Aloxistatin

Base Information

• Chemical Name: Aloxistatin
• CAS No.: 88321-09-9
• Deprecated CAS: 207396-71-2
• Molecular Formula: C₁₇H₃₀N₂O₅
• Molecular Weight: 342.436
• Hs Code.: 29242990
• European Community (EC) Number: 635-831-3
• UNII: L5W337AOUR
• DSSTox Substance ID: DTXSID00904150
• Nikkaji Number: J22.181C
• Wikipedia: Aloxistatin
• Wikidata: Q27177634
• NCI Thesaurus Code: C76907
• ChEMBL ID: CHEMBL63440
• Mol file: 88321-09-9.mol

Synonyms:(2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester;aloxistatin;E64d inhibitor;EP 453;EP-453;epoxysuccinyl-leucylamide(3-methyl)butane ethyl ester;ethyl (+)-(2S,3S)-2,3-epoxy-N-((S)-1-(isopentylcarbamoyl)-3-methylbutyl)succinamate;ethyl 3-(3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl)-2-oxiranecarboxylate;ethyl epoxysuccinyl-leucylamido-3-methylbutane;loxistatin;loxistatin, (2S-(2alpha,3beta(R*)))-isomer;protease inhibitor E64d

Chemical Property of Aloxistatin

Chemical Property:

• Vapor Pressure: 1.2E-11mmHg at 25°C
• Melting Point: 126.2°C
• Refractive Index: 1.5800 (estimate)
• Boiling Point: 538°C at 760 mmHg
• Flash Point: 279.2°C
• PSA: 97.03000
• Density: 1.102g/cm³
• LogP: 1.79190
• Storage Temp.: −20°C
• Solubility.: Soluble in DMSO, DMF or ethanol
• XLogP3: 2.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 11
• Exact Mass: 342.21547206
• Heavy Atom Count: 24
• Complexity: 450

Purity/Quality:

96% 1H NMR ^*data from raw suppliers

E-64d ^*data from reagent suppliers

Safty Information:

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-24/25

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOC(=O)C1C(O1)C(=O)NC(CC(C)C)C(=O)NCCC(C)C
• Isomeric SMILES: CCOC(=O)[C@@H]1[C@H](O1)C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C
• Description: E-64d is an irreversible, membrane-permeable inhibitor of lysosomal and cytosolic cysteine proteases and has diverse biological activities. It is a synthetic analog of E-64 and prodrug form of E-64c that inhibits calpain and the cysteine proteases cathepsins F, -K, -B, -H, and -L. E-64d (20-200 μM) induces cell cycle arrest at the G2/M phase in A431 human epidermoid carcinoma cells. It inhibits protease-resistant prion protein accumulation in scrapie-infected neuroblastoma cells with an IC50 value of 0.5 μM. E-46d also inhibits entry of vesicular stomatitis virus (VSV) particles pseudotyped with severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 spike glycoprotein into Vero cells, an effect that is reduced by expression of the serine protease TMPRSS2.
• Uses: E-64d has been used as a lysosomal inhibitor in human acute promyelocytic leukemia NB4 cells and Huh-7?cells. It has also been used as a protease inhibitor in free calcium physiological tyrode solution for perfusion into the isolated heart samples. E-64d is an inhibitor of cathepsins B and L as well as a potential inhibitor of calpain. E-64d has been shown to inhibit lysosomal proteases. E-64d has been used in combination with Prepstatin A to in terfere with autolysosomal digestion. E-64d displays neurovascular and neuronal protective effects after focal cerebral ischemia in rats. E-64d is an inhibitor of cathepsins B and L as well as a potential inhibitor of calpain. E-64d has been shown to inhibit lysosomal proteases. E-64d has been used in combination with Prepstatin A to interfere with autolysosomal digestion. E-64d displays neurovascular and neuronal protective effects after focal cerebral ischemia in rats.

Technology Process of Aloxistatin

There total 19 articles about Aloxistatin which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

ethyl (2S,3S)-2,3-epoxysuccinate (63734-73-6,66647-16-3,68521-71-1,89886-73-7,93061-20-2,149884-11-7) + (S)-1-(isopentylamino)-2-amino-4-methyl-1-oxopentan hydrochloride (84851-37-6,167693-86-9) → aloxistatin (88321-09-9)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 0 - 20 ℃; for 3h; Reagent/catalyst; Inert atmosphere;

Reference yield: 99.0%

(S)-1-(isopentylamino)-4-methyl-1-oxopentan-2-aminium 4-methylbenzenesulfonate + ethyl (2S,3S)-2,3-epoxysuccinate (63734-73-6,66647-16-3,68521-71-1,89886-73-7,93061-20-2,149884-11-7) → aloxistatin (88321-09-9)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 0 - 20 ℃; for 4h; Reagent/catalyst; Temperature; Solvent; Inert atmosphere;

Reference yield: 82.0%

1-amino-3-methylbutane (107-85-7) + N-[(2S,3S)-3-trans-ethoxycarbonyloxirane-2-carbonyl]-L-leucine (174759-66-1) → aloxistatin (88321-09-9)

Guidance literature:

With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; In chloroform; at 0 - 23 ℃;

DOI:10.1055/s-1999-3648

upstream raw materials:

N¹-isoamylleucinamide

2-ethyl 3-(4-nitrophenyl) (2S,3S)-oxirane-2,3-dicarboxylate

(S)-1-(isopentylamino)-2-amino-4-methyl-1-oxopentan hydrochloride

1-amino-3-methylbutane

Downstream raw materials:

(2S,3S)-Oxirane-2,3-dicarboxylic acid 2-(benzyloxy-amide) 3-{[(S)-3-methyl-1-(3-methyl-butylcarbamoyl)-butyl]-amide}

(2S,3S)-3-[(S)-3-Methyl-1-(3-methyl-butylcarbamoyl)-butylcarbamoyl]-oxirane-2-carboxylic acid (S)-2-((S)-2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-hexyl ester

5-<3-<2-ethyl>-1H-indolyl> (+)-(2S,3S)-3-<<(S)-3-methyl-1-<(3-methylbutyl)carbamoyl>butyl>carbamoyl>-2-oxiranecarboxylate

N-<2-<5-(benzyloxy)-1H-indol-3-yl>ethyl> (2S,3S)-3-<<(S)-3-methyl-1-<(3-methylbutyl)carbamoyl>butyl>carbamoyl>-2-oxiranecarboxamide

Refernces

• 1、 Yu, Ying-Ying,Sun, Wei,Dong, Lei,Liu, Hai-Dong,Jiang, Dan,Xiao, Jun-Hai,Yang, Xiao-Hong,Li, Song. "Design, synthesis, and screen of cathepsin K inhibitors". . p. 715 - 718. Retrieved 2013/07/26.
• 2、 Roush, William R.,Hernandez, Alejandro Alvarez,Zepeda, Gerardo. "A new synthesis of peptidyl epoxysuccinates for probing cysteine protease-inhibitor P3/S3 binding interactions". . p. 1500 - 1504. Retrieved 2007/10/03.