Per–O–acetyl Lactosyl Isothiourea Derivatives: Synthesis and Antimicrobial Activities

Glycosyl (iso) thioureas being an important intermediate in the synthesis of thioureido carbohydrates herein we reported the synthesis of per–O–acetyl lactosyl aryl isodithiobiuret derivatives. These compounds were synthesized by nucleophilic addition of per-O-acetyl lactosyl aryl isothiourea to tolyl isothiocyanate. Structures of these compounds were confirmed on the basis of IR, HNMR, Mass spectra and elemental analysis. These compounds were also screened for their in vitro antimicrobial activities against bacteria S. aureus, E. coli, P. vulgaris, P. aeruginosa and fungi A. niger, Penicillium.

Thiobiurets (mono and di) are also important derivatives of (thio) urea which may increase the biological activity of (thio)ureas. 1-Allyl-2-thiobiuret was shown to regulate the growth of germinating wheat and cucumber seeds 9 . Oliver and coworkers 10 reported chemosterlising action of some dithiobiuret derivatives in male house flies. The mono and dithiobiuret derivative are effective fungicides, bactericides, herbicides and also have demonstrated effective growth regulating activity 11 . Some thiobiuret derivatives also showed analgesic 12 , anticonvulsant and hypnotic activity 13 . Glycosyl urea and their biuret derivatives are reported as potential glycoenzyme inhibitors 14 . Mangte and Deshmukh 15 reported antibacterial and antifungal activities of per−O−acetylated lactosyl iso(di)thiobiurets.
In view of the advantage conferred by glycosyl thiourea synthesis that allows rapid, convenient access to a wide array of thioureido carbohydrates 16 , together with the notable biological activities of nucleoside analogues, a great deal of work has focused on the development of novel glycosyl thiourea derivatives. However, there are little reports on the synthesis and bioactivity of lactosyl thiourea derivatives. In this paper, a very efficient synthetic route to novel lactosyl isothiourea derivatives and their antimicrobial activities are reported.

RESULTS AND DISCUSSION
The The 1 HNMR spectrum of these compounds distinctly displayed signals due to aromatic protons at 7.6−6.8 ppm, protons of lactosyl ring at 5.3−3.4 ppm and acetyl protons at 2.1−1.9 ppm.
The structures of the compounds 3a−g were confirmed by elemental analysis and IR, HNMR, Mass spectra. The IR spectra [18][19] of the compounds showed strong characteristic absorption of lactosyl protons in the range of 900-910, 1000-1100 cm -1 for stretching vibration of C-H bond.
Mass spectra [21][22]  exhibited comparable inhibitory activity as compared to the control against S. aureus whereas others showed moderate to less activity. 3c and 3f showed inhibition as good as control drug against P. aeruginosa and 3a was inactive. Other compounds showed moderate to less activity while some were inactive Table 2.
Antifungal Activity The synthesized compounds have also been evaluated for their antifungal activity against two representative fungi viz., Penicillium and A. niger by cup plate agar diffusion method using Fluconazole as standard drug. Compounds 3g exhibited comparable activity against A. niger and others were moderately active against fungi. Although the rest of the compounds showed varying degree of inhibition, none were as effective as Fluconazole Table 2.
Then solvent was distilled off, sticky mass obtained was triturated with petroleum ether (60-80 o ). The granular solid obtained was crystallized from ethanol−water. (