494-97-3

Basic information

• Product Name: NORNICOTINE, DL-(RG)
• Synonyms: NORNICOTINE, DL-(RG);(S)-2-(3-Pyridyl)pyrrolidine;(s)-nicotin;dl-Norcitine;l-Nor-nicotine;Nicotine, 1'-demethyl-, (S)-;Nornicotin;Pyridine, 3-(2-pyrrolidinyl)-, (S)-
• CAS NO: 494-97-3
• Molecular Formula: C₉H₁₂N₂
• Molecular Weight: 148.20498
• Product Categories: pharmacetical;Heterocycles;Metabolites & Impurities;Nicotine Derivatives
• Mol File: 494-97-3.mol

Chemical Properties

• Boiling Point: bp 270°; bp11 131°; bp3 105-107°
• Flash Point: 111.291°C
• Appearance: /
• Density: d420 1.0737
• Vapor Pressure: 0.007mmHg at 25°C
• Refractive Index: nD20 1.5378
• Storage Temp.: Refrigerator, under inert atmosphere
• Solubility: Acetonitrile (Slightly), Chloroform (Slightly), Methanol (Sparingly)
• PKA: 9.09±0.10(Predicted)
• Stability: Light Sensitive
• CAS DataBase Reference: NORNICOTINE, DL-(RG)(CAS DataBase Reference)
• NIST Chemistry Reference: NORNICOTINE, DL-(RG)(494-97-3)
• EPA Substance Registry System: NORNICOTINE, DL-(RG)(494-97-3)

Safety Data

• Hazardous Substances Data: 494-97-3(Hazardous Substances Data)

Usage

Uses

Used in Chemical Synthesis:
NORNICOTINE, DL-(RG) is used as a catalyst in the chemical synthesis industry for its ability to catalyze aqueous aldol reactions, which are important in the formation of various organic compounds.
Used in Agricultural or Horticultural Applications:
In the agricultural and horticultural industries, NORNICOTINE, DL-(RG) is used as an insecticide to protect crops and plants from pests, contributing to increased yield and better quality produce.

Safety Profile

Poison by intraperitoneal andintravenous routes. About 1/3 the toxicity of nicotine.Causes faintness, prostration, muscular weakness, severenausea, vomiting, diarrhea, and collapse withoutconvulsions. An insecticide. When heated todecomposition it em

InChI:InChI=1/C9H12N2/c1-3-8(7-10-5-1)9-4-2-6-11-9/h1,3,5,7,9,11H,2,4,6H2

Synthetic route

(S)-1-(2,3,4,6-Tetra-O-pivaloyl-β-D-galactopyranosyl)-2-(3-pyridyl)pyrrolidine (252005-64-4) → 2,3,4,6-Tetra-O-pivaloyl-α/β-D-galactopyranose (135865-76-8, 135865-81-5, 144102-44-3, 148968-87-0, 150737-36-3) + nornicotine (494-97-3)

Conditions	Yield
In hydrogenchloride; methanol Hydrolysis;	A n/a B 95%

(S)-3-(1-azido-but-3-enyl)pyridine (314280-29-0) → nornicotine (494-97-3)

Conditions	Yield
With bis(cyclohexanyl)borane In tetrahydrofuran at -15 - 20℃; for 12h;	85%

(S)-5-bromonornicotine (R)-(+)-α-methoxy-α-trifluoromethylphenyl acetic acid salt → nornicotine (494-97-3)

Conditions	Yield
Stage #1: (S)-5-bromonornicotine (R)-(+)-α-methoxy-α-trifluoromethylphenyl acetic acid salt With potassium hydroxide In water for 1h; Stage #2: With palladium 10% on activated carbon; hydrogen; triethylamine In ethanol at 20℃;	69%

rac-nornicotine (5746-86-1) → nornicotine (494-97-3)

Conditions	Yield
With borane-ammonia complex; 6-hydroxy-D-nicotine oxidase E350L/E352D mutant for 28h; Kinetics; Enzymatic reaction; enantioselective reaction;	60%
With 6,6′-dinitro[1,1′-biphenyl]-2,2′-dicarboxylic acid

nicotin (54-11-5) → nornicotine (494-97-3)

