27262-48-2 Usage
Description
Levobupivacaine was first launched in the US for the production of
local anesthesia for surgery and obstetrics and for post-operative pain management. It is
the (S)-enantiomer of the long acting, highly potent local anesthetic bupivacaine
(Marcaine) that can be prepared by a three step sequence from (S)-pipecolic acid or from
(S)-lysine by oxidative deamination and stereospecific ring closure to (S)-pipecolamide
core structure. Levobupivacaine exhibits its long-acting local anesthetic effect by blocking
neuronal sodium channel ion flow in nerve axons. Clinical studies demonstrated an
efficacy and a general profile closely resembling those of the racemic bupivacaine
currently in use; however, it produced an enhanced safety profile, in particular
substantially reduced (about one-third) cardiotoxicity (less effect on myocardial contractility
and QT, prolongation) and CNS depressive side effects. Onset and duration of blockade
were also equivalent or even better.
Chemical Properties
white crystalline powder
Originator
Chiroscience (UK)
Uses
Levobupivacaine hydrochloride has been used as an analyte in tandem mass spectrometry. It may be used to test its inhibitory effect on phosphorylation of extracellular signal-regulated kinase (ERK) mediated by capsaicin It may also be used as a component of poly(D,L-lactide-co-glycolide) (PLGA) microparticles for testing its sustainable release by electrospraying technique.
Definition
ChEBI: Levobupivacaine hydrochloride (anhydrous) is the monohydrochloride salt of levobupivacaine. It has a role as a local anaesthetic, an adrenergic antagonist, an amphiphile, an EC 3.1.1.8 (cholinesterase) inhibitor and an EC 3.6.3.8 (Ca(2+)-transporting ATPase) inhibitor. It contains a levobupivacaine(1+). It is an enantiomer of a dextrobupivacaine hydrochloride (anhydrous).
Manufacturing Process
Synthesis of L-pipecolic acid 2,6-xylidide (Patent US 4,695,576)130 g of pipecolic acid and 158.6 g of Laevo (+)-tartaric acid are dissolved
under stirring in 2 L 95% ethyl alcohol and 125 ml water at 80°C. The
solution is allowed to cool to room temperature and after two days the
crystallized D-pipecolic-tartrate is separated. The L-pipecolic-tartrate remains
in solution. The filtrate is evaporated and dissolved in 5% acetic acid. Finally
the solution is treated with Amberlite IR 45* in an ion exchanger. The eluate
thus obtained is evaporated and the resulting crystalline residue is dried with
potassium hydroxide in vacuo. The product obtained consists of L-pipecolic
acid [α]D24 = -26.2°(C = 5, H2O).4 g of phosphorus pentachloride was added to a suspension of 4 g of Lpipecolic acid hydrochloride in 40 ml acetylchloride. The initial reaction is
effected at a temperature of about 35°C under stirring for 2 hours. The
chlorination is completed by adding during a time period of about 10 minutes
an additional two grams of phosphorus pentachloride and stirring over a
further period of 4 hours while maintaining the suspension at a temperature
of about 35°C. The resulting L-pipecolic acid chloride hydrochloride is filtered
and washed with toluene and acetone. The crystalline residue is then dried in
vacuo, m.p. 155°C.A mixture of 2.7 ml 2,6-dimethylaniline, 4 ml acetone, and 4 ml Nmethylpyrrolidone is gradually added under stirring for 2 hours at 70°C to a
suspension of 4 g of L-pipecolic acid chloride hydrochloride. This yields a
crystalline product, which is filtered, washed with acetone and dried. This
crystalline product is then dissolved in water and the base is precipitated by
the addition of ammonia. The base is then extracted by the use of toluene and
is recovered by evaporation. The base is recrystallized from a mixture of
hexane and ethanol to yield L-pipecolic acid 2,6-xylidide. The melting point of
this compound is 129-130°C.Preparation of L-N-n-butylpipecilic acid 2,6-xylidide may de carried out by
analogy with the preparation of L-N-n-propylpipecolic acid 2,6-xylidide (Patent
US 5,777,124).n-Butylbromide and potassium carbonate are added to a solution of L-pipecolic
acid 2,6-xylidide dissolved in isopropyl alcohol. Thereafter, 5 ml of water is
added to the mixture and the reaction is carried out for 4 hours at 72°C.To complete the reaction, a further 0.8 ml n-butylbromide are added under
continuous stirring and heating for 4 hours. The residue is treated with a
mixture of 250 ml toluene and an equal amount of water at 50°C. The toluene
layer is separated and washed three times with 100 ml warm water (40°C). A
175 ml portion of the toluene is removed by evaporation and the remainder is
stored at +5°C for 6 hours to achieve crude crystalline L-N-n-butylpipecilic
acid 2,6-xylidide. The crystalline product is separated by filtration, washed
with some cooled toluene and dried at 70°C. Recrystallization may be carried
from toluene. This product is dissolved in 100 ml ethanol and neutralized with
concentrated hydrochloric acid. Ethanol is removed by evaporation and the
hydrochloride product obtained is vacuum dried. Finally the latter is
recrystallized from isopropyl alcohol.
