7633-32-1Relevant articles and documents
COMPOSITIONS AND METHODS RELATED TO MOLECULAR CONJUGATION
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Page/Page column 56-58, (2021/06/11)
The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.
Synthesis and In Vitro Biological Evaluation of Psoralen-Linked Fullerenes
Hashimoto, Akiko,Takamura-Enya, Takeji,Oda, Yoshimitsu
, p. 1403 - 1411 (2019/09/03)
Photodynamic therapy (PDT) is a widely used medicinal treatment for the cancer therapy that utilizes the combination of a photosensitizer (PS) and light irradiation. In this study, we synthesized two novel C60 fullerene derivatives, compounds 1 and 2, with a psoralen moiety that can covalently bind to DNA molecules via cross-linking to pyrimidine under photoirradiation. Along with several fullerene derivatives, the biological properties of several novel compounds have been evaluated. Compounds 1 and 2, which have been shown to induce the production of hydroxyl radicals using several ROS detecting reagents, induced DNA strand breaks with relatively weak activities in the in vitro detection system using a supercoiled plasmid. However, the psoralen-bound fullerene with carboxyl groups (2) only showed genotoxicity in the genotoxicity assay system of the umu test. Compound 2 was also seen to have cytotoxic activities in several cancer cell lines at higher doses compared to water-soluble fullerenes.
A General Amino Acid Synthesis Enabled by Innate Radical Cross-Coupling
Ni, Shengyang,Garrido-Castro, Alberto F.,Merchant, Rohan R.,de Gruyter, Justine N.,Schmitt, Daniel C.,Mousseau, James J.,Gallego, Gary M.,Yang, Shouliang,Collins, Michael R.,Qiao, Jennifer X.,Yeung, Kap-Sun,Langley, David R.,Poss, Michael A.,Scola, Paul M.,Qin, Tian,Baran, Phil S.
supporting information, p. 14560 - 14565 (2018/10/24)
The direct union of primary, secondary, and tertiary carboxylic acids with a chiral glyoxylate-derived sulfinimine provides rapid access into a variety of enantiomerically pure α-amino acids (>85 examples). Characterized by operational simplicity, this radical-based reaction enables the modular assembly of exotic α-amino acids, including both unprecedented structures and those of established industrial value. The described method performs well in high-throughput library synthesis, and has already been implemented in three distinct medicinal chemistry campaigns.
Facile access to modified and functionalized PNAs through Ugi-based solid phase oligomerization
Saarbach, Jacques,Masi, Daniela,Zambaldo, Claudio,Winssinger, Nicolas
supporting information, p. 5171 - 5177 (2017/09/26)
Peptide nucleic acids (PNAs) derivatized with functional molecules are increasingly used in diverse biosupramolecular applications. PNAs have proven to be highly tolerant to modifications and different applications benefit from the use of modified PNAs, in particular modifications at the γ position. Herein we report simple protocols to access modified PNAs from iterative Ugi couplings which allow modular modifications at the α, β or γ position of the PNA backbone from simple starting materials. We demonstrate the utility of the method with the synthesis of several bioactive small molecules (a peptide ligand, a kinase inhibitor and a glycan)-PNA conjugates.
Novel fullerene derivatives as dual inhibitors of Hepatitis C virus NS5B polymerase and NS3/4A protease
Kataoka, Hiroki,Ohe, Tomoyuki,Takahashi, Kyoko,Nakamura, Shigeo,Mashino, Tadahiko
supporting information, p. 4565 - 4567 (2016/09/13)
We evaluated the Hepatitis C virus (HCV) NS5B polymerase and HCV NS3/4A protease inhibition activities of a new set of proline-type fullerene derivatives. All of the compounds had the potential to inhibit both the enzymes, indicating that the fullerene derivatives may be dual inhibitors against NS5B and NS3/4A and could be novel lead compounds for the treatment of HCV infections.
