- Method for synthesizing chiral nicotine from butyrolactone
-
The invention discloses a method for synthesizing chiral nicotine from butyrolactone. The fumarates and γ - butyrolactone are condensed under the action of a basic catalyst to yield 4 - chloro -1 - (3 - pyridine) -1 -butanone by reaction with hydrochloric acid and reacted with a chlorination reagent to produce (- B -) S (-4 -1 -dichlorobutyl) pyridine which is reacted with an amine reagent under basic conditions to give (-3 -) -1 -methyl nicotine and (S)-3 - nicotinic acetylbutanolamines obtained by the reaction with the aminating reagent under an alkaline condition to produce a chiral hydroxy S S group - (1) S- methylnicotine or a (4 -) S nicotinic acid. The application can determine whether a methylation reaction is needed according to the type of amination reagent. The yield of (S)- nicotine was high.
- -
-
Paragraph 0057; 0060
(2021/11/03)
-
- Asymmetric preparation method of nicotine
-
The invention relates to a preparation method of nicotine, in particular to a preparation method of nicotine from nicotinic acid ester as a starting material through five-step reaction. The method comprises the following specific steps: (1) a condensation reaction of the nicotinate with N - methylpyrrolidinone in a suitable reaction vessel, and adding a strong acid to react to obtain 4 - methylamino -1 - (3 - pyridine) - butanone hydrochloride after the reaction is finished. (2) The amino group is protected with a suitable amino protecting reagent to give an intermediate (4). (3) The chiral alcohol intermediate (5) is obtained by asymmetric reduction. (4) The chiral alcohol intermediate can be converted into nicotine through two-step conversion. The asymmetric reduction reaction of metal catalysis is a key step of the method, so that the chiral alcohol intermediate with high optical activity can be obtained, and nicotine can be prepared through two-step conversion. The nicotine preparation method provided by the invention is simple to operate, low in cost, mild in reaction condition and suitable for industrial production.
- -
-
-
- Preparation method of chiral nicotine synthesized by chiral tert-butyl sulfinamide
-
The preparation method comprises the following steps: 3 - pyridine formaldehyde and chiral tert-butyl sulfinamide are subjected to condensation reaction under the action of titanate. Further, magnesium bromide reacts with (1, 3 - dioxan -2 -ethyl) magnesium bromide. Cyclization is carried out under acidic conditions. Finally, by reduction and amine methylation, chiral nicotine is obtained. The method has the advantages of short reaction route, easily available and cheap raw materials, high yield of chiral nicotine generated by reaction, high ee-value and reduced production cost of chiral nicotine.
- -
-
-
- Synthesis method of nicotine
-
The invention belongs to the technical field of nicotine synthesis, and particularly relates to a synthesis method of nicotine. The invention discloses a synthesis method of nicotine. The synthesis method comprises the following steps: S1, synthesizing 1-(1-butenyl)-3-nicotyl-2-pyrrolidone, namely reacting 1-(1-butenyl)-pyrrolidone with nicotine ethyl ester under the condition of NaH catalysis by using an N,N-dimethyl formamide solution carrier to obtain the 1-(1-butenyl)-3-nicotyl-2-pyrrolidone; S2, synthesizing 3-cyclopentenyl amino-pyridine, namely concentrating the 1-(1-butenyl) 3-nicotinyl-2-pyrrolidone obtained in the step S1 under a certain condition, so as to obtain the 3-cyclopentenyl amino-pyridine, S3, synthesis of a nicotine precursor: introducing hydrogen into 3-cyclopentenyl amino-pyridine under the action of a Pd/C catalyst to obtain the nicotine precursor; and S4, synthesizing nicotine, namely obtaining nicotine from the nicotine precursor obtained in S3 under the action of formaldehyde and formic acid, wherein the chemical formulas are shown in specification.
- -
-
-
- Preparation process of high-purity nicotine
-
The invention discloses a novel process for preparing high-purity nicotine from nicotine sulfate, and the process specifically comprises the following steps: neutralizing a 35-55% nicotine sulfate aqueous solution with a 25-35% sodium hydroxide aqueous solution, cooling the system after neutralization, keeping the temperature of the solution at 5-10 DEG C, and performing standing; performing filtering after the sodium sulfate decahydrate precipitates completely; heating the filtrate to 75-85 DEG C, standing for layering, collecting upper-layer nicotine after layering, performing drying to remove water, performing filtering to obtain coarse nicotine, and rectifying the coarse nicotine to obtain high-purity nicotine. The method can greatly reduce the consumption of the extraction agent and the energy consumption of evaporation and concentration of the extraction liquid, saves energy, reduces emission, and shortens the process time.
