69622-67-9Relevant academic research and scientific papers
Cu(OTf)2catalyzed Ugi-type reaction ofN,O-acetals with isocyanides for the synthesis of pyrrolidinyl and piperidinyl 2-carboxamides
Feng, Yi-Man,Lin, Guo-Qiang,Mao, Zhuo-Ya,Nie, Xiao-Di,Si, Chang-Mei,Wei, Bang-Guo
supporting information, p. 9248 - 9251 (2021/09/20)
The Cu(OTf)2catalyzed Ugi-type reactions ofN,O-acetals with isocyanides have been described for the synthesis of pyrrolidinyl and piperidinyl 2-carboxamides. 4-Hydroxy-5-substituted-prolinamides can be obtained in high diastereoselectivities (2
A General Method for Photocatalytic Decarboxylative Hydroxylation of Carboxylic Acids
Khan, Shah Nawaz,Zaman, Muhammad Kashif,Li, Ruining,Sun, Zhankui
, p. 5019 - 5026 (2020/05/01)
A general and practical method for decarboxylative hydroxylation of carboxylic acids was developed through visible light-induced photocatalysis using molecular oxygen as the green oxidant. The addition of NaBH4 to in situ reduce the unstable peroxyl radical intermediate much broadened the substrate scope. Different sp3 carbon-bearing carboxylic acids were successfully employed as substrates, including phenylacetic acid-type substrates, as well as aliphatic carboxylic acids. This transformation worked smoothly on primary, secondary, and tertiary carboxylic acids.
Strategies for the Asymmetric Construction of Pelletierine and its Use in the Synthesis of Sedridine, Myrtine, and Lasubine
Zaidan, Raed K.,Evans, Paul
, p. 5354 - 5367 (2019/06/25)
Three methods for the asymmetric synthesis of both enantiomers of pelletierine 6 are reported. Bella's proline-based Mannich process gave (R)- and (S)-Cbz-protected 6 in good yields from Δ1-piperideine 14 and in reasonable enantiomeric excess (74–80 % ee). An intramolecular aza-Michael, cinchona-based, organocatalytic method is also reported. With commercially available 9-amino quinine (24a) and quinidine (24b) catalysts, Cbz-protected α,β-unsaturated ketone 23 also gave (R)- and (S)-Cbz-protected 6 in good yields and enantiomeric excess (90–99 % ee). This material was used to synthesize both optically active forms of deoxyhalofuginone (26), an analogue of febrifugine which is of interest as an anti-fibrotic agent. Finally, a resolution of racemic pelletierine using (R)- and (S)-mandelic acid 27 is reported. This scalable method gave both enantiomers of Cbz- and Boc-protected 6 in excellent enantiomeric excess (≥ 99 %). Both highly enantioenriched forms of 6 (obtained from the resolution study) were used to synthesize several alkaloids. Firstly, (–)-(S)-Cbz-protected pelletierine 17 was used to prepare naturally occurring sedridine (32) and its epimer allosedridine (8). Then the preparation of both enantiomers of the quinolizidine myrtine (33) by an olefination-intramolecular aza-Michael sequence is reported. Finally, the synthesis of the epimeric quinolizidine alkaloids, lasubine I (34) and lasubine II (35), from (+)- and (–)-Boc-protected pelletierine (29) respectively, is discussed.
HtrA1 Proteolysis of ApoE in Vitro Is Allele Selective
Chu, Qian,Diedrich, Jolene K.,Vaughan, Joan M.,Donaldson, Cynthia J.,Nunn, Michael F.,Lee, Kuo-Fen,Saghatelian, Alan
supporting information, p. 9473 - 9478 (2016/08/12)
Apolipoprotein E (ApoE) belongs to a large class of proteins that solubilize lipids for physiological transport. Humans have three different APOE alleles, APOE e2, APOE e3, and APOE e4, and genetic studies identified ApoE4 as the strongest genetic risk factor for Alzheimer's disease (AD). People who are homozygous for ApoE4 (i.e., ApoE4/E4) are an order of magnitude more likely to develop late-onset AD (LOAD) than ApoE3/E3 carriers. Several differences between ApoE3 and ApoE4 may contribute to AD including the observation that ApoE4 is degraded to a greater extent than ApoE3 in the human brain. Experiments with high-temperature requirement serine peptidase A1 (HtrA1), which is found in the nervous system, demonstrate that HtrA1 is an allele-selective ApoE-degrading enzyme that degrades ApoE4 more quickly than ApoE3. This activity is specific to HtrA1, as similar assays with HtrA2 showed minimal ApoE4 proteolysis and trypsin had no preference between ApoE4 and ApoE3. HtrA1 has also been reported to cleave the tau protein (Tau) and the amyloid protein precursor (APP) to hinder the formation of toxic amyloid deposits associated with AD. Competition assays with ApoE4, ApoE3, and Tau revealed that ApoE4 inhibits Tau degradation. Thus, the identification of ApoE4 as an in vitro HtrA1 substrate suggests a potential biochemical mechanism that links ApoE4 regulation of AD proteins such as Tau.
