Biomimetic reactions concept

Eschenmoser [15] has recently alluded to the concepts of structure-directed synthesis and autochthonous reactivity — the propensity of certain systems to undergo reactions as a consequence of their intrinsic molecular structural factors — within the context of certain biomolecules, particularly the organic cofactor, vitamin B12. The formation of the AD ring junction in the corrin ligand had to be regarded as a major hurdle in any proposed chemical synthesis of cobyric acid (5) (Fig. 2), and hence of vitamin B12. However, driven initially by the desire to identify a dark, and therefore potentially biomimetic, variant of the photochemical... 

For recent reviews, see (a) Berkessel, A. and Groger, H. (2005) Asymmetric Organocatalysis From Biomimetic Concepts to Potveiful Methods for Asymmetric Synthesis, Wiley VCH Verlag GmbH, Weinheim (b) Dalko, P.L (ed.) (2007) Enantioselective Organocatalysis Reactions and Experimental Procedures, John Wiley Sons, New York. 

The biomimetic phosphoric acid mixed anhydride concept stimulated further search for activating reagents that produce derivatives of acylamino acids (and peptides) in more simple ways than the ones mentioned earlier in the Chapter (on p. 78) An interesting attempt in this direction is the so called Bates reagent [47] which on reaction with carboxylic acids yields acyloxyphosphonium salts. 

In the light of the above-mentioned nonexhaustive list of examples, MOFs are used in the fine chemical synthesis either as self-supported catalysts or as catalyst carriers in a ship-in-a-hotth concept by encapsulation or grafting of active species. However, we need to look critically at the possibility to generalize these key examples in order to design ideal and universal hybrid catalysts. The development of future applications of these functionalized solids requires taking into account the synthetic limitations of MOF materials and, motivated by early examples of homochiral MOF catalysts (Section 10.4), it seems necessary to focus efforts toward soft reaction conditions and sophisticated biomimetic applications. 

The immense potency of domino reactions cannot be presented in a better way as in their apphcation to the total synthesis of complex natural products. Though nature has aheady shown that the domino concept is very useful in this field and several of the described natural product syntheses follow a biomimetic way, a multitude of other approaches have been developed over the last years, and we are convinced that in future most of the pubhshed total syntheses will be based on domino reactions. 

In this chapter we summarize key molecular concepts in biocatalysis and compare them with the molecular understanding of reaction mechanisms in heterogeneous catalysis that was developed in the previous chapters. The first four sections of this chapter emphasize enzyme catalysis. Biomimetic approaches are described in later sections. 

A further step has been achieved by designing bionanoreactors to function as artificial organelles, because of the retention of their activity upon cellular uptake [8], Such systems, which have a high potential for therapeutic applications, are motivating further efforts to diversify the variety of artificial organelles to truly mimic natural ones, and to offer solutions for pathological conditions. In a biomimetic approach, the concept of multicompartmentalized polymersomes has been introduced for reactions between different inner compartments encapsulated in giant structures that can serve as models for simple cellular compartments [11,15]. We include a summary of requirements needed for successful applications and models or translational examples in the development of bionanoreactors. 

The site isolation concept with simple weso-tetraaryl porphyrin hgands has found widespread apphcation in oxidation catalysis with immobihzed metallopor-phyrins, for example, catechol and lignin oxidation with Mn Cl(TPP) complexes 46 and H2O2 as oxidant [55, 56] or hydroquinone and thiol oxidation with Co (TPP) complexes 47 and O2 as oxidant [57, 58]. Although these reactions are of considerable synthetic utility [59], truly functional biomimetic models with a detailed knowledge of elementary reaction steps have not yet been developed. 

Berkessel, A. Groger, H. Chapter 8 Cycloaddition Reactions. Asymmetric Organocatalysis From Biomimetic Concepts to Applications in Asymmetric Synthesis. Wemheim Wiley-VCH. 2005, p. 256-268. ISBN 3-527-30517-3. 

In 2005, Huang et al. reported a tandem asymmetric conjugate reduction-fluorina-tion reaction by an efficient combination of iminium and enamine catalysis using two distinct secondary amine catalysts [16]. This method offered direct access to chiral multifunctionalized aldehydes from P-substituted enals and electrophilic florinated reagents in a biomimetic way (Schane 9.13). The diastereoselectivity of the products varied depending on the catalyst combination (Scheme 9.14). The chemistry presented here demonstrated for the first time the power of the multicatalysis process for control of the product diastereoselectivity based on the cycle-specific catalysis concept. 

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