Bio-chemo cascade

Here, bio- and chemocatalysis as well as stoichiometric organic chemistry can work together. The different approaches can be categorized in bio-bio, chemo-chemo and bio-chemo cascades. Their relative development over the years (by number of publications, as shown in Fig. 13.5) reflects the following major features ... 

Although the focus here is on the integration of biocatalysis with chemocataly-sis (bio-chemo cascades) for carbohydrates as renewable feedstocks, some representative examples (from laboratory to industrial scale) of both bio-bio and chemo-chemo cascades are also given below for comparison of their relative scope and limitations. 

Fig. 13.9 Facsimile of a molecular and kinetic scheme of the one-pot glucose into mannitol bio-chemo cascade, showing the many different species that undergo interconversion during the overall process, involving enzymatic isomerization, homogeneous mutarotation and heterogeneous hydrogenation. For simplicity, the various sugar-borate species have been omitted [23, 24],...

Table 13.1 Kinetics of three types of catalysis that are in concert in the one-pot glucose-to-mannitol bio-chemo cascade conversion [19].

A similar picture has been obtained very recently for novel multi-step bio-chemo cascade reactions starting from both galactose-derived polyols and aliphatic mono- and diols [29]. Galactose oxidase and alcohol oxidase show complementary synthetic use for this range of alcohols (Table 13.3) [30], allowing in situ... 

Fig. 13.16 Merging reaction parameters of chemocatalysis (blank area) to that of biocatalysis (black area) to exploit fully the scope of bio-chemo cascade conversions.

Effective and simple immobilization of enzymes can be obtained by the cross-linking of enzyme aggregates, so-called CLEAs [55]. In this way, essentially any enzyme, including crude preparations, can be transformed into a heterogeneous type of material, insoluble in both water and organic solvents, that is stable and recyclable with high retention of the enzyme s original activity [56], These enzyme preparations are, therefore, of special value for both bio-bio and bio-chemo cascade processes. 

Three-or-more-step bio-chemo cascades comprising different types of catalysts are rare, which is related to incompatibility of many chemocatalytic steps with enzymes in terms of reaction parameters such as substrates, solvents, pH, temperature, etc. 

The general concept of cascade conversions is demonstrated by a representative selection of illustrative bio-bio, chemo-chemo, and bio-chemo catalytic examples on a laboratory scale as well as on a pilot- or industrial-scale. 

Table 13.2 Benefits of the one-pot bio-chemo catalytic cascade as compared with the traditional step-wise stoichiometric organic synthesis of 4-deoxyglucose [27, 28].

Catalytic methods, chemo- as well as bio-catalysis, are of vital importance in the conversion of natural products into derivatives (semi-synthesis). In chemo-catalysis conventional catalysts, such as mineral acids, are being replaced by recyclable solid catalysts. Further progress is also expected in cascade processes in which synthesis steps are combined to one pot methods. 

Nowadays interest in mankind-designed cascade reactions is rapidly growing. A recent review of Bmggink et al.[ 18] lists a total of 62 cascade reactions, of which 21 examples involve bio-bio catalysis by mixtures of enzymes, 26 examples involve bio-chcmo catalysis, combined action of an enzyme and a chemo-catalyst, and 15 examples pertain to the action of two or more chemo-catalysts. 

Fig. 8.38 Chemo-bio cascade catalysis for hydrogenation of acetophenone (A), followed by acylation of the formed ff-1-phenyl ethyl alcohol (B) with ethylacetate (Q) to / -1-phenyl ethyl acetate (P) other products were S-1 -phenyl ethyl alcohol (C), ethanol (I), and ethyl benzene (F). (From S. Sahin, J. Wdrna, P. Maki-Arvela, T. Salmi, D.Yu. Murzin, Kinetic modeling of lipase-mediated one- pot chemo-bio cascade synthesis of R- 7 -phenyl ethyl acetate starting from acetophenone, J. Chem. Technol. Biotechnol. 85 (2010) 192-198. Copyright 2010 Wiley).

Fig. 8.39 Reaction mechanism in chemo-bio cascade catalysis for hydrogenation of acetophenone.

S. Sahin, J. Wama, P. Maki-Arveh, T. Salmi, D.Yu. Murzin, Kinetic modeling ofUpase-mediated one-pot chemo-bio cascade synthesis of R-l-phenyl ethyl acetate starting from acetophenone, J. Chem. Technol. Biotechnol. 85 (2) (2010) 192-198. 

---