Conditions	Yield
bioconversion, by cell suspension of Nicotiana plumbaginifolia;	53.2%
With potassium permanganate
With water; silver(l) oxide

(S)-5-bromonornicotine (+)-MTPA → nornicotine (494-97-3)

Conditions	Yield
Stage #1: (S)-5-bromonornicotine (+)-MTPA With potassium hydroxide In diethyl ether Stage #2: With palladium 10% on activated carbon; hydrogen; triethylamine In ethanol for 1h;	53%

rac-nornicotine (5746-86-1) → nornicotine (494-97-3) + (+)-nornicotine (7076-23-5)

Conditions	Yield
With Chiralpak AD-H In methanol; N,N-dimethyl-ethanamine Resolution of racemate;	A 30% B 25%

nicotin (54-11-5) → nornicotine (494-97-3) + S-(-)-Norcotinine (5980-06-3) + cotinine (486-56-6) + Nicotine-N-oxide (491-26-9, 29419-54-3, 29419-55-4, 51020-67-8, 51095-86-4, 63551-14-4)

Conditions	Yield
With air; cofactor solution; phenobarbitone-induced rabbit hepatic homogenate In phosphate buffer at 37℃; for 1h; pH=7.4; Oxidation; demethylation; Further byproducts given;	A 15.9% B n/a C 27.5% D n/a

(S)-5-bromo-3-(1H-2-pyrrolidinyl)pyridine (83023-58-9) → nornicotine (494-97-3)

Conditions	Yield
With triethylamine; palladium on activated charcoal In ethanol under 760 Torr; for 1h; Yield given;
With hydrogen
With hydrogen; triethylamine; palladium on activated charcoal In ethanol under 760.051 Torr; for 1h;	621 mg

nicotin (54-11-5) → N-methylmyosmine (525-74-6) + nornicotine (494-97-3)

Conditions	Yield
In water at 28℃; for 120h; Product distribution; Cunninghamella echinulata IFO-4444; other times, other fungi;

nicotin (54-11-5) → N-formyl-2-(3-pyridyl)pyrrolidine (38840-03-8) + nornicotine (494-97-3)

Conditions	Yield
at 25℃; Nicotiana tabacum L. cv Wisconsin-38;

1-(N-methyl)-1,5-pentanediamine (32752-52-6) → N-methylanabasine (24380-92-5) + nornicotine (494-97-3) + nicotin (54-11-5) + anatabine (581-49-7)

Conditions	Yield
With Nicotiana rustica Condensation; Enzymatic reaction; Further byproducts given;

N-ethylcadaverine (258818-11-0) → N-ethylanabasine (68245-76-1) + nornicotine (494-97-3) + nicotin (54-11-5) + anatabine (581-49-7)

Conditions	Yield
With Nicotiana rustica Condensation; Enzymatic reaction; Further byproducts given;

N-(4-aminobutyl)propylamine (70862-18-9) → nornicotine (494-97-3) + nicotin (54-11-5) + anatabine (581-49-7) + N'-Propylnornicotine

Conditions	Yield
With Nicotiana rustica Condensation; Enzymatic reaction; Further byproducts given;

N-(4-aminobutyl)butylamine (70862-19-0) → nornicotine (494-97-3) + nicotin (54-11-5) + anatabine (581-49-7) + N-n-butylnornicotine

Conditions	Yield
With Nicotiana rustica Condensation; Enzymatic reaction; Further byproducts given;

N-propylcadaverine → N-propylanabasine (68245-77-2) + nornicotine (494-97-3) + nicotin (54-11-5) + anatabine (581-49-7)

Conditions	Yield
With Nicotiana rustica Condensation; Enzymatic reaction; Further byproducts given;

