Synthesis carbonate biomimetic

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]. 

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. 

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... 

The oxidative activation of arenes is a powerful and versatile synthetic tactic that enables dearomatization to give useful synthons. Central to this chemistry are hydroxylated arenes or arenols, the phenolic functions of which can be exploited to facilitate the dearomatizing process by two-electron oxidation. Suitably substituted arenols can hence be converted, with the help of oxygen- or carbon-based nucleophiles, into ortho-quinone monoketals and ortho-quinols. These 6-oxocyclohexa-2,4-dienones are ideally functionalized for the construction of many complex and polyoxygenated natural product architectures. Today, the inherent and multiple reactivity of arenol-derived ortho-quinone monoketals and ortho-quinols species is finding numerous and, in many cases, biomimetic applications in modern organic synthesis. 

Rosseeva EV, Buder J, Simon P, Schwarz U, Frank-Kamenetskaya OV, Kniep R (2008) Synthesis, characterization, and morphogenesis of carbonated fluorapatite-gelatine nanocomposites a complex biomimetic approach toward the mineralization of hard tissues. Chem Mater 20(19) 6003-6013... 

In another attempt to mimic the in vivo cyclization of humulene, Mlotkiewicz et have shown that treatment of humulene 4,5-epoxide (272) with boron trifluoride etherate leads to the formation of the two tricyclic alcohols (273) and (274) in 70% yield. The carbon skeleton of these two compounds is exactly that found in africanol (276) and the more recently isolated keto-angelate (275). Further elaboration of the alcohol (273) has in fact resulted in a biomimetic synthesis of the keto-alcohol corresponding to (275). This work constitutes the first example of the direct conversion of a humulene derivative into a naturally occurring compound. 

Biomimetic Synthesis of Solerone. We applied pyruvate decarboxylase [EC 4.1.1.1] (PDC) as key enzyme for the biomimetic synthesis elucidating the formation of solerone 1 figure 1). The thiamine diphosphate depending enzyme from Saccharomyces cerevisiae is responsible for the decarboxylation of pyruvate in the course of alcoholic fermentation. After loss of carbon dioxide from 2-oxoacids the resulting aldehyde is released. Alternatively, the cofactor-bound decarboxylation product can react with a further aldehyde. By the latter acyloin condensation a new carbon-carbon bond will be formed, thus opening a biosynthetic way to a-hydroxy carbonyl compounds 11J2). 

Volume 4 is dedicated to three important topics Catalysis (Part 4.1), Heterogeneous Systems (Part 4.2), and Gas Phase Systems (Part 4.3). The six chapters of Part 4.1 cover the most important aspects of electron transfer catalysis, from fundamental concepts to organic synthesis, from carbon dioxide fixation to protein catalysis, from redox modulation to biomimetic catalysis. Part 4.2 deals with the basic aspects and the latest developments in electron transfer on semiconductors, dye-sensitized electrodes, mono- and multilayers, intercalated compounds, zeolites, micelles and related systems. Part 4.3 covers gas phase systems, from atoms to small molecules, exciplexes, and supermolecules. 

Carbon dioxide or its reduced forms have been used for the synthesis of chemicals using enzymes and biomimetic metal systems as catalysts. In several cases quite interesting results have been obtained that make this way very promising for a number of applications. 

Transannulation of the mesylate (33), derived from 4,8-dimethylcycloocta-4-en-l-ol, using sodium carbonate in aqueous dioