117625-90-8Relevant articles and documents
Piv-Proψ[CH2-NH-O]Gly-NHiPr
Corbier, Catherine,Didierjean, Claude,Thevenet, Laurent,Vanderesse, Regis,Marraud, Michel
, p. 995 - 996 (2000)
The pseudodipeptide, (S)-N-isopropyl {[N-(pivaloytypyrrolidin-2-yl]methylaminooxy)acetamide, C15F29N3O3, adopts a global extended conformation with the hydroxylamine group in the g+lg- structure. The C-terminal amide NH interacts intramolecularly with the hydroxylamine O atom. Both NH bonds of each molecule are hydrogen bonded to the C-terminal amide carbonyl of a neighbouring molecule.
Total synthesis and isolation of citrinalin and cyclopiamine congeners
Mercado-Marin, Eduardo V.,Garcia-Reynaga, Pablo,Romminger, Stelamar,Pimenta, Eli. F.,Romney, David K.,Lodewyk, Michael W.,Williams, David E.,Andersen, Raymond J.,Miller, Scott J.,Tantillo, Dean J.,Berlinck, Roberto G. S.,Sarpong, Richmond
, p. 318 - 324 (2014)
Many natural products that contain basic nitrogen atoms-for example alkaloids like morphine and quinine-have the potential to treat a broad range of human diseases. However, the presence of a nitrogen atom in a target molecule can complicate its chemical synthesis because of the basicity of nitrogen atoms and their susceptibility to oxidation. Obtaining such compounds by chemical synthesis can be further complicated by the presence of multiple nitrogen atoms, but it can be done by the selective introduction and removal of functional groups that mitigate basicity. Here we use such a strategy to complete the chemical syntheses of citrinalinB and cyclopiamineB. The chemical connections that have been realized as a result of these syntheses, in addition to the isolation of both 17-hydroxycitrinalinB and citrinalinC (which contains a bicyclo[2.2.2]diazaoctane structural unit) through carbon-13 feeding studies, support the existence of a common bicyclo[2.2.2]diazaoctane-containing biogenetic precursor to these compounds, as has been proposed previously.
Synthesis of a tetracyclic substructure of manzamine A via the Diels-Alder reaction of dihydropyridinones
Torisawa, Yasuhiro,Hosaka, Toshihiro,Tanabe, Kiyoshi,Suzuki, Naoko,Motohashi, Yumiko,Hino, Tohru,Nakagawa, Masako
, p. 10597 - 10608 (1996)
Synthesis of the tetracyclic core (19) of manzamine A (1) was achieved via Diels-Alder reaction of the dihydropyridinones (5, 6). Conversion of the two D-A products (7, 8) to the key tricyclic ketone (10) was conducted through a conventional pathway as well as a new pathway developed. For effective construction of the required azocine ring systems, model studies were carried out to find intramolecular amide formation by pentafluorophenyl ester and DPPA methods, which were successfully applied to the real substrate to furnish the titled core structure (19).
Highly selective bisphosphine ligands for asymmetric hydroformylation of heterocyclic olefins
Zheng, Xin,Xu, Kun,Zhang, Xumu
, p. 1149 - 1152 (2015)
The bisphosphine ligand 1c is highly efficient and selective for the asymmetric hydroformylation (AHF) of dihydrofuran and pyrrolines. The AHF of 2,3-dihydrofuran yielded the 2-carbaldehyde in up to 93% ee. The remarkable highest regioselectivity of 2,5-dihydrofuran was obtained to date up to 499 β-isomer/α-isomer with ligand 1c. Furthermore, the highest 96% and 92% ee values were accomplished using the same catalytic system in the AHF of N-Boc pyrroline 11 and 14.
Synthesis, characterisation, cytotoxicity and radioprotective effect of novel chiral nitronyl nitroxyl radicals
Qin, Xiang-Yang,Ding, Gui-Rong,Wang, Xiao-Wu,Tan, Juan,Guo, Guo-Zhen,Sun, Xiao-Li
, p. 511 - 514 (2009)
Nitroxyl compounds have been previously investigated as potential radioprotection drugs. To develop new radioprotectors, two kinds of novel chiral nitronyl nitroxyl radicals: Z-tert-butyl 2-(4, 5-dihydro-4, 4, 5, 5-tetramethyl- 3-oxido-1H-imidazol-3-ium-1
A formal synthesis of (-)-cephalotaxine
Esmieu, William R.,Worden, Stephen M.,Catterick, David,Wilson, Claire,Hayes, Christopher J.