Formal homo-nazarov and other cyclization reactions of activated cyclopropanes
De Simone, Filippo,Saget, Tanguy,Benfatti, Fides,Almeida, Sofia,Waser, Jerome
, p. 14527 - 14538 (2012/02/04)
The Nazarov cyclization of divinyl ketones gives access to cyclopentenones. Replacing one of the vinyl groups by a cyclopropane leads to a formal homo-Nazarov process for the synthesis of cyclohexenones. In contrast to the Nazarov reaction, the cyclization of vinyl-cyclopropyl ketones is a stepwise process, often requiring harsh conditions. Herein, we describe two different approaches for further polarization of the three-membered ring of vinyl-cyclopropyl ketones to allow the formal homo-Nazarov reaction under mild catalytic conditions. In the first approach, the introduction of an ester group α to the carbonyl on the cyclopropane gave a more than tenfold increase in reaction rate, allowing us to extend the scope of the reaction to non-electron-rich aryl donor substituents in the β position to the carbonyl on the cyclopropane. In this case, a proof of principle for asymmetric induction could be achieved using chiral Lewis acid catalysts. In the second approach, heteroatoms, especially nitrogen, were introduced β to the carbonyl on the cyclopropane. In this case, the reaction was especially successful when the vinyl group was replaced by an indole heterocycle. With a free indole, the formal homo-Nazarov cyclization on the C3 position of indole was observed using a copper catalyst. In contrast, a new cyclization reaction on the N1 position was observed with BrAnsted acid catalysts. Both reactions were applied to the synthesis of natural alkaloids. Preliminary investigations on the rationalization of the observed regioselectivity are also reported.
Asymmetric organocatalytic intramolecular aza-michael addition of enone carbamates: Catalytic enantioselective access to functionalized 2-substituted piperidines
Liu, Jian-Dong,Chen, Ying-Chun,Zhang, Guo-Biao,Li, Zhi-Qiang,Chen, Peng,Du, Ji-Yuan,Tu, Yong-Qiang,Fan, Chun-An
supporting information; experimental part, p. 2721 - 2730 (2011/12/04)
The synthetically useful functionalized 2-substituted piperidines containing a lateral ketone group have been strategically accessed via an organocatalytic enantioselective intramolecular aza-Michael addition of enone carbamates, in which a novel internal substrate combination of the enone moiety as Michael acceptor and the carbamate moiety as Michael donor was revealed in asymmetric bifunctional organocatalysis. This heteroatom conjugate addition, which was realized by using a catalytic chiral Cinchona-based primary-tertiary diamine and an achiral Bronsted acid, mostly proceeded in high yield and good to excellent stereocontrol (up to 99% ee). This reaction provides an alternative catalytic asymmetric method for installing the stereogenic nitrogen-containing carbon center in functionalized 2-substituted piperidines, leading to the development of a straightforward and expeditious synthesis of some naturally occurring bioactive 2-substituted piperidine alkaloids. Copyright
One-pot formation of piperidine- and pyrrolidine-substituted pyridinium salts via addition of 5-alkylaminopenta-2,4-dienals to N-acyliminium ions: Application to the synthesis of (±)-nicotine and analogs
Peixoto, Sabrina,Nguyen, Tuan Minh,Crich, David,Delpech, Bernard,Marazano, Christian
supporting information; experimental part, p. 4760 - 4763 (2010/12/25)
Addition of 5-alkylaminopenta-2,4-dienals onto N-acyliminium ions, generated in situ from α-hydroxycarbamates derived from pyrrolidine or piperidine, in the presence of zinc triflate, followed by dehydrative cyclization, allowed the formation of pyridinium salts substituted at their 3-position by a five- or six-membered nitrogen heterocycle. Subsequent N-dealkylation of the pyridinium moiety and deprotection of the secondary amine or reduction of the carbamate function led to (±)-nicotine and analogs.
Catalytic selective cyclizations of aminocyclopropanes: Formal synthesis of aspidospermidine and total synthesis of goniomitine
De Simone, Filippo,Gertsch, Jürg,Waser, Jér?me
supporting information; experimental part, p. 5767 - 5770 (2010/11/02)
(Figure Presented) Mild control: Selective cyclization of aminocyclopropanes at either the N1 or C3 position of an indole ring was achieved by tuning the reaction conditions (see scheme). This strategy was applied to the formal synthesis of aspidospermidi
Novel use of N-carboalkoxy α,β-unsaturated iminium ions as dienophiles in Diels-Alder reactions
O'Connor, Patrick D.,K?rber, Karsten,Brimble, Margaret A.
scheme or table, p. 1036 - 1038 (2009/04/11)
Tricyclic spiro-N,O-acetals have been assembled in a single step by cycloaddition of hydroxymethyl-substituted dienes to iminium ion activated dienophiles that were generated by acidolysis of α,β-unsaturated-N- carboalkoxy-N,O-acetals or β-methoxymethyl-N
Hemiaminals as substrates for sulfur ylides: Direct asymmetric syntheses of functionalised pyrrolidines and piperidines
Kokotos, Christoforos G.,Aggarwal, Varinder K.
, p. 2156 - 2158 (2008/03/14)
Phenyl stabilised chiral sulfur ylides react with five-membered-ring hemiaminals to give functionalised pyrrolidines directly with high enantioselectivity. The reaction can be diverted to give piperidines instead by isolation of the intermediate epoxide and treatment with TMSOTf. The Royal Society of Chemistry 2006.