Brand name
Chirocaine (Purdue).
Therapeutic Function
Local anesthetic
Biological Functions
Levobupivacaine hydrochloride (Chirocaine) is the
S-enantiomer of bupivacaine. It too has long action.
Animal studies show that it has less CNS and cardiac
toxicity than does bupivacaine. It also is slightly more
motor sparing than is bupivacaine.
General Description
Levobupivacaine belongs to the N-alkyl substituted pipecoloxylidide family and comprises amino-amide group.
Biochem/physiol Actions
Levobupivacaine hydrochloride is a sodium channel blocker used as a long-acting local anaesthetic for epidural anesthesia. Levobupivacaine is the (S)-isomer of bupivacaine, with efficacy similar to that of bupivacaine with a reduced risk of cardiotoxicity.
Mode of action
Levobupivacaine Hydrochloride is the hydrochloride salt of levobupivacaine, an amide derivative with anesthetic property. Levobupivacaine reversibly binds voltage-gated sodium channels to modulate ionic flux and prevent the initiation and transmission of nerve impulses (stabilizing neuronal membrane), thereby resulting in analgesia and anesthesia. In comparison with racemic bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action.
Check Digit Verification of cas no
The CAS Registry Mumber 27262-48-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,7,2,6 and 2 respectively; the second part has 2 digits, 4 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 27262-48:
(7*2)+(6*7)+(5*2)+(4*6)+(3*2)+(2*4)+(1*8)=112
112 % 10 = 2
So 27262-48-2 is a valid CAS Registry Number.
InChI:InChI=1/C18H28N2O.ClH/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3;/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21);1H/t16-;/m0./s1
27262-48-2Relevant articles and documents
Preparation method of levobupivacaine hydrochloride
-
, (2017/07/19)
The invention belongs to the technical field of chemical synthesis and in particular relates to a preparation method of levobupivacaine hydrochloride. The preparation method takes racemic or S-configuration 2-piperidinecarboxylic acid as a starting raw material and comprises the following steps: taking the starting raw material and n-butylaldehyde to react and carrying out borohydride reduction reaction to obtain 1-butylpiperidine-2-carboxylic acid; taking the 1-butylpiperidine-2-carboxylic acid and 2,6-dimethylaniline to be subjected to condensation reaction, so as to generate bupivacaine or levobupivacaine; carrying out subsequent treatment to obtain a final product levobupivacaine hydrochloride. Compared with an existing synthesis route, the preparation method has the advantages of short synthesis route, simple method, convenience for operation, low cost and easiness for industrial production; reaction conditions of each step are relatively moderate, a process is stable, a strong-corrosion chlorination reagent is not used, the pollution to environment is reduced and the like.
Preparation process of bupivacaine hydrochloride
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Paragraph 0024; 0025; 0026; 0027, (2017/07/20)
The invention discloses a preparation process of bupivacaine hydrochloride. According to the specific scheme, N-(2,6-xylyl)-2-piperidine formamide is adopted as a starting raw material and dissolved in methylbenzene, then a deacidification agent, a phase transfer catalyst and bromobutane are added, certain temperature is kept for reacting, and after the reaction is finished, filtering is carried out at room temperature, and a bupivacaine solution is obtained; the bupivacaine solution is acidized with an acidification agent, aftertreatment is carried out, and bupivacaine hydrochloride is obtained through drying. According to the preparation process, the solvent can be recycled, the production cost can be reduced, environmental pollution can be reduced, meanwhile, byproducts of other products of the company are fully utilized, refuse reclamation is achieved, and generated waste gas, waste water and industrial residues are reduced.
PROCESS FOR ENANTIOMERIC ENRICHMENT OF 2 ', 6 ' - PIPECOLOXYLIDIDE
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Page/Page column 18-19, (2014/02/15)
The invention discloses a process for enantiomeric enrichment of 2',6'-pipecoloxylidide using a chiral carbamoyl benzoic acid to provide (S)-enantiomer in high yield and high enantiomeric purity. The invention also discloses novel intermediates formed in the process of enantiomeric enrichment of 2',6'-pipecoloxylidide, preparation of N- substituted amidic acids and alkylation of 2',6'-pipecoloxylidide.
