74685-00-0Relevant articles and documents
Synthesis and biological activity of novel acyclic versions of neplanocin A
Wu, Ying,Hong, Joon Hee
, p. 517 - 521 (2005)
Novel acyclic Neplanocin A analogues were designed and synthesized. The coupling of the alkyl bromide 6 with nucleosidic bases (T, U, 5-FU, 5-IU, C, A) and desilylation afforded a series of novel acyclic nucleosides. The synthesized compounds 13-18 were evaluated for their antiviral and antitumor activity.
Nitroxides: Synthesis and paramagnetic properties of an α-hydroxymethyl derivative of DOXYL
Chaouni-Benabdallah, Aziz,Subra, Guy,Bonnet, Pierre A.,Fernandez, Jean P.,Chapat, Jean P.,Vallet, Patrick,Muller, Robert N.
, p. 12923 - 12932 (1994)
The synthesis of new but unstable α-(hydroxymethyl)oxazolidin-3-oxyls was achieved after protection by silylation of the hydroxyl groups in order to avoid decomposition in diamagnetic nitrones. Relaxivity studies of (R,S)-4-(hydroxymethyl)-2,2,4-trimethyloxazolidin-3-oxyl 1 show no beneficial effect due to the presence of an hydroxymethyl group in the vicinity of the N-O group on the paramagnetic properties of nitroxides.
BICYCLIC SULFONAMIDES
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Paragraph 0186, (2020/08/28)
Provided herein are compounds of Formulae (I) and (II), or pharmaceutically acceptable salts of the foregoing, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein
Hydrogenative metathesis of enynes via piano-stool ruthenium carbene complexes formed by alkyne gem-hydrogenation
Peil, Sebastian,Bistoni, Giovanni,Goddard, Richard,Fürstner, Alois
supporting information, p. 18541 - 18553 (2020/11/17)
The only recently discovered gem-hydrogenation of internal alkynes is a fundamentally new transformation, in which both H atoms of dihydrogen are transferred to the same C atom of a triple bond while the other position transforms into a discrete metal carbene complex. [Cp?RuCl]4 is presently the catalyst of choice: the resulting piano-stool ruthenium carbenes can engage a tethered alkene into either cyclopropanation or metathesis, and a prototypical example of such a reactive intermediate with an olefin ligated to the ruthenium center has been isolated and characterized by X-ray diffraction. It is the substitution pattern of the olefin that determines whether metathesis or cyclopropanation takes place: a systematic survey using alkenes of largely different character in combination with a computational study of the mechanism at the local coupled cluster level of theory allowed the preparative results to be sorted and an intuitive model with predictive power to be proposed. This model links the course of the reaction to the polarization of the double bond as well as to the stability of the secondary carbene complex formed, if metathesis were to take place. The first application of "hydrogenative metathesis"to the total synthesis of sinularones E and F concurred with this interpretation and allowed the proposed structure of these marine natural products to be confirmed. During this synthesis, it was found that gem-hydrogenation also provides opportunities for C-H functionalization. Moreover, silylated alkynes are shown to participate well in hydrogenative metathesis, which opens a new entry into valuable allylsilane building blocks. Crystallographic evidence suggests that the polarized [Ru-Cl] bond of the catalyst interacts with the neighboring R3Si group. Since attractive interligand Cl/R3Si contacts had already previously been invoked to explain the outcome of various ruthenium-catalyzed reactions, including trans-hydrosilylation, the experimental confirmation provided herein has implications beyond the present case.
Hydrogenative Cyclopropanation and Hydrogenative Metathesis
Peil, Sebastian,Guthertz, Alexandre,Biberger, Tobias,Fürstner, Alois
supporting information, p. 8851 - 8856 (2019/05/28)
The unusual geminal hydrogenation of a propargyl alcohol derivative with [CpXRuCl] as the catalyst entails formation of pianostool ruthenium carbenes in the first place; these reactive intermediates can be intercepted with tethered alkenes to give either cyclopropanes or cyclic olefins as the result of a formal metathesis event. The course of the reaction is critically dependent on the substitution pattern of the alkene trap.
NEW SUBSTITUTED AZAINDOLINE DERIVATIVES AS NIK INHIBITORS
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Page/Page column 160, (2019/01/21)
The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.
