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Multistep Synthesis (multistep + synthesis)

Distribution by Scientific Domains

Chemistry	80%

Selected Abstracts

ChemInform Abstract: An Alternative Approach Toward 2-Aryl-2H-pyrazolo[4,3-c]quinolin-3-ones by a Multistep Synthesis.

CHEMINFORM, Issue 18 2010
Marisa J. Lopez Rivilli
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

Synthesis of Enantiopure Tricarbonyl(indan-1,2-dione)chromium

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 24 2005
Dirk Leinweber
Abstract A multistep synthesis of the planar chiral tricarbonyl(,6 -indan-1,2-dione)chromium, based on acetal protection of the keto groups, is presented. Since common deacetalization procedures failed, an oxidative deprotection with triphenylcarbenium tetrafluoroborate was used. Tricarbonyl(,6 -indan-1,2-dione)chromium is regarded as a potential precursor for dianionic oxy-Cope rearrangements upon alkenyllithium diaddition. As an unexpected side product in the synthesis, an indan-1,2-dione complex with a triphenylmethyl substituent at C-3 was obtained. Attempts directed towards the formation of enantiomerically pure material include the first reported investigation into an enantioselective ketone reduction with two methoxy substituents present in the , position. Although enantiomeric excesses of up to 84.5,% were achieved, the chemical yields decreased with increasing ee. A classical resolution was therefore undertaken, giving access to the enantiomerically pure title compound (99.4,% ee). The absolute configuration was verified by an X-ray structure analysis of an intermediate. First experiments concerning the alkenyllithium addition showed that a single addition is possible while a second one does not occur, presumably due to enolate formation. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source]

Designed Synthesis of Coaxial SnO2@carbon Hollow Nanospheres for Highly Reversible Lithium Storage

ADVANCED MATERIALS, Issue 24 2009
Xiong Wen Lou
A proof-of-concept structural design is demonstrated for high-capacity lithium-ion batteries anode materials by multistep synthesis of coaxial SnO2@carbon hollow nanospheres. This material integrates two beneficial features: hollow structure and carbon nanopainting. When evaluated for reversible lithium storage, these functional materials manifest excellent cycling performance and rate capabilities. [source]

Silicon Analogues of the RXR-Selective Retinoid Agonist SR11237 (BMS649): Chemistry and Biology

CHEMMEDCHEM, Issue 7 2009
W. Peter Lippert
Abstract C/Si switch: Twofold sila-substitution (C/Si exchange) in the RXR-selective retinoids 4,a (SR11237) and 5,a leads to 4,b (disila-SR11237) and 5,b, respectively. Chemistry and biology of the C/Si pairs are reported. SR11237 (BMS649, 4,a) is a pan-RXR-selective retinoid agonist. Its silicon analogue, disila-SR11237 (4,b; twofold C/Si exchange), was prepared in a multistep synthesis by starting from 1,2-bis(ethynyldimethylsilyl)ethane. In addition, the related C/Si analogues 5,a and 5,b, with an indane (disila-indane) instead of a tetraline (disila-tetraline) skeleton, were synthesized. The C/Si pairs 4,a/4,b and 5,a/5,b were studied for their interaction with retinoid receptors and were demonstrated to be highly potent RXR-selective ("rexinoid") agonists. Interestingly, twofold C/Si exchange in the indane moiety of 5,a resulted in a 10-fold increase in biological activity of the corresponding silicon-containing rexinoid 5,b, possibly resulting from an increased receptor affinity or a divergent allosteric effect on co-regulator-binding surfaces. The crystal structures of the ternary complexes formed by 5,a and 5,b, respectively, with the ligand-binding domain of hRXR, and a peptide of the co-activator TIF2/GRIP1 revealed additional interactions of the disila analogue 5,b with the H7 and H11 residues, supporting the first option of increased binding affinity. This is the first demonstration of an increase in binding affinity of a ligand to a nuclear receptor by C/Si replacement, thereby adding this C/Si switch strategy to the repertoire of nuclear receptor ligand design. [source]

Unexpected Novel Binding Mode of Pyrrolidine-Based Aspartyl Protease Inhibitors: Design, Synthesis and Crystal Structure in Complex with HIV Protease

CHEMMEDCHEM, Issue 1 2006
Edgar Specker Dr.
Abstract At present nine FDA-approved HIV protease inhibitors have been launched to market, however rapid drug resistance arising under antiviral therapy calls upon novel concepts. Possible strategies are the development of ligands with less peptide-like character or the stabilization of a new and unexpected binding-competent conformation of the protein through a novel ligand-binding mode. Our rational design of pyrrolidinedimethylene diamines was inspired by the idea to incorporate key structural elements from classical peptidomimetics with a non-peptidic heterocyclic core comprising an endocyclic amino function to address the catalytic aspartic acid side chains of Asp,25 and 25,. The basic scaffolds were decorated by side chains already optimized for the recognition pockets of HIV protease or cathepsin,D. A multistep synthesis has been established to produce the central heterocycle and to give flexible access to side chain decorations. Depending on the substitution pattern of the pyrrolidine moiety, single-digit micromolar inhibition of HIV-1 protease and cathepsin,D has been achieved. Successful design is suggested in agreement with our modelling concepts. The subsequently determined crystal structure with HIV protease shows that the pyrrolidine moiety binds as expected to the pivotal position between both aspartic acid side chains. However, even though the inhibitors have been equipped symmetrically by polar acceptor groups to address the flap water molecule, it is repelled from the complex, and only one direct hydrogen bond is formed to the flap. A strong distortion of the flap region is detected, leading to a novel hydrogen bond which cross-links the flap loops. Furthermore, the inhibitor addresses only three of the four available recognition pockets. It achieves only an incomplete desolvation compared with the similarly decorated amprenavir. Taking these considerations into account it is surprising that the produced pyrrolidine derivatives achieve micromolar inhibition and it suggests extraordinary potency of the new compound class. Most likely, the protonated pyrrolidine moiety experiences strong enthalpic interactions with the enzyme through the formation of two salt bridges to the aspartic acid side chains. This might provide challenging opportunities to combat resistance of the rapidly mutating virus. [source]