors: Optimization of antibacterial activity and efficacy》 was published in Bioorganic & Medicinal Chemistry Letters in 2011. These research results belong to Sherer, Brian A.; Hull, Kenneth; Green, Oluyinka; Basarab, Gregory; Hauck, Sheila; Hill, Pamela; Loch, James T. III; Mullen, George; Bist, Shanta; Bryant, Joanna; Boriack-Sjodin, Ann; Read, Jon; DeGrace, Nancy; Uria-Nickelsen, Maria; Illingworth, Ruth N.; Eakin, Ann E.. Synthetic Route of C6H4Cl2N2O The article mentions the following:

The pyrrolamides are a new class of antibacterial agents targeting DNA gyrase, an essential enzyme across bacterial species and inhibition results in the disruption of DNA synthesis and subsequently, cell death. The optimization of biochem. activity and other drug-like properties through substitutions to the pyrrole, piperidine, and heterocycle portions of the mol. resulted in pyrrolamides with improved cellular activity and in vivo efficacy.2,6-Dichloroisonicotinamide(cas: 89281-13-0Synthetic Route of C6H4Cl2N2O) was used in this study.

2,6-Dichloroisonicotinamide(cas: 89281-13-0) belongs to anime. The methylamines occur in small amounts in some plants. Many polyfunctional amines (i.e., those having other functional groups in the molecule) occur as alkaloids in plants—for example, mescaline, 2-(3,4,5-trimethoxyphenyl)ethylamine; the cyclic amines nicotine, atropine, morphine, and cocaine; and the quaternary salt choline, N-(2-hydroxyethyl)trimethylammonium chloride, which is present in nerve synapses and in plant and animal cells.Synthetic Route of C6H4Cl2N2O

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Category: amides-buliding-blocksOn March 5, 2021, Aizpurua, Jesus M.; Miranda, Jose I.; Irastorza, Aitziber; Torres, Endika; Eceiza, Maite; Sagartzazu-Aizpurua, Maialen; Ferron, Pablo; Aldanondo, Garazi; Lasa-Fernandez, Haizpea; Marco-Moreno, Pablo; Dadie, Naroa; Lopez de Munain, Adolfo; Vallejo-Illarramendi, Ainara published an article in European Journal of Medicinal Chemistry. The article was 《Discovery of a novel family of FKBP12 “”reshapers”” and their use as calcium modulators in skeletal muscle under nitro-oxidative stress》. The article mentions the following:

The hypothesis of rescuing FKBP12/RyR1 interaction and intracellular calcium homeostasis through mol. “”reshaping”” of FKBP12 was investigated. To this end, novel 4-arylthioalkyl-1-carboxyalkyl-1,2,3-triazoles were designed and synthesized, and their efficacy was tested in human myotubes. A library of 17 compounds (10a-n) designed to dock the FKBP12/RyR1 hot-spot interface contact residues, was readily prepared from free α-amino acids and arylthioalkynes using CuAAC “”click”” protocols amenable to one-pot transformations in high overall yields and total configurational integrity. To model nitro-oxidative stress, human myotubes were treated with the peroxynitrite donor SIN1, and evidence was found that some triazoles 10 were able to normalize calcium levels, as well as FKBP12/RyR1 interaction. For example, compound 10 b at 150 nM rescued 46% of FKBP12/RyR1 interaction and up to 70% of resting cytosolic calcium levels in human myotubes under nitro-oxidative stress. All compounds 10 analyzed showed target engagement to FKBP12 and low levels of cytotoxicity in vitro. Compounds 10b, 10c, 10h, and 10iR were identified as potential therapeutic candidates to protect myotubes in muscle disorders with underlying nitro-oxidative stress, FKBP12/RyR1 dysfunction and calcium dysregulation. After reading the article, we found that the author used H-Lys(Boc)-OH(cas: 2418-95-3Category: amides-buliding-blocks)

H-Lys(Boc)-OH(cas: 2418-95-3) belongs to amino acids. These amino acids may be present in low concentrations and play a vital part as an intermediate in a biosynthetic pathway, e.g., ornithine, homoserine, or cystathionine. In contrast they may act as a major storage form of nitrogen, e.g., canavanine in the seed of Canavalia ensiformis, or may be formed in high amounts in response to an external stress, e.g., γ-aminobutyrate.Category: amides-buliding-blocks It is possible that some of these nonprotein amino acids may serve as insecticidal or fungicidal agents.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application In Synthesis of H-Lys(Boc)-OHOn May 12, 2021 ,《Peptide bond formation of amino acids by transient masking with silylating reagents》 appeared in Journal of the American Chemical Society. The author of the article were Muramatsu, Wataru; Yamamoto, Hisashi. The article conveys some information:

