Types of Biotransformation

Enzymes involved in alkaloid transformations have been arbitrarily divided into two major classes or types of biotransformations. The classification used here is that which has evolved from early descriptions of mammalian detoxica-... 

This section of the review will consider various types of biotransformations of alkaloids from both chemical and biochemical perspectives. We have attempted to avoid serious repetition of published work previously covered by Holland (2) in this series by presenting material published since 1980 and by inclusion of a few examples that were not mentioned earlier. For convenience, we have organized our review in essentially the same style used by Holland. 

Stereoselective enzymatic hydrolyses of esters represent a further type of biotransformation that has been used for the synthesis of optically active organosilicon compounds. The first example of this particular type of bioconversion is illustrated in Scheme 15. Starting from the racemic (l-acetoxyethyl)silane rac-11, the optically active (l-hydroxyethyl)silane (5)-41 was obtained by a kinetic racemate resolution using porcine liver esterase (PLE E.C. 3.1.1.1) as the biocatalyst7. The silane (5)-41 (isolated with an enantiomeric purity of 60% ee bioconversion not optimized) is the antipode of compound (R)-41 which was obtained by an enantioselective microbial reduction of the acetylsilane 40 (see Scheme 8). 

Enantioselective enzymatic ester hydrolyses of prochiral trimethylsilyl-substituted diesters of the malonate type have been applied for the synthesis of the related optically active monoesters68. As an example of this particular type of biotransformation, the enantioselective conversion of the diester 82 is illustrated in Scheme 17. Hydrolysis of compound 82 in phosphate buffer, catalyzed by porcine liver esterase (PLE E.C. 3.1.1.1) or horse liver acetonic powder (HLAP), gave the optically active monoester 83 (absolute configuration not reported) in 86% and 49% yield, respectively. The enantiomeric purities... 

Enantioselective enzymatic transesterifications have been used as a complementary method to enantioselective enzymatic ester hydrolyses. The first example of this particular type of biotransformation is the synthesis of the optically active 2-acetoxy-l-silacyclohexane (5 )-78 (Scheme 19). This compound was obtained by an enantioselective transesterification of the racemic l-silacyclohexan-2-ol rac-43 with triacetin (acetate source) in isooctane, catalyzed by a crude lipase preparation from Candida cylindracea (CCL, E.C. 3.1.1.3)62. After terminating the reaction at 52% conversion (relative to total amount of substrate rac-43), the product (S)-78 was separated from the nonreacted substrate by column chromatography on silica gel and isolated in 92% yield (relative to total amount of converted rac-43) with an enantiomeric purity of 95% ee. The remaining l-silacyclohexan-2-ol (/ )-43 was obtained in 76% yield (relative to total amount of nonconverted rac-43) with an enantiomeric purity of 96% ee. Repeated recrystallization of (R)-43 led to an improvement of enantiomeric purity by up to >98% ee. Compound (R)-43 has already earlier been prepared by an enantioselective microbial reduction of the l-silacyclohexan-2-one 42 (see Scheme 8)53. The l-silacyclohexan-2-ol (R)-43 is the antipode of compound (.S j-43 which was obtained by a kinetic enzymatic resolution of the racemic 2-acetoxy-l-silacyclohexane rac-78 (see Scheme 15)62. For further enantioselective enzymatic transesterifications of racemic organosilicon substrates, with a carbon atom as the center of chirality, see References 64 and 70-72. 

Type of Biotransformation Net Transformation Nominal m/z Shift Exact m/z Shift... 

Phase-1 metabolism leads to mass shifts relative to the mass of the parent drag (Table 10.1). In principle, the type of biotransformation can be derived from this mass shift, while more information on the actual site of the modification can be derived from mass shifts of the fragment ions in the MS-MS spectrum. Identification approaches are based on the fact that metabolites generally retain a... 

Nitrogen and oxygen functionalities are commonly found in most drugs and foreign compounds sulfur functionalities occur only occasionally. Metabolic oxidation of carbon-nitrogen. carbon-oxygen, and carbon-.sulfur systems principally involves two basic types of biotransformation processes ... 

It is possible to distinguish between two major types of biotransformation. On the one hand, there are xenobiotic transformations in which the substrate is completely alien to the microorganism whilst, on the other hand, there are biosynthetically-patterned biotransformations in which the substrate bears a formal relationship to an intermediate of one of the natural biosynthetic pathways that the organism possesses. 

One of the most useful characteristics of this work is the fact that these epoxides could be routinely produced at yields approaching (at best) 1 g L-1 after simple overnight shaking using whole-cell or even crude cell-free systems. Thus, these results clearly opened the way to a new type of biotransformation which should be very useful for organic synthesis. 

As a rule, saturated alcohols are formed by treatment of a./i-unsaturated aldehydes with baker s yeast. It is remarkable to note that the corresponding saturated carboxylic acids were obtained in the yeast-catalyzed reaction of these sulfur-containing a,/f-unsaturated aldehydes. This type of biotransformation has so far only been observed with the fungus Geotrichum candidum21. 

There are two broad types of biotransformation, called phase I and phase II. 

One type of biotransformation of Cr(VI) yields DNA bound Cr(III) products (170). Neutron activation analysis of the Cr distribution between different cellular fractions following the uptake of [ °Cr04] by yeast cells revealed the highest Cr concentrations in the DNA fraction (48%), followed by RNA (34%) and protein (6%) fractions (199). Recently, this was supported by scanning micro-SRIXE analyses (employing a 0.3 pm-diameter focused X-ray beam) of thin-sectioned chromate-treated V79 cells that showed localization of Cr in P- and Zn-rich regions (which is characteristic of the cell nucleus) (91,... 

These results indicate that this organism is capable of three different types of biotransformation, including reduction of the a,jS-unsaturated-y-lactone, epoxi-dation, and cyclization. In another biogenetically motivated experiment it has been demonstrated that selenium dioxide oxidation of costunolide (354) proceeds with isomerization of the double bond to produce the melampolide-type compounds (364) and (365). 

Although the above-mentioned criteria are difficult to meet experimentally, the benefits are impressive. Examples of this type of biotransformation have increased recently [83-89] several examples are given in subsequent chapters. 

---