(1S,2R,5S,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone

Base Information

• Chemical Name: (1S,2R,5S,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone
• CAS No.: 191114-48-4
• Molecular Formula: C43H65N5O10
• Molecular Weight: 812.017
• Wikipedia: Telithromycin
• NCI Thesaurus Code: C61963
• Mol file: 191114-48-4.mol

Synonyms:Telithromycin

Chemical Property of (1S,2R,5S,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 176-188 °C
• Boiling Point: 966.2 °C at 760 mmHg
• PKA: 10.85±0.70(Predicted)
• Flash Point: 538.2 °C
• PSA: 171.85000
• Density: 1.26 g/cm³
• LogP: 4.86710
• Storage Temp.: -20?C Freezer
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• Water Solubility.: Sparingly soluble in water
• XLogP3: 4.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 13
• Rotatable Bond Count: 11
• Exact Mass: 811.47314329
• Heavy Atom Count: 58
• Complexity: 1440

Purity/Quality:

99% ^*data from raw suppliers

Telithromycin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiinfective Agents
• Canonical SMILES: CCC1C2(C(C(C(=O)C(CC(C(C(C(=O)C(C(=O)O1)C)C)OC3C(C(CC(O3)C)N(C)C)O)(C)OC)C)C)N(C(=O)O2)CCCCN4C=C(N=C4)C5=CN=CC=C5)C
• Isomeric SMILES: CC[C@@H]1[C@@]2([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H](C(=O)[C@@H](C(=O)O1)C)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC)C)C)N(C(=O)O2)CCCCN4C=C(N=C4)C5=CN=CC=C5)C
• Recent ClinicalTrials: Controlled Trial: 5-day Course of Telithromycin Versus Doxycycline for the Treatment of Mild to Moderate Scrub Typhus
• Recent EU Clinical Trials: Prospective, Randomized, Double-Blind Trial to Evaluate the Efficacy and Safety of Faropenem Medoxomil 600 mg PO, BID for 5 Days Versus Placebo Versus Telithromycin In the Treatment of Acute Exacerbation of Chronic Bronchitis
• Description: Telithromycin was first launched in Germany as a once-daily oral treatment for respiratory infections including community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, acute sinusitis and tonsillitis/pharyngitis. This semisynthetic derivative of the natural macrolide erythromycin is the first marketed ketolide, a new class of antibiotics featuring a C3-ketone instead of the L-cladinose group. The 14-membered ring antibacterial agent prevents bacterial protein synthesis by binding to two domains of the 50S subunit of bacterial ribosomes. It shows potent in vitro activity against common respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes as well as other atypical pathogens. The 3-keto group confers increased acidic stability and reduced induction of macrolide-lincosamide-streptogramin B resistance that is frequently observed with macrolides. The substituted C11-C12 carbamate residue appears not only to increase affinity for the ribosomal binding site but also to stabilize the compound against esterase hydrolysis and avoid resistance due to elimination of macrolides from the cell by an efflux pump encoded by the mef gene in certain pathogens. Telithromycin is both a competitive inhibitor and a substrate of CYP3A4. However, unlike several macrolides such as troleandomycin, it does not form a stable inhibitory CYP P-450 Fe2+-nitrosoalkane metabolite complex which is potentially hepatotoxic. The drug is well tolerated and well distributed into pulmonary tissues, bronchial secretions, tonsils and saliva. It turns out to be highly concentrated in azurophil granules of polymorphonuclear neutrophils thereby facilitating its delivery to the phagocytosed bacteria.
• Uses: Telithromycin is a ketolide antibiotic, used to treat respiratory infections Telithromycin represents the first member of the current generation of erythromycin descendants, belonging to the ketolide class. The ketolides are characterised by the hydrolysis of the cladinose sugar and subsequent oxidation of the alcohol to a ketone. Telithromycin is acid stabile and has good activity against erythromycin-resistant S. aureus, and improved pharmacokinetics. A ketolide antibiotic, used to treat respiratory infections

Technology Process of (1S,2R,5S,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone

There total 34 articles about (1S,2R,5S,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-15-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone 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: 98.9%

2',4-di-O-bis(trimethylsilyl)-11-amino-11-N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]-11-deoxy-6-O-methylerythromycin A-11,12-cycliccarbamate (1001326-77-7) → telithromycin (191114-48-4)

Guidance literature:

With methanol; at 20 ℃; for 7h; Product distribution / selectivity; Heating / reflux;

Reference yield: 98.9%

10-(4-dimethylamino-6-methyl-3-trimethylsilanyloxy-tetrahydro-pyran-2-yloxy)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-[4-(4-pyridin-3-yl-imidazol-1-yl)-butyl]-octahydro-3,5-dioxa-1-aza-cyclopentacyclotetradecene-2,6,8,14-tetraone (306770-60-5) → telithromycin (191114-48-4)

Guidance literature:

With methanol; at 20 ℃; for 7h; Product distribution / selectivity; Heating / reflux;

Reference yield: 90.0%

2'-hydroxy-11-amino-11-N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]-11-deoxy-5-O-desosaminyl-6-O-methylerythronolide A 11,12-cyclic carbamate → telithromycin (191114-48-4)

Guidance literature:

2'-hydroxy-11-amino-11-N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]-11-deoxy-5-O-desosaminyl-6-O-methylerythronolide A 11,12-cyclic carbamate; With Dess-Martin periodane; In dichloromethane; at 20 ℃; for 0.5h;

With sodium hydrogencarbonate; In dichloromethane; water; for 0.5h; Product distribution / selectivity;

upstream raw materials:

2'-O-acetyl-10,11-didehydro-11-deoxy-12-O-(1H-1-imidazoylcarbonyl)-3-O-descladinosyl-3-oxo-6-O-methyl-erythromycin A

4-[4-(3-pyridyl)imidazol-1-yl]butylamine

2',4-di-O-bis(trimethylsilyl)-11-amino-11-N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]-11-deoxy-6-O-methylerythromycin A-11,12-cycliccarbamate

10-(4-dimethylamino-6-methyl-3-trimethylsilanyloxy-tetrahydro-pyran-2-yloxy)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-[4-(4-pyridin-3-yl-imidazol-1-yl)-butyl]-octahydro-3,5-dioxa-1-aza-cyclopentacyclotetradecene-2,6,8,14-tetraone

Downstream raw materials:

HMR 3562

Refernces

• 1、 -. "14-MEMBERED KETOLIDES AND METHODS OF THEIR PREPARATION AND USE". . . Retrieved 2016/05/02.
• 2、 -. "Novel process for the preparation of telithromycin". Page/Page column 14. . Retrieved 2008/06/13.