Biomimetics process synthesis

A later one-step synthesis was designed as a biomimetic process (18). The N-methyl pyrrolidine ring in alkaloids such as nicotine is derived from ornithine via... 

We call reductive amination a biomimetic ( mimicking the biological process ) synthesis because it resembles the biological synthesis of amino acids. The biosynthesis begins with reductive amination of a-ketoglutaric acid (an intermediate in the... 

Trost et al. have exploited the Cp2TiCl-promoted 6-exo cyclization of 10 to 13 for the first enantioselective biomimetic total synthesis of the antifungal metabolite (-)-siccanin (15) (Scheme 21) [109]. These authors also observed a minor amount (20%) of by-product 14, presumably derived from the radical intermediate 12 by a process reminiscent of the Sr2 reaction described by Gansauer s group [66]. They took advantage of 14 for the preparation of (-)-5-epz-siccanin (16) (Scheme 21) [109]. 

Despite considerable efforts, the progress toward a generic sequence independent synthesis of TT-conjugated oligomers and polymers, it is evident that the biomimetic processes of peptide and nucleic acid syntheses present superior possibilities and flexibility in making new materials as well as parallel synthesis possible. 

Reduction-triggered pericyclic reaction has been used for the biomimetic total synthesis of endiandric acids A-G [72]. Endiandric acids are polycychc natural products isolated from the Australian plant Endiandra introrsa and exist naturally as a racemic mixture which is found to have very high antibacterial effect [73]. In 1980, Black and coworkers [74] proposed a hypothesis that these polycyclic systems are formed in nature by a series of electrocycUzation reactions. On the basis of this hypothesis, Nicolaou et al. [72c] in 1982 reported an excellent domino reduction/electrocyclization process for the synthesis of endiandric acid A 127 (Scheme 9.25). Selective hydrogenation using a Lindlar catalyst of diacetylenic diol 123 afforded the bicyclic diol 126. The reaction presumably proceeds via polyene 124, which then undergoes a spontaneous 8 [i-electrocyclization to give 125. It follows a second 6n-electrocyclization to afford bicyclic 126, which is further converted to endiandric acid A 127. 

The new challenge on the theory is about the prediction of biomimetic ammonia-synthesis path at room temperature and atmospheric pressure. There are some reports on the study of photocatalytic, bio-catalytic and electrochemical ammonia synthesis catalysts. The latter should be achieved preferably by electrochemical processes with efficiency similar to the synthesis strategies that are available today. 

One example of an early PGF synthesis is Robinson s 1917 landmark synthesis of tropinone 96 [80] (Scheme 13.15). By the combination of succinaldehyde 93, methylamine 94, and acetone dicarboxylic acid 95, tropinone resulted from what can be assumed to be a biomimetic process [81]. Another classic PGF synthesis is Danishefsky s 1968 preparation of patchouli alcohol (100) [82]. The atom-economical first step of this sequence, the Diels-Alder reaction of diene 97 and methyl vinyl ketone (98), is one of but not the only reason this example was chosen. Not to take away from the beauty of Danishefsky s synthesis, functionality contained within patchouli alcohol is minimal and as a result limited PG usage would be expected. Also, during the decades of the two syntheses the... 

The domino approach is also used by Nature for the synthesis of several alkaloids, the most prominent example being the biosynthesis of tropinone (0-16). In this case, a biomimetic synthesis was developed before the biosynthesis had been disclosed. Shortly after the publication of a more than 20-step synthesis of tropinone by Willstatter [14], Robinson [15] described a domino process (which was later improved by Schopf [16]) using succinaldehyde (0-13), methylamine (0-14) and acetonedicarboxylic acid (0-15) to give tropinone (0-16) in excellent yield without isolating any intermediates (Scheme 0.5). 

Vassilikogiannakis and coworkers described a simple sequential process for the biomimetic synthesis of litseaverticillol B (4-159) which includes a cycloaddition of 4-158 and singlet oxygen to give 4-160, followed by ring opening to afford the hydro-genperoxide 4-161 (Scheme 4.34) [55]. Reduction of 4-161 led to the hemiacetal 4-162, which underwent an aldol reaction to afford 4-159. 

As mentioned earlier, biological systems have developed optimized strategies to design materials with elaborate nanostructures [6]. A straightforward approach to obtaining nanoparticles with controlled size and organization should therefore rely on so-called biomimetic syntheses where one aims to reproduce in vitro the natural processes of biomineralization. In this context, a first possibility is to extract and analyze the biological (macro)-molecules that are involved in these processes and to use them as templates for the formation of the same materials. Such an approach has been widely developed for calcium carbonate biomimetic synthesis [13]. In the case of oxide nanomaterials, the most studied system so far is the silica shell formed by diatoms [14]. 

An impressive example of a multi-step biomi-metic domino process is the synthesis of codaphni-phyllin by Heathcock et al. (see scheme 14). Another example is the highly efficient biomimetic synthesis of (+)-hirsutine by my group (see scheme 13). In addition several other total syntheses of natural products have been developed using domino processes these are described in the different sections of this chapter. 

The biomimetic-type cyclization of polyisoprenoids is an important industrial process for terpene synthesis. In most cases, a large excess of coned. H SO and SnCl. has been employed For example, ionone, a precursor of vitamin A, is prepared by coned. H2SO4 catalyzed cyclization of pseudoionone. The disadvantage of this process is undoubtedly the requirement of bases to neutralize the large excess of acid. The EGA method offers a promising alternative for this purpose. Thus, Electrolysis of 15 and 17 in a ClCHjCH Cl—LiClO —Et NClO — (Pt) system provides 16 and 18, respectively in reasonable yields and the neutralization of the reaction solution can be performed simply by addition of a small amount of pyridine... 

In natural processes, metal ions are often in high oxidation states (2 or 3), whereas in chemical systems the metals are in low oxidation states (0 or 1). This fact inverts the role of the metal center, such that it acts as a one-electron sink in a natural system, but as a nucleophile in an artificial ones (see other chapters of this book and the review by Aresta et al. [109]). Nevertheless, important biochemical processes such as the reversible enzymatic hydration of C02, or the formation of metal carbamates, may serve as natural models for many synthetic purposes. Starting from the properties of carbonic anhydrase (a zinc metalloenzyme that performs the activation of C02), Schenk et al. proposed a review [110] of perspectives to build biomimetic chemical catalysts by means of high-level DFT or ah initio calculations for both the gas phase and in the condensed state. The fixation of C02 by Zn(II) complexes to undergo the hydration of C02 (Figure 4.17) the use of Cr, Co, or Zn complexes as catalysts for the coordination-insertion reaction of C02 with epoxides and the theoretical aspects of carbamate synthesis, especially for the formation of Mg2+ and Li+ carbamates, are discussed in the review of Schenk... 

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