5497-67-6Relevant academic research and scientific papers
Synthesis of 2,5-difunctionalised-3,3-dimethylpiperidines via ω-halogenated imines
Stevens, Christian V,Peristeropoulou, Maria,De Kimpe, Norbert
, p. 7865 - 7870 (2001)
2,5-Difunctionalised-3,3-dimethylpiperidines were prepared by addition of nucleophiles to piperideinium salts, formed by electrophile-induced cyclisation of γ,δ-unsaturated imines with N-bromosuccinimide in alcoholic medium.
Synthesis and DNA cleavage activity of bis-3-chloropiperidines as alkylating agents
Zuravka, Ivonne,Roesmann, Rolf,Sosic, Alice,Wende, Wolfgang,Pingoud, Alfred,Gatto, Barbara,G?ttlich, Richard
, p. 2178 - 2185 (2014)
Nitrogen mustards are an important class of bifunctional alkylating agents routinely used in chemotherapy. They react with DNA as electrophiles through the formation of highly reactive aziridinium ion intermediates. The antibiotic 593A, with potential antitumor activity, can be considered a naturally occurring piperidine mustard containing a unique 3-chloropiperidine ring. However, the total synthesis of this antibiotic proved to be rather challenging. With the aim of designing simplified analogues of this natural product, we developed an efficient bidirectional synthetic route to bis-3-chloropiperidines joined by flexible, conformationally restricted, or rigid diamine linkers. The key step involves an iodide-catalyzed double cyclization of unsaturated bis-N-chloroamines to simultaneously generate both piperidine rings. Herein we describe the synthesis and subsequent evaluation of a series of novel nitrogen-bridged bis-3-chloropiperidines, enabling the study of the impact of the linker structure on DNA alkylation properties. Our studies reveal that the synthesized compounds possess DNA alkylating abilities and induce strand cleavage, with a strong preference for guanine residues.
Consecutive borylcupration/C-C coupling of ?-alkenyl aldehydes towards diastereoselective 2-(borylmethyl)cycloalkanols
Carbó, Jorge J.,Fernández, Elena,Maza, Ricardo J.,Royes, Jordi
supporting information, p. 5973 - 5976 (2020/06/05)
Copper(i) catalyzes the borylative cyclization of ?-alkenyl aldehydes through chemo- and regioselective addition of Cu-B to C?C and concomitant intramolecular 1,2-addition of Cu-C on C?O. The products are formed in an exclusive diastereoselective manner and computational analysis identifies the key points for the observed chemo- and diastereoselectivity.
Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells
Helbing, Tim,Carraro, Caterina,Francke, Alexander,Sosic, Alice,De Franco, Michele,Gandin, Valentina,G?ttlich, Richard,Gatto, Barbara
supporting information, p. 2040 - 2051 (2020/09/21)
In this study, we describe the synthesis and biological evaluation of a set of bis-3-chloropiperidines (B?CePs) containing rigid aromatic linker structures. A modification of the synthetic strategy also enabled the synthesis of a pilot tris-3-chloropiperidine (Tri-CeP) bearing three reactive meta-chloropiperidine moieties on the aromatic scaffold. A structure–reactivity relationship analysis of B?CePs suggests that the arrangement of the reactive units affects the DNA alkylating activity, while also revealing correlations between the electron density of the aromatic system and the reactivity with biologically relevant nucleophiles, both on isolated DNA and in cancer cells. Interestingly, all aromatic 3-chloropiperidines exhibited a marked cytotoxicity and tropism for 2D and 3D cultures of pancreatic cancer cells. Therefore, the new aromatic 3-chloropiperidines appear to be promising contenders for further development of mustard-based anticancer agents aimed at pancreatic cancers.
A One-Pot Intramolecular Tandem Michael-Aldol Annulation Reaction for the Synthesis of Chiral Pentacyclic Terpenes
Lu, Jianyu,Koldas, Serkan,Fan, Huafang,Desper, John,Day, Victor W.,Hua, Duy H.
, p. 3964 - 3972 (2019/10/28)
A chiral tricyclic terpene possessing a 6,6,6-tricyclic framework and a 3,3-dimethyl-7-oxooctylidenyl side chain undergoes a double ring-closing reaction to give two chiral pentacyclic terpenes in a ratio of 4:3 via an intramolecular Michael addition followed by aldol condensation under basic conditions. Three new stereogenic centers are introduced in the initial Michael annulation reaction. Stereoselective installation of an ethoxycarbonyl group at C17 of the two pentacyclic terpenes separately gives the corresponding highly functionalized pentacyclic terpenoids with seven stereogenic centers. The structures and stereochemistry of key intermediates and products are established through X-ray crystallographic analysis. A mechanism is proposed for explaining the stereochemistry in the Michael annulation reaction.
