SYNTHETIC AND BIOLOGICAL UTILITY OF 2,3-DICHLORO-1,4- NAPHTHOQUINONE: A REVIEW

2,3-Dichloro-1,4-naphthoquinones (dichlone) have attracted considerable attention for the construction of biologically active tricyclic and tetracyclic 1,4-quinones and other derivatives. A diversified reaction of 2,3-dichloro-1,4-naphthoquinones such as cycloaddition, condensation, photo induced and nucleophilic substitution reactions with suitable nucleophiles viz. carbon, nitrogen, oxygen, sulfur, selenium etc have been explored. Various synthesized compounds have also explored for their biological activity such as antifungal, antibacterial, anticancer, antiplatlet, anti-inflamentry, anti-allergic and anti HIV. This review describes the chemistry and biological activity of compounds synthesized from 2,3-dichloro-1,4-naphthoquinones during the last three decades.

A quinone analog (129) containing molecular switching property was synthesized by nucleophilic substitution reaction of 1 with piperazine and dansyl chloride; Scheme 27 [60].
Scheme 34: Grubb's catalyst based ring-closing olefin metathesis in the synthesis of quinone fused heterocycles.
Tandon et. al. [79,80] have been optimize various reaction condition and synthesized various oxygen containing 1,4-naphthoquinone derivatives (188,191,193,194) chemoselectively by an economical, viable green methodology approach using water as solvent with or without surfactants such as SDS as well as LD (laundry detergent) in high yields (< 99%), Scheme 40. The bichromophoric ether (205) was synthesized in three steps from readily available starting material 1, 203 and 204 [92] and ethers were synthesized from corresponding alcohols in the presence of TEA/CHCl3 [53] as shown in Scheme 42.
Scheme 50: Synthesis of naphthoquinone fused sulfur containing crown ethers.

Anti-Platlet, Anti-Inflammatory and Anti-Allergic Agents
Compounds

Anti HIV Agents
Several pyranylated binapthoquinones (507) and simple binaphthoquinones (508) were synthesized and studied for their anti HIV activity using MTT assay. Compound 507a (ID50=0.62 M) was shown better anti HIV activity than other derivatives [30]; Figure 20. Compounds 509-510 showed excellent Trypanosoma brucei inhibitory activity with low cytotoxicity and found that electron withdrawing group such as NO2,CF3 and Cl and electron density rich groups (phenylamine ring and aromatic ring) at particular positions on the naphthoquinone as the backbone structure are important to T. brucei inhibitory activity [67] while trizole compound 511 have shown 42 M activity against T. cruzi. [74]; Figure 21.
Graphical abstract

Conclusion
A variety of hetero-1,4-naphthoquinones have synthesized through nucleophilic substitution, cycloaddition, condensation and photo induced methods and were found to posses good to excellent biological activity as antifungal, antibacterial, anticancer, anti HIV, anti trypanosidal etc and exploring regularly in the search of more potent biological active naphthoquinone derivative.