Cilastatin

The Cilastatin with CAS registry number of 82009-34-5 is also known as 2-Heptenoic acid,7-[[(2R)-2-amino-2-carboxyethyl]thio]-2-[[[(1S)-2,2-dimethylcyclopropyl]carbonyl]amino]-,(2Z)-. The IUPAC name is (Z)-7-[(2R)-2-Amino-2-carboxyethyl]sulfanyl-2-[[(1S)-2,2-dimethylcyclopropanecarbonyl]amino]hept-2-enoic acid. It belongs to product categories of Chiral Reagents; Intermediates & Fine Chemicals; Pharmaceuticals. Its EINECS registry number is 279-875-8. In addition, the formula is C₁₆H₂₆N₂O₅S and the molecular weight is 358.45.

Physical properties about Cilastatin are: (1)ACD/LogP: 2.42; (2)# of Rule of 5 Violations: 1; (3)ACD/LogD (pH 5.5): -0.97; (4)ACD/LogD (pH 7.4): -1.11; (5)ACD/BCF (pH 5.5): 1; (6)ACD/BCF (pH 7.4): 1; (7)ACD/KOC (pH 5.5): 1; (8)ACD/KOC (pH 7.4): 1; (9)#H bond acceptors: 7; (10)#H bond donors: 5; (11)#Freely Rotating Bonds: 12; (12)Index of Refraction: 1.569; (13)Molar Refractivity: 92.17 cm³; (14)Molar Volume: 280.9 cm³; (15)Surface Tension: 58.6 dyne/cm; (16)Density: 1.275 g/cm³; (17)Flash Point: 350.2 °C; (18)Enthalpy of Vaporization: 105.28 kJ/mol; (19)Boiling Point: 655.5 °C at 760 mmHg; (20)Vapour Pressure: 7.13E-19 mmHg at 25 °C.

Preparation of Cilastatin. Firstly, ethyl 2,2-diethoxyacetate and 1,3-propanedithiol are mixed to get ethyl 1,3-dithiane-2-carboxylate, which will react with 1,5-dibromopentane and NBS to generate ethyl 7-bromine-2-oxoheptanoate. What's more, 7-Bromine-2-oxoheptanoic acid is obtained by acid hydrolysis. Secondly, 2,2-dimethyl-1,3-propanediol is mixed with p-tolylsulfonyl chlorine followed by esterification, cyclization, hydrolysis to obtain racemic 2,2-dimethylcyclopropanecarboxylic acid. Then the compound is mixed with N-trifluorineacetoxybutylimide to get (+)-(S)-2,2-dimethylcyclopropanecarboxamide after pure (S) configuration is isolated. At last, 7-Bromine-2-oxoheptanoic acid and (+)-(S)-2,2-dimethylcyclopropanecarboxamide are refluxed in toluene, reacts with L-cystine to obtain product.

Uses of Cilastatin: it can inhibit the human enzyme dehydropeptidase. When combined intravenously with imipenem, it can protect antibiotic imipenem from dehydropeptidase and prolong its antibacterial effect.

You can still convert the following datas into molecular structure:
1. Canonical SMILES: CC1(CC1C(=O)NC(=CCCCCSCC(C(=O)O)N)C(=O)O)C
2. Isomeric SMILES: CC1(C[C@@H]1C(=O)N/C(=C\CCCCSC[C@@H](C(=O)O)N)/C(=O)O)C
3. InChI: InChI=1S/C16H26N2O5S/c1-16(2)8-10(16)13(19)18-12(15(22)23)6-4-3-5-7-24-9-11(17)14(20)21/h6,10-11H,3-5,7-9,17H2,1-2H3,(H,18,19)(H,20,21)(H,22,23)/b12-6-/t10-,11+/m1/s1
4. InChIKey: DHSUYTOATWAVLW-WFVMDLQDSA-N

The toxicity data is as follows:

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
mouse	LD50	unreported	8gm/kg (8000mg/kg)		Pharmacy International. Vol. 5, Pg. 133, 1984.
rat	LD50	unreported	8gm/kg (8000mg/kg)		Pharmacy International. Vol. 5, Pg. 133, 1984.