78306-92-0

Basic information

• Product Name: D-1-Naphthylalanine
• Synonyms: 1-Naphthyl-D-Alanine;3-(1-NAPHTHYL)-D-ALANINE·HCL 99%;(2R)-2-amino-3-naphthalen-1-ylpropanoic acid;3-Naphth-1-yl-D-phenylalanine;3-(1-NAPHTHYL)-D-ALANINE 99% MIN;3-Naphth-1-yl-D-alanine;D-1-Nal-OH;H-D-1-Nal-OH ,98%
• CAS NO: 78306-92-0
• Molecular Formula: C₁₃H₁₃NO₂
• Molecular Weight: 215.25
• Product Categories: Amino Acids;Phenylalanine analogs and other aromatic alpha amino acids;Alanine [Ala, A];Unusual Amino Acids;Amino hydrochloride;Amino Acids;I - Z;Modified Amino Acids;a-amino
• Mol File: 78306-92-0.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 412.3 °C at 760 mmHg
• Flash Point: 203.2 °C
• Appearance: /Solid
• Density: 1.254 g/cm³
• Vapor Pressure: 1.14E-08mmHg at 25°C
• Refractive Index: 1.678
• Storage Temp.: 2-8°C
• Solubility: 2 M HCl: 50 mg/mL, clear, yellow
• PKA: 2.21±0.30(Predicted)
• CAS DataBase Reference: D-1-Naphthylalanine(CAS DataBase Reference)
• NIST Chemistry Reference: D-1-Naphthylalanine(78306-92-0)
• EPA Substance Registry System: D-1-Naphthylalanine(78306-92-0)

Safety Data

• Hazard Codes: Xi
• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 78306-92-0(Hazardous Substances Data)

Usage

Uses

3-(1-Naphthyl)-D-alanine is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff.

InChI:InChI=1/C13H13NO2/c1-9(13(15)16)14-12-8-4-6-10-5-2-3-7-11(10)12/h2-9,14H,1H3,(H,15,16)/t9-/m1/s1

Synthetic route

(R)-3-Naphthalen-1-yl-2-((4S,5R)-2-oxo-4,5-diphenyl-oxazolidin-3-yl)-propionic acid benzyl ester (161633-96-1) → 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
With hydrogen; palladium dihydroxide In tetrahydrofuran; methanol under 3102.9 Torr; for 19h;	89%

(R)-2-Acetylamino-3-naphthalen-1-yl-propionic acid ethyl ester (136086-24-3) → 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
With hydrogenchloride for 2h; Heating;	55%

2-amino-3-naphthalen-1-yl-propionic acid tert-butyl ester; hydrochloride → L-1-naphthylalanine (55516-54-6) + 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
With hydrogenchloride Heating;

diethyl (N-acetylamino)[(1-naphthyl)methyl]malonate (5440-57-3) → 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 87 percent / 1 M NaOH / aq. ethanol / 6 h / Ambient temperature 2: 94 percent / 0.17 h / 160 °C 3: 96 percent 4: 55 percent / 6 N aq. HCl / 2 h / Heating View Scheme

2-Acetylamino-2-naphthalen-1-ylmethyl-malonic acid monoethyl ester (136015-49-1) → 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / 0.17 h / 160 °C 2: 96 percent 3: 55 percent / 6 N aq. HCl / 2 h / Heating View Scheme

2-Acetylamino-3-naphthalen-1-yl-propionic acid ethyl ester (125761-75-3) → 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96 percent 2: 55 percent / 6 N aq. HCl / 2 h / Heating View Scheme

2-(bromomethyl)naphthalene (3163-27-7) → 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 90 percent / EtONa / ethanol / 6 h / Heating 2: 87 percent / 1 M NaOH / aq. ethanol / 6 h / Ambient temperature 3: 94 percent / 0.17 h / 160 °C 4: 96 percent 5: 55 percent / 6 N aq. HCl / 2 h / Heating View Scheme

2-amino-3-(1-naphthyl)propanoic acid (28095-56-9) → L-1-naphthylalanine (55516-54-6) + 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
With chiral stationary phase including isopropyl-functionalized CF6 In methanol; acetic acid; triethylamine; acetonitrile at 0℃; Purification / work up;

2-amino-3-(1-naphthyl)propanoic acid (28095-56-9) → 3-(naphthalene-1-yl)-2-oxopropanoic acid (62741-58-6) + 3-(1-naphthyl)-D-alanine (78306-92-0)

Conditions	Yield
With L-amino acid deaminase from Proteus myxofaciens; oxygen In aq. phosphate buffer pH=7; Kinetics; Enzymatic reaction;
With L-amino acid deaminase from Proteus myxofaciens F318A/V412A/V438P mutant In aq. phosphate buffer at 25℃; for 2h; pH=7.5; Kinetics; Reagent/catalyst; Concentration; Resolution of racemate; Enzymatic reaction;

