80714-61-0

Basic information

• Product Name: ACTH (4-7), Pro-Gly-Pro-
• Synonyms: ACTH (4-7), Pro-Gly-Pro-;ACTH (4-7), Pro-Gly-Pro trifluoroacetate salt;L-Methionyl-L-a-glutamyl-L-histidyl-L-phenylalanyl-L-prolylglycyl-L-proline trifluoroacetate salt;Met-Glu-His-Phe-Pro-Gly-Pro;Semax;SemaxAcetate
• CAS NO: 80714-61-0
• Molecular Formula: C₃₇H₅₁N₉O₁₀S
• Molecular Weight: 813.929
• Mol File: 80714-61-0.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 1335.2°Cat760mmHg
• Flash Point: 761.3°C
• Appearance: white to tan/
• Density: 1.391g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.617
• Storage Temp.: ?20°C
• Solubility: H2O: >2mg/mL
• PKA: 3.43±0.20(Predicted)
• CAS DataBase Reference: ACTH (4-7), Pro-Gly-Pro-(CAS DataBase Reference)
• NIST Chemistry Reference: ACTH (4-7), Pro-Gly-Pro-(80714-61-0)
• EPA Substance Registry System: ACTH (4-7), Pro-Gly-Pro-(80714-61-0)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 80714-61-0(Hazardous Substances Data)

Usage

Description

Semax is a synthetic analogue of the adrenocorticotropic hormone, a hormone responsible for the production of cortisol which in turn regulates glucose and lipid metabolism and helps to maintain blood pressure. In the hippocampus, Semax rapidly elevates the levels of brain-derived neurotrophic factor (BDNF), a protein important in encouraging growth and differentiation of new neurons and synapses. BDNF is active in the hippocampus, cortex, and forebrain and is important for memory, coordination, concentration, and learning. Semax also works to activate the dopaminergic and serotonergic systems to help prime the brain for action and to induce a controlled state of mental stress.

benefits

Over continued use, guests have seen benefits such as:Reduces anxiety and depression;Improves mental clarity, memory, and focus

Mechanism of action

Semax has been prescribed for anxiety, memory improvement, ischemic events, stroke, nerve regeneration, ADHD, opioid withdrawal and even chronic diseases such as ALS, Parkinson’s Disease, and Alzheimer’s. Semax has been known to be used as an Adderall alternative.

Clinical Use

Semax has undergone extensive study in Russia and is on the Russian List of Vital & Essential Drugs approved by the Russian Federation government on December 7, 2011. Medical uses for Semax include treatment of stroke, transient ischemic attack, memory and cognitive disorders, peptic ulcers, optic nerve disease, and to boost the immune system.

InChI:InChI=1/C37H51N9O10S/c1-57-16-13-24(38)32(50)42-25(11-12-31(48)49)33(51)43-26(18-23-19-39-21-41-23)34(52)44-27(17-22-7-3-2-4-8-22)36(54)46-15-5-9-28(46)35(53)40-20-30(47)45-14-6-10-29(45)37(55)56/h2-4,7-8,19,21,24-29H,5-6,9-18,20,38H2,1H3,(H,39,41)(H,40,53)(H,42,50)(H,43,51)(H,44,52)(H,48,49)(H,55,56)/t24-,25-,26?,27-,28-,29-/m0/s1

Synthetic route

C50H75N9O12S (111491-74-8) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions	Yield
With dimethylsulfide; trifluoroacetic acid In various solvent(s) at 30℃; for 3h;	88%

Boc-Met-Glu-His-Phe-Pro-Gly-Pro (92411-06-8) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions	Yield
With hydrogenchloride In acetic acid for 0.5h; Ambient temperature;	57%

1-(tert-butoxycarbonyl)-L-proline (15761-39-4) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 9 steps 1: 53 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 2: 100 percent / CH2Cl2 / 0.67 h / Ambient temperature 3: 70 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 4: CH2Cl2 / Ambient temperature 5: 75 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 6: CH2Cl2 / Ambient temperature 7: 1.) aq. H2SO4, 2.) 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / 2.) THF, room temp., 3 days 8: 76 percent / 1,4-cyclohexadiene / Pd-black / ethanol / 2 h / Heating 9: 57 percent / 1 N HCl / acetic acid / 0.5 h / Ambient temperature View Scheme

