Biotransformations functional group transformation

Plant biotransformation parallels liver biotransformation and is conceptually divided into three phases. Phase I typically consist of oxidative transformations in which polar functional groups such as OH, NH2, or SH are introduced. However, reductive reactions have been observed for certain nitroaromatic compounds. Phase II involves conjugation reactions that result in the formation of water soluble compounds such as glucosides, glutathiones, amino acids, and malonyl conjugates or water-insoluble compounds that are later incorporated or bound into cell wall biopolymers. In animals, these water-soluble Phase H metabolites would typically be excreted. In Phase III, these substances are compartmentalized in the plant vacuoles or cell walls. For additional details, the reader is referred to reviews on the subject by Komossa and Sandermann (1995), Pflugmacher and Sandermann (1998), and Burken (2003). Enzymatic conversion rates typically follow Michaelis-Menten kinetics and are temperature-dependent (Larsen et al., 2005 Yu et al., 2004,2005, 2007). 

The general aims of yeast-mediated biotransformations focus on the introduction of chiral centers, file resolution of racemates, and the selective conversion of functional groups among several groups of similar reactivities. Several excellent reviews have been published on microbial transformations also covering yeast-mediated conversions [13-17]. To avoid excessive echoing of these reviews, background material will be limited to the... 

Biotransformation of non-polar, non-volatile toxicants is a two-phase biochemical reaction. In the first phase (Phase I), the body s enzyme system introduces a polar group into the toxicant (e.g., by oxidation, reduction, or hydrolysis). See Figure 9.28. The enzymes responsible for these transformations are part of a mixed function oxidase system (MFO) of smooth endoplasmatic reticulum present in liver parenchyma cells and in other tissues (e.g., intestine and gill). 

Two phases can be distinguished in the pathways of biotransformation. Phase I involves addition of functionally reactive groups by oxidation, reduction or hydrolysis. Phase II consists of conjugation of reactive groups, present either in the parent molecule or after phase I transformation. Phenytoin, for example, is first hydroxylated by a phase I reaction and subsequently conjugated with glucuronic acid. The various phase I and phase II reactions are summarized in Tables 30.3 and 30.5. 

To start with the first option of such a chemoenzymatic process sequence, namely initial biotransformation and subsequent chemocatalytic or classical chemical reaction(s), an early example from the Gijsen and Wong [40] already in 1995 demonstrated a one-pot process for the synthesis of a cyclitol, which is based on an initial enzymatic aldol reaction of aldehyde 37 with 0-monophosphorylated dihy-droxyacetone, followed by a subsequent spontaneous cyclization via intramolecular Horner-Wadsworth-Emmons olefination reaction (Scheme 19.14). Furthermore, the resulting functionalized cyclopentene derivative 39 was deprotected in situ in the presence of an added phosphatase. By means of this one-pot three-step process, the desired trihydroxylated cyclopentene derivative 40 was formed, which was then further transformed via acetylation into the desired product 41 with an overall yield of 71%. A closely related process represents the combination of an enzymatic aldol reaction with a subsequent nitroaldol reaction (Henry reaction). Examples for such a type of process were developed independently by the Wong [41] and Lemaire [42] groups. 

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