, p. 3045 - 3048 (2008)
(Chemical Equation Presented) An enantioselective formal synthesis of the alkaloid (-)-cephalotaxine has been completed, using an alkylidene carbene 1,5-CH insertion reaction as a key step to construct the spiro[4.4]azanonane core D/E-ring system. A Heck-type cyclization was used to close the tetrahydroazepine C-ring and a selective epoxidation-rearrangement sequence was used to elaborate the E-ring.
Enantiospecific synthesis of functionalised indolizidines. Synthesis of (8S, 8aR)-6,7-dehydro-8-hydroxyindolizidine
Koskinen,Paul
, p. 6853 - 6856 (1992)
A stereocontrolled route for the title compound has been realised using L-proline as starting material. The route is amenable to modifications to provide a variety of stereoisomers of glycosidase inhibitors.
Short asymmetric synthesis of (S,S)-PDP using l-prolinol derivative as economic starting material
Song, Xiao-Nan,Yao, Zhu-Jun
, p. 2589 - 2593 (2010)
(S,S)-PDP (5d) and its backbone (2S,2′S)-bipyrrolidine (1) have been extensively applied as the scaffold of various chiral ligands in catalytic asymmetric syntheses. In this study, new short asymmetric syntheses of these two important C2-symmetrical nitrogen heterocycles have been accomplished employing economically available l-prolinol derivative 10 as the starting material. Excellent diastereoselectivity was achieved of the key Grignard addition to imine intermediate utilizing (S)-N-tert-butanesulfinamide as the chiral auxiliary.
Synthesis and 11C-labelling of two selective high affinity nicotinic cholinergic agonists for evaluation as radioligands for PET studies
Dolle, Frederic,Dolci, Lilian,Valette, Heric,Bottlaender, Michel,Fournier, Denis,Fuseau, Chantai,Vaufrey, Francoise,Crouzel, Christian
, p. 1099 - 1112 (1996)
ABT-418 ((S)-3-methyl-5-[1-methyl-2-pyrrolidinyl]isoxazole) and N-methylcytisine (N-methyl- 1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido-[1,2-a][1,5]diazocin-8-one) are two high affinity nicotinic cholinergic agonists. ABT-418 was synthesized in 7 steps from commercially available (S)-Boc- proline in 35% overall yield. Methylation of commercial cytisine cleanly gave N-methyl-cytisine. ABT-418 and N-methylcytisine were labelled using [11C]methyl iodide by methylation of the corresponding nor-precursors for their in vivo evaluation as positron emission tomography (PET) probes of the nicotinic cholinergic receptors in baboon brain. As for [11C]nicotine, specific binding in vivo could not be demonstrated for ABT-418. Therefore, further experiments are needed to determine the full PET pharmacological profile and the subsequent potential clinical applications of ABT-418 as a tracer for PET experiments. For labelled N-methyl-cytisine, radioactivity in the cerebral cortex and in tile blood were similar. Thus, 11C-labelled N-methylcytisine does not appear to be a suitable ligand for mapping brain nAChR.
Photo-induced Substitutive Introduction of the Aldoxime Functional Group to Carbon Chains: A Formal Formylation of Non-Acidic C(sp3)?H Bonds
Kamijo, Shin,Takao, Go,Kamijo, Kaori,Hirota, Masaki,Tao, Keisuke,Murafuji, Toshihiro
, p. 9695 - 9699 (2016)
A photo-induced substitutive introduction of an aldoxime functional group to carbon chains was achieved using photo-excited 4-benzoylpyridine as a C(sp3)?H bond cleaving agent and arylsulfonyl oxime as an aldoxime precursor. The non-acidic C?H bonds in various substances, including cycloalkanes, ethers, azacycles, and cyclic sulfides, were chemoselectively converted at ambient temperature under neutral conditions. The present transformation is a formal formylation of non-acidic C(sp3)?H bonds in a single step.
