Daptomycin

Base Information

• Chemical Name: Daptomycin
• CAS No.: 103060-53-3
• Molecular Formula: C72H101 N17 O26
• Molecular Weight: 1620.69
• Hs Code.: 29419090
• Mol file: 103060-53-3.mol

Synonyms:Benzenebutanoic acid, N-(1-oxodecyl)-L-tryptophyl-D-asparaginyl-L-a-aspartyl-L-threonylglycyl-L-ornithyl-L-a-aspartyl-D-alanyl-L-a-aspartylglycyl-D-seryl-(3R)-3-methyl-L-a-glutamyl-a,2-diamino-g-oxo-, (13?;4)-lactone, (aS)-;Cidecin;Cubicin;Dapcin;Daptomicina;Daptomycine;Daptomycinum;Deptomycin;LY 146032;N-(1-Oxodecyl)-L-tryptophyl-D-asparaginyl-L-a-aspartyl-L-threonylglycyl-L-ornithyl-L-a-aspartyl-D-alanyl-L-a-aspartylglycyl-D-seryl-(3R)-3-methyl-L-a-glutamyl-(aS)-a,2-diamino-g-oxobenzenebutanoicacid (13?;

Chemical Property of Daptomycin

Chemical Property:

• Appearance/Colour: White powder
• Melting Point: 202-204?C
• Boiling Point: 2078.2 °C at 760 mmHg
• PKA: 4.00±0.10(Predicted)
• Flash Point: 1210.7 °C
• PSA: 702.02000
• Density: 1.45 g/cm³
• LogP: 0.88280
• Storage Temp.: Store at -20°C
• Solubility.: methanol: soluble5mg/mL

Purity/Quality:

98%min ^*data from raw suppliers

Daptomycin ≥95%(HPLC) ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Interactions: Daptomycin has synergistic effect when used in combination with netilmicin, amikacin, imipenem, and fosfomycin. This can improve the antibacterial activity. Combination with teicoplanin, vancomycin has a good antibacterial activity against Sma GmrBla-enterococci. Combination of daptomycin with gentamicin also has synergistic effects on resistant glycopeptide antibiotics-resistant Streptococcus faecalis. This has been demonstrated in animal models. Combination of daptomycin and tobramycin for therapy can reduce the nephrotoxicity of the latter drug, which is just opposite with vancomycin.
• Uses: Pharmaceutical intermediates, used in the treatment of concurrent skin and skin structure infections caused by a number of Gram-positive caused by susceptible strains. Cyclic lipopeptide antibiotic derived from a fermentation product of Streptomyces roseosporus; disrupts plasma membrane function in gram-positive bacteria. Antibacterial. Daptomycin is a member of the A 21978 complex of high molecular weight cyclic lipopeptides with potent antibiotic activity, notably against MRSA, VISA and VRSA bacterial strains. Originally isolated from Streptomyces roseosprous by Eli Lily in the 1980s, daptomycin was selected and developed by Cubist Pharmaceticals for human use. Daptomycin exhibits Ca-dependent depolarisation of the bacterial membrane resulting in loss of membrane potential leading to inhibition of DNA, RNA and protein synthesis which results in cell death. immunosuppressant
• Description: Daptomycin is the first entry of a new class of cyclic lipopeptide antibiotics that disrupts multiple aspects of bacterial membrane function including disruption of membrane potential and amino acid transport, inhibition of lipoteichoic acid synthesis and inhibition of peptidoglycan synthesis. It is indicated for the treatment of complicated skin and skinstructure infections (cSSSI) caused by a range of Gram-positive bacteria. This is distinct from previous classes of antibiotics that inhibit bacterial cell wall biosynthesis, bacterial DNA replication, and folate coenzyme biosynthesis. Due to this unique mechanism, cross-resistance has not been noted with any other class of antibiotics. It is produced by the fermentation of Streptomyces roseporus. The fatty acid side chain is a key determinant of acute toxicity, with the ten-carbon chain least acutely toxic to mice. Daptomycin has shown efficacy in a variety of animal models versus several Grampositive infectious agents including methicillin-susceptible S aureus, vancomycinresistant E faecalis, spyogenes and S pneumoniae. It retains in vitro activity against methicillin, vancomycin and linezolid-resistant strains including Staphylococcus aureus (MRSA and VRSA), which is the leading cause of hospital-acquired infections (nosocomial infections (Nis)). The MIC values against Gram-positive pathogens are relatively low, ranging from 0.06 to 2.0 mg/mL. In two clinical studies treating patients (ca. 1090 for both arms of both studies) with complicated skin and soft tissue infections (cSSTIs) in which gram-positive pathogens were suspected and parenteral antibiotics were required, daptomycin provided similar clinical success rates as compared to standard therapy with vancomycin or semisynthetic penicillins such as cloxacillin, oxacillin, or flucloxacillin. The daptomycin treated group showed more rapid improvement as noted by scoring on day three or four and also had a shorter duration of treatment versus the standard therapy group (7 vs 8 days). It is dosed once daily (4 mg/kg/day) by intravenous infusion and has a half-life of 8.1 h. It is primarily cleared renally and thus requires dosing adjustments for those with severe renal insufficiency (CLCR ,30 mL/min). Clinical safety of daptomycin is similar to other antibiotics.
• Clinical Use: Daptomycin is a fermentation product having a cyclic lipopeptide structure. It is primarily active against Gram-positive infections, especially those involved in skin/skin structure infections. It is given IV but must be administered over a period of 30 minutes or more. It binds to cell membranes and causes depolarization, which interrupts protein, DNA, and RNA synthesis. Daptomycin is bactericidal. Although resistance can be achieved in vitro, resistance has been slow to emerge in the clinic. Patients should be monitored for muscle pain or weakness, because some incidence of elevated serum creatinine phosphokinase is associated with its use. A small number of clinical trial patients also developed conditions related to decreases in nerve conduction (e.g., paresthesias and Bell's palsy). Daptomycin is eliminated primarily by the kidney, so dose adjustment may be necessary in cases of renal insufficiency.
• Drug interactions: In vitro experiments using human hepatocytes demonstrated that daptomycin has no effects on hepatic CYP450-mediated drug metabolism and, therefore, suggest that daptomycin is unlikely to show potential for pharmacokinetic interactions with concomitantly administered drugs that are metabolized by CYP450 isoforms. Drug interaction single- and multiple-dose studies were performed in healthy subjects. No clinically relevant interactions were found when daptomycin 2–6 mg/kg was administered with aztreonam, tobramycin, warfarin, simvastatin, and probenecid. Although no specific drug interactions have been detected when daptomycin is co-administered with HMG-CoA reductase inhibitors (e.g. simvastatin), a number of patients who developed creatine phosphokinase (CPK) increases in a study of daptomycin efficacy in S. aureus bacteremia/endocarditis were receiving concomitant HMGCoA reductase inhibitors. Thus, monitoring of CPK levels is probably warranted in patients with risk factors and timely cessation of potential agents if myopathy is noted.