A Short Synthesis of the Mould Metabolite (R)-(+)-Carolinic Acid from (S)-Lactic Acid
Linder, David,Schobert, Rainer
, p. 4564 - 4568 (2016/12/14)
(R)-(+)-Carolinic acid was prepared in seven steps and 59% yield from inexpensive benzyl l-lactate, the configuration of which was inverted by a Mitsunobu reaction with trifluoroacetate. The resulting benzyl d-lactate was cyclised by a domino addition-Wittig alkenation reaction with Ph3PCCO. The product tetronic acid was acylated with a second equivalent of this ylide to give a 3-acylylidenetetronic acid, which was olefinated directly with tert-butyl glyoxylate. The product alkene was hydrogenated and deprotected to afford pure crystalline (R)-(+)-carolinic acid, which proved inactive against Staphylococcus aureus and Escherichia coli mutant D21f2.
Microwave assisted solid phase synthesis of highly functionalized N-alkylated oligobenzamide α-helix mimetics
Long, Kérya,Edwards, Thomas A.,Wilson, Andrew J.
, p. 4034 - 4040 (2013/07/27)
Protein-protein interactions (PPIs) mediate cellular pathways and are implicated in numerous aberrant conditions. α-Helix mimetics - small molecules that reproduce the spatial projection of key residues from an α-helix involved in a PPI - are attractive generic templates for development of screening libraries, however library syntheses of α-helix mimetics with diverse functionality are less established. This manuscript describes the automated, microwave assisted solid phase synthesis based on one such scaffold; an N-alkylated oligobenzamide.
Asymmetric addition of arylboronic acids to glyoxylate catalyzed by a ruthenium/Me-BIPAM complex
Yamamoto, Yasunori,Shirai, Tomohiko,Miyaura, Norio
, p. 2803 - 2805 (2012/04/23)
The enantioselective synthesis of α-hydroxy esters by ruthenium-catalyzed 1,2-addition of arylboronic acids to tert-butyl glyoxylate is described. The use of RuCl2(PPh3)3 with (R,R)-Me-BIPAM gave optically active mandelic acids of up to 99% ee. Addition of a fluoride salt such as potassium fluoride (KF) or caesium fluoride (CsF) was effective for achieving high enantioselectivities. The Royal Society of Chemistry 2012.
PROCESS FOR PRODUCING OSELTAMIVIR PHOSPHATE AND INTERMEDIATE COMPOUND
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Page/Page column 26, (2011/04/24)
Disclosed are a process suited to large scale synthesis with high yield for producing oseltamivir phosphate, in which a preparation of oseltamivir phosphate which is highly safe as a pharmaceutical product can be produced, and an intermediate compound for producing oseltamivir phosphate. In this production process, an intermediate compound represented by general formula (V) is synthesized by employing Michael reaction/Michael reaction/Horner-Wadsworth-Emmons reaction, and oseltamivir phosphate is produced by converting the substituent groups in this intermediate compound.
High-yielding synthesis of the anti-influenza neuraminidase inhibitor (-)-oseltamivir by two one-pot sequences
Ishikawa, Hayato,Suzuki, Takaki,Orita, Hideo,Uchimaru, Tadafumi,Hayashi, Yujiro
supporting information; experimental part, p. 12616 - 12626 (2011/01/12)
The efficient asymmetric total synthesis of (-)-oseltamivir, an antiviral reagent, has been accomplished by using two one-pot reaction sequences, with excellent overall yield (60%) and only one required purification by column chromatography. The first one-pot reaction sequence consists of a diphenylprolinol silyl ether mediated asymmetric Michael reaction, a domino Michael reaction/Horner-Wadsworth-Emmons reaction combined with retro-aldol/Horner-Wadsworth-Emmons reaction and retro Michael reactions, a thiol Michael reaction, and a base-catalyzed isomerization. Six reactions can be successfully conducted in the second one-pot reaction sequence; these are deprotection of a tert-butyl ester and its conversion into an acyl chloride then an acyl azide, Curtius rearrangement, amide formation, reduction of a nitro group into an amine, and a retro Michael reaction of a thiol moiety. A column-free synthesis of (-)-oseltamivir has also been established. Fighting the flu: Two one-pot and column-free asymmetric sequences are used to accomplish the synthesis of (-)-oseltamivir, known as the anti-influenza drug Tamiflu (see scheme; TMS: trimethylsilyl). This high-yielding synthesis takes advantage of a diphenylprolinol silyl ether as an organocatalyst and single-pot domino operations.