Dihydropyridinone approach to manzamines: An expedient construction of the tetracyclic core of manzamine A
Nakagawa, Masako,Torisawa, Yasuhiro,Hosaka, Toshihiro,Tanabe, Kiyoshi,Date, Tadamasa,Okamura, Kimio,Hino, Tohru
, p. 4543 - 4546 (1993)
A construction of the central tetracyclic core (19) of manzamine A (1) was successfully achieved by a highly efficient Diels-Alder reaction of the suitably protected dihydropyridinones (5) and Danishefsky's diene as a key strategy. Expedient conversion of
First stereoselective synthesis of a pro-pro E-alkene dipeptide isostere
Bandur, Nina G.,Harms, Klaus,Koert, Ulrich
, p. 773 - 776 (2005)
A stereoselective synthesis of a proline-proline E-alkene isostere is described. Starting from N-Boc-L-proline the new stereocenter is generated by diastereoselective alkenylation and subsequent Ireland-Claisen rearrangement. The relative configuration of the double bond and the new generated stereocenter were determined by X-ray crystallography.
Synthesis of chiral α-acetylenic cyclic amines from α-amino acids: Applications to differentially constrained oxotremorine analogues as muscarinic agents
Chung,Wasicak
, p. 3957 - 3960 (1990)
Application of the Cory-Fuchs reaction on Boc-prolinal, Boc-4-hydroxyprolinal, Boc-piperidinal and Boc-serinal derivatives to give chiral 2-pyrrolidinyl-, 2-piperidinyl- and 4-oxazolidinyl-acetylene derivatives provided rapid access to a number of differentially constrained oxotremorine analogues as muscarinic agents.
Organocatalysis Intermediates as Platforms to Study Noncovalent Interactions: Integrating Fluorine Gauche Effects in Iminium Systems to Facilitate Acyclic Conformational Control
Molnár, István Gábor,Holland, Mareike C.,Daniliuc, Constantin,Houk,Gilmour, Ryan
, p. 1051 - 1055 (2016)
Achieving acyclic conformational control over several bonds has been realized by the strategic installation of a vicinal difluoroethane bridge in a generic proline-derived organocatalyst. The torsion angle φFCCF is governed by stabilizing hyperconjugative interactions (σ→σ?), thus ensuring a 60° relationship. This effect has been telescoped by positioning a stereogenic fluorine center proximal to the nucleophilic amine. Upon iminium formation, this center is rendered electron deficient, thus triggering a dynamic fluorine iminium ion gauche effect. Consequently, conformational control over five atoms and four bonds can be achieved by reversible formation of an iminium π-bond.
Process Development and GMP Production of a Conjugate Warhead: Auristatin F-HPA-Ala/TFA (XMT-1864/TFA)
Conlon, Patrick R.,Gurijala, Venu Reddy,Kaufman, Michael,Li, Dachang,Li, Jiuyuan,Li, Yuanyuan,Reddy, Bollu Satyanarayan,Wagler, Thomas,Wang, Zedong,Xu, Zhongmin,Yin, Mao,Yurkovetskiy, Aleksandr V.,Zhu, Lei
, (2022/03/01)
An efficient, large-scale manufacturing process is described for XMT-1864/TFA (1-TFA), an auristatin F derivative, used as a novel, highly potent, cytotoxic warhead in Mersana's oncology antibody-drug conjugate platforms. The process achieves high diastereomeric purity and controls the impurities with all intermediates readily isolated by crystallization or precipitation in high yield and purity. Protecting groups were selected to ensure tolerability, scalability, and stability of the intermediates under various solution-phase peptide coupling conditions. Crystallization of the final product was developed to remove specified impurities and provide a high-purity active warhead molecule for use in the bioconjugation processing. The convergent synthesis involving six non-GMP steps and five GMP steps has been carried out in multiple cGMP productions on 1-kg scale to produce 1-TFA in >98% chemical purity and 1% total diastereomeric contamination with ～50% overall yield for the GMP steps.
NOVEL CONNECTED BODY AND USE THEREOF IN SPECIFIC CONJUGATION BETWEEN BIOMOLECULE AND DRUG
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, (2021/05/14)
PROBLEM TO BE SOLVED: To provide: a method for producing a connected body; a method for using the connected body in the production of a uniform conjugate; and a method for applying the conjugate in the treatment of cancer, infectious diseases, and autoimmune diseases. SOLUTION: A novel connected body is provided that includes a 2,3-di-substituted succinic acid group or a 2-mono-substituted or 2,3-di-substituted fumaric acid or maleic acid (trans (E)- or cis (Z)-butenedioic acid) group for conjugating 2 or more compounds/cytotoxic agents per connected body with a cell-binding molecule by specifically bridge-linking to a pair of thiol on the cell-binding molecule. The connected body is exemplified by the following general formula. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