3-(1-naphthyl)-D-alanine (78306-92-0) + (1S,3E)-5-<(2,5-dioxo-1-pyrrolidinyl)oxy>-1-<(1R,2E)-1-methyl-3-phenyl-2-propenyl>-5-oxo-3-pentenyl-(2S)-<3-<<(1,1-dimethylethoxy)carbonyl>amino>-2,2-dimethyl-1-oxopropoxy>-4-methylpentanoate (188346-51-2) → N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-3-(1-naphthalenyl)-D-alanine (240428-62-0)

Conditions	Yield
With N,O-bis-(trimethylsilyl)-acetamide In N,N-dimethyl-formamide at 55 - 60℃;	77%

2-(4-(triphenylmethylthio)phenyl)acetic acid (883566-52-7) + D-norleucine (327-56-0) + Boc-(R)-Ala (3744-87-4, 7764-95-6, 15761-38-3) + N-Boc-O-benzyl-L-threonine (15260-10-3) + L-4-fluorophenylalanine (1132-68-9) + Boc-Arg(MTS)-OH (68262-71-5) + Boc-Trp-OH (13139-14-5) + 3-(1-naphthyl)-D-alanine (78306-92-0) + Nα-t-butoxycarbonyl-Nδ-xanthydryl-L-glutamine (55260-24-7) → C83H116FN25O15S

Conditions

Yield

Stage #1: 2-(4-(triphenylmethylthio)phenyl)acetic acid With phosphorus tribromide; N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide for 18h; Stage #2: With triethylsilane; trifluoroacetic acid In dichloromethane; water; N,N-dimethyl-formamide Stage #3: D-norleucine; Boc-(R)-Ala; N-Boc-O-benzyl-L-threonine; L-4-fluorophenylalanine; Boc-Arg(MTS)-OH; Boc-Trp-OH; 3-(1-naphthyl)-D-alanine; Nα-t-butoxycarbonyl-Nδ-xanthydryl-L-glutamine Further stages;

16%

...Expand

3-(1-naphthyl)-D-alanine (78306-92-0) + CR 2194 (137795-35-8) → (R)-2-[(R)-5-(8-Aza-spiro[4.5]dec-8-yl)-4-(3,5-dichloro-benzoylamino)-5-oxo-pentanoylamino]-3-naphthalen-1-yl-propionic acid

Conditions	Yield
With chloroformic acid ethyl ester; triethylamine 1.) THF, -10 deg C, 15 min, 2.) THF, DMF, H2O, a) -10 deg C, 1 h, b) RT, overnight; Multistep reaction;

methanol (67-56-1) + 3-(1-naphthyl)-D-alanine (78306-92-0) → D-3-(1-naphthyl)alanine methylester (223771-37-7)

Conditions	Yield
With hydrogenchloride at 0 - 20℃; for 18h; Fischer esterification;
Stage #1: methanol; 3-(1-naphthyl)-D-alanine With chloro-trimethyl-silane at 20℃; Stage #2: With triethylamine In methanol; diethyl ether at -10℃; for 1h;

3-(1-naphthyl)-D-alanine (78306-92-0) → 3-(naphthalene-1-yl)-2-oxopropanoic acid (62741-58-6)

Conditions	Yield
With oxygen; D-amino acid oxidase (M213G mutant, Rhodotorula gracilis) In phosphate buffer at 25℃; pH=8.5; Enzyme kinetics; Enzymatic reaction;
With oxygen; D-amino acid oxidase (wild type, yeast Rhodotorula gracilis) In phosphate buffer at 25℃; pH=8.5; Enzyme kinetics; Enzymatic reaction;

3-(1-naphthyl)-D-alanine (78306-92-0) → (2R)-2-[(2-bromobenzoyl)amino]-3-naphthalen-1-ylpropanoic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: HCl (gas) / 18 h / 0 - 20 °C 2: EDC; HOBT; DIPEA / dimethylformamide / 2 h / 20 °C 3: aq. LiOH / tetrahydrofuran / 1 h / 20 °C View Scheme

3-(1-naphthyl)-D-alanine (78306-92-0) → (R)-2-(2-Bromo-benzoylamino)-3-naphthalen-1-yl-propionic acid methyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl (gas) / 18 h / 0 - 20 °C 2: EDC; HOBT; DIPEA / dimethylformamide / 2 h / 20 °C View Scheme

3-(1-naphthyl)-D-alanine (78306-92-0) → D-3-(1-naphthyl)alanine methylester (223771-37-7)

Conditions	Yield
With thionyl chloride In methanol at 20℃; for 21h;

3-(1-naphthyl)-D-alanine (78306-92-0) → (S)-1-naphthylalanine methyl ester (119357-91-4)

Conditions	Yield
With thionyl chloride In methanol

methanol (67-56-1) + 3-(1-naphthyl)-D-alanine (78306-92-0) → (D)-1-naphthylalanine methyl ester hydrochloride (188256-28-2)

Conditions	Yield
With thionyl chloride Reflux;

3-(1-naphthyl)-D-alanine (78306-92-0) → C25H29NO5S

Conditions	Yield
Multi-step reaction with 3 steps 1.1: chloro-trimethyl-silane / 20 °C 1.2: 1 h / -10 °C 2.1: sodium tetrahydroborate / methanol / 20 °C 3.1: sodium hydroxide / 1,4-dioxane View Scheme

