Origin of natural products

Throughout history, mankind has always been interested in naturally occurring compounds from prebiotic, microbial, plants and animals sources. Various extracts of flowers, plants and insects have been used for isolating compounds whose task, color and odor could be used for various purposes. Many natural products, such as plant hormones, have a regulatory role, while others function as chemical defense against pests. The role of certain compounds is to act as chemical messengers, such as sex-attractants (pheromones) in insects, terrestrial and marine animals and humans. What is the origin of natural products ... 

Simmons TL, et al. Biosynthetic origin of natural products isolated from marine microorganism-invertebrate assemblages. Proc. Natl. Acad. Sci. U.S.A. 2008. 

G.J. Martin, M.L. Martin, F. Mabon, J. Bricout (1982) A new method for the identification of the origin of natural products. Quantitative H-NMR at the natural abundance level applied to the characterization of anetholes. J. Am. Chem. Soc. 104. 2658-2659... 

A. The origin of natural products H. Procurement of large-scale NATURAL PRODUCTS AS... 

With the development of HPLC, a new dimension was added to the tools available for the study of natural products. HPLC is ideally suited to the analysis of non-volatile, sensitive compounds frequently found in biological systems. Unlike other available separation techniques such as TLC and electrophoresis, HPLC methods provide both qualitative and quantitative data and can be easily automated. The basis for the HPLC method for the PSP toxins was established in the late 1970 s when Buckley et al. (2) reported the post-column derivatization of the PSP toxins based on an alkaline oxidation reaction described by Bates and Rapoport (3). Based on this foundation, a series of investigations were conducted to develop a rapid, efficient HPLC method to detect the multiple toxins involved in PSP. Originally, a variety of silica-based, bonded stationary phases were utilized with a low-pressure post-column reaction system (PCRS) (4,5), Later, with improvements in toxin separation mechanisms and the utilization of a high efficiency PCRS, a... 

The original Robinson synthesis (66) of tropinone (124), which consists of a reaction between succinaldehyde (140), methylamine (141), and the calcium salt of acetonedicarboxylic acid (142), proceeds in low yield (Scheme 2). However, it has the great merit of being the pioneering achievement in the field of biomimetic syntheses of natural products. 

To date, there are only few examples of applying the VNS reaction in the synthesis of natural products. Several natural products such as O-methylnordehydrobuffotenine (Scheme 9.10),91 an alkaloid of animal origin, l,3,4,5-tetrahydro[cd]indole (Scheme 9.11),92 and 7,8-dimethoxy-2-oxo-l,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline as key intermediates for marine alkaloids (Scheme 9.12)93 have been prepared via VNS reactions. 

The studies on the biosynthetic origin of secondary metabolites in marine molluscs are reviewed. Although the majority of natural products found in marine molluscs appears to have a dietary origin, de novo biosynthetic ability towards particular classes of compounds has been demonstrated. Marine molluscs are also able to modify metabolites sequestered from their specific prey. 

The use of BRMs to treat human disease has its origins in the use of bacterial toxins to treat cancer by William B. Coley.73 These early studies resulted in the use of microbi-ally-derived substances such as BCG, Picibanil, carbohydrates from plants or fungi such as Krestin and Lentinan, other products such as Biostim and Broncho-Vaxom, as well as thymic extracts (Table 9.4). However, the lot-to-lot variation in the manufacture of these drugs has dampened enthusiasm. Equally, the focus on MOAs in drug development strategies has also dampened developmental efforts. The particulate nature of some BRMs can also result in pulmonary thrombosis and respiratory distress following i.v. injection. However, BRMs are commonly used to treat bladder cancer and derivatives of natural products are routinely used clinically. 

Fig. 1.2 Biosynthetic origin of the major classes of natural products...

The second largest class of compounds reported from macroalgae is the polyketides, which comprise approximately a quarter of known algal compounds (Blunt et al. 2007). Polyketides are polymers of acetate (C2) and occasionally propionate (C3) and are very similar to fatty acids in their biosynthetic origin. Polyketides can be found in plants, animals, bacteria, and fungi. With a range of activities as broad as their structures, the polyketides are a diverse family of natural products classified based upon the polyketide synthases (PKSs) responsible for their biosynthesis, primarily type I and type II. 

The majority of natural products from tropical macroalgae are terpenoids (mainly sesqui- and diterpenoids), followed by acetogenins (acetate-derived compounds), and metabolites of mixed biosynthetic origin (such as meroditerpenes), frequently composed of terpenoid and aromatic portions (Blunt et al. 2007 and previous reviews see Chap. 1). 

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