Biomimetic inspired syntheses

Scheme 3. Biomimetically inspired total synthesis of (+)-torreyanic acid (21). (Porco etal., 2000) ...

Nicolaou KC, Sasmal PK, Xu H. Biomimetically inspired total synthesis and structure activity relationships of 1-0-methyllaterifiorone. 6n -Electrocyclizations in organic synthesis. J. Am. Chem. Soc. 2004 126(17) 5493-5501. 

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. 

Macrocyclic complexes of zinc have inspired interest in varied areas such as supramolecular and biomimetic chemistry including hydrolysis enzymes, such as phosphatases and esterases, and also for the fluorescent detection of zinc. The polyaza macrocycles and their A--functionalized derivatives are particularly well represented. An important aspect of macrocycle synthesis is the use of metal templates to form the ligand. Examples of zinc as a template ion will be discussed where relevant. 

In the first place, the structure of the target molecule is submitted to a rational analysis in order to perceive the most significant structural features, and it may be useful to use different types of molecular models at this point. It should be remembered that a molecular structure has "thousand faces" and finding the most convenient perspective may greatly simplifly the synthetic problem. The synthesis of opium alkaloids, for instance, is much simplified if one realises that they are, in fact, derivatives of benzyltetrahydroisoquinoline (18) (see Scheme 3.8). This was indeed the inspired intuition of Sir Robert Robinson which led to the structural elucidation of morphine (19) and to a first sketch of the biogenetic pathway [22], and later on to the biomimetic synthesis of thebaine 20 [23] [24]. 

When new and academic-looking reactions are discovered in the laboratory, it often seems only a short time before they are found in nature as well. However, the development of polyolefin cycliza-tion reactions in synthesis occurred by the reverse philosophy—it was inspiration from Nature that led W. S. Johnson to use the reactions in synthesis, including steroid synthesis. This is biomimetic synthesis, a strategy that is bound to work provided we can just master the practical details. 

Currently, there is a growing need to develop environmentally benign nanoparticle synthesis processes that do not use toxic chemicals in the synthesis protocol. As a result, researchers in the held of nanoparticles synthesis and assembly have turned to biological systems for inspiration. The secrets gleaned from nature have led to the development of biomimetic approaches to the growth of advanced nanomaterials (Sastry et al., 2003). Besides this, the utilization of nontoxic chemicals. 

Figure 4.1 Synthesis of bone-like composites through a biomimetic strategy inspired from bone biomineralization, (a) Biomimetic composites were obtained by first cross-linking maleic chitosan with PEGDA under UV light in water to form 3-D hydrogel networks, followed by biomimetic mineralization Images of maleic chitosan/PEGDA hydrogel (b) before and (c) after mineralization.

Strictly speaking, biomimetic synthesis implies that one prepares a compound by the same method used by Nature for the biosynthesis of compound. However, chemists commonly use the term in a more general way-meaning that a synthesis is inspired by a probable or even possible biosynthetic construction of bonds. That is, it is often possible to deduce from the structure of a natural product what the starting material must be, and by application of sound mechanistic ideas about electron movement, it is often possible to propose a sequence of steps that may be used by Nature. When a chemist is inspired by such considerations to design a synthesis, and then proceeds to reduce the plan to practice by experiment, this is often called a biomimetic synthesis, even if there has been absolutely no experimental work directed at determining the actual biosynthetic pathway. 

Natural products syntheses of numerous compounds have been inspired by nature. In other words, the pathway taken by nature to a given natural product often suggests a synthetic strategy that one might follow in the laboratory. Such syntheses are sometimes refered to as biomimetic syntheses and numerous examples permeate the literature. The notion of mimicing nature is quite old, but it is time-tested, often used, and still always stimulating to think about this approach to designing a laboratory synthesis of a new natural product. 

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