5-bromopyridine-3-carbaldehyde (113118-81-3) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 97 percent / Zn / tetrahydrofuran / 1 h / 20 °C 2: 100 percent / DMP / CH2Cl2 / 0.5 h / 20 °C 3: (+)-B-chlorodiisopinocampheylborane / tetrahydrofuran / -30 °C 4: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 5: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 6: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 7: H2 View Scheme
Multi-step reaction with 6 steps 1.1: DMP / CH2Cl2 1.2: tetrahydrofuran 2.1: (+)-B-chlorodiisopinocampheylborane / tetrahydrofuran / -30 °C 3.1: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 4.1: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 5.1: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 6.1: H2 View Scheme
Multi-step reaction with 5 steps 1: diethyl ether / 1 h / -100 °C 2: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 3: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 4: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 5: H2 View Scheme

5-bromo-3-pyridinecarboxylic acid (20826-04-4) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: DMF; oxalyl chloride / acetonitrile; tetrahydrofuran; pyridine / 1.5 h / -30 °C 1.2: 63 percent / CuI; tri-tert-butoxyaluminium hydride / acetonitrile; tetrahydrofuran; pyridine / 0.25 h / -78 °C 2.1: 97 percent / Zn / tetrahydrofuran / 1 h / 20 °C 3.1: 100 percent / DMP / CH2Cl2 / 0.5 h / 20 °C 4.1: (+)-B-chlorodiisopinocampheylborane / tetrahydrofuran / -30 °C 5.1: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 6.1: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 7.1: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 8.1: H2 View Scheme
Multi-step reaction with 7 steps 1.1: DMF; oxalyl chloride / acetonitrile; tetrahydrofuran; pyridine / 1.5 h / -30 °C 1.2: 63 percent / CuI; tri-tert-butoxyaluminium hydride / acetonitrile; tetrahydrofuran; pyridine / 0.25 h / -78 °C 2.1: DMP / CH2Cl2 2.2: tetrahydrofuran 3.1: (+)-B-chlorodiisopinocampheylborane / tetrahydrofuran / -30 °C 4.1: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 5.1: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 6.1: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 7.1: H2 View Scheme
Multi-step reaction with 6 steps 1.1: DMF; oxalyl chloride / acetonitrile; tetrahydrofuran; pyridine / 1.5 h / -30 °C 1.2: 63 percent / CuI; tri-tert-butoxyaluminium hydride / acetonitrile; tetrahydrofuran; pyridine / 0.25 h / -78 °C 2.1: diethyl ether / 1 h / -100 °C 3.1: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 4.1: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 5.1: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 6.1: H2 View Scheme

1-(5-bromopyridin-3-yl)but-3-en-1-ol (360767-43-7) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 100 percent / DMP / CH2Cl2 / 0.5 h / 20 °C 2: (+)-B-chlorodiisopinocampheylborane / tetrahydrofuran / -30 °C 3: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 4: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 5: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 6: H2 View Scheme

1-(5-bromopyridin-3-yl)but-3-en-1-one (360767-46-0) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: (+)-B-chlorodiisopinocampheylborane / tetrahydrofuran / -30 °C 2: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 3: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 4: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 5: H2 View Scheme

(R)-1-(5-bromopyridin-3-yl)but-3-en-1-ol (360767-40-4) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 2: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 3: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 4: H2 View Scheme

(S)-3-(1-azidobut-3-enyl)-5-bromopyridine (360767-36-8) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 2: H2 View Scheme

(R)-methanesulfonic acid 1-(5-bromopyridin-3-yl)but-3-enyl ester (360767-38-0) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 83 percent / NaN3 / dimethylformamide / 4 h / 60 °C 2: 62 percent / cyclohexene; BH3*Me2S / tetrahydrofuran / 12 h / -15 - 20 °C 3: H2 View Scheme

3-pyridinecarboxaldehyde (500-22-1) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrahydrofuran / 1 h / -100 °C 2: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 3: 97 percent / NaN3 / dimethylformamide / 4 h / 60 °C 4: 85 percent / dicyclohexylborane / tetrahydrofuran / 12 h / -15 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: tetrahydrofuran / 1 h / -100 °C 2: 88 percent / diphenylphosphorylazide; DBU / toluene / 72 h / 20 °C 3: 85 percent / dicyclohexylborane / tetrahydrofuran / 12 h / -15 - 20 °C View Scheme