- -
-
Paragraph 0014-0015
(2021/04/03)
-
- Method for preparing bioactive (S)-(-)-nicotine
-
The invention relates to the field of organic synthesis, and discloses a method for preparing bioactive (S)-(-)-nicotine. The method comprises the steps of carrying out first reaction on methyl nicotinate and tert-butyl succinic acid diester, and then carrying out second reaction; and carrying out contact reaction on the system after the second reaction and an acidic material to obtain 4-oxo-4-(3-pyridyl) butyric acid; carrying out asymmetric reduction reaction on 4-oxo-4-(3-pyridyl) butyric acid and (R)-(+)-2-methyl-CBS-oxazoborane to obtain 5-(3-pyridyl) dihydrofuran-2 (3H)-ketone; carrying out third reaction on the 5-(3-pyridyl) dihydrofuran-2 (3H)-ketone and methylamine hydrobromide to obtain 1-methyl-5-(3-pyridyl)-2-pyrrolidone; and carrying out fourth reaction on the 1-methyl-5-(3-pyridyl)-2-pyrrolidone and a reducing agent to obtain the bioactive (S)-(-)-nicotine. According to the method, the bioactive body (S)-(-)-nicotine can be obtained with high yield and high purity.
- -
-
-
- Method for preparing nicotine
-
The invention relates to a method for preparing nicotine. The method comprises the following steps: (1) adding N-Cbz pyrrolidone, nicotinate, an alkaline catalyst and a reaction solvent into a reaction container, carrying out a reaction, quenching until the system is neutral, and removing the reaction solvent to obtain a first solid mixture; (2) adding the first solid mixture into an acidic solution, and carrying out a reflux reaction to obtain a second reaction mixture; and (3) adding formic acid or formate solid and a formaldehyde solution into the second reaction mixture, reacting, and purifying the product to obtain racemic nicotine. The preparation method disclosed by the invention has high yield, and the prepared racemic nicotine and the S-nicotine have high purity.
- -
-
Paragraph 0066-0067
(2020/04/22)
-
- PROCESS FOR THE PREPARATION OF (S)-NICOTIN FROM MYOSMINE
-
A process for synthetically producing (S)-nicotine ([(S)-3-(1 -methylpyrrolidin-2-yl)pyridine]) is provided.
- -
-
Page/Page column 17-20
(2020/06/05)
-
- Photorelease of Pyridines Using a Metal-Free Photoremovable Protecting Group
-
The photorelease of bioactive molecules has emerged as a valuable tool in biochemistry. Nevertheless, many important bioactive molecules, such as pyridine derivatives, cannot benefit from currently available organic photoremovable protecting groups (PPGs). We found that the inefficient photorelease of pyridines is attributed to intramolecular photoinduced electron transfer (PET) from PPGs to pyridinium ions. To alleviate PET, we rationally designed a strategy to drive the excited state of PPG from S1 to T1 with a heavy atom, and synthesized a new PPG by substitution of the H atom at the 3-position of 7-dietheylamino-coumarin-4-methyl (DEACM) with Br or I. This resulted in an improved photolytic efficiency of the pyridinium ion by hundreds-fold in aqueous solution. The PPG can be applied to various pyridine derivatives. The successful photorelease of a microtubule inhibitor, indibulin, in living cells was demonstrated for the potential application of this strategy in biochemical research.
- Dong, Zaizai,Fang, Xiaohong,Kou, Xiaolong,Tan, Weihong,Tang, Xiao-Jun,Wu, Yayun,Zhang, Zhen,Zhao, Rong,Zhou, Wei
-
supporting information
p. 18386 - 18389
(2020/08/24)
-
- Preparation method of nicotine with optical activity
-
The invention discloses a preparation method of nicotine with optical activity, which comprises the following steps: adding a nitrogen-containing or phosphorus-containing chiral ligand and a metal catalyst into an organic solvent, preparing a catalyst, sequentially adding an imine salt and a reducing agent to carry out a reduction reaction, and adding an extracting agent to extract the nicotine compound. According to the preparation method disclosed by the invention, the imine salt derivative is used as a precursor, the initial raw material cost is low, the reaction conditions are mild (for example, catalysis and reduction reactions occur in a temperature range near normal temperature), the catalyst and the reducing agent are common chemical substances, the synthesis yield and the chemicalpurity of the final product nicotine are high, and large-scale industrial production is convenient to realize.
