280-74-0Relevant academic research and scientific papers
Synthesis and coordination chemistry of N,N-diallylbispidine
Cui, Huiling,Goddard, Richard,Poerschke, Klaus-Richard
, p. 6241 - 6252 (2011)
The synthesis of 3,7-diallyl-3,7-diazabicyclo[3.3.1]nonane (C 7H12N2allyl2, 3) has been revisited, and several hitherto undetected byproducts have been identified. Pure 3 and these byproducts were isolated by both prep-GC and column chromatography. Monoprotonated 3 in the form of the PF6 salt [(C7H 13N2allyl2]PF6 (9) and the addition complexes of 3 to Ni(acac)2 and CuI, (C7H 12N2allyl2)Ni(acac)2 (10) and {(C7H12N2allyl2)Cu(μ-I)} 2 (11), have been prepared. From the reactions of {(η3-C3H5)M(μ-X)}2 (M = Ni, Pd, Pt; X = Cl, Br) with 3 and TlPF6 the complexes [(C 7H12N2allyl2)M(η3- C3H5)]PF6 (M = Ni (12a), Pd (12b), Pt (12c)) were obtained. Compounds 9-11 and 12b were characterized by X-ray crystallography. The reaction of (1,5-hexadiene)PtCl2 with 3 gave, after HCl elimination, monomeric {C7H12N 2(C3H5)CH=CHCH2}PtCl (13a), and the presence of MeOH afforded {C7H12N2(C 3H5)CH2CH(OMe)CH2}PtCl (13b), both compounds featuring novel anionic tridentate ligands. Furthermore, chiral N,N′-bis((R)-1-phenylethyl)-1,7-octadiene-(S,S)-4,5-diamine (15) reacts with CuI to give [{(C3H5)2C2H 4N2(CHMePh)2}Cu(μ-I)]2 (16). The unbound N-allyl functions on the ligands in the product complexes allow for immobilization of the transition metal complexes on polyester fibers.
Modulation of prion polymerization and toxicity by rationally designed peptidomimetics
Srivastava, Ankit,Sharma, Sakshi,Sadanandan, Sandhya,Gupta, Sakshi,Singh, Jasdeep,Gupta, Sarika,Haridas,Kundu, Bishwajit
, p. 123 - 147 (2017/03/17)
Misfolding and aggregation of cellular prion protein is associated with a large array of neurological disorders commonly called the transmissible spongiform encephalopathies. Designing inhibitors against prions has remained a daunting task owing to limited information about mechanism(s) of their pathogenic self-assembly. Here, we explore the antiprion properties of a combinatorial library of bispidine-based peptidomimetics (BPMs) that conjugate amino acids with hydrophobic and aromatic side chains. Keeping the bispidine unit unaltered, a series of structurally diverse BPMs were synthesized and tested for their prion-modulating properties. Administration of Leu- and Trp-BPMs delayed and completely inhibited the amyloidogenic conversion of human prion protein (HuPrP), respectively. We found that each BPM induced the HuPrP to form unique oligomeric nanostructures differing in their biophysical properties, cellular toxicities and response to conformation-specific antibodies. While Leu-BPMs were found to stabilize the oligomers, Trp-BPMs effected transient oligomerization, resulting in the formation of non-toxic, nonfibrillar aggregates. Yet another aromatic residue, Phe, however, accelerated the aggregation process in HuPrP. Molecular insights obtained through MD (molecular dynamics) simulations suggested that each BPM differently engages a conserved Tyr 169 residue at the α2-β2 loop of HuPrP and affects the stability of α2 and α3 helices. Our results demonstrate that this new class of molecules having chemical scaffolds conjugating hydrophobic/aromatic residues could effectively modulate prion aggregation and toxicity.
