Chemical pathways, unusual

Some Unusual Chemical "Pathways and Reactions of One-Carbon Fragments... 

It is most unusual for female moths to utilize just one compound as the pheromone. Rather a blend of compounds produced in precise ratios make up the species-specific pheromone. The production of this precise blend of chemical components is regulated in the biosynthetic pathway. The inherent specificities found within key enzymes in the pathway and combinations of enzymes is what is responsible for producing species specific ratios [13,31]. 

A quantum chemical investigation of the biosynthesis of farnesyl pyrophosphate through the condensation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate suggests that the mechanism is concerted, although the transition state has carbocationic character.164 Quantum chemical calculations were performed on the cyclization of the farnesyl cation to the sesquiterpene pentalenene.165 Two distinct pathways with similar activation barriers were identified, each differing from previous proposed mechanisms, and each involving unusual carbocationic intermediates. Mechanisms previously proposed for enzyme-catalysed formation of the sesquiterpene trichodiene involve carbocation intermediates with a 1,4-hydride transfer as the key step, e.g. (89) -> (90) - (91).166 Quantum chemical calculations, however, show a... 

In the intervening 13 years the subject has expanded dramatically over 60 compounds are now classified as Erythrina alkaloids, and the structures of most of these have been deduced from a combination of mass spectral fragmentation analysis, H-NMR spectral interpretations, and chemical correlations with alkaloids of known structures. Some unusual alkaloids have been obtained from certain Cocculus species and a new, as yet small, subgroup, the Homoerythrina alkaloids, has been recognized. The biosynthetic pathway from tyrosine through the aromatic bases to the ery-throidines has been elucidated, and some significant advances have been made in methods of total synthesis. Reviews of the Erythrina alkaloids since 1966 have appeared (3-6). 

It should also be noted that some pathways to be discussed below depend on highly unusual chemical reactions. To give just one example, the formation of the pyridine ring system of vitamin Be depends on a protein that catalyzes a complex series of reactions, including carbohydrate isomerization, imine formation, ammonia addition, aldol-type condensation, cycliza-tion, and aromatization (9). 

The chemical transactions of DNA end joining are predictably similar to other DNA repair pathways and even to replication in that all of these processes manipulate base-pairing and phospho-diester bonds to create intact duplex molecules. However, the direct repair of DSBs presents biochemical challenges nniqne to these substrates. In this section, I consider both the general and the specific chemical requirements of nonhomologons DSB repair, how they are manifest in the two main pathways of repair, and the sometimes unusual properties of key enzymes that determine their function in these pathways. 

Copper Lewis acids have also found utility in hetero-Diels-Alder reactions. In these transformations the Lewis acid can activate either the diene or the dienophile and both types of reaction have been reported. Evans et al. have evaluated unsaturated acyl phosphonates [95] and acyl esters (amides) [87] as dienes in hetero-Diels-Alder reactions. The reactions proceed with excellent chemical efficiency and high stereoselectivity with as little as 0.2 mol % of the catalyst (Sch. 50). The reaction tolerates a variety of substituents on the diene and the dienophile. A square-planar model 226 wherein the phosphonate and the carbonyl groups form a chelate with copper, and addition occurring from the less hindered face, accounts for the selectivity observed. It is interesting to note that the reaction of 185 with phosphonate 228 gives 230, an inverse-electron-demand product, in preference to the normal Diels-Alder adduct 229. This unusual reaction pathway has been attributed to the electron-withdrawing capacity of the phosphonate group. 

In the past, compounds from nature often opened up completely new therapeutic approaches. Moreover, natural compounds substantially contributed to identify and understand novel biochemical pathways in vitro and in vivo, and consequently proved to make available not only valuable drugs but also essential tools in biochemistry, and molecular cell biology. It is worth while studying exhaustively the molecular basis of biological phenomena of new and/or unusual chemical structures from nature. Numerous examples from medicine impressively demonstrate the innovative potential of natural products and their impact on progress in drug discovery and development as discussed below. 

---