Metal-Free Oxidative Decarbonylative [3+2] Annulation of Terminal Alkynes with Tertiary Alkyl Aldehydes toward Cyclopentenes
Zou, Hua-Xu,Li, Yang,Yang, Xu-Heng,Xiang, Jiannan,Li, Jin-Heng
, p. 8581 - 8588 (2018/06/13)
A new metal-free oxidative decarbonylative [3+2] annulation of terminal alkynes with tertiary alkyl aldehydes is presented, which features broad substrate scope and excellent selectivity. The selectivity of this reaction toward cyclopentenes and indenes relies on the nature of the aldehyde substrates. While treatment of tertiary γ,δ-unsaturated aldehydes with common terminal alkynes assembles cyclopentenes, 2-methyl-2-arylpropanals succeed in accessing indenes.
Synthesis of a biofuel target through conventional organic chemistry
Page, Jordan P.,Robinson, Joshua W.,Albrecht, Karl O.,Cosimbescu, Lelia
supporting information, p. 1421 - 1423 (2018/03/07)
In this work, the biofuel target compound 2-ethyl-5,5-dimethylcyclopenta-1,3-diene (1) and its exo isomers (9a and 9b), were successfully synthesized via two different pathways from the common intermediate 4,4-dimethylcyclopent-2-ene-1-one (2). The first pathway produced the endocyclic product as a pure isomer via a triflate intermediate obtained from ketone 2 in 60% yield, followed by copper-catalyzed coupling with ethyl magnesium bromide in 63% yield. The second pathway employed a Grignard reaction with ketone 2, which generated an alcohol that was immediately subjected to mild acid-catalyzed elimination to yield primarily a mixture of exo isomers 9a and 9b in 46% yield. The preparation method developed by this work allowed for the production of a sufficient quantity of these targets to evaluate their fuel properties, which will be reported in a separate study.
Synthesis and Neurotrophic Activity Studies of Illicium Sesquiterpene Natural Product Analogues
Richers, Johannes,P?thig, Alexander,Herdtweck, Eberhardt,Sippel, Claudia,Hausch, Felix,Tiefenbacher, Konrad
supporting information, p. 3178 - 3183 (2017/03/13)
Neurotrophic natural products hold potential as privileged structures for the development of therapeutic agents against neurodegeneration. However, only a few studies have been conducted to investigate a common pharmacophoric motif and structure–activity relationships (SARs). Here, an investigation of structurally more simple analogues of neurotrophic sesquiterpenes of the illicium family is presented. A concise synthetic route enables preparation of the carbon framework of (±)-Merrilactone A and (±)-Anislactone A/B on a gram scale. This has allowed access to a series of structural analogues by modification of the core structure, including variation of oxidation levels and alteration of functional groups. In total, 15 derivatives of the natural products have been synthesized and tested for their neurite outgrowth activities. Our studies indicate that the promising biological activity can be retained by structurally simpler natural product analogues, which are accessible by a straightforward synthetic route.
Nickel-Catalyzed α-Allylation of Aldehydes and Tandem Aldol Condensation/Allylation Reaction with Allylic Alcohols
Bernhard, Yann,Thomson, Brodie,Ferey, Vincent,Sauthier, Mathieu
supporting information, p. 7460 - 7464 (2017/06/13)
An additive-free nickel-catalyzed α-allylation of aldehydes with allyl alcohol is reported. The reaction is promoted by 1 mol % of in situ formed nickel complex in methanol, and water is the sole by-product of the reaction. The experimental conditions allow the conversion of various α-branched aldehydes and α,β-unsaturated aldehydes as nucleophiles. The same catalyst and reaction conditions enabled a tandem aldol condensation of aldehyde/α-allylation reaction.
Bis-3-chloropiperidines containing bridging lysine linkers: Influence of side chain structure on DNA alkylating activity
Zuravka, Ivonne,Roesmann, Rolf,Sosic, Alice,G?ttlich, Richard,Gatto, Barbara
, p. 1241 - 1250 (2015/03/04)
A series of bis-3-chloropiperidines containing lysine linkers was synthesised as DNA alkylating model compounds by using a bidirectional synthetic strategy. These novel piperidine mustard based agents have been evaluated for their alkylating properties towards nucleic acids and were shown to alkylate and cleave DNA with strong preference for guanine residues. Our studies reveal that the introduction of aromatic groups in the side chain of the lysine linker has an impact on DNA alkylating activity. Analysis by ESI mass spectrometry enabled the verification of the reactive aziridinium ion formation. Overall, the results confirm our recently proposed reaction mechanism of bis-3-chloropiperidines.
