Purine base ring system

Figure 3-3. Origin of the atoms of the purine base ring system (RP = pentose phosphate).

Fischer carried out extensive work on the chemistry of purine and on those compounds containing its nucleus. Purine is one of the two nitrogen base ring systems present in DNA. Fischer synthesized approximately 150 members of this class of heterocyclic compounds (including the first synthesis of the alkaloid caffeine (see Experiment [IIB]), uric add, and the xanthines (also see Experiment [IIB]). He developed a general s)mthesis of another nitrogen heterocyde, indole, which was so effective that it has become one of the classic synthetic methods of organic chemistry and is known today as the "Fischer indole synthesis" ... 

Nucleic acids can contain of any one of three kinds of pyrimidine ring systems (uracil, cytosine, or thymine) or two types of purine derivatives (adenine or guanine). Adenine, guanine, thymine, and cytosine are the four main base constituents found in DNA. In RNA molecules, three of these four bases are present, but with thymine replaced by uracil to make up the fourth. Some additional minor derivatives are found in messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), particularly the N4,N4-dimethyladenine and N7-methylguanine varieties. 

Alkaloids are basic plant natural products that typically have a nitrogen atom as part of a heterocyclic ring system and indeed are classified on this basis. Thus major classes of alkaloids are based on indole, isoquinoline, pyrrolidine, piperidine, pyrrolizidine, quinoline, tropane, quinolizidine or other heterocyclic ring systems. Other alkaloids are basic monoterpenoid, sesquiterpenoid, diterpenoid, steroid, purine, pyrimidine or peptide entities. Some of these compounds are exceptionally toxic [1,6, 7-12]. 

Caffeine (1.10), found in coffee (Coffea arabica), was introduced to Europe through Constantinople (modem Istanbul) in the 1500s (Figure 1.5). The stimulant effects of coffee were widely acknowledged, but coffee was recognized as a useful diuretic. Caffeine was first synthesized by Emil Fischer in 1882. Two related compounds, theobromine (1.11) and theophylline (1.12), found in cacao seeds (Theobroma cacao) and tea (Camellia sinensi), respectively, are more potent diuretics than caffeine.1 All three compounds are based on the purine ring system (1.13). 

The purine bases have a 9-membered double-ring system with four nitrogens and five carbons. 

The caffeine structure is shown below. It is classed as an alkaloid, meaning that with the nitrogen present, the molecule has base characteristics (alkali-like). In addition, the molecule has the purine ring system, a framework which plays an important role in living systems. 

The alkaloids are basic compounds in which an N atom is typically part of a heterocyclic ring but in some cases is merely a substituent of an alicyclic or aromatic ring system (as for example with colchicine, some peptide alkaloids and some Amaryllidaceae alkaloids). Various N-based heterocyclics such as the purine and pyrimidine bases of DNA and RNA (see Chapter 2) and the methylxanthine purine derivatives variously found in tea and coffee (caffeine, theobromine and theophylline) are sometimes referred to as pseudoalkaloids and for consistency will be included as alkaloids in this classification. Indeed all plant heterocyclics with a ring N will be conveniendy lumped in with the alkaloids in the tables for didactic simplicity and consistency. 

The purine bases are formed from the parent compound purine, which in turn is formed by the fusion of a pyrimidine and an imidazole ring. The parent purine structure and systematic numbering are shown in Fig. 2. Like the pyrimidine class of compounds, purine ring systems are it electron deficient however, unlike pyrimidines, there is no position in the ring... 

X-Ray crystallographic studies of purine and its various substituted derivatives have been of special value in providing (a) fine structural details of the ring system of simple molecules in their various neutral and protonated, and to a lesser extent, deprotonated forms (b) a source of molecular geometries for theoretical calculations and related purposes and (c) information about the precise arrangement of purine (and pyrimidine) bases in the various nucleic acids, and the way in which interaction of such bases with extraneous materials including intercalated or absorbed compounds occurs. 

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