Biosynthetic route

One of the most exciting discoveries related to quinone/hydroquinone chemistry is thek synthesis by biosynthetic routes (12,13). Using bacterial enzymes to convert D-glucose [50-99-7] (7) to either 1,2- or l,4-ben2enediol allows the use of renewable raw material to replace traditional petrochemicals. The promise of reduced dependence on caustic solutions and the use of transition-metal catalysts for thek synthesis are attractive in spite of the scientific and economic problems still to be solved. 

One of the most interesting uses for cinnamic acid in recent years has been as a raw material in the preparation of L-phenylalanine [63-91-2] the key intermediate for the synthetic dipeptide sweetener aspartame (25). Genex has described a biosynthetic route to L-phenylalanine which involves treatment of immobilized ceUs of R rubra containing the enzyme phenylalanine ammonia lyase (PAT,) with ammonium cinnamate [25459-05-6] (26). 

Terpenoid substances are of broad distribution and diverse function in insects. One set, elaborated by the mandibular glands of Acanthomyops claviger, acts both as a defensive secretion and as an alarm releaser. When fed Cu-labeled acetate or mevalonate, laboratory colonies of these ants produce radioactive citronellal and citral, providing unambiguous evidence for de novo synthesis of these terpenes by the ant. The incorporations of these precursors implicate the mevalonic acid pathway as the likely biosynthetic route. 

Still more confusion plagued early researches, when it was not realized that the biosynthetic routes to thiamine in prokaryotes and eukaryotes are quite different, a fact not expected at the outset. Thus, evidence collected from the study of yeast could not be transposed to bacteria, and vice-versa. For instance, formate is a most efficient precursor of one of the carbon atoms of the pyrimidine part of thiamine (pyramine), both in yeasts and enterobacteria, but incorporates at C-2 in bacteria and at C-4 in yeast. However, as is briefly covered in Section VIII, this dichotomy of pathways might have a deep significance in the perspective of biochemical evolution during primitive life on Earth. 

VII, The Distribution of the Four Biosynthetic Routes in Nature 1. Biosynthesis of Pyramine... 

The biosynthetic route to cephalosporin C is identical to that of the penicillins as far as isopeniciUin N (section 3.4.3). The further route to cephalosporin C is shown on p. 160. Note the branch into a third series of /3-lactam drugs, the cephamycins (see Chapter 5). 

FIGURE 2.4.1 Biosynthetic routes leading to betalains and anthocyanins. ... 

The spirobenzylisoquinoline alkaloids have been reviewed (1,2,7-10,147) and compiled (148). The exact biosynthetic route to spirobenzylisoquinolines from protoberberine alkaloids has not yet been elucidated (149). 

Ager, D.J., Li, T., Pantaleone, D.P. et al. (2001) Novel biosynthetic routes to non-proteinogenic amino acids as chiral pharmaceutical intermediates. Journal of Molecular Catalysis B, Enzymatic, 11 (4—6), 199-205. 

Table 8.2 According to the co-evolution theory proposed by Wong, the biosynthetic routes to amino acids from their precursors could perhaps provide information on the evolution of the genetic code (Wong, 1975)...

The Indo-Pacific sponge Strcmgylophora durissima is noteworthy as it contains essentially one sterol, (24R)-24-ethyl-27-methylcholesta-5,25-dien-3/ -ol (strongylosterol, 63). Four possible biosynthetic routes to this unconventional sterol have been proposed [41-44]. Incorporation experiments with ten radiolabeled precursors were carried out, which demonstrated that only one of the four hypothetical biosynthetic routes is operational. As summarized in Scheme 9 [44], this pathway involves three successive bioalkylations of desmosterol (34), codisterol (52) and 24(28)-dehydroaplysterol (64). No stereoselectivity at C-25 was observed, yet high selectivity at C-24 was found, as epicodisterol (51) was not metabolized. 

Acetaldehyde combines with 2,3-O-isopropylidene-D-glycerose, in the presence of potassium carbonate, to give 2-deoxy-4,5-O-isopropylidene-D-ribose and -D-xylose,46 suggesting a possible biosynthetic route (see Reference 46). The suggestion that 2-deoxy-D- ribose (2-deoxy-D-erythro-pentose) arises by combination of acetaldehyde with D-glycerose 3-phosphate to give 2-deoxy-D-ribose 5-phosphate (LX) was verified by using enzyme... 

Since tryptophan (and its decarboxylation product, tryptamine) serve as precursors in many synthetic and biosynthetic routes to /J-carbolincs, it is not surprising that C-1 of the /J-carbolinc ring is the most common site of substitution (as it is the only ring atom of the /J-carbolinc ring system not derived from tryptophan). Indeed, this is the only site of substitution for many /J-carboline natural products. Two examples of naturally occurring /J-carbolines substituted only at C-1 which possess antitumor activity are manzamine A and manzamine C (Fig. 2). Owing to its greater simplicity and nearly equal antitumor activity, most initial synthetic efforts were directed toward manzamine C [11,12]. 

Cyclic peptides, self-assembly of, 24 59-60 Cyclic peroxides, 18 436, 447-448, 459 Cyclic poly(aliphatic disulfide)s, 23 712 Cyclic poly(disulfide)s, available information related to, 23 713 Cyclic polyethers, 12 658 chelating agents, 5 710 Cyclic reforming operations, 25 166 Cyclic sesquiterpenoids, biosynthetic routes to, 24 472 Cyclic siloxanes... 

FIGURE 1.4 Proposed biosynthetic route for the biosynthesis of (A) squalene oxide (squalene-2,3-oxide) via the isoprenoid pathway and (B) triterpene saponins of the dammarane-type and oleanane-type from squalene oxide. PP, diphosphate group GPS, geranyl phosphate synthase FPS, farnesyl phosphate synthase NADPH, nicotinamide adenine dinucleotide phosphate. 

FIGURE 1.5 Possible biosynthetic route for ginsenosides of the dammarenediol-, protopanaxadiol-, and protopanaxatriol-type via dammarenediol. 

The chemical route to orlistat was ultimately favoured over the biosynthetic route as the latter required complex downstream processing that eliminated the benefits gained from the biotransformation itself. More recent advances in metabolic engineering and drownstream processing might have resulted in the development of a more competitive process. 

In addition to this, it has been reported that nonprotein amino acids could be formed by structural modifications to protein amino acids (methylation, hydroxylation, and halogenation) through modified L-a-amino acid biosynthetic pathways and through novel biosynthetic routes. Some examples of the nonprotein amino acids derived through these biosynthetic pathways are given below (Figure 3). A detailed discussion of known biosyntheses for certain nonprotein amino acids will be discussed later in this chapter. 

---