3684-26-2

Usage

Structure

Unique bicyclic structure containing a nitrogen atom

Classification

Tertiary amine and alcohol combination

Use

Intermediate in the synthesis of pharmaceuticals and agrochemicals

Bicyclic structure

Building block for the synthesis of complex organic molecules

Chiral auxiliary

Potential in asymmetric synthesis

Catalyst

Potential use in organic reactions

Drug delivery

Explored for its potential use in drug delivery systems

Organometallic chemistry

Ligating properties and potential use as a ligand

Upstream product

• 1619-34-7 3-quinuclidinol 
• 59653-42-8 (-)-Aceclidine 
• 221671-41-6 (S)-quinuclidin-3-yl benzoate 
• 65732-89-0 quinuclidin-3-yl butyrate b 
• 827-61-2 3-acetoxyquinuclidine 
• 3731-38-2 3-Quinuclidinone 
• 1838-39-7 ethyl N-ethoxycarbonylmethyl-4-piperidinecarboxylate 
• 1193-65-3 3-quinuclidinone hydrochloride 
• 1200405-02-2 (S)-quinuclidin-3-ol butyric acid salt 
• 34286-16-3 2-ethoxycarbonyl-3-quinuclidinone 
• 946513-99-1 4-nitrobenzoic acid (S)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester fumarate 
• 603121-51-3 isobutyric acid 1-aza-bicyclo[2.2.2]oct-3-yl ester 

Downstream Products

• 124838-74-0 (S)-1-Butyl-3-hydroxy-1-azonia-bicyclo[2.2.2]octane; bromide 
• 124838-73-9 (S)-1-Hexyl-3-hydroxy-1-azonia-bicyclo[2.2.2]octane; bromide 
• 124838-79-5 3S-benzyloxy-4RS-(2'-hydroxyethyl)-1-benzylpiperidine 
• 124838-75-1 3S-benzyloxy-1-benzylquinuclidinium chloride 
• 124838-72-8 (S)-N-benzyl-3-hydroxyquinuclidinium chloride 
• 102585-08-0 9H-Xanthene-9-carboxylic acid (S)-(1-aza-bicyclo[2.2.2]oct-3-yl) ester 
• 107757-79-9 (S)-2-Hydroxy-2-phenyl-propionic acid (S)-(1-aza-bicyclo[2.2.2]oct-3-yl) ester 
• 107757-79-9 (R)-2-Hydroxy-2-phenyl-propionic acid (S)-(1-aza-bicyclo[2.2.2]oct-3-yl) ester 
• 107770-18-3 3(S)-<<(3-oxo-4(R),7,7-trimethyl-2-oxabicyclo<2.2.1>hept-1(S)-yl)carbonyl>oxy>-1-azabicyclo<2.2.2>octane 
• 81039-90-9 (S)-(+)-azabicyclo<2.2.2>oct-3-yl (RS)-α-hydroxy-α-(4-aminophenyl)-α-phenylacetate 
• 91704-71-1 (-)-2S,3'R-3-quinuclidinyl 2-(3-thienyl)-2-cyclohexyl-2-hydroxy-acetate 
• 91704-71-1 (+)-2R,3'R-3-quinuclidinyl 2-(3-thienyl)-2-cyclohexyl-2-hydroxy-acetate 
• 82326-69-0 (S)-1-azabicyclo<2.2.2>-oct-3-yl-(R,S)-α-hydroxy-α-(4-bromophenyl)-α-phenylacetate 
• 139563-14-7 (S,S)-IQNB 

Relevant academic research and scientific papers

Borneol dehydrogenase from Pseudomonas sp. TCU-HL1 possesses novel quinuclidinone reductase activities

Borneol dehydrogenase (BDH) catalyses the last step of the camphor biosynthetic pathway in plants and the first reaction in the borneol degradation pathway in soil microorganisms. Native or engineered BDH can be used to produce optically pure borneol and camphor. The recently reported apo-form crystal structure of BDH (PDB ID: 6M5N) from Pseudomonas sp. TCU-HL1 superimposes well with that of 3-quinuclidinone reductase (QR) (PDB ID: 3AK4) from Agrobacterium tumefaciens. QR catalyses the conversion of 3-quinuclidinone into (R)-3-(?)-quinuclidinol, an important chiral synthone for several drugs. However, the kinetic parameter, kcat, of QR was not determined in the previous reports even though both BDH and QR have various potential industrial applications. Here, we aimed to further characterise their structural and functional relationship. Recombinant QR with the native sequence was cloned, expressed in E. coli, and purified. We found that 3-quinuclidinone can be used as an alternative substrate for BDH. Only (R)-3-(?)-quinuclidinol was detected in this BDH-catalysed reaction. The results of 3 D molecular docking simulation show that 3-quinuclidinone and (+)-/(-)- borneol were docked to two different parts of the QR active site. In contrast, all three compounds are docked uniformly to the alpha-1 helix of BDH. There results explain why BDH can turnover 3-quinuclidinone, while QR can not act on (+)-/(-)-borneol.

Preparation method of optical activity 3-quinuclidinol

The invention relates to an intermediate synthesis method, belongs to the field of organic synthesis, and particularly relates to a preparation method of optical activity 3-quinuclidinol with the advantages that the operation is simple and convenient, the cost is low, and the method is suitable for industrial production. An intermediate of 3-quinuclidinol is obtained by using 4-nipecotic acid as astarting material through esterification, nucleophilic substitution, Dieckmann condensation, decarboxylation, salification, reduction, acetylization, chemical resolution and the like. The reaction formula is shown in the description.

A process for producing 3-quinuclidinone hydrochloride by oxidation of unwanted isomer 3-S-quinuclidinol

An industrially efficient method was developed synthetic process for the preparation of 3-quinuclidinone HCl by recycling of 3-S-quinuclidinol in one step sequence of oxidation process. Oxidation of secondary alcohol of 3-S-quinuclidinol which utilises complexes of a sulfide such as dimethyl sulfide with N-chlorosuccinimide to give target compound in high yield.

Microbial stereospecific reduction of 3-quinuclidinone with newly isolated Nocardia sp. and Rhodococcus erythropolis

Two bacterium strains, Nocardia sp. WY1202 and Rhodococcus erythropolis WY1406, were isolated from soil samples. They catalyzed the asymmetric reduction of 3-quinuclidinone to give enantiomeric pure (R)- and (S)-3-quinuclidinol, respectively. The optimal temperatures for the bioreduction by Nocardia sp. and R. erythropolis were 30 °C and 37 °C, respectively, while both strains showed highest activity at pH 8.0. Without external addition of expensive NADH or NADPH, (R)-3-quinuclidinol and (S)-3-quinuclidinol were obtained with 93% and 92% isolated yield and >99% enantiomeric excess. As such, microbial reduction by Nocardia sp. WY1202 or R. erythropolis WY1406 offers a new stereospecific approach to both antipodes of 3-quinuclidinol of pharmaceutical importance.

"In situ" activation of racemic RuII complexes: Separation of trans and cis species and their application in asymmetric reduction

Ruthenium(II) dichlorides with racemic atropos-biaryl-based diphosphanes and optically active 1,2-diphenylethane-1,2-diamine (DPEN) as ligands have been synthesised. trans and cis isomers were formed due to the low basicity of the diphosphane ligands, in particular, with BITIANP and BIMIP. The trans and cis species were easily separated by filtration. In particular, when rac-BITIANP was used in combination with chiral DPEN, the asymmetric separation of optically pure complexes in cis and trans arrangements was realised and they were used as precatalysts in the asymmetric hydrogenation of ketones. Matching and mismatching combinations exhibited different performances.

Chiral ruthenabicyclic complexes: Precatalysts for rapid, enantioselective, and wide-scope hydrogenation of ketones

A novel ruthenabicyclic complex with base shows excellent catalytic activity in the asymmetric hydrogenation of ketones. The turnover frequency of the hydrogenation of acetophenone reaches about 35 000 min-1 in the best case, affording 1-phenylethanol in >99% ee. Several aliphatic and base-labile ketones are smoothly converted to the corresponding alcohols in high enantioselectivity. The catalytic cycle for this hydrogenation, in which the ruthenabicyclic structure of the catalyst is maintained, is proposed on the basis of the deuteration experiment and spectroscopic analysis data.

RUTHENIUM COMPLEX AND METHOD FOR PREPARING OPTICALLY ACTIVE ALCOHOL COMPOUND

The present invention provides a novel ruthenium complex which has an excellent catalytic activity in terms of reactivity for asymmetric reduction of a carbonyl compound and enantioselectivity, a catalyst using the ruthenium complex, and a method for preparing optically active alcohol compounds using the ruthenium complex. The present invention relates to a ruthenium complex having ruthenacycle structure, a catalyst for asymmetric reduction consisting of the ruthenium complex, and a method for preparing optically active alcohol using the ruthenium complex.

Asymmetric hydrogenation of bicyclic ketones catalyzed by BINAP/IPHAN-Ru(II) complex

(Equation Presented). Hydrogenation of 3-quinuclidinone and bicyclo[2.2.2]octan-2-one with a combined catalyst system of RuCl 2[(S)-binap][(R)-iphan] and t-C4H9OK in 2-propanol afforded the chiral alcohols in 97-98% ee. 2-Diphenylmethyl-3- quinuclidinone was hydrogenated with the same catalyst to the cis alcohol with perfect diastereo-and enantioselectivity. The reaction of unsymmetrical ketones with a bicyclo[2.2.1] or-[2.2.2] skeleton gave the corresponding alcohols with high stereoselectivity.

Ruthenium complexes of chiral diphosphinite ligands with cyclohexane or chiro-inositol backbones as catalysts for asymmetric hydrogenation reactions

Treatment of [RuCl2(COD)]n with the chiral diphosphinite ligand (1S,2S)-1,2-trans-bis-(O-diphenylphosphino)cyclohexane [(1S,2S)-14] and triethylamine gives the bis(diphosphinite) complex RuHCl[(1S,2S)-14]2 (15) in good yield. If (rac)-1,2-trans-bis-(O-diphenylphosphino)-cyclohexane [(rac)-14] is used in place of (1S,2S)-14 in this reaction, a racemic mixture of RuHCl[(1S,2S)-14]2 and RuHCl[(1R,2R)-14]2 [(rac)-16] is formed. The X-ray crystal structure of (rac)-16 (2.5CH2Cl2) has been determined. Treatment of (rac)-16 with hydrogen in iso-propanol leads to the formation of a racemic mixture of RuH2[(1S,2S)-14]2 and RuH2[(1R,2R)-14]2 [(rac)-17]. The structure of (rac)-17 was confirmed by the X-ray analysis of a racemic crystal. Ruthenium mono(diphosphinite), diamine complexes of the general formula RuCl2(NN)(PP) are formed by the treatment of RuCl2(PPh3)3 with the appropriate diphosphinite (PP) and diamine (NN) ligands. In this way, the following complexes have been synthesized: RuCl2[(+)-DPEN][(1S,2S)-14] (18), RuCl2(-)-DPEN][(1S,2S)-14] (19), RuCl2[(+)-DPEN][(1R,2R)-14] (20), RuCl2[(-)-DPEN][(1R,2R)-14] (21), RuCl2[(+)-DPEN][(rac)-14] (22), RuCl2[(-)-DPEN][(rac)-14] (23), RuCl2(D-NN2)[(1S,2S)-14] (24), RuCl2(EDA)[(1S,2S)-14] (25), RuCl2(D-NN2)(D-10) (26), RuCl2(EDA)(D-10) (27), RuCl2[(+)-DPEN](D-10Et) (28), RuCl2(D-NN2)(D-10Et) (29), [where DPEN=1,2-diphenylethylenediamine, D-NN2=1D-1,2-dideoxy-1,2-diamino-3,4,5,6-tetra-O-benzyl-myo-inositol, EDA=1,2-diaminoethane, D-10=1D-3,4-bis(O-diphenylphosphino)-1,2,5, 6-tetra-O-methyl-chiro-inositol, D-10Et=1D-3,4-bis(O-diphenylphosphino)-1,2,5,6-tetra-O-ethyl-chiro-inositol]. These ruthenium complexes catalyze the hydrogenation of the ketones acetophenone and 3-quinuclidinone to give the corresponding alcohols in high yields, but with moderate to low enantiomeric excesses.