| Summary: | Mitragyna speciosa contains many alkaloids and mitragynine (MG) is its
most abundant alkaloid and has received much attention due to its analgesic
property. In this work, a series of MG analogues, which includes 7-
hydroxymitragynine (7-0HMG), Na salts of 7-hydroxymitragynine (Na 7-0HMG),
K salts of 7-hydroxymitragynine (K 7-0HMG), reduced 7-hydroxymitragynine
(reduced 7-0HMG) and nicotinic ester 7-hydroxymitragynine (nicotinic ester 7-
OHMG) were synthesized, characterized and evaluated for their analgesic activity.
Various oxidants were used to produce 7-0HMG from MG. Oxidation reaction using
tert-butyl hydroperoxide (TBHP), hydrogen peroxide (H202) or metachloroperoxybenzoic
acid (MCPBA) was carried out in the presence of palladium
(Pd) as a catalyst while (bis(trifluoroacetoxy)iodo )benzene (PIFA) was used without
any catalyst. H202 was found to be the best oxidant, producing around 99% yield of
7-0HMG, followed by TBHP, MCPBA and PIFA. Na 7-0HMG and K 7-0HMG
were synthesized by neutralizing 7-0HMG with sodium hydroxide (NaOH) or
potassium hydroxide (KOH) and the best yield was observed when the molar ratio of
7-0HMG: NaOHIKOH at 1: l was used with the yield of 59 and 78% for Na 7-
OHMG and K 7-0HMG, respectively. The reduction of 7-0HMG using sodium
borohydride (NaBH4) successfully produced reduced 7-0HMG with 99% yield.
Whilst, the esterification of nicotinic acid to 7-0HMG in the presence of N,N'Dicyclohexy1carbodiimide
(DCC) and 4-Dimethylaminopyridine (DMAP) as a
coupling agent and catalyst, respectively has been carried out and produced around
94% yield of nicotinic ester 7-0HMG.
|
|---|