- -
-
Paragraph 0061-0063; 0095-0097
(2020/06/20)
-
- PREPARATION OF RACEMIC NICOTINE BY REACTION OF ETHYL NICOTINATE WITH N-VINYLPYRROLIDONE IN THE PRESENCE OF AN ALCOHOLATE BASE AND SUBSEQUENT PROCESS STEPS
-
The present invention relates to a method of preparing racemic nicotine comprising: (i) reacting ethyl nicotinate and N-vinylpyrrolidone in the presence of an alcoholate base to 3-nicotinoyl-1-vinylpyrrolidin-2-one; (ii) reacting the 3-nicotinoyl-1-vinylpyrrolidin-2-one with an acid to myosmine; (iii) reducing the myosmine to nornicotine using a reducing agent; and (iv) methylating the nornicotine to obtain the racemic nicotine.
- -
-
Page/Page column 17
(2019/07/13)
-
- ENANTIOMERIC SEPARATION OF RACEMIC NICOTINE BY ADDITION OF AN O,O'-DISUBSTITUTED TARTARIC ACID ENANTIOMER
-
The present invention relates to a method of separating racemic nicotine of Formula (l-a) as a mixture of the (R)- and (S)-enantiomers into the enantiomerically pure (S)- and (R)-nicotine represented by Formula (l-b) and (l-c), by adding a mixture of the L- and the D-enantiomer of a O,O'-disubstituted tartaric acid, wherein the molar ratio of the L- to the D-enantiomer is from 80:20 to 95:5, and obtaining the (S)-nicotine of formula (l-b), or by adding O,O'-dibenzoyl-D-tartaric acid and obtaining the (R)-nicotine of formula (l-c).
- -
-
Page/Page column 18; 19; 20
(2019/07/13)
-
- Preparation method of artificially synthesized nicotine
-
The invention discloses a preparation method of artificially synthesized nicotine, and belongs to the technical field of chemical synthesis. According to the synthesis method of a racemate (+/-)-(R,S)-nicotine and a natural optical active enantiomer (-)-(S)-nicotine, nicotinate and diester of succinic acid (or N-alkyl succinimide) are taken as the primary raw materials; and defects of a conventional nicotine synthesis technology such as difficulty for massive production, high cost, and the like, are overcome. Specifically, the provided synthesis method has the advantages that the primary raw materials are easily available, the preparation technology is simple, the cost is low, the prepared nicotine does not contain any other harmful tobacco compound, and the preparation method is suitable for industrial large-scale production.
- -
-
-
- Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
-
A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.
- Hellinghausen, Garrett,Lopez, Diego A.,Lee, Jauh T.,Wang, Yadi,Weatherly, Choyce A.,Portillo, Abiud E.,Berthod, Alain,Armstrong, Daniel W.
-
p. 1067 - 1078
(2018/08/01)
-
- Methods of using QIAPINE
-
Uses of QIAPINE? to treat internal bleeding, such as subdural hematoma and subarachinoid hemorrhage, and ocular bleeding, such as such as hyphema and vitreous hemorrhage, in a subject are described. Also described are uses of QIAPINE? to treat vision loss resulting from hyphema or vitreous hemorrhage.
- -
-
-
- SYNTHESIS AND RESOLUTION OF NICOTINE
-
The present disclosure generally relates to methods of preparing nicotine and resolving R,S nicotine to enrich the (S)(?) enantiomer. The method may comprise combining N-methyl-2-pyrrolidone or a salt thereof with a nicotinate compound in the presence of a solvent and a strong base to form 1-methyl-3-nicotinoyl-2-pyrrolidone or a salt thereof; and reducing the 1-methyl-3-nicotinoyl-2-pyrrolidone or salt thereof in solution with Na2S2O4 to produce racemic nicotine or salt thereof. Resolving the racemic nicotine (or other enantiomeric mixture) may comprise combining the nicotine with (?)-O,O′-di-p-toluoyl-L-tartaric acid (L-PTTA).
- -
-
-
- Nicotine and pesticide poisonous chenopodium album method for the asymmetric synthesis of alkali
-
The invention relates to an asymmetric synthesis method for botanical pesticide nicotine and anabasine. The low-cost and easily acquired 2,5-dibromopyridine is taken as an initial raw material and is processed in two steps, so that the hydrogenation precursor annular imine is acquired; under the induction of the chiral catalyst, iridium-phosphine oxazoline, an important hydrogenated product intermediate is acquired through high enantioselectivity; the intermediate is processed in two steps, so that L-nicotine is acquired; the intermediate is converted into L-anabasine in one step. The asymmetric hydrogenation of the annular imine containing pyridine gene is taken as the key step of the method. According to the invention, the chiral catalyst, iridium-phosphine oxazoline, is used for catalyzing the asymmetric hydrogenation and the key intermediate with ultrahigh ee value is acquired, and then the methylation and reduction bromine-removing two-step reaction is performed for converting, so that the target products, natural nicotine and anabasine, are acquired. According to the invention, the operation is stable, the purity is high and the cost is low.
- -
-
-
- Iridium-catalyzed asymmetric hydrogenation of 2-pyridyl cyclic imines: A highly enantioselective approach to nicotine derivatives
-
A highly efficient asymmetric hydrogenation of cyclic imines containing a pyridyl moiety was established by using iridium catalysts with chiral spiro phosphine-oxazoline ligands. This process will facilitate the development of new nicotine-related pharmaceuticals. The introduction of a substituent at the ortho position of the pyridyl ring to reduce its coordinating ability ensures the success of the hydrogenation and excellent enantioselectivity.
- Guo, Cui,Sun, Dong-Wei,Yang, Shuang,Mao, Shen-Jie,Xu, Xiao-Hua,Zhu, Shou-Fei,Zhou, Qi-Lin
-
-
- Ring Opening of Donor-Acceptor Cyclopropanes with the Azide Ion: A Tool for Construction of N-Heterocycles
-
A general method for ring opening of various donor-acceptor cyclopropanes with the azide ion through an SN2-like reaction has been developed. This highly regioselective and stereospecific process proceeds through nucleophilic attack on the more-substituted C2 atom of a cyclopropane with complete inversion of configuration at this center. Results of DFT calculations support the SN2 mechanism and demonstrate good qualitative correlation between the relative experimental reactivity of cyclopropanes and the calculated energy barriers. The reaction provides a straightforward approach to a variety of polyfunctional azides in up to 91% yield. The high synthetic utility of these azides and the possibilities of their involvement in diversity-oriented synthesis were demonstrated by the developed multipath strategy of their transformations into five-, six-, and seven-membered N-heterocycles, as well as complex annulated compounds, including natural products and medicines such as (-)-nicotine and atorvastatin. A new world of opportunities: Stereospecific ring opening of donor-acceptor cyclopropanes with the azide ion gives rise to densely functionalized building blocks that are valuable for the assembly of a diverse range of N-heterocycles (see scheme; EDG=electron donating group; EWG=electron withdrawing group). These synthetic opportunities are provided by the simultaneous presence of the N3 group, which reacts as a latent amine or 1,3-dipole, easily modifiable donor and acceptor substituents, as well as the activated CH fragment.
- Ivanov, Konstantin L.,Villemson, Elena V.,Budynina, Ekaterina M.,Ivanova, Olga A.,Trushkov, Igor V.,Melnikov, Mikhail Ya.
-
supporting information
p. 4975 - 4987
(2015/03/18)
-
- Development of an R-selective amine oxidase with broad substrate specificity and high enantioselectivity
-
Amine oxidases are useful bio-catalysts for the synthesis of enantiomerically pure 1°, 2° and 3° chiral amines. Enzymes in this class (e.g., MAO-N from Aspergillus niger) reported previously have been shown to be highly S selective. Herein we report the development of an enantiocomplementary R-selective amine oxidase based on 6-hydroxy-D-nicotine oxidase (6-HDNO) with broadened substrate scope and high enantioselectivity. The engineered 6-HDNO enzyme has been applied to the preparative deracemisation of a range of racemic amines to yield S-configured products, for example, (S)-nicotine, in high ee. Nicotine rush: An R-selective amine oxidase based on 6-hydroxy-D-nicotine oxidase (6-HDNO) with broadened substrate scope and high enantioselectivity has been developed. The engineered 6-HDNO enzyme is applied to the preparative deracemization of a range of racemic amines to yield S-configured products, for example, (S)-nicotine, in high ee.
- Heath, Rachel S.,Pontini, Marta,Bechi, Beatrice,Turner, Nicholas J.
