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
• Article Data: 24

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

Chemical Properties

Pale Yellow to Reddish Brown Oil

Uses

Different sources of media describe the Uses of 494-97-3 differently. You can refer to the following data:
1. (S)-Nornicotine is a metabolite of Nicotine (N412420). Can catalyze aqueous aldol reactions.
2. Agricultural or horticultural insecticide.

Definition

ChEBI: A pyridine alkaloid that is nicotine lacking the methyl group on the pyrrolidine nitrogen.

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

• 5746-86-1 rac-nornicotine 
• 54-11-5 nicotin 
• 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 
• 69730-90-1 (S)-2-pyridin-3-yl-pyrrolidine-1-carboxylic acid ethyl ester 

Relevant articles and documents

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.

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

An enantioselective domino process for the synthesis of substituted 1,2-dihydronaphthalenes has been developed by the combination of chiral amines and a bidentate Lewis acid in an orthogonal catalysis. This new method is based on an inverse electron-demand Diels?Alder and a subsequent group exchange reaction. An enamine is generated in situ from an aldehyde and a chiral secondary amine catalyst that reacts with phthalazine, activated by the coordination to a bidentate Lewis acid catalyst. The absolute configuration of the product is controlled by chiral information provided by the amine. The formed ortho-quinodimethane intermediate is then transformed via a group exchange reaction with thiols. The new method shows a broad scope and tolerates a wide range of functional groups with enantiomeric ratios up to 91 : 9. All-in-all, this enantioselective synthesis tool provides an easy access to complex 1,2-dihydronaphthalenes starting from readily available phthalazine, aldehydes and thiols in a combinatorial way.

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.