818377-18-3Relevant academic research and scientific papers
Expedient Synthesis of 1,5-Diketones by Rhodium-Catalyzed Hydroacylation Enabled by C-C Bond Cleavage
Guo, Rui,Zhang, Guozhu
supporting information, p. 12891 - 12894 (2017/09/26)
A rhodium-catalyzed intermolecular hydroacylation reaction of vinyl cyclobutanols with non-chelating aldehydes has been developed. This reaction offers a new and atom-economical approach for the selective preparation of 1,5-diketones in high yields. Experimental data suggest a sequential ring-opening, transfer hydrogenation, and hydroacylation mechanism. We propose that aldehyde decarbonylation is avoided by the formation of a novel rhodium enolate species that also accounts for the compatibility of a broad range of aldehydes and its anti-Markovnikov selectivity.
B(C6F5)3-Catalyzed Cascade Reduction of Pyridines
Liu, Zhi-Yun,Wen, Zhi-Hui,Wang, Xiao-Chen
supporting information, p. 5817 - 5820 (2017/05/12)
B(C6F5)3 has been found to be an effective catalyst for reduction of pyridines and other electron-deficient N-heteroarenes with hydrosilanes (or hydroboranes) and amines as the reducing reagents. The success of this development hinges upon the realization of a cascade process of dearomative hydrosilylation (or hydroboration) and transfer hydrogenation. The broad functional-group tolerance (e.g. ketone, ester, unactivated olefins, nitro, nitrile, heterocycles, etc.) implies high practical utility.
Iterative direct C(sp3)-H functionalization of amines: diastereoselective divergent syntheses of ??,α′-disubstituted alicyclic amines
Mahato, Sujit,Jana, Chandan K.
, p. 1655 - 1660 (2017/02/23)
A novel iterative C(sp3)-H oxygenation/C-C bond formation strategy, which avoids repetitive N-protection/-deprotection steps, was developed for direct α,α′-difunctionalization of alicyclic amines. The method is highly efficient and stereoselective in producing syn-α,α′-disubstituted aliphatic N-heterocycles. Synthetic potential and practicability of the method was demonstrated by an easy and straightforward synthesis of neuroactive alkaloid nor-lobelane and its derivatives.
Defunctionalized lobeline analogues: Structure-activity of novel ligands for the vesicular monoamine transporter
Zheng, Guangrong,Dwoskin, Linda P.,Deaciuc, Agripina G.,Norrholm, Seth D.,Crooks, Peter A.
, p. 5551 - 5560 (2007/10/03)
(-)-Lobeline (2R,6S,10S; 1a), an antagonist at nicotinic acetylcholine receptors (nAChRs), inhibits the neurochemical and behavioral effects of methamphetamine and inhibits dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) function. VMAT2 is a target for the development of treatments for methamphetamine abuse. Structural modification of lobeline affords the defunctionalized analogues meso-transdiene (MTD) and lobelane, which have high potency and selectivity for VMAT2. To establish the structure-activity relationships within this novel class of VMAT2 ligands, specific stereochemical forms of MTD, lobelane, and other structurally related analogues have been synthesized. These compounds have been evaluated for inhibition of [3H]nicotine ([3H]NIC) binding (α4β2* nAChR), [3H]methyllycaconitine ([ 3H]MLA) binding (α7* nAChR), and [3H] dihydrotetrabenazine ([3H]DTBZ) binding (VMAT2). Generally, all of these analogues had lower affinities at α4β2* and α7* nAChRs compared to lobeline, thereby increasing selectivity for VMAT2. The following structural modifications resulted in only modest changes in affinity for VMAT2, affording analogues that were less potent than the lead compound, lobelane: (1) altering the stereochemistry at the C-2 and C-6 positions of the piperidino ring, (2) varying unsaturation in the piperidino C-2 and C-6 substituents, (3) introducing unsaturation into the piperidine ring, (4) ring-opening or eliminating the piperidine ring, and (5) removing the piperidino N-methyl group. Furthermore, incorporating a quaternary ammonium group into defunctionalized lobeline molecules in the cis-series resulted in significant loss of affinity for VMAT2, whereas only a modest change in affinity was obtained in the trans-series. The most potent (Ki = 630 nM) and VMAT2-selective compound evaluated was the N-methyl-2,6-cts- bis(naphthaleneethyl)piperidine analogue 28b (1-NAP-lobelane), in which the phenyl groups of lobelane were replaced with 1-naphthyl moieties. Thus, initial structure-activity relationship studies reveal that the most promising structural changes to the lobeline molecule that lead to enhancement of VMAT2 affinity and selectivity are defunctionalization, affording lobelane and MTD, and replacement of the phenyl rings of lobelane with other aromatic moieties that have a π-extended structure.