-
p. 996 - 1002
(2014/05/06)
-
- Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes
-
Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology. Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts. To address this, we show that incorporation of a d 6 -piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis. To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades. Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine and (iv) regeneration of NADH to promote a monooxygenase-catalysed oxyfunctionalization reaction.
- Koehler,Wilson,Duerrenberger,Ghislieri,Churakova,Quinto,Knoerr,Haeussinger,Hollmann,Turner,Ward
-
-
- PROCESS FOR THE RESOLUTION OF (R,S)-NICOTINE
-
(R,S)-Nicotine was resolved through diastereomeric salt formation using dibenzoyl-d-tartaric acid and dibenzoyl-l-tartaric acid to obtain enantiomerically pure (S)-nicotine and (R)-nicotine.
- -
-
Page/Page column 3
(2012/08/08)
-
- A process for the resolution of (R,S)-nicotine
-
(R,S)-Nicotine was resolved through diastereomeric salt formation using dibenzoyl-d-tartaric acid and dibenzoyl-l-tartaric acid to obtain enantiomerically pure (S)-nicotine and (R)-nicotine.
- -
-
-
- Reduction of amine N-oxides by diboron reagents
-
Facile reduction of alkylamino-, anilino-, and pyridyl-N-oxides can be achieved via the use of diboron reagents, predominantly bis- (pinacolato)- and in some cases bis(catecholato)diboron [(pinB)2 and (catB)2, respectively]. Reductions occur upon simply mixing the amine N oxide and the diboron reagent in a suitable solvent, at a suitable temperature. Extremely fast reductions of alkylamino- and anilino-N-oxides occur, whereas pyridyl-N-oxides undergo slower reduction. The reaction is tolerant of a variety of functionalities such as hydroxyl, thiol, and cyano groups, as well as halogens. Notably, a sensitive nucleoside N-oxide has also been reduced efficiently. The different rates with which alkylamino- and pyridyl-N-oxides are reduced has been used to perform stepwise reduction of the N,N-dioxide of (S)-(-)-nicotine. Because it was observed that (pinB)2 was unaffected by the water of hydration in amine oxides, the feasibility of using water as solvent was evaluated. These reactions also proceeded exceptionally well, giving high product yields. In constrast to the reactions with (pinB)2, triethylborane reduced alkylamino-N oxides, but pyridine N-oxide did not undergo efficient reduction even at elevated temperature. Finally, the mechanism of the reductive process by (pinB)2 has been probed by 1H and 11B NMR. (Figure presented) ; 2011 American Chemical Society.
- Kokatla, Hari Prasad,Thomson, Paul F.,Bae, Suyeal,Doddi, Venkata Ramana,Lakshman, Mahesh K.
-
experimental part
p. 7842 - 7848
(2011/12/01)
-
- Enantioselective, palladium-catalyzed α-arylation of N-Boc pyrrolidine: In situ react IR spectroscopic monitoring, scope, and synthetic applications
-
A comprehensive study of the enantioselective Pd-catalyzed α-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et2O at -78 °C, transmetalation with ZnCl2 and Negishi coupling using Pd(OAc)2, t-Bu3P-HBF4 and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation-Negishi coupling reaction; extension to a wide range of heteroaromatic bromides; total synthesis of (R)-crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and examples of α-vinylation of N-Boc pyrrolidine using vinyl bromides exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus establishing its configuration as (R)). In this way, the full scope and limitations of the methodology are delineated.
- Barker, Graeme,McGrath, Julia L.,Klapars, Artis,Stead, Darren,Zhou, George,Campos, Kevin R.,O'Brien, Peter
-
experimental part
p. 5936 - 5953
(2011/10/09)
-
- The pyrolysis of (-)-(S)-nicotine: Racemization and decomposition
-
The pyrolytic behaviour of (1)-(S)-nicotine in methanol was investigated using on-line pyrolysis GC/MS to establish whether racemization to the R(+) antipode occurs and to identify other products of pyrolysis. The conditions used included pyrolysing the sample for 15 seconds in an atmosphere of 9% oxygen in nitrogen (275ml/min total flow) across the temperature range of 200°C-1000°C. A chiral Cyclodex-B analytical column (30m × 0.25mm i.d. × 0.25 μm film thickness) was used to separate the enantiomers of nicotine, although the two enantiomer peaks were not baseline resolved. The results of the experiment shows that there is no increase in (+)-(R)-nicotine levels across a wide temperature range. This suggests that the elevated levels of (+)-R-nicotine observed in tobacco smoke (compared to tobacco leaf material) are not due to the pyrolytic auto-racemization of (1)-(S)-nicotine but are a result of more complex interactions between (-)-(S)-nicotine and other smoke components. The pyrolysis of isotopically labelled nicotine established that nicotine undergoes thermal decomposition to β-nicotyrine which in turn may decompose to other products. Chirality 22:442-446, 2010.