One-Step Synthesis of 3,4-Disubstituted 2-Oxazolidinones by Base-Catalyzed CO2 Fixation and Aza-Michael Addition
Mannisto, Jere K.,Sahari, Aleksi,Lagerblom, Kalle,Niemi, Teemu,Nieger, Martin,Sztanó, Gábor,Repo, Timo
supporting information, p. 10284 - 10289 (2019/08/01)
2-Oxazolidinones are saturated heterocyclic compounds, which are highly attractive targets in modern drug design. Herein, we describe a new, single-step approach to 3,4-disubstituted 2-oxazolidinones by aza-Michael addition using CO2 as a carbonyl source and 1,1,3,3-tetramethylguanidine (TMG) as a catalyst. The modular reaction, which occurs between a γ-brominated Michael acceptor, CO2 and an arylamine, aliphatic amine or phenylhydrazine, is performed under mild conditions. The regiospecific reaction displays good yields (av. 75 %) and excellent functional-group compatibility. In addition, late-stage functionalization of drug and drug-like molecules is demonstrated. The experimental results suggest a mechanism consisting of several elementary steps: TMG-assisted carboxylation of aniline; generation of an O-alkyl carbamate; and the final ring-forming step through an intramolecular aza-Michael addition.
Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses
Davey, Martin S.,Malde, Roshni,Mykura, Rory C.,Baker, Alfie T.,Taher, Taher E.,Le Duff, Cécile S.,Willcox, Benjamin E.,Mehellou, Youcef
, p. 2111 - 2117 (2018/03/21)
The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of Vγ9/Vδ2 T-cells, which were then able to lyse bladder cancer cells in vitro. This work highlights the promise of this prodrug technology in the discovery of novel immunotherapeutics.
Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji-Trost coupling
Bretzke, Sebastian,Scheeff, Stephan,Vollmeyer, Felicitas,Eberhagen, Friederike,Rominger, Frank,Menche, Dirk
supporting information, p. 1111 - 1121 (2016/07/06)
The design, development and application of an efficient procedure for the concise synthesis of the 1,3-syn- and anti-tetrahydropyrimidine cores of manzacidins are reported. The intramolecular allylic substitution reaction of a readily available joint urea-type substrate enables the facile preparation of both diastereomers in high yields. The practical application of this approach is demonstrated in the efficient and modular preparation of the authentic heterocyclic cores of manzacidins, structurally unique bromopyrrole alkaloids of marine origin. Additional features of this route include the stereoselective generation of the central amine core with an appending quaternary center by an asymmetric addition of a Grignard reagent to a chiral tert-butanesulfinyl ketimine following an optimized Ellman protocol and a cross-metathesis of a challenging homoallylic urea substrate, which proceeds in good yields in the presence of an organic phosphoric acid.
Ruthenium-catalyzed oxidative kinetic resolution of unactivated and activated secondary alcohols with air as the hydrogen acceptor at room temperature
Mizoguchi, Hirotaka,Uchida, Tatsuya,Katsuki, Tsutomu
supporting information, p. 3178 - 3182 (2014/04/03)
Enantiopure alcohols are versatile building blocks for asymmetric synthesis and the kinetic resolution (KR) of racemic alcohols is a reliable method for preparing them. Although many KR methods have been developed, oxidative kinetic resolution (OKR), in which dioxygen is used as the hydrogen acceptor, is the most atom-efficient. Dioxygen is ubiquitous in air, which is abundant and safe to handle. Therefore, OKR with air has been intensively investigated and the OKR of benzylic alcohols was recently achieved by using an Ir catalyst without any adjuvant. However, the OKR of unactivated alcohols remains a challenge. An [(aqua)Ru(salen)] catalyzed OKR with air as the hydrogen acceptor was developed, in which the aqua ligand is exchanged with alcohol and the Ru complex undergoes single electron transfer to dioxygen and subsequent alcohol oxidation. This OKR can be applied without any adjuvant to activated and unactivated alcohols with good to high enantioselectivity. The unique influence of substrate inhibition on the enantioselectivity of the OKR is also described. Alcohol resolution: An (aqua)ruthenium salen complex catalyzes the efficient oxidative kinetic resolution of both activated and unactivated secondary alcohols with air as the hydrogen acceptor at room temperature. The reaction is compatible with various functional groups, including halogen, ether, silyl ether, and ester groups. The reaction rate is lower at higher substrate concentrations as a result of substrate inhibition.