Bispidine as a secondary structure nucleator in peptides
Haridas,Sadanandan, Sandhya,Sharma, Yogesh K.,Chinthalapalli, Srinivas,Shandilya, Ashutosh
, p. 623 - 626 (2012/03/07)
Here we describe bispidine as a scaffold for inducing open turn-like and beta sheet conformations on the attached peptides depending on the mode of attachment of peptides to the scaffold. Various bispidine-peptide conjugates were designed and synthesized to demonstrate the versatility of the scaffold.
Novel heteroaryl-diazabicycloalkanes
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, (2008/06/13)
The present invention relates to novel heteroaryl-diazabicycloalkanes which are found to be cholinergic ligands at the nicotinic Acetyl Choline Receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment
Convenient synthesis of 3,7-diazabicyclo[3.3.1]nonane (bispidine)
Miyahara,Goto,Inazu
, p. 364 - 366 (2007/10/03)
Bispidine 1a is conveniently synthesized via a route involving double Mannich reaction of 1-allylpiperidin-4-one to N,N′-diallylbispidinone, Wolff-Kishner reduction of the bispidinone, and deallylation of the resulting N,N′-diallylbispidine by treatment with ethyl chloroformate in the presence of NaI, followed by alkaline hydrolysis.
Synthesis of chiral amino alcohols embodying the bispidine framework and their application as ligands in enantioselectively catalyzed additions to C=O and C=C groups
Spieler, Jan,Huttenloch, Oliver,Waldmann, Herbert
, p. 391 - 399 (2007/10/03)
Two generally applicable routes for the synthesis of chiral amino alcohols embodying the bispidine framework have been developed. In linear route A the bispidine framework is built up successively from chiral primary amines via intermediate formation of a piperidinone and a bispidinone. In convergent route B an achiral bispidine is formed first and then the N- substituents are introduced by reaction of the nitrogen bases with chiral electrophiles. In order to determine if the bispidine core and its N- substituents can influence the steric course of enantioselective transformations, bispidine amino alcohols built up by these two routes were investigated as chiral ligands in the enantioselectively catalyzed addition of diethylzinc to aldehydes and chalcone. In general, tridentate ligands containing one chiral amino alcohol fragment and a second amino substituent without a stereogenic center were more efficient than tetradentate ligands with two amino alcohol structural units. With the best ligands the enantioselective addition of diethylzinc to aromatic and aliphatic aldehydes proceeded with 83-98% ee and the nickel-catalyzed addition of diethylzinc to chalcone was achieved with up to 85% ee.
Guest/host relationships in the synthesis of the novel cage-based zeolites SSZ-35, SSZ-36, and SSZ-39
Wagner, Paul,Nakagawa, Yumi,Lee, Greg S.,Davis, Mark E.,Elomari, Saleh,Medrud, Ronald C.,Zones
, p. 263 - 273 (2007/10/03)
Here, we report the synthesis and structure of three high-silica molecular sieves, SSZ-35, SSZ-36, and SSZ-39, that are prepared from a library of 37 different cyclic and polycyclic quaternized amine molecules that are used as structure-directing agents (SDAs). The size and shape of the quaternized amine molecules are purposely designed in order to obtain novel zeolite structures, and the synthesis of these molecules is presented. The selectivity for the three molecular sieve phases is found to depend on both the SDA and the degree of heteroatom lattice substitution of Al3+ or B3+ in the silicate framework. Molecular modeling is utilized to probe the effects of the nonbonded SDA/zeolite-framework interaction energy on the selectivity for the observed molecular sieve phase. The Rietveld refinement of the powder X-ray data confirms the structure of the SSZ-39 zeolite to be isomorphous with the aluminophosphate molecular sieve, SAPO-18 (AEI). The structure of SSZ-36 is found to possess a range of fault probabilities between the two-dimensional channel system, end-member polymorphs, ITQ-3 and RUB-13 (International Zeolite Association Codes ITE and RTH, respectively). The SSZ-35 structure is reported to contain a one-dimensional pore system possessing stacked cages circumscribed by alternating rings of 10 and 18 tetrahedral atoms (10- and 18-membered rings).
