89771-75-5

Basic information

• Product Name: (3R,4S,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxy-3-(phosphonooxy)cyclohex-1-ene-1-carboxylic acid
• Synonyms: 5-enol-pyruvoylshikimate 3-phosphate (EPSP)
• CAS NO: 89771-75-5
• Molecular Formula: C₁₀H₁₃O₁₀P
• Molecular Weight: 324.178
• Mol File: 89771-75-5.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 724°C at 760 mmHg
• Flash Point: 391.6°C
• Density: 1.75g/cm³
• Vapor Pressure: 3.34E-24mmHg at 25°C
• Refractive Index: 1.602
• CAS DataBase Reference: (3R,4S,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxy-3-(phosphonooxy)cyclohex-1-ene-1-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4S,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxy-3-(phosphonooxy)cyclohex-1-ene-1-carboxylic acid(89771-75-5)
• EPA Substance Registry System: (3R,4S,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxy-3-(phosphonooxy)cyclohex-1-ene-1-carboxylic acid(89771-75-5)

Safety Data

• Hazardous Substances Data: 89771-75-5(Hazardous Substances Data)

Usage

General Description

The chemical compound (3R,4S,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxy-3-(phosphonooxy)cyclohex-1-ene-1-carboxylic acid is a complex molecule with carboxylic acid, hydroxy, and phosphonooxy functional groups. It is a cyclohexene derivative with a carboxyethenyl group attached to the 5th position, a hydroxy group at the 4th position, and a phosphonooxy group at the 3rd position. The compound's IUPAC name indicates its stereochemistry, with the (3R,4S,5R) designation referring to the three stereocenters in the molecule. (3R,4S,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxy-3-(phosphonooxy)cyclohex-1-ene-1-carboxylic acid's structure and functional groups suggest potential applications in pharmaceuticals, organic synthesis, and chemical research.

Synthetic route

phosphoenolpyruvic acid (138-08-9) + shikimate 3-phosphate (S3P) (63959-45-5) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions	Yield
5-enol-pyruvoylshikimate 3-phosphate (EPSPS);
With ammonium heptamolybdate; EcaroA-T42M enolpyruvylshikimate 3-phosphate synthase; N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid at 30℃; pH=7.0; Enzyme kinetics; Further Variations:; Reagents;

(4aR,8R,8aS)-8-{Bis-[2-(4-nitro-phenyl)-ethoxy]-phosphoryloxy}-3-methylene-2-oxo-2,3,4a,5,8,8a-hexahydro-benzo[1,4]dioxine-6-carboxylic acid methyl ester (96251-72-8) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions	Yield
With sodium hydroxide; 1,8-diazabicyclo[5.4.0]undec-7-ene 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C; Multistep reaction;

(3R-(3α,4α,5β))-O-3-phospho-O-5-(1S-1-carboxy-1-(phosphooxy)-ethyl)shikimic acid (625091-49-8) → phosphoenolpyruvic acid (138-08-9) + shikimic acid (138-59-0) + 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5) + (3aR,7R,7aS)-2-Methyl-7-phosphonooxy-3a,4,7,7a-tetrahydro-benzo[1,3]dioxole-2,5-dicarboxylic acid

Conditions	Yield
With glycine at 25℃; pH=2.5 - 3.5; Product distribution; Kinetics; Further Variations:; pH-values; Reagents;

methyl 3,4-O-isopropylideneshikimate (88165-26-8) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions

Yield

Multi-step reaction with 9 steps 1: 85 percent / Rh2(OAc)4 / benzene / Heating 2: Et3N / CH2Cl2 3: CH2Cl2 / Ambient temperature 4: 83 percent / dimethylsulfoxide / 6 h / 95 °C 5: 90 percent / 80percent aqueous acetic acid / 3 h / 65 - 70 °C 6: NaOH / tetrahydrofuran; H2O / 3 h / 0 °C 7: water-soluble carbodiimide, DMAP / tetrahydrofuran / 3 h / Ambient temperature 9: 1.) diazabicyclo<5.4.0>undec-7-ene, 2.) aqueous NaOH / 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C View Scheme

methyl <(4aR),4aβ,8α,8aα>-2,3,4a,5,8,8a-hexahydro-2-oxo-3-methylene-8-hydroxy-1,4-benzodioxin-6-carboxylate (96251-71-7) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions	Yield
Multi-step reaction with 2 steps 2: 1.) diazabicyclo<5.4.0>undec-7-ene, 2.) aqueous NaOH / 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C View Scheme

compound Z1 (96251-70-6) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: water-soluble carbodiimide, DMAP / tetrahydrofuran / 3 h / Ambient temperature 3: 1.) diazabicyclo<5.4.0>undec-7-ene, 2.) aqueous NaOH / 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C View Scheme

(3R,4R,5R)-3,4-Dihydroxy-5-(1-methoxycarbonyl-vinyloxy)-cyclohex-1-enecarboxylic acid methyl ester (96251-69-3) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaOH / tetrahydrofuran; H2O / 3 h / 0 °C 2: water-soluble carbodiimide, DMAP / tetrahydrofuran / 3 h / Ambient temperature 4: 1.) diazabicyclo<5.4.0>undec-7-ene, 2.) aqueous NaOH / 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C View Scheme

methyl <(1R),1α,5β,6α>-5-<<1-(methoxycarbonyl)ethenyl>oxy>-8,8-dimethyl-7,9-dioxabicyclo<4.3.0>non-2-ene-3-carboxylate (99655-79-5) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 90 percent / 80percent aqueous acetic acid / 3 h / 65 - 70 °C 2: NaOH / tetrahydrofuran; H2O / 3 h / 0 °C 3: water-soluble carbodiimide, DMAP / tetrahydrofuran / 3 h / Ambient temperature 5: 1.) diazabicyclo<5.4.0>undec-7-ene, 2.) aqueous NaOH / 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C View Scheme

methyl <(1R),1α,5β,6α>-5--8,8-dimethyl-7,9-dioxabicyclo<4.3.0>non-2-ene-3-carboxylate (96283-92-0) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions

Yield

Multi-step reaction with 8 steps 1: Et3N / CH2Cl2 2: CH2Cl2 / Ambient temperature 3: 83 percent / dimethylsulfoxide / 6 h / 95 °C 4: 90 percent / 80percent aqueous acetic acid / 3 h / 65 - 70 °C 5: NaOH / tetrahydrofuran; H2O / 3 h / 0 °C 6: water-soluble carbodiimide, DMAP / tetrahydrofuran / 3 h / Ambient temperature 8: 1.) diazabicyclo<5.4.0>undec-7-ene, 2.) aqueous NaOH / 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C View Scheme

2-Dimethylaminomethyl-2-((3aS,4R,7aR)-6-methoxycarbonyl-2,2-dimethyl-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-yloxy)-malonic acid dimethyl ester (96251-67-1) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions

Yield

Multi-step reaction with 7 steps 1: CH2Cl2 / Ambient temperature 2: 83 percent / dimethylsulfoxide / 6 h / 95 °C 3: 90 percent / 80percent aqueous acetic acid / 3 h / 65 - 70 °C 4: NaOH / tetrahydrofuran; H2O / 3 h / 0 °C 5: water-soluble carbodiimide, DMAP / tetrahydrofuran / 3 h / Ambient temperature 7: 1.) diazabicyclo<5.4.0>undec-7-ene, 2.) aqueous NaOH / 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C View Scheme

[2,2-Bis-methoxycarbonyl-2-((3aS,4R,7aR)-6-methoxycarbonyl-2,2-dimethyl-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-yloxy)-ethyl]-trimethyl-ammonium; iodide (96283-93-1) → 5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5)

Conditions	Yield
Multi-step reaction with 6 steps 1: 83 percent / dimethylsulfoxide / 6 h / 95 °C 2: 90 percent / 80percent aqueous acetic acid / 3 h / 65 - 70 °C 3: NaOH / tetrahydrofuran; H2O / 3 h / 0 °C 4: water-soluble carbodiimide, DMAP / tetrahydrofuran / 3 h / Ambient temperature 6: 1.) diazabicyclo<5.4.0>undec-7-ene, 2.) aqueous NaOH / 1.) C5H5N, rt, 72h, 2.) 5h, 0 deg C View Scheme

5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5) → chorismic acid (617-12-9)

Conditions	Yield
Neurospora crassa chorismate synthase;
With 2-[Bis(2-hydroxyethyl)imino]-2-(hydroxymethyl)-1,3-propanediol Hydrochloride; potassium chloride; Flavin mononucleotide; NADPH; magnesium chloride at 25℃; Neurospora crassa chorismate synthase, pH 7.0; isotope effect;
With sodium dithionite; 17 μM chorsmate synthase; 20μM reduced flavin cofactor (FMNH2) In water at 25℃; Rate constant; Mechanism; detection of modified flavin mononucleotide (FMN) intermediate during the catalytic cycle;
With sodium dithionite; recombinant Escherichia coli chorismate synthase; reduced FMN In various solvent(s) at 25℃; pH=7.5; Kinetics; Further Variations:; Reagents;

5-enol-pyruvoylshikimate 3-phosphate (EPSP) (89771-75-5) → shikimate 3-phosphate (S3P) (63959-45-5) + 2-oxo-propionic acid (127-17-3)

Conditions	Yield
With perchloric acid at 25℃; Rate constant;

Upstream product

• 96283-93-1 [2,2-Bis-methoxycarbonyl-2-((3aS,4R,7aR)-6-methoxycarbonyl-2,2-dimethyl-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-yloxy)-ethyl]-trimethyl-ammonium; iodide 
• 96251-67-1 2-Dimethylaminomethyl-2-((3aS,4R,7aR)-6-methoxycarbonyl-2,2-dimethyl-3a,4,5,7a-tetrahydro-benzo[1,3]dioxol-4-yloxy)-malonic acid dimethyl ester 
• 96283-92-0 methyl <(1R),1α,5β,6α>-5--8,8-dimethyl-7,9-dioxabicyclo<4.3.0>non-2-ene-3-carboxylate 
• 99655-79-5 methyl <(1R),1α,5β,6α>-5-<<1-(methoxycarbonyl)ethenyl>oxy>-8,8-dimethyl-7,9-dioxabicyclo<4.3.0>non-2-ene-3-carboxylate 
• 96251-69-3 (3R,4R,5R)-3,4-Dihydroxy-5-(1-methoxycarbonyl-vinyloxy)-cyclohex-1-enecarboxylic acid methyl ester 
• 96251-70-6 compound Z₁ 
• 96251-71-7 methyl <(4aR),4aβ,8α,8aα>-2,3,4a,5,8,8a-hexahydro-2-oxo-3-methylene-8-hydroxy-1,4-benzodioxin-6-carboxylate 
• 88165-26-8 methyl 3,4-O-isopropylideneshikimate 
• 625091-49-8 (3R-(3α,4α,5β))-O-3-phospho-O-5-(1S-1-carboxy-1-(phosphooxy)-ethyl)shikimic acid 
• 96251-72-8 (4aR,8R,8aS)-8-{Bis-[2-(4-nitro-phenyl)-ethoxy]-phosphoryloxy}-3-methylene-2-oxo-2,3,4a,5,8,8a-hexahydro-benzo[1,4]dioxine-6-carboxylic acid methyl ester 
• 138-08-9 phosphoenolpyruvic acid 
• 63959-45-5 shikimate 3-phosphate (S₃P) 

Downstream Products

• 63959-45-5 shikimate 3-phosphate (S₃P) 
• 127-17-3 2-oxo-propionic acid 
• 617-12-9 chorismic acid 

Relevant articles and documents

A T42M substitution in bacterial 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) generates enzymes with increased resistance to glyphosate.

Mutants of class I enolpyruvylshikimate 3-phosphate synthase (EPSPS) with resistance to glyphosate were produced in a previous study using the staggered extension process with aroA genes from S. typhimurium and E. coli. Two of these mutants shared a common amino acid substitution, T42M, near the hinge region between the large globular domains of EPSPS. Using site-directed mutagenisis, we produced the T42M mutants without the other amino acid changes of the original mutants. The T42M substitution alone produced enzymes with a 9- to 25-fold decreased K(m)[PEP] and a 21- to 26-fold increased K(i)[glyphosate] compared to the wild-type enzymes. These results provide more testimony for the powerful approach for protein engineering by the combination of directed evolution and rational design.

Synthesis and evaluation of two new inhibitors of EPSP synthase

The enzyme EPSP synthase, EPSPS, (EC 2.5.1.19) catalyzes an unusual transfer reaction of the enolpyruvoyl moiety from phosphoenol pyruvate (2, PEP) regiospecifically to the 5-OH of shikimate 3-phosphate (1, S3P) to form 5-enol-pyruvoylshikimate 3-phosphate (3, EPSP). Two new inhibitors, (4, and 5) were prepared to probe the S3P binding site.