Technology Process of Daptomycin

There total 1 articles about Daptomycin 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: 9.0%

1-decanoic acid (334-48-5) + N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + (2S,3R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-(tert-butoxy)-3-methyl-5-oxopentanoic acid (1429504-34-6) + C23H20N4O3 + C62H58N4O15 + N-(9-fluorenylmethoxycarbonyl)-D-alanine (35661-38-2,35661-39-3,79990-15-1,136132-75-7) + Fmoc-Thr-OH (73731-37-0) + (R)-N-(fluoren-9-ylmethoxycarbonyl)serine (73724-45-5,136083-72-2,116861-26-8) + Fmoc-Orn(Boc)-OH (109425-55-0,118476-89-4) + p-toluenesulfonic acid salt of glycine allyl ester (88223-98-7) + (S)-3-(((9H-fluoren-9-yl)methoxy)carbonylamino)-4-(allyloxy)-4-oxobutanoic acid (144120-53-6) + 4-(1,1-dimethylethyl) ester of Nα-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-aspartic acid allyl ester (144120-52-5) + (S)-(?)-4-tert-butyl 2-azidosuccinic acid (333366-23-7) + (S)-2-azido-3-(1-(tert-butoxycarbonyl)-1H-indol-3-yl)propanoic acid → daptomycin (103060-53-3)

Guidance literature:

(S)-3-(((9H-fluoren-9-yl)methoxy)carbonylamino)-4-(allyloxy)-4-oxobutanoic acid; With N-ethyl-N,N-diisopropylamine; In dichloromethane; for 4h; 2-chlorotrityl chloride resin

With tetrakis(triphenylphosphine) palladium⁽⁰⁾; 1,3-dimethylbarbituric acid; In dichloromethane; N,N-dimethyl-formamide; for 1h; 2-chlorotrityl chloride resin

1-decanoic acid; N-(fluoren-9-ylmethoxycarbonyl)glycine; (2S,3R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-(tert-butoxy)-3-methyl-5-oxopentanoic acid; C₂₃H₂₀N₄O₃; C₆₂H₅₈N₄O₁₅; N-(9-fluorenylmethoxycarbonyl)-D-alanine; Fmoc-Thr-OH; (R)-N-(fluoren-9-ylmethoxycarbonyl)serine; Fmoc-Orn(Boc)-OH; p-toluenesulfonic acid salt of glycine allyl ester; 4-(1,1-dimethylethyl) ester of Nα-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-aspartic acid allyl ester; (S)-(?)-4-tert-butyl 2-azidosuccinic acid; (S)-2-azido-3-(1-(tert-butoxycarbonyl)-1H-indol-3-yl)propanoic acid; Further stages;

DOI:10.1021/acs.orglett.5b00043

Reference yield: 60.0%

daptomycin (103060-53-3) + dimethylallyl pyrophosphate (22679-02-3) → C77H109N17O26

Guidance literature:

In aq. buffer; at 37 ℃; for 12h; pH=8;

DOI:10.1038/nchembio.2285

Reference yield: 48.0%

daptomycin (103060-53-3) + C82H102N6O16 → C153H199N23O42

Guidance literature:

C₈₂H₁₀₂N₆O₁₆; With 4-methyl-morpholine; isobutyl chloroformate; In tetrahydrofuran; at 0 ℃; for 1h;

daptomycin; With sodium hydrogencarbonate; In tetrahydrofuran; water; at 0 - 20 ℃;

upstream raw materials:

1-decanoic acid

N-(fluoren-9-ylmethoxycarbonyl)glycine

(2S,3R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-(tert-butoxy)-3-methyl-5-oxopentanoic acid

N-(9-fluorenylmethoxycarbonyl)-D-alanine

Refernces