67655-94-1

Usage

Uses

Used in Pharmaceutical Industry:
Amastatin is used as a pharmaceutical agent for its potential therapeutic properties. It has been found to exhibit inhibitory effects on certain enzymes and pathways, making it a promising candidate for the development of drugs targeting specific diseases.
Used in Research Applications:
Amastatin is used as a research tool for studying the mechanisms of action and potential applications of bioactive peptides. Its unique structure and properties allow researchers to investigate its interactions with biological systems and explore its potential as a therapeutic agent.
Used in Drug Development:
Amastatin is used in drug development as a lead compound for the design and synthesis of new drugs. Its unique structure and biological activity provide a foundation for the development of novel therapeutic agents with improved efficacy and selectivity.

InChI:InChI=1/C21H38N4O8/c1-9(2)7-12(22)17(28)20(31)25-16(11(5)6)19(30)24-15(10(3)4)18(29)23-13(21(32)33)8-14(26)27/h9-13,15-17,28H,7-8,22H2,1-6H3,(H,23,29)(H,24,30)(H,25,31)(H,26,27)(H,32,33)/t12-,13+,15+,16+,17+/m1/s1

Synthetic route

(2S,3R)-<3-<<(tert-Butyloxy)carbonyl>amino>-2-hydroxy-5-methylhexanoyl>-L-valyl-L-valyl-aspartic Acid Dibenzyl Ester (73397-34-9) → amastatin (67655-94-1)

Conditions	Yield
With palladium on activated charcoal; hydrogen; trifluoroacetic acid 1.) room temperature, 30 min 2.) methanol, 24 h; Yield given. Multistep reaction;

(S)-2-{(S)-2-[(S)-2-((2S,3R)-3-Benzyloxycarbonylamino-2-hydroxy-5-methyl-hexanoylamino)-3-methyl-butyrylamino]-3-methyl-butyrylamino}-succinic acid dibenzyl ester → amastatin (67655-94-1)

Conditions	Yield
With hydrogen; palladium on activated charcoal

t-Boc-L-valine (13734-41-3) → amastatin (67655-94-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: DCC, HOBt, Et3N 2: TFA 3: DCC, HOBt, Et3N 4: TFA 5: DCC, HOBt, Et3N 6: H2 / Pd-C View Scheme
Multi-step reaction with 4 steps 1: 80 percent / triethylamine, DCC, HOBt / CH2Cl2 / 5 °C 2: 1.) HCl, 2.) triethylamine, DCC, HOBt 3: 1.) hydrochloric acid, 2.) triethylamine, DCC, HOBt / 1.) dioxane, 30 min, 25 deg C 2.) methylene chloride 4: 1.) TFA, 2.) H2, Pd/C / 1.) room temperature, 30 min 2.) methanol, 24 h View Scheme

Boc-Val-Asp(OBzl)-OBzl (70853-19-9) → amastatin (67655-94-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: TFA 2: DCC, HOBt, Et3N 3: TFA 4: DCC, HOBt, Et3N 5: H2 / Pd-C View Scheme
Multi-step reaction with 3 steps 1: 1.) HCl, 2.) triethylamine, DCC, HOBt 2: 1.) hydrochloric acid, 2.) triethylamine, DCC, HOBt / 1.) dioxane, 30 min, 25 deg C 2.) methylene chloride 3: 1.) TFA, 2.) H2, Pd/C / 1.) room temperature, 30 min 2.) methanol, 24 h View Scheme

<(tert-Butyloxy)carbonyl>-L-valyl-L-valyl-L-aspartic Acid Dibenzyl Ester (70853-22-4) → amastatin (67655-94-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: TFA 2: DCC, HOBt, Et3N 3: H2 / Pd-C View Scheme
Multi-step reaction with 2 steps 1: 1.) hydrochloric acid, 2.) triethylamine, DCC, HOBt / 1.) dioxane, 30 min, 25 deg C 2.) methylene chloride 2: 1.) TFA, 2.) H2, Pd/C / 1.) room temperature, 30 min 2.) methanol, 24 h View Scheme

Val-Asp(OBzl)-OBzl (70853-20-2) → amastatin (67655-94-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: DCC, HOBt, Et3N 2: TFA 3: DCC, HOBt, Et3N 4: H2 / Pd-C View Scheme

Val-Val-Asp(OBzl)-OBzl (70853-23-5) → amastatin (67655-94-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: DCC, HOBt, Et3N 2: H2 / Pd-C View Scheme

(R)-4-methyl-1-oxopentane-2-benzylcarbamate (70853-26-8) → amastatin (67655-94-1)

Conditions

Yield

Multi-step reaction with 5 steps 1: 1.) NaHSO3 / 1.) 5 deg C, overnight, 2.) ethyl acetate, water, room temp., 4 h 2: 90 percent / concentrated HCl / dioxane / 12 h / Heating 3: 73 percent / triethylamine / H2O; dioxane / 25 °C 4: 1.) hydrochloric acid, 2.) triethylamine, DCC, HOBt / 1.) dioxane, 30 min, 25 deg C 2.) methylene chloride 5: 1.) TFA, 2.) H2, Pd/C / 1.) room temperature, 30 min 2.) methanol, 24 h View Scheme