L-phenylalanine benzyl ester p-toluene-sulfonic acid salt (1738-78-9) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 9 steps 1: 88 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 2: 93 percent / cyclohexene / Pd-black / ethanol / 1 h / Heating 3: 70 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 4: CH2Cl2 / Ambient temperature 5: 75 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 6: CH2Cl2 / Ambient temperature 7: 1.) aq. H2SO4, 2.) 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / 2.) THF, room temp., 3 days 8: 76 percent / 1,4-cyclohexadiene / Pd-black / ethanol / 2 h / Heating 9: 57 percent / 1 N HCl / acetic acid / 0.5 h / Ambient temperature View Scheme

Boc-His-Phe-OBzl (92411-01-3) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 8 steps 1: 93 percent / cyclohexene / Pd-black / ethanol / 1 h / Heating 2: 70 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 3: CH2Cl2 / Ambient temperature 4: 75 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 5: CH2Cl2 / Ambient temperature 6: 1.) aq. H2SO4, 2.) 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / 2.) THF, room temp., 3 days 7: 76 percent / 1,4-cyclohexadiene / Pd-black / ethanol / 2 h / Heating 8: 57 percent / 1 N HCl / acetic acid / 0.5 h / Ambient temperature View Scheme

Boc-His-Phe (92411-02-4) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 7 steps 1: 70 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 2: CH2Cl2 / Ambient temperature 3: 75 percent / 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / tetrahydrofuran / 48 h / Ambient temperature 4: CH2Cl2 / Ambient temperature 5: 1.) aq. H2SO4, 2.) 1-hydroxybenzotriazole, N,N'-dicyclohexylcarbodiimide, triethylamine / 2.) THF, room temp., 3 days 6: 76 percent / 1,4-cyclohexadiene / Pd-black / ethanol / 2 h / Heating 7: 57 percent / 1 N HCl / acetic acid / 0.5 h / Ambient temperature View Scheme

L-proline tert-butyl ester hydrochloride (5497-76-7) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 6 steps 1: 1) (CH3)3SiCl; 2) Et3N, butyl chloroformate / 1) CH2Cl2-DMFA 2) CH2Cl2. 2: 88 percent / 80percent AcOH / 1 h / 40 °C 3: 1) (CH3)3SiCl; 2) Et3N, butyl chloroformate / 1) CH2Cl2-DMFA; 2) CH2Cl2. 4: 73 percent / hydrogen, Pd black / methanol / 3 h 5: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 6: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

glycylproline tert-butyl ester (60166-68-9) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1) (CH3)3SiCl; 2) Et3N, butyl chloroformate / 1) CH2Cl2-DMFA; 2) CH2Cl2. 2: 73 percent / hydrogen, Pd black / methanol / 3 h 3: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 4: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

(S)-1-[2-(Trityl-amino)-acetyl]-pyrrolidine-2-carboxylic acid tert-butyl ester (111491-71-5) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 5 steps 1: 88 percent / 80percent AcOH / 1 h / 40 °C 2: 1) (CH3)3SiCl; 2) Et3N, butyl chloroformate / 1) CH2Cl2-DMFA; 2) CH2Cl2. 3: 73 percent / hydrogen, Pd black / methanol / 3 h 4: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 5: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

phenylalanylprolylglycylproline tert-butyl ester (111491-73-7) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 2: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

(S)-4-((S)-2-tert-Butoxycarbonylamino-4-methylsulfanyl-butyrylamino)-4-[(S)-1-hydrazinocarbonyl-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-butyric acid tert-butyl ester (24734-96-1) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 2: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

(S)-1-(2-{[(S)-1-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionyl)-pyrrolidine-2-carbonyl]-amino}-acetyl)-pyrrolidine-2-carboxylic acid tert-butyl ester (111491-72-6) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 73 percent / hydrogen, Pd black / methanol / 3 h 2: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 3: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

(2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-3-phenylpropanoyl)tetrahydro-1H-pyrrole-2-carboxylic acid (7669-64-9, 17460-56-9, 17460-57-0) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1) (CH3)3SiCl; 2) Et3N, butyl chloroformate / 1) CH2Cl2-DMFA; 2) CH2Cl2. 2: 73 percent / hydrogen, Pd black / methanol / 3 h 3: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 4: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

l-histidine methyl ester dihydrochloride (4467-54-3, 5619-10-3, 7389-87-9, 18684-16-7, 22888-60-4, 32381-17-2, 92742-29-5, 100009-20-9) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 5 steps 1: 1) (CH3)3SiCl; 2) Et3N, ethyl chloroformate / 1) CH2Cl2-DMF; 2) CH2Cl2. 2: 1) hydrogen, Pd black, HCl; 2) Et3N, pivaloyl chloride / 1) DMFA, 2) CH2Cl2, 0 to -5 deg C, 12 h. 3: 89 percent / hydrazine hydrate / methanol / 11 h / Ambient temperature 4: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 5: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

