The Biomimetic Approach

The biomimetic approach to total synthesis draws inspiration from the enzyme-catalyzed conversion of squalene oxide (2) to lanosterol (3) (through polyolefinic cyclization and subsequent rearrangement), a biosynthetic precursor of cholesterol, and the related conversion of squalene oxide (2) to the plant triterpenoid dammaradienol (4) (see Scheme la).3 The dramatic productivity of these enzyme-mediated transformations is obvious in one impressive step, squalene oxide (2), a molecule harboring only a single asymmetric carbon atom, is converted into a stereochemically complex polycyclic framework in a manner that is stereospecific. In both cases, four carbocyclic rings are created at the expense of a single oxirane ring. 

The biomimetic approach can be easily extended to the synthesis of [26]porphyrins(3.3.3.3) 32 when symmetrically -substituted 2-(3-hydroxypropen-l-yl)pyrroles 30 are used as mono-pyrrolic building blocks.1 la h... 

These results have demonstrated that the biomimetic approach of copying the supramolecular principle of archaeal cell envelopes opens new possibilities for exploiting functional hpid membranes at meso- and macroscopic scales. Moreover, this technology has the potential to initiate a broad spectrum of developments in such areas as sensor technology, diagnostics, biotechnology, and electronic or optical devices. 

The biomimetic approach to the core skeleton of C-nor-D-homosteroid was first developed by the Merck research group (Scheme 2.1) [16]. In the Merck procedure,... 

In this chapter, we will introduce a bioinspired approach to biomineralization. First, a fundamental concept of the bioinspired approach is compared with the biomimetic approach. Here is a question, What is a bioinspired approach If we want to fly in the sky, when we look at flying birds what do we have to do Two kinds of typical answer were considered, as shown in Figure 6.4. One is Bird-Man, in the Edo period (AD 1600) in Japan, a man named Kokichi attempted to fly. He wore wide, large wings on both his arms, and fluttered his arms vigorously, but in vain. This is a typical biomimetic approach. He only mimicked the style of a flying bird, so his innovative idea ended in failure. 

Rao et al. [100] for the first time report the biomimetic approach for the synthesis of a single enantiomer of p-aminoalcohol. In this approach p-cyclodextrin formed by the inclusion of complex 77 with racemic aryloxyepoxide which reacted enantioselectively with amines imder solid state condition to give the product in 100% ee and 70-79% isolated yield. The yield which was above 50% was explained in terms of continuous racemization of the... 

A unique feature of the biomimetic approach is the ability to construct model compounds that combine all the required parameters gained over time in a single molecule and to examine to which extent the new structures sustain bioactivity. Motifs that have not been incorporated in the assembled structures will be exposed, either by reduced bioactivity or by the lack of it altogether, thus providing an indication that some parameters have been omitted, and should be searched for and introduced. 

The biomimetic approach to the synthesis of new siderophores has not been restricted to studies in the USA Kontoghiorghes241 242,269) has synthesized hydroxypyridones (34, 35) and demonstrated their ability to mobilize iron(III) from ferritin. Intragastric administration of l,2-dimethyl-3-hydroxy-pyrid-4-one (34) proved to be as effective as intramuscular DFOA in mobilizing iron from the iron-overloaded rat. This effectiveness of an orally administered chelating agent is particularly noteworthy. 

Palmore also explained that the biomimetic approach uses inspiration from biology to develop new chemistry to perform catalysis. Palmore focused on using biology to do the energy conversion, both in the free form as purified enzyme extract and where new organisms have been isolated and coupled with electrode surfaces (Figure 4.4). 

It is evident that the biomimetic approach using polypeptide hybrid polymers is very successful in the creation of novel superstructures with hierarchical order. Although started about 30 years ago in the mid-1970s, this field is still in a premature state. The greatest munber of systematic studies on the aggregation behaviour in solution is younger than 5 to 10 years. A comprehensive picture of the processes involved in the formation of hierarchical superstructures has not yet emerged. 

Rueping et al. extended the biomimetic approach to the reduction of quinolines, benzoxazines, benzothiazines, and benzoxazinones (Equation 10.38) [81], The reduction of benzoxazines, in particular, is highly stereoselective, reducing the catalyst load of 21g to as low as 0.01 mol% without a substantial loss of reactivity or selectivity. 

The synthesis of the spirocyclic core [70-77] is obviously the most difficult task, the biomimetic approach being the most frequent way of preparing it. The strategy is based on the hipervalent iodine-mediated oxidative hydroxylation of a tyrosinal derivative followed by a cis-bisepoxidation. The shortest way [75] involved the introduction of the side chain as an amide of tyrosine ethyl ester. Aranorosin was obtained after DIBAL reduction to the aldehyde, oxidation to the dienone with phenyliodosyl bis(trifluoroacetate) (PIFA) and final epoxidation (Scheme 24). 

The final example illustrates yet another use of the biomimetic approach. Figure 10.9shows a retro-synthetic analysis for Masamune s synthesis of deoxyerythronolide B (213). The biosynthetic building blocks of this and other macrolide antibiotics are known to be acetate and/or propionate units combined head-to-tail, as seen in 213. 7 xhe stereocenters in 213 are clearly shown in the acyclic (seco acid) form of the macrolide 215. The specific biopathway is not utilized but rather modified to include the basic building blocks, seven propionate units (bold lines in 213).Seco acid 215 was constructed by sequential aldol condensation reactions (sec. 9.4.A) of propionaldehyde units, as shown by the disconnections in Figure 10.9. Asymmetric... 

Therefore, the biomimetic approach, that is the aeation of chemical analogues of enzymes, seems to be especially promising in this respect. The aeation of chemical models of the enzymatic oxidation of alkanes and arenes makes it possible not only to understand its mechanisms better, but also to develop what are likely to be fundamentally new processes for the conversion of the hydrocarbon raw material. 

Despite the merit of pioneering the biomimetic approach to 5,6-dihydroxyindole synthesis, some of these papers contained incorrect structural conclusions that were highlighted in revisions by subsequent workers. Thus, for example, Heacock and co-workers (63JA1825) provided unambiguous proof that in iodo- and bromo-aminochromes the halogen occupies the 7- and not the 2-position, as previously believed. Independent total syntheses of 5,6-dimethoxy-7-iodoindole and of... 

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