[(S)-1-((S)-Cyano-hydroxy-methyl)-3-methyl-butyl]-carbamic acid benzyl ester (63219-62-5, 73397-23-6, 73397-24-7, 106868-70-6, 106868-79-5) → amastatin (67655-94-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 90 percent / concentrated HCl / dioxane / 12 h / Heating 2: 73 percent / triethylamine / H2O; dioxane / 25 °C 3: 1.) hydrochloric acid, 2.) triethylamine, DCC, HOBt / 1.) dioxane, 30 min, 25 deg C 2.) methylene chloride 4: 1.) TFA, 2.) H2, Pd/C / 1.) room temperature, 30 min 2.) methanol, 24 h View Scheme

(2RS,3R)-3-Amino-2-hydroxy-5-methylhexanoic Acid (62023-30-7, 70853-11-1, 70853-17-7, 73397-20-3, 73397-21-4, 75556-30-8) → amastatin (67655-94-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 73 percent / triethylamine / H2O; dioxane / 25 °C 2: 1.) hydrochloric acid, 2.) triethylamine, DCC, HOBt / 1.) dioxane, 30 min, 25 deg C 2.) methylene chloride 3: 1.) TFA, 2.) H2, Pd/C / 1.) room temperature, 30 min 2.) methanol, 24 h View Scheme

(2RS,3R)-3-<<(tert-Butyloxy)carbonyl>amino>-2-hydroxy-5-methylhexanoic Acid (73397-25-8, 73397-26-9, 73397-27-0, 73397-28-1, 77119-88-1) → amastatin (67655-94-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) hydrochloric acid, 2.) triethylamine, DCC, HOBt / 1.) dioxane, 30 min, 25 deg C 2.) methylene chloride 2: 1.) TFA, 2.) H2, Pd/C / 1.) room temperature, 30 min 2.) methanol, 24 h View Scheme

Cbz-D-Leu-OMe (73397-22-5) → amastatin (67655-94-1)

Conditions

Yield

Multi-step reaction with 6 steps 1: Diisobutylaluminum hydride / toluene / 0.1 h / -78 °C 2: 1.) NaHSO3 / 1.) 5 deg C, overnight, 2.) ethyl acetate, water, room temp., 4 h 3: 90 percent / concentrated HCl / dioxane / 12 h / Heating 4: 73 percent / triethylamine / H2O; dioxane / 25 °C 5: 1.) hydrochloric acid, 2.) triethylamine, DCC, HOBt / 1.) dioxane, 30 min, 25 deg C 2.) methylene chloride 6: 1.) TFA, 2.) H2, Pd/C / 1.) room temperature, 30 min 2.) methanol, 24 h View Scheme

Upstream product

• 73397-22-5 Cbz-D-Leu-OMe 
• 73397-25-8 (2RS,3R)-3-<<(tert-Butyloxy)carbonyl>amino>-2-hydroxy-5-methylhexanoic Acid 
• 62023-30-7 (2RS,3R)-3-Amino-2-hydroxy-5-methylhexanoic Acid 
• 63219-62-5 [(S)-1-((S)-Cyano-hydroxy-methyl)-3-methyl-butyl]-carbamic acid benzyl ester 
• 70853-26-8 (R)-4-methyl-1-oxopentane-2-benzylcarbamate 
• 70853-23-5 Val-Val-Asp(OBzl)-OBzl 
• 70853-20-2 Val-Asp(OBzl)-OBzl 
• 70853-22-4 <(tert-Butyloxy)carbonyl>-L-valyl-L-valyl-L-aspartic Acid Dibenzyl Ester 
• 70853-19-9 Boc-Val-Asp(OBzl)-OBzl 
• 13734-41-3 t-Boc-L-valine 
• 73397-34-9 (2S,3R)-<3-<<(tert-Butyloxy)carbonyl>amino>-2-hydroxy-5-methylhexanoyl>-L-valyl-L-valyl-aspartic Acid Dibenzyl Ester 

Relevant academic research and scientific papers

Synthesis of (2S,3R)-3-Amino-2-hydroxy-5-methylhexanoic Acid Derivatives. Application to the Synthesis of Amastatin, an Inhibitor of Aminopeptidases

Methods are reported for the synthesis of optically pure derivatives of (2S,3R)-3-amino-2-hydroxy-5-methylhexanoic acid. -D-leucine methyl ester was reduced in 95percent yield with diisobutylaluminum hydride to the aldehyde which was converted via the cyanohydrin to (2RS,3R)-3-amino-2-hydroxy-5-methylhexanoic acid (AHMHA).The mixture of diastereomers was converted to the corresponding Boc-AHMHA methyl ester derivatives and separated by chromatography over silica gel.The optical purity of the diastereomers at C-3 was established by converting each to diastereomeric Boc-AHMHA-Leu-OMe and separating these dipeptides by chromatography.Pure (2S,3R)-Boc-AHMHA was coupled with valyl-valyl-aspartic acid dibenzyl ester by using dicyclohexylcarbodiimide/ 1-hydroxybenzotriazole in 63percent yield.The Boc group was removed by using trifluoroacetid acid, and the benzyl groups were removed by hydrogenolysis.The product, (2S,3R)-AHMHA-L-Val-L-Val-L-Asp, amastatin, was found to be identical with the natural product.