Sunil Kumar Talapatra

Polyketide Pathway. Biosynthesis of Diverse Classes of Aromatic Compounds

In 1893, a young chemist, John Norman Collie at London University serendipitously discovered a set of reactions while establishing the structure of dehydroacetic acid [1]. On boiling dehydroacetic acid with Ba(OH)2 and its subsequent work up with acid, Collie obtained a phenol, orcinol, whose structure he could correctly assign [1, 2]. He even offered an explanation on the formation of orcinol from dehydroacetic acid (Fig. 14.1). This concept of a triketone formation as the intermediate has been the cornerstone of the polyketide pathway [3].

Alkaloids. General Introduction

Alkaloids constitute a major class of natural products. The compulsory presence of nitrogen/s in their elemental contents confers basic character in these compounds to save a few. Pelletier (Appendix A-22) collaborated with Dumas and showed the presence of nitrogen in alkaloids. The basic or alkali like property of alkaloids was first observed by Serturner while working with opium constituents and he used the term “vegetable alkali.” The term alkaloid [(derived from “alkali” and Greek oeides (like)] was coined by W. Meissner, an apothecary of Halle, in 1819. It later became a generally accepted term.

Important Biological Events Occurring in Plants

“Photosynthesis is undoubtedly the most important single metabolic innovation in the history of life on the planet” [1]. It is looked upon as the mother of all biological events of life since essentially all free energy needed for biological systems originates from solar energy via photosynthesis, the most successful of all natural energy storage processes. Thus, all forms of life evolved to exploit oxygen for their well-being depend for their energy, directly or indirectly on this phenomenon, which truly belongs to an interdisciplinary field involving radiation physics, solid state physics, chemistry, enzymology, physiology, and ecology. The present discussion is mainly based on chemistry. Photosynthesis is a green plant process, the means of converting light into chemical energy, taking place into organelles called chloroplasts. In this process chlorophyll, the green coloring matter of plants utilizes the solar energy in converting CO2 and H2O into carbohydrates, and oxygen and some water are evolved. Bacteria with bacteriochlorophyll can also achieve photosynthesis—bacteria do not evolve oxygen like green plants [2]. Since oxygen is a by-product of the green plant photosynthesis, the latter is sometimes called oxygenic photosynthesis, and it is the major source of oxygen in the atmosphere. The chemistry of the green plant or green algae photosynthesis will be discussed briefly. The plant photosynthesis utilizes the solar light. The bacterial photosynthesis utilizes the light in the infrared region. However, photons of far-infrared region have too low energies to be utilized for any photochemical reaction. The splitting regions (approximately) of white sunlight, as seen after diffraction through prism or in rainbows (VIBGYOR), are shown in Fig. 3.1

Natural Products in the Parlor of Pharmaceuticals

Whenever there is life there are diseases, decay, and death. Death is the most inevitable biological event of a living system. Since life is the most precious gift of Nature, people want to preserve it as along as possible. In an endeavor to arrest the approach of death, our ancestors had not only to withstand the fury of Nature but also had to fight against diseases and decay. People were thus in search of remedial measures since the dawn of human intellect. The relationship of man and Nature was symbiotic and the immediate source of such remedial measures had been the forests, the home of our ancestors. They used to roam in and around the forests, and through thousands of years of interactions with Nature by trial and error methods, and under the pressure of experience and need they could discover a large number of plants with varying healing properties. These plants are referred to as the medicinal plants, and the people having the knowledge of their curative applications were known as medicine men. Thus a wealth of information on the curative properties of plants resulted.

Triterpenes (C 30 )

Triterpenoids belong to a large and structurally diverse class of natural products which occur abundantly in plant kingdom, especially in higher plants in cases of pentacyclic and tetracyclic triterpenes, while mono-, bi-, and tricyclic triterpenes are prevalent in ferns and nonflowering lower plants (cryptogams). Some of them were found in fossils as such and also as their diagenetic products.

Morphine. Codeine. Thebaine: Modified Benzyltetrahydroisoquinoline Alkaloids

The word “analgesic” is almost synonymous with morphine, the major alkaloid of “opium.” Morphine has no peer till date in controlling the excruciating pain, especially of postsurgical patients, and in intensive burn and severe fracture cases. Opium is the rubbery viscous exudate that oozes out from the sacrificed or pricked unripe seed capsules of opium poppy, Papaver somniferum Linn. (Papaveraceae). The exudates, when collected and dried, and pressed into bricks, form the opium of commerce. The use of opium in the form of tincture has been known for thousands of years. Babylonians and Egyptians recorded the use of opium preparations as an effective pain reliever. Hippocrates, Dioscorides, Galen, and other physicians wrote about its miraculous power “to lull all pain and anger, and bring relief to every sorrow.” [1] The seventeenth century pioneer of English medicine, Thomas Sydenham wrote, “Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium” [1]. The use of opium to induce mystical or spiritual experiences has been known since antiquity.

Natural Products Chemistry: A General Treatment

The most important part of the natural products chemistry work is the isolation of the constituents in the pure state from their source/s. Since natural products possess different structural patterns and properties the procedures for their isolation need a lot of manipulations and modifications over the usual general procedures (Figs. 4.1, 4.2, 4.3, 4.4, and 4.5) given as models. Further, with the advent of new isolation techniques and refinements of the old ones, it is now possible to isolate most of the secondary metabolites including the trace ones present in the crude extract. This was almost an impossible task till the mid-twentieth century when only the major components could be isolated. The earlier laborious procedures have now been reduced to some time-saving efficient procedures. The crude extracts of the plant materials should first be fractionated adopting some suitable procedures, and the different fractions may then be subjected to easily available classical separation techniques, such as column chromatography (CC) (Sect. 4.1.6), flash chromatography (FC) (Sect. 4.1.7), and thin-layer chromatography (Sect. 4.1.8), as needed. These techniques have been discussed in some detail, based on the experience of the authors in sixties to eighties. These details will be handy and useful, especially to those who are working in different corners of the world with profuse plant resources, but lacking the expensive materials/tools needed. The fractions remaining after isolation of the major constituents may then be subjected for isolation of minor or/inseparable constituents to sophisticated expensive separation techniques like HPLC, MPLC, GC-MS, etc., in laboratories where these are available. The high-resolution NMR spectroscopy if available in any organic chemistry laboratory may preferably be used for monitoring the constituents (natural or synthetic) starting from their crude states.

Important Outcomes of Chemical Studies on Natural Products

The intellectual ferment of chemical enquiry began with the man’s ability to notice, observe, and reflect on things around him and with his interest and appreciation for beautiful colors, flavors, fragrance, taste, and medicinal and curative properties of plants. Thus from the dawn of civilization Nature has been appearing to be an enigma to human beings because of their innate curiosity.

Introduction: Enzymes. Cofactors/Coenzymes. Primary and Secondary Metabolites. Natural Products and their Functions. Plant Chemical Ecology. Biosynthesis. Metabolic Pathways

The evolution of natural products (secondary metabolites) in plants, their functions, environmental interactions with living organisms, and some participating components involved in these dynamic biological processes are briefly presented in this chapter.

Dimeric Indole Alkaloids. Vinblastine (Vincaleukoblastine), Vincristine (Leurocristine), and Their Derivatives

The dimeric indole alkaloid vinblastine (vincaleukoblastine) (VLB), serendipitously discovered from Madagascan periwinkle (Catharanthus roseus syn. Vinca rosea, Apocynaceae) [1], exhibits remarkable cancer-fighting activity and contributed immensely to dispel the sufferings of human beings caused by certain types of cancer (see Chap. 33). Subsequent discovery of a few more dimeric indole alkaloids leurocristine (LCR) (also known as vincristine), leurosine, and leurosidine (vinrosidine) from the same plant (Fig. 28.1) and the study of their anticancer activities add another name vincristine to the list of important cancer-fighting drugs. The molecular structures of vincristine and vinblastine with some stereochemical reservations have been proposed from the studies of their spectral properties, degradations, characterizations of their degradation products, and on biogenetic grounds [2–4].