- Clayton, Peter,Lu, Annhelen,Bishop, Louise
-
experimental part
p. 442 - 446
(2010/08/06)
-
- Enantioselective syntheses of 2-substituted pyrrolidines from allylamines by domino hydroformylation-condensation: Short syntheses of (S)-nicotine and the alkaloid 225C
-
Short routes to chiral 2-substituted pyrrolidines based on rhodium-catalyzed hydroformylations of allylamines and their N-alkyl and N-acyl derivatives, which were prepared by asymmetric allylic substitutions, are described. The outcome of the hydroformyla
- Dübon, Pierre,Farwick, Andreas,Helmchen, Günter
-
scheme or table
p. 1413 - 1416
(2009/10/23)
-
- Hydroformylation of homoallylic azides: A rapid approach toward alkaloids
-
(Chemical Equation Presented) Unprecedented hydroformylation of homoallylic azides combined with useful one-pot operations provides an expeditive access to alkaloids.
- Spangenberg, Thomas,Breit, Bernhard,Mann, Andre
-
supporting information; experimental part
p. 261 - 264
(2009/08/08)
-
- Esters of pyromellitic acid. Part II. Esters of chiral alcohols: Para pyromellitate diesters as a novel class of resolving agents and use of pyromellitates as duplicands for chiral purification
-
(Chemical Equation Presented) Methods are presented for the preparation of pyromellitate esters of chiral terpene alcohols, including d-(3) or l-menthol (4), d-isomenthol (7), l-borneol (8), or d- (5) or l-isopinocampheol (6). Alcoholysis of PMDA in CH2Cl2/Et3N led to the formation of monoesters (e.g., 18) or diesters (11, 12), as needed, relying on the differential reactivity of the two anhydride groups. The easily isolated para diester (11) crystallized before the meta diester (12) from HOAc. Nicotine (1, 14) was efficiently resolved as 1:1 salts with the menthyl (11a, 11b) or bornyl (11f) para diesters, prototypes of what promises to be a large class of novel resolving agents. Recrystallization of para-di-d-menthyl pyromellitate (11a) greatly improved the chiral purity of the contained d-menthol (3), an example of purification by "duplication". An alternative synthesis of specific diesters took advantage of the easily separated benzyl diesters and their derived acid chlorides (19, 21), with the benzyl esters serving as temporary blocking groups removable by catalytic hydrogenolysis. Pyromellitate tetraesters (26) were prepared by base-catalyzed transesterification of the tetraethyl ester (25). Tri-l-menthyl pyromellitate (27b) was obtained by catalytic hydrogenolysis of benzyl tri-l-menthyl pyromellitate (31b), itself prepared from the alcoholysis of benzyl pyromellitate triacid chloride (30) with l-menthol (4).
- Paine III, John B.
-
p. 4939 - 4948
(2008/12/21)
-
- Regioselective 5-, 4-, and 2-substitution of (S)-6-chloronicotine and 4-substitution of (S)-5-chloronicotine
-
A variety of novel 2-, 4-, and 5-substituted 6-chloronicotine and 4-substituted 5-chloronicotine derivatives have been synthesized in a regioselective manner in moderate to high yield from (S)-6-chloronicotine and (S)-5-chloronicotine, respectively. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Wagner, Florence F.,Comins, Daniel L.
-
p. 3562 - 3565
(2007/10/03)
-
- Enantioselective synthesis of (+)(R)- And (-)(S)-nicotine based on Ir-catalysed allylic amination
-
The synthesis of nicotine with enantiomeric excess of >99% ee was accomplished by asymmetric Ir-catalysed allylic amination followed by ring closing metathesis and racemisation-free double bond reduction. The Royal Society of Chemistry 2005.
- Welter, Carolin,Moreno, Rosa M.,Streiff, Stephane,Helmchen, Guenter
-
p. 3266 - 3268
(2007/10/03)
-
- Studies on the diastereoselective allylation of aldehydes with enantiopure 2-sulfinylallyl building blocks
-
A comparative study on the allylation of aldehydes with enantiopure (SS)-2-(p-tolylsulfonyl)-prop-2-en-1-ol (SS)-1a and the corresponding chloride (SS)-1b under two different reaction systems is reported. In general, better yields were obtained from chloride (SS)-1b, whereas higher diastereoinduction was observed from alcohol (SS)-1a. The sense of diastereoinduction is the same in both systems and the stereochemistry of the major diastereomer has been determined. Moreover, the configurational stability of the sulfoxide group on the resulting sulfinyl homoallylic alcohols 3 has been proven in each reaction system, which demonstrates the efficiency of the sulfoxide group as chiral auxiliary in these allylation processes. Finally, as an example of the synthetic potential of the resulting adducts, a total synthesis of natural enantioenriched (S)-nicotine from sulfinylalcohol 3h is reported.
- Marquez, Francesc,Llebaria, Amadeu,Delgado, Antonio
-
p. 1625 - 1634
(2007/10/03)
-
- Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco
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An enantiomeric synthesis of six piperidine and pyrrolidine alkaloids, (S)-nornicotine 1, (S)-nicotine 2, (S)-anatabine 3, (S)-N-methylanatabine 4, (S)-anabasine 5, and (S)-N-methylanabasine 6, known as natural products in tobacco, was established from a common chiral homoallylic (S)-3-(1-azidobut-3-enyl)-pyridine 15. An intramolecular hydroboration-cycloalkylation of the homoallylic azide intermediate 15 served as the key step in the pyrrolidine ring formation. A ring closing metathesis reaction (RCM) of a diethylenic amine intermediate (S)-allyl-(1-pyridin-3-yl-but-3-enyl)-carbamic acid benzyl ester 20 served as the key step in the piperidine ring formation. From the commercially available 3-pyridinecarboxaldehyde 13, a short and convenient enantiomeric synthesis of tobacco alkaloids is described: (S)-nornicotine I (5 steps, with an overall yield of 70%), (S)-hicotine 2 (6 steps, 65%), (S)-anatabine 3 (8 steps, 30%), (S)-N-methylanatabine 4 (8 steps, 25%), (S)-anabasine 5 (8 steps, 35%), and (S)-N-methylanabasine 6 (8 steps, 25%).
- Felpin,Girard,Vo-Thanh,Robins,Villieras,Lebreton
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p. 6305 - 6312
(2007/10/03)
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- Metabolism of N-alkyldiamines and N-alkylnortropinones by transformed root cultures of Nicotiana and Brugmansia
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A range of analogues of N-methylputrescine and tropinone were fed to transformed root cultures of Nicotiana rustica and/or a Brugmansia candida x aurea hybrid. These cultures were made by the transformation of the relevant plant species with Agrobacterium rhizogenes. A number of the metabolites, notably those showing a relatively modest alteration in the N-alkyl substituent, were metabolized in vivo to form homologues of the normal alkaloids biosynthesized by these roots. These products were identified by GC/MS and comparison with some synthetic reference materials. Analogues with major alterations in the size of the N-alkyl substituent were not metabolized at all. In the N. rustica cultures, the analogues fed at 1 mM significantly affected the profile of normal alkaloids, with up to a 4-fold diminution in nicotine being found in the presence of N-n-propylputrescine. The ratio between alkaloids of the pyrrolidine series and the piperideine series was also affected. In contrast, the presence of the analogues in the B. candida x aurea hybrid culture at 1 mM did not inhibit or substantially interfere with the accumulation of the normal spectrum of alkaloids. The potential for using these cultures to make complex novel products from simple precursors is discussed.
- Boswell, Henry D.,Draeger, Birgit,Eagles, John,McClintock, Carol,Parr, Adrian,Portsteffen, Andreas,Robins, David J.,Robins, Richard J.,Walton, Nicholas J.,Wong, Chi
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p. 855 - 869
(2007/10/03)
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- Di and trisubstituted pyridines
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Substituted pyridines of the general formula: STR1 wherein R1 is hydroxyl or chlorine, and a) X is hydrogen or chlorine, R2 and R3 together are =O, R4 is a group of the formula --OR5 and R5 is hydrogen, C1 -C4 -alkyl or benzyl, or b) X is hydrogen and R2, R3 and R4 together are =N--NH--, or c) X and R2 each is hydrogen and R3 and R4 together are --O--, or d) X and R2 each is hydrogen, R3 is hydroxyl and R4 is amino or hydroxyl. The compounds are obtained by subjecting nicotine to microbiological oxidation to give 5-succinoyl-2-pyridone, followed by chemical reactions. The compounds are suitable as intermediates for the preparation of pharmaceutically active compounds.