A one-pot peptide bond-forming reaction has been developed using unprotected amino acids and peptides. Two different silylating reagents, HSi[OCH(CF3)2]3 and MTBSTFA, are instrumental for the successful implementation of this approach, being used for the activation and transient masking of unprotected amino acids and peptides at C-termini and N-termini, resp. Furthermore, CsF and imidazole are used as catalysts, activating HSi[OCH(CF3)2]3 and also accelerating chemoselective silylation. This method is versatile as it tolerates side chains that bear a range of functional groups, while providing up to >99% yields of corresponding peptides without any racemization or polymerizationH-Lys(Boc)-OH(cas: 2418-95-3Application In Synthesis of H-Lys(Boc)-OH) was used in this study.

H-Lys(Boc)-OH(cas: 2418-95-3) belongs to amino acids. These amino acids may be present in low concentrations and play a vital part as an intermediate in a biosynthetic pathway, e.g., ornithine, homoserine, or cystathionine. In contrast they may act as a major storage form of nitrogen, e.g., canavanine in the seed of Canavalia ensiformis, or may be formed in high amounts in response to an external stress, e.g., γ-aminobutyrate.Application In Synthesis of H-Lys(Boc)-OH It is possible that some of these nonprotein amino acids may serve as insecticidal or fungicidal agents.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Hattori, Tomohiro; Yamamoto, Hisashi published an article on February 2 ,2022. The article was titled 《Synthesis of silacyclic dipeptides: Peptide elongation at both N- and C-termini of dipeptide》, and you may find the article in Journal of the American Chemical Society.Synthetic Route of C11H22N2O4 The information in the text is summarized as follows:

A new type of peptide bond formation utilizing silacyclic amino acids or peptides is described. This work has the following advantages: (1) imidazolylsilane is a highly fascinating coupling reagent for dipeptide synthesis from N-,C-terminal unprotected amino acids with amino acid tert-Bu esters; (2) deprotection of the tert-Bu ester at the C-terminus and cyclization sequentially proceed depending on reaction conditions to afford novel silacyclic dipeptides; (3) the cyclized products show a remarkable capacity as substrates of peptide elongation because the silacyclic compounds can act as both nucleophiles and electrophiles, and this capacity lead to one-pot site-selective tetra- and oligopeptide syntheses. These innovative advantages will help to simplify classical peptide synthesis significantly. In the experimental materials used by the author, we found H-Lys(Boc)-OH(cas: 2418-95-3Synthetic Route of C11H22N2O4)

H-Lys(Boc)-OH(cas: 2418-95-3) belongs to amino acids. In addition to subunits of proteins, amino acids have many other functions as well, including osmoregulation (proline), neurotransmitters (gamma-aminobutyric acid), metabolic intermediates (ornithine and citrulline), and inhibitors (dehydroproline).Synthetic Route of C11H22N2O4

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

In 2011,Cambeiro, Xacobe C.; Martin-Rapun, Rafael; Miranda, Pedro O.; Sayalero, Sonia; Alza, Esther; Llanes, Patricia; Pericas, Miquel A. published 《Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline》.Beilstein Journal of Organic Chemistry published the findings.Recommanded Product: 71432-55-8 The information in the text is summarized as follows:

The application of polystyrene-immobilized proline-based catalysts in packed-bed reactors for the continuous-flow, direct, enantio-selective α-aminoxylation of aldehydes is described. The system allows the easy preparation of a series of β-aminoxy alcs. (after a reductive workup) with excellent optical purity and with an effective catalyst loading of ca. 2.5% (four-fold reduction compared to the batch process) working at residence times of ca. 5 min.tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8Recommanded Product: 71432-55-8) was used in this study.

tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8) belongs to anime. Nitrous acid converts secondary amines (aliphatic or aromatic) to N-nitroso compounds (nitrosamines): R2NH + HNO2 → R2N―NO. Some nitrosamines are potent cancer-inducing substances, and their possible formation is a serious consideration when nitrites, which are salts of nitrous acid, are present in foods or pharmaceutical preparations. Tertiary amines give rise to nitrosamines more slowly; an alkyl group is eliminated as an aldehyde or ketone, along with nitrous oxide, N2O.Recommanded Product: 71432-55-8

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

In 2013,Legros, Caline; Matthey, Ulrich; Grelak, Teresa; Pedragona-Moreau, Sandrine; Hassler, Werner; Yous, Said; Thomas, Emmanuel; Suzenet, Franck; Folleas, Benoit; Lefoulon, Francois; Berthelot, Pascal; Caignard, Daniel-Henri; Guillaumet, Gerald; Delagrange, Philippe; Brayer, Jean-Louis; Nosjean, Olivier; Boutin, Jean A. published 《New radioligands for describing the molecular pharmacology of MT1 and MT2 melatonin receptors》.International Journal of Molecular Sciences published the findings.Quality Control of tert-Butyl N,N’-diisopropylcarbamimidate The information in the text is summarized as follows:

Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[125I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted, including the discovery of agonists and antagonists for the receptors and minute details about their mol. behavior. Recently, we attempted to expand the panel of radioligands available for studying the melatonin receptors by using the newly discovered compounds SD6, DIV880, and S70254. These compounds were characterized for their affinities to the hMT1 and hMT2 recombinant receptors and their functionality in the classical GTP S system. SD6 is a full agonist, equilibrated between the receptor isoforms, whereas S70254 and DIV880 are only partial MT2 agonists, with Ki in the low nanomolar range while they have no affinity to MT1 receptors. These new tools will hopefully allow for additions to the current body of information on the native localization of the receptor isoforms in tissues. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8Quality Control of tert-Butyl N,N’-diisopropylcarbamimidate)

tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8) belongs to anime. The reaction of alkyl halides, R―X, where X is a halogen, or analogous reagents with ammonia (or amines) is useful with certain compounds. Not all alkyl halides are effective reagents; the reaction is sluggish with secondary alkyl groups and fails with tertiary ones. Its usefulness is largely confined to primary alkyl halides (those having two hydrogen atoms on the reacting site).Quality Control of tert-Butyl N,N’-diisopropylcarbamimidate

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

《Catalytic, Directed C-C Bond Functionalization of Styrenes》 was published in Journal of the American Chemical Society in 2020. These research results belong to Onodera, Shunsuke; Togashi, Ryo; Ishikawa, Soya; Kochi, Takuya; Kakiuchi, Fumitoshi. Application In Synthesis of N-Methoxy-N-methylacetamide The article mentions the following:

A method for catalytic conversion of C(aryl)-C(alkenyl) bonds in styrene derivatives R1-2-R2C6H3C(=CHR4)R3 (R1 = H, 4-Me, 3-Cl, 5-Me, etc.; R2 = 1-pyrazolyl, 2-pyridyl; R3 = H, Me, Ph, 4-methoxyphenyl, etc.; R4 = H, Ph, 4-chlorophenyl) to new C-C bonds is developed. In the presence of a rhodium catalyst, the alkenyl groups of styrenes bearing a pyrazolyl directing group were efficiently converted to other carbon substituents upon reacting with various alkenes RCH=CH2 (R = 4-methylhex-1-en-1-yl, 2-cyclohexylethenyl, 2-phenylethenyl, etc.) and allyl alcs. R5CH(OH)CH=CH2(R5 = cyclohexyl, Me, Et, etc.). It is also indicated that the C-C bond cleavage proceeded via a hydrometalation/β-carbon elimination pathway. The experimental part of the paper was very detailed, including the reaction process of N-Methoxy-N-methylacetamide(cas: 78191-00-1Application In Synthesis of N-Methoxy-N-methylacetamide)

N-Methoxy-N-methylacetamide(cas: 78191-00-1) belongs to anime. Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine (NClH2).Application In Synthesis of N-Methoxy-N-methylacetamide

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

《1,2,3-Triazoles as Amide Bond Mimics: Triazole Scan Yields Protease-Resistant Peptidomimetics for Tumor Targeting》 was published in Angewandte Chemie, International Edition in 2013. These research results belong to Valverde, Ibai E.; Bauman, Andreas; Kluba, Christiane A.; Vomstein, Sandra; Walter, Martin A.; Mindt, Thomas L.. Application In Synthesis of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide The article mentions the following:

The authors report a “”triazole-based scan”” of a bombesin peptide fragment, [Nle14]-BBN(7-14), for identifying novel peptidomimetics with improved properties. Using click chem.-based synthetic strategy, a triazole replacement for the peptide bond was incorporated into the above bombesin peptide fragment, and this led to the synthesis of a series of peptide-based radiotracers with retained nanomolar receptor affinity and an up-to-five fold improved serum stability. In vivo evaluation of a backbone-modified peptide analogs demonstrated the enhanced stability of the vector and its improved tumor-targeting capability. The authors expect that this new methodol. for the stabilization of peptides will find broader application in the field of tumor targeting with small peptides for drug delivery, imaging and peptide receptor radiotherapy. In addition to this study using (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide, there are many other studies that have used (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Application In Synthesis of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide) was used in this study.

(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) belongs to amides. Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors.Application In Synthesis of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide In primary and secondary amides, the presence of N–H dipoles allows amides to function as H-bond donors as well.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics