Preparation of benzoate esters of morphine and its derivatives

S. Béni, Gergo Tóth, B. Noszál, Sándor Hosztafi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Sustained analgesia is crucial for patients suffering from long-acting pain. Ester derivatives of morphine could enhance the lipophilicity of morphine; consequently its transdermal delivery as well as its duration of action are also increased. Therefore, twenty-one 3-O-, 6-O-, and 14-Obenzoate esters of morphine and their derivatives were synthesized in order to elaborate different synthetic methods suitable for esterification of these widely used compounds. Schotten-Baumann reaction was applied with sodium hydrogen carbonate, triethylamine, or pyridine in methylene chloride or 1,2-dichloroethane as solvents. The presence of 4-dimethylaminopyridine catalyst was also successfully utilized mainly in the case of tertiary alcohols. A novel synthesis of dihydromorphine via diacetyl morphine free of by-products is also presented. Structures of all synthesized compounds were elucidated by 1H nuclear magnetic resonance (NMR), 13CNMR, high-resolution mass spectrometry (HRMS), and electron ionizationmass spectrometry (EI-MS). The log D (pH 7.4) values of the synthesized compounds were determined by a reversed-phase high-performance liquid chromatography (HPLC)-MS-based method, and calculated hydrolysis rate constants are also provided. The synthesized benzoate esters are potential prodrugs of the parent morphine with enhanced lipophilicity, derivatives which can also be used in transdermal drug delivery as prospective long-acting narcotic analgesics.

Original languageEnglish
Pages (from-to)1431-1440
Number of pages10
JournalMonatshefte fur Chemie
Volume143
Issue number10
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Morphine Derivatives
Benzoates
Morphine
Esters
Dihydromorphine
Diacetyl
Sodium Bicarbonate
Methylene Chloride
Narcotics
Prodrugs
Esterification
High performance liquid chromatography
Drug delivery
Spectrometry
Mass spectrometry
Byproducts
Hydrolysis
Rate constants
Alcohols
Nuclear magnetic resonance

Keywords

  • Alkaloids
  • Catalysts
  • Dihydromorphine
  • Lipophilic prodrug
  • NMR spectroscopy

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Preparation of benzoate esters of morphine and its derivatives. / Béni, S.; Tóth, Gergo; Noszál, B.; Hosztafi, Sándor.

In: Monatshefte fur Chemie, Vol. 143, No. 10, 10.2012, p. 1431-1440.

Research output: Contribution to journalArticle

Béni, S. ; Tóth, Gergo ; Noszál, B. ; Hosztafi, Sándor. / Preparation of benzoate esters of morphine and its derivatives. In: Monatshefte fur Chemie. 2012 ; Vol. 143, No. 10. pp. 1431-1440.
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