3-(1-naphthyl)-D-alanine (78306-92-0) → C27H31NO4S

Conditions	Yield
Multi-step reaction with 4 steps 1.1: chloro-trimethyl-silane / 20 °C 1.2: 1 h / -10 °C 2.1: sodium tetrahydroborate / methanol / 20 °C 3.1: sodium hydroxide / 1,4-dioxane 4.1: sodium hydroxide / N,N-dimethyl-formamide / 50 °C View Scheme

3-(1-naphthyl)-D-alanine (78306-92-0) → C34H39N3O3S

Conditions	Yield
Multi-step reaction with 5 steps 1.1: chloro-trimethyl-silane / 20 °C 1.2: 1 h / -10 °C 2.1: sodium tetrahydroborate / methanol / 20 °C 3.1: sodium hydroxide / 1,4-dioxane 4.1: sodium hydroxide / N,N-dimethyl-formamide / 50 °C 5.1: benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C View Scheme

3-(1-naphthyl)-D-alanine (78306-92-0) → C13H15NO

Conditions	Yield
Multi-step reaction with 2 steps 1.1: chloro-trimethyl-silane / 20 °C 1.2: 1 h / -10 °C 2.1: sodium tetrahydroborate / methanol / 20 °C View Scheme

Upstream product

• 28095-56-9 2-amino-3-(1-naphthyl)propanoic acid 
• 3163-27-7 2-(bromomethyl)naphthalene 
• 125761-75-3 2-Acetylamino-3-naphthalen-1-yl-propionic acid ethyl ester 
• 136015-49-1 2-Acetylamino-2-naphthalen-1-ylmethyl-malonic acid monoethyl ester 
• 5440-57-3 diethyl (N-acetylamino)[(1-naphthyl)methyl]malonate 
• 161633-96-1 (R)-3-Naphthalen-1-yl-2-((4S,5R)-2-oxo-4,5-diphenyl-oxazolidin-3-yl)-propionic acid benzyl ester 
• 136086-24-3 (R)-2-Acetylamino-3-naphthalen-1-yl-propionic acid ethyl ester 

Downstream Products

• 119357-91-4 (S)-1-naphthylalanine methyl ester 
• 223771-37-7 D-3-(1-naphthyl)alanine methylester 
• 240428-62-0 N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-3-(1-naphthalenyl)-D-alanine 

Relevant articles and documents

In vitro evolution of an l-amino acid deaminase active on l-1-naphthylalanine

l-Amino acid deaminase from Proteus myxofaciens (PmaLAAD) is a promising biocatalyst for enantioselective biocatalysis that can be exploited to produce optically pure d-amino acids or α-keto acids. In this study, we improved the catalytic efficiency of PmaLAAD on l-1-naphthylalanine (l-1-Nal), a synthetic amino acid of biotechnological interest. Eight evolvable positions were identified by a molecular docking and evolutionary conservation analysis. These positions were subjected to site-saturation mutagenesis, producing smaller but smarter libraries of variants. The best variant (F318A/V412A/V438P PmaLAAD) possesses a ～5-fold lower Km (0.17 mM) and a ～7-fold higher catalytic efficiency (9.2 s-1 mM-1) on l-1-Nal than the wild-type enzyme. Molecular docking analysis suggests that the substitutions increase the active site volume, allowing better binding of the bulky l-1-Nal substrate. Bioconversion reactions showed that the F318A/V412A/V438P PmaLAAD variant outperforms the wild-type enzyme in the deracemization of d,l-1-Nal: the complete conversion of 0.6 mM of the l-enantiomer was achieved in about 15 min, which is ～7.5-fold faster than the wild-type enzyme. In addition, the F318A/V412A/V438P PmaLAAD is efficiently employed, together with the M213G d-amino acid oxidase variant, to produce 1-naphtylpyruvate from racemic d,l-1-Nal in one pot.

COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS

The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.

Asymmetric synthesis of α-amino acids by copper-catalyzed conjugate addition of Grignard reagents to optically active carbamatoacrylates

Optically active ene carbamates were α-lithiated by lithium tetramethylpiperidide in the presence of trialkylstannyl chlorides to produce α-stannylated compounds. These underwent facile palladium-catalyzed couplings with acid chlorides to produce α-keto ene carbamates in good yield. Treatment of the α-stannyl ene carbamates with butyllithium followed by quenching with carbon dioxide and esterification gave optically active carbamatoacrylates. Copper-catalyzed addition of tert-butyl-, 1-naphthyl-, 2-propenyl-, p-methoxyphenyl-, (trimethylsilyl)methyl-, cyclohexyl-, 1-adamantyl-, and isopropyl Grignard reagents followed by quenching at -10 to 25°C and removal of the protecting groups gave the corresponding α-amino acids in 70-90% yield and 73-97% ee. Quenching the reaction at low temperature resulted in little if any asymmetric induction.