Nα-benzyloxycarbonyl(γ-tert-butyl)glutamylhistidine methyl ester (3967-22-4) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 4 steps 1: 1) hydrogen, Pd black, HCl; 2) Et3N, pivaloyl chloride / 1) DMFA, 2) CH2Cl2, 0 to -5 deg C, 12 h. 2: 89 percent / hydrazine hydrate / methanol / 11 h / Ambient temperature 3: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 4: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

Nα-benzoyloxycarbonyl(γ-O-tert-butyl)glutamylhistidine methyl ester (24692-53-3) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 89 percent / hydrazine hydrate / methanol / 11 h / Ambient temperature 2: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 3: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

L-proline (147-85-3) → H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0)

Conditions

Yield

Multi-step reaction with 5 steps 1: 1) (CH3)3SiCl; 2) Et3N, pivaloyl chloride / 1) CH2Cl2-DMFA (5:1), 20 min, room temp.; 2) CH2Cl2, -5 deg C, 1 h, 0 deg C, 12 h. 2: 1) (CH3)3SiCl; 2) Et3N, butyl chloroformate / 1) CH2Cl2-DMFA; 2) CH2Cl2. 3: 73 percent / hydrogen, Pd black / methanol / 3 h 4: 76 percent / 1) isoamyl nitrite, Et3N, HCl / dioxane; CHCl3; dimethylformamide / 1) 0 to 4 deg C, 12 h; 2) 20-25 deg C, 5 h. 5: 88 percent / CF3COOH, dimethyl sulfide / various solvent(s) / 3 h / 30 °C View Scheme

H-Met-Glu-His-Phe-Pro-Gly-Pro (80714-61-0) → L-methionyl-L-glutamic acid (14517-44-3) + His-Phe-Pro-Gly-Pro

Conditions	Yield
With pig kidney microsomal aminopeptidase M pH=7.4; Kinetics; Time; aq. phosphate buffer; Enzymatic reaction;

Upstream product

• 92411-06-8 Boc-Met-Glu-His-Phe-Pro-Gly-Pro 
• 111491-74-8 C₅₀H₇₅N₉O₁₂S 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 1738-78-9 L-phenylalanine benzyl ester p-toluene-sulfonic acid salt 
• 92411-01-3 Boc-His-Phe-OBzl 
• 92411-02-4 Boc-His-Phe 
• 92411-03-5 Boc-His-Phe-Pro-Gly-Pro-OBzl 
• 92411-04-6 Boc-γ-Bzl-Glu-His-Phe-Pro-Gly-Pro-OBzl 
• 92411-05-7 Boc-Met-γ-Bzl-Glu-His-Phe-Pro-Gly-Pro-OBzl 
• 92411-00-2 Boc-Pro-Gly-Pro-OBzl 
• 1161-13-3 N-Cbz-L-Phe 
• 3886-08-6 5-tert-butyl N-benzyloxycarbonyl-L-glutamate 
• 5497-76-7 L-proline tert-butyl ester hydrochloride 
• 60166-68-9 glycylproline tert-butyl ester 

Downstream Products

• 14517-44-3 L-methionyl-L-glutamic acid 

Relevant articles and documents

SYNTHESIS OF A HEPTAPEPTIDE FORMING A MODIFIED ACTH 4-10 FRAGMENT

A scheme is given for the synthesis of a heptapeptide representing a modified ACTH 4-10 fragment on the basis of which it is possible to create a preparation that is an effective adaptogen of peptide nature.A proposed variant of the synthesis permits a peptide with an adequate degree of purity to be obtained comparatively simply on a large scale.The intermediate compunds and the final products were obtained with good yields and were distinguished by chromatographic homogeneity.The heptapeptide synthesized did not differ with respect to its physicochemical characteristics and biological action from the analogous compound obtained previously.Some physicochemical characteristics of the compound obtained (angles of optical rotation, chromatographic mobilities) are given.