(R)-1-(pyridin-3-yl)but-3-en-1-ol (314280-28-9) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 100 percent / Et3N / CH2Cl2 / 0.17 h / 0 °C 2: 97 percent / NaN3 / dimethylformamide / 4 h / 60 °C 3: 85 percent / dicyclohexylborane / tetrahydrofuran / 12 h / -15 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: 88 percent / diphenylphosphorylazide; DBU / toluene / 72 h / 20 °C 2: 85 percent / dicyclohexylborane / tetrahydrofuran / 12 h / -15 - 20 °C View Scheme

(R)-methanesulfonic acid 1-pyridin-3-yl-but-3-enyl ester (372519-16-9) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 97 percent / NaN3 / dimethylformamide / 4 h / 60 °C 2: 85 percent / dicyclohexylborane / tetrahydrofuran / 12 h / -15 - 20 °C View Scheme

4-(3-pyridyl)-4-oxobutanol (59578-62-0) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 82 percent / (COCl)2; NEt3 / dimethylsulfoxide 2.1: molecular sieves 4 Angstroem / CH2Cl2 / 16 h / 20 °C 2.2: 45 percent / NaCNBH3 / methanol; acetic acid / 16 h / 0 - 20 °C 3.1: 95 percent / aq. HCl; methanol View Scheme

4-Oxo-1-(3-pyridyl)-1-butanone (76014-80-7) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: molecular sieves 4 Angstroem / CH2Cl2 / 16 h / 20 °C 1.2: 45 percent / NaCNBH3 / methanol; acetic acid / 16 h / 0 - 20 °C 2.1: 95 percent / aq. HCl; methanol View Scheme

ethyl 5-bromo-3-pyridinecarboxylate (20986-40-7) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 4 steps 2: 79 percent / NaBH4 / methanol; acetic acid / -40 - -20 °C 4: Et3N / 10percent Pd/C / ethanol / 1 h / 760 Torr View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran 2.1: sodium tetrahydroborate; acetic acid; methanol 2.2: Resolution of racemate 3.1: potassium hydroxide / diethyl ether View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / mineral oil; hexane; tetrahydrofuran / 1 h / Reflux; Inert atmosphere 1.2: Reflux 2.1: acetic acid; sodium tetrahydroborate / methanol; acetonitrile / 0.17 h / -40 - 20 °C 3.1: ethyl acetate / 0.25 h 4.1: potassium hydroxide / diethyl ether 4.2: 1 h View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydride / mineral oil; tetrahydrofuran / 1 h / Reflux; Inert atmosphere 1.2: Reflux; Inert atmosphere 2.1: acetic acid; sodium tetrahydroborate / methanol / 0.5 h / -40 - 20 °C 3.1: ethyl acetate / 0.25 h / 20 °C 4.1: potassium hydroxide / water / 1 h 4.2: 20 °C View Scheme

5-Bromo-3-(2-pyrrolidinyl)pyridine (71719-06-7) → nornicotine (494-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 2: Et3N / 10percent Pd/C / ethanol / 1 h / 760 Torr View Scheme
Multi-step reaction with 2 steps 1.1: ethyl acetate / 0.25 h 2.1: potassium hydroxide / diethyl ether 2.2: 1 h View Scheme
Multi-step reaction with 2 steps 1.1: ethyl acetate / 0.25 h / 20 °C 2.1: potassium hydroxide / water / 1 h 2.2: 20 °C View Scheme

methyl 4-iodobutanoate (14273-85-9) + nornicotine (494-97-3) → (S)-methyl 4-(2-(pyridin-3-yl)pyrrolidin-1-yl)butanoate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	78%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	78%

methyl 6-iodohexanoate (14273-91-7) + nornicotine (494-97-3) → (S)-methyl 6-(2-(pyridin-3-yl)pyrrolidin-1-yl)hexanoate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	75%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	75%

4-(4-bromo-2-chloro-phenoxy)-benzaldehyde (1040051-31-7) + nornicotine (494-97-3) → C22H20BrClN2O

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃; for 15h; Inert atmosphere;	74%

methyl trans-γ-iodocrotonate (65495-78-5) + nornicotine (494-97-3) → methyl (E)-4-((S)-2-(pyridin-3-yl)pyrrolidin-1-yl)but-2-enoate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	73%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	73%

3-chloro-4-(4-formylphenoxy)benzamide (676494-59-0) + nornicotine (494-97-3) → (S)-3-chloro-4-(4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenoxy)benzamide (1346133-08-1)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃;	68%

(6-iodohexyl)-carbamic acid 1,1-dimethylethyl ester (172846-36-5) + nornicotine (494-97-3) → [6-[(2S)-2-(3-pyridinyl)-1-pyrrolidinyl]hexyl]-carbamic acid 1,1-dimethylethyl ester (350820-82-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 15h;	59%

benzyl 4-iodobutanoate (118058-69-8) + nornicotine (494-97-3) → (2S)-2-(3-pyridinyl)-1-pyrrolidinebutanoic acid phenylmethyl ester (350820-86-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃;	58%

N-(tert-butoxycarbonyl)piperidine-4-carboxylic acid N-(4-iodobutyl)amide + nornicotine (494-97-3) → N-(tert-butoxycarbonyl)piperidine-4-carboxylic acid N-(4-((S)-2-(pyridin-3-yl)pyrrolidin-1-yl)butyl)amide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	51%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	51%

tert-butyl 4-((5-iodopentyl)carbamoyl)piperidine-1-carboxylate + nornicotine (494-97-3) → (S)-tert-butyl 4-((5-(2-(pyridin-3-yl)pyrrolidin-1-yl)pentyl)carbamoyl)piperidine-1-carboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 18h;	49%

Upstream product

• 70862-18-9 N-(4-aminobutyl)propylamine 
• 70862-19-0 N-(4-aminobutyl)butylamine 
• 69963-21-9 4-Chloro-1-(3-pyridinyl)-1-butanone 
• 93-60-7 methyl 3-pyridinecarboxylate 
• 71278-11-0 4-amino-1-(pyridin-3-yl)-1-butanone 
• 532-12-7 Myosmine 
• 17708-87-1 5-(pyridin-3-yl)pyrrolidin-2-one 
• 74299-85-7 dimethyl 2-[(pyridin-3-yl)methylidene]malonate 
• 70898-36-1 4-amino-4-(pyridin-3-yl)butan-1-ol 

Downstream Products

• 54-11-5 nicotin 
• 5979-94-2 N-acetylnornicotine 
• 5979-92-0 N'-ethyl-S-nornicotine 
• 5979-93-1 3-((S)-1-allyl-pyrrolidin-2-yl)-pyridine 
• 16543-55-8 N'-Nitrosonornicotine 

Relevant articles and documents

Orthogonal Catalysis for an Enantioselective Domino Inverse-Electron Demand Diels?Alder/Substitution Reaction

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Method for synthesizing chiral nicotine from butyrolactone

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Preparation method of chiral nicotine synthesized by chiral tert-butyl sulfinamide

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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.

Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo

Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC50) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and activates B cells.

METHODS OF RATIONAL NICOTINE HAPTEN DESIGN AND USES THEREOF

Provided herein are methods for rational design of nicotine haptens. More particularly, provided herein are methods for designing, selecting, and synthesizing nicotine haptens and nicotine hapten conjugates. Also provided herein are novel nicotine haptens and methods for using nicotine haptens to treat nicotine addiction.

NOVEL NICOTINE DNA VACCINES

The present invention provides DNA-nanostructures comprising and at least one targeting moiety, wherein the at least one targeting moiety is linked to the DNA-nanostructure; and wherein the at least one targeting moiety is nicotine or a nicotine analogue. These compounds elicit an immunogenic response in individuals and are useful as vaccines for ameliorating nicotine dependence.

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.

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.