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- A Practical and Efficient Synthesis of the Selective Neuronal Acetylcholine-Gated Ion Channel Agonist (S)-(-)-5-Ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine Maleate (SIB-1508Y)
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An efficient, high-yielding synthetic procedure for the preparation of the novel neuronal acetylcholinegated ion channel agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine maleate [(S)-2, SIB-1508Y] is described. The key steps in the process include the lithium bis(trimethylsilyl)amide-mediated acylation of N-vinylpyrrolidinone with ethyl 5-bromonicotinate, a high-yielding sodium borohydride reduction of imine 5, and a new heteroaryl-alkyne cross-coupling protocol for the introduction of the ethyne moiety in (S)-2. The preparation of enantiomerically pure (S)-2 was accomplished via a combination of enantioselective reduction of imine 5 and crystallization of enantiomerically enriched 5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine (7) as the dibenzoyl-L-tartaric acid salt.
- Bleicher, Leo S.,Cosford, Nicholas D. P.,Herbaut, Audrey,Stuart McCallum,McDonald, Ian A.
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p. 1109 - 1118
(2007/10/03)
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- Compositions and method comprising aminoalcohol derivatives as membrane penetration enhancers for physiological active agents
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A method and compositions for enhancing absorption of topically administered physiologically active agents through the skin and mucous membranes of humans and animals in a transdermal device or formulation for local or systemic use, comprising a therapeutically effective amount of a pharmaceutically active agent and a non-toxic, effective amount of penetration enhancing agent of the formula I or a physiologically acceptable salt thereof: STR1 wherein: R1, R2, R3 and R4 are as defined herein.
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- Use of disulfonyl methanes for the control of parasites
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The present invention is directed to the use of disulfonyl methane compounds for the control of parasites in vertebrate animals.
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- REDUCTION OF N-OXIDE WITH BAKER'S YEAST
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Reduction of N-oxides with baker's yeast has been examined.In the reduction of acetylpyridine N-oxides, selective reduction takes place to give chiral pyridylethanol N-oxides.
- Takeshita, Mitsuhiro,Yoshida, Sachiko
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p. 871 - 874
(2007/10/02)
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- Enantioselective Hydrosilylation and Hydrogenation of Alkaloid Precursors
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Enantioselective hydrosilylations of the 3,4-dihydropyrrole derivatives 1a-c and 5 with in-situ catalysts consisting of 2 and optically active phosphines yield the N-silyl compounds 2a-c and 6 in up to 66.1percent ee.The N-silyl derivatives were treated with acetic formic anhydride or trifluoroacetic anhydride to give the N-formyl and N-trifluoroacetyl compounds 3a-c, 4a-c, 7, and 8.The alkaloids nicotine and macrostomine were synthesized with 63.3 and 33percent ee by reduction of the N-formyl compounds 8 and 12.Enantioselective hydrogenations of the N-formyl and N-trifluoroacetyl-2-phenylpyrrolines 14 and 15 with the same in-situ catalysts produce the cyclic amides 3a and 4a in up to 36.1percent ee.
- Brunner, Henri,Kuerzinger, Alfred,Mahboobi, Siavosh,Wiegrebe, Wolfgang
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- APPLICATIONS OF ATMOSPHERIC GASES IN HIGH PRESSURE EXTRACTION.
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This study presents results of solubility measurements as well as extraction experiments using CO//2 and mixtures of CO//2 with atmospheric gases like N//2 or Ar as solvents under high pressures. Influences of additional components to a single component gaseous solvent are discussed with respect to solvent properties and possible new applications of the HPE-process.
- Gaehrs
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p. 894 - 897
(2007/10/02)
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- Synthesis and preliminary binding studies of 4,4-ditritio(-)nicotine of high specific activity
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4,4-Ditritio-(-)nicotine (5) of high specific activity (4.7 Ci/mmol) has been synthesized from (-) nicotine via the readily prepared 4,4-dibromocotinine. Scatchard analysis of the binding of 5 to the crude mitochondrial fraction of whole rat brain revealed a K(a) of 4.7 x 106 M-1 and 13 fmol of binding sites/mg of protein.
- Vincek,Martin,Aceto,Bowman
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p. 960 - 962
(2007/10/02)
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This product is a nationally controlled contraband, and the Lookchem platform doesn't provide relevant sales information.
