Synthesis of lapachol derivatives and their antibacterial activity

Several lapachol derivatives were synthesized from lapachol and tested for their antibacterial activity.

Lapachol was found to be active against X oryzae, Psuedomonas (non-fluorescent) and E. coli at 750 ppm but inactive to others even at 1500 ppm. 2-Benzoyllapachol was the only active compound towards P prutidi and X citri. Hydroxylapachol and its diacetate were inactive towards all the bacterial strains. The cyclized derivative was effective to four strains except X citri. It seemed to exhibit a better activity than lapachol : (i) good zone exhibition at same concentration and (ii) good activity at lower concentration, indicating that cyclization of the hydroxy group oflapachol leads to good activity.
The zone of inhibition against X oryzae at 475 ppm for 2-benzoyl, 2-nitrobenzoyl, 2-acetyl, is around 13 mm as against no activity for parent compound. At the same concentration, for Pseudomonas (non-fluorescent), the inhibi- tion of the cyclized derivative is more than twice (16 mm) and 2-benzoyl-and 2-(p-nitro)benzoyllapachols are mrore effective (II mm) than lapachol (6 mm). For P. prutidi, X citri and E. coli, the inhibition was only at 750 ppm, exhibiting only marginal activity (6 mm). Experimental M.ps. were taken in open capillary tubes and are uncorrected. IR spectra (KBr) were recorded on Perkin-Elmer 1600 FTIR and UV spectra (MeOH) on Perkin-Elmer 2-3 instruments.
The root was procured from local market and identified at the Botany Department of Central Research Institute (Siddha), Chennai.

2-(p-Nitrobenzoyl)/apacho/ (S) :
A mixture of pnitrobenzoic acid (0.9144 g, 5.6 mmol) and pure thionyl chloride (4 ml) was heated on a water-bath with frequent 766 siirring until the reaction commenced (30 min) till the vigorous evolution of HCl had almost ceased. A pale yellow homogenous liquid formed was chilled in ice till it solidified and crystallized from CCI 4 to yield p-nitrobenzoyl chloride (0.960 g).
Diacetate oflapachol (7): To I (500 mg, 2 mmol) dissolved in acetic anhydride (2.5 ml), zinc powder(0.5 g) and anhyd. sodium acetate (0.1 g) were added, the gently warmed till the yellow colour of the quinone disappeared and boiled ( 1 h). Acetic acid (glacial, 2 ml) was added to it and boiled to dissolve precipitated zinc acetate and zinc. The solution was heated to boiling and water was added sufficiently to hydrolyze the acetic anhydride and to produce turbidity. It was then cooled in ice, extracted with the ether (2 x 150 ml), washed with water, dried, evaporated and crystallized from EtOH, (455 mg), m.p. 135°, vmax 1800, 1617, 1057 cm-1 .