Isolation, chemical, transformation of natural products and synthesis of natural product analogues of biological importance

Abstract

The inherent character of natural products as therapeutic agents has been utilised, since the birth of human life on earth. Since ages, the active constituents of most natural sources have been used, which were generally plant-based, were unknown and their usage were in form of decoctions or powder form or as a whole. However, in 1817 discovery of Morphine from the opium and in the 1940s, antibiotic Penicillin from moulds was undoubtedly the starting point for the natural product drug discovery. These discovery triggers usage of natural products as sources of drug directly, or semi-synthetic natural product analogues, or indirectly their use as an inspiration for the synthetic medicinal chemistry as pharmacophores.1 Accordingly, many synthetic strategies used to generate natural product and related scaffolds. Additionally, synthetic, semi-synthesis and biosynthetic techniques has important role in providing ample of natural product scaffolds for the drug discovery. A natural product ideally provides space for the functionalisation to increase its bioactivity. This approach requires either total synthesis or semi-synthesis to achieve new and better molecule. In process of this strategy sometime functionalised scaffold lost its activity, still the exploration of natural products seems to have viable interest. Natural product provides uniqueness in terms of diversity, selectivity, binding efficiency which increases its interaction to the biological targets.2 These natural products however always been the roadmap in the drug discovery and NPs and NP derived drug has tremendous potential in area of tuberculosis and microbial diseases.3 Antibacterial has been mainly derived from microorganism and one of the main source for the discovery of antibacterials. 4 In current medication, major antibiotics are directly derived or isolated from microbial biosynthetic pathways which is metabolites with pharmaceutical properties5. Natural products role for providing effective anti‐tuberculosis agents has a very successful journey.6 The currently used medicines, the Rifamycin’s, which is most critical front‐line treatment in tuberculosis are natural product and many of its advanced derivative are in process of development. Furthermore, among other natural products for example the Streptomycin, Kanamycin and Capreomycin are part of the treatment of anti-tuberculosis drugs. These natural products have been the source to provide platform for the potential lead for the drug development against tuberculosis. Tuberculosis (TB) is mainly caused by Mycobacterium tuberculosis (M.tb.) and it is a chronic disease which created havoc worldwide. According to World Health Organisation (WHO), Mycobacterium tuberculosis (TB) infection is among one-third of world’s population and causes millions of death world-wide, which points to the huge unmet need of effective therapeutic as wells as preventive strategies for this disease.7 Infected people has a very high chance of development of disease and a persons with compromised immune systems, such as people living with HIV, malnutrition or diabetes, or people who use tobacco, have a much higher risk to get disease.