Structure of natural products

In the following sections we review the compositions of the main chemical classes and their biochemical functions. These functions are related to the structure and shape of the basic carbon skeleton of a molecule and the functional groups (see Box 2.1) attached to it. 

Atoms within organic molecules are held together by covalent bonds, which are formed by adjacent atoms sharing pairs of electrons (usually each atom donates one of its outermost, or valency, electrons to the bond). Single, double and even triple bonds can be formed, in which one, two and three electron pairs are shared, respectively, although triple bonds are rare among natural 

As well as strong covalent bonds, there are weaker, electrostatic interactions between molecules that influence their properties, one of the most important of 

R—OH hydroxyl alcohol (R = alkyl group) phenol (R = phenyl group) 

Heteroatoms can be incorporated into cyclic systems, and some of the geochemically important are shown in Table 2.2. 

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Dehydrogenation (the conversion of alicycllc or hydroaroraatic compounds into their aromatic counterparts by removal of hydrogen and also, in some cases, of other atoms or groups) finds wide appUcation in the determination of structure of natural products of complex hydroaroraatic structure. Dehydrogenation is employed also for the synthesis of polycyclic hydrocarbons and their derivatives from the readily accessible synthetic hydroaroraatic compounds. A very simple example is the formation of p-raethylnaphthalene from a-tetra-lone (which is itself prepared from benzene—see Section IV,143) ... 

Development and applications of new reactions for construction of basic structures of natural products, in particular proapoporphine alkaloids and lactones 99YZ357. 

FIGURE 4.10 Structures of natural products used as substrates or inducers. 

In summary, NMR spectroscopy is an extremely versatile tool useful that enables researchers to understand the structure of natural products such as carotenoids. For a full structural assignment, the compound of interest has to be separated from coeluents. Thus, it is a prerequisite to employ tailored stationary phases with high shape selectivity for the separation in the closed-loop on-line LC-NMR system. For the NMR detection, microcoils prove to be advantageous for small quantities of sample. Overall, the closed-loop system of HPLC and NMR detection is very advantageous for the structural elucidation of air- and UV-sensitive carotenoids. 

Table 4. Chemical structures of natural product Psammaplin A through J, with HD AC and DNA methyltransferase (DNTB) inhibition values. Not tested shown as nt.

Fig. 16. Chemical structures of natural product (a) trapoxin A and (b) trapoxin B. Table 10. IC50 values of trapoxin A and trapoxin B against HDAC isoforms.

Fig. 18. Chemical structure of natural product romidepsin. Note the disulfide bond which is likely cleaved in vivo.

Since the discovery of triazole formation from phenyl azide and dimethyl acetylenedicarboxylate in 1893, synthetic applications of azides as 1,3-dipoles for the construction of heterocychc frameworks and core structures of natural products have progressed steadily. As the 1,3-dipolar cycloaddition of azides was comprehensively reviewed in the 1984 edition of this book (2), in this chapter we recount developments of 1,3-dipolar cycloaddition reactions of azides from 1984 to 2000, with an emphasis on the synthesis of not only heterocycles but also complex natural products, intermediates, and analogues. 

Enantiomerically pure cyclopropanes are a frequent motif in the structure of natural products. Their synthesis is often demanding and many approaches have been made [50, 51]. Porcine pancreatic lipase (PPL) was used for the stereoselective desymmetrization of a cyclopropane dibutanoate (Fig. 2). The asymmetric hydrolysis of the meso compound yielded the corresponding enantiopure alcohol almost quantitatively. The intermediate obtained was successfully applied in the total synthesis of dictyopterenes A and C, sexual pheromones of brown algae [52], and constanolactones (see below) [53]. 

All the structures of natural products are very beautiful and attractive. Then, I would like only to relate them to my favorite compounds, carbohydrates. In my opinion, carbohydrates are the language of chiral natural products therefore, I have focused on the use of carbohydrates as chiral precursors in organic synthesis. 

The chromophores that are prevalent in the molecular structures of natural products are the aromatic ring and the carbonyl functional group. Symmetry elements associated with these functional groups means that they are achiral chromophores, so chirality has to be induced by their structural... 

The chemical structure of natural products can be identified quickly with a limited amount of materials by utilizing NMR equipment containing cryo probes [60]. More predictable chemical shifts coupled with a reasonable amount of published and internal NMR data [61] will significantly improve the time and accuracy of the structure elucidation process [62,63,64],... 

As described above genetic methods to alter the structure of natural products have been developed in the last 10 years. Many new compounds have been generated, some of them with improved characteristics. The genetic approaches to generate novel molecules can be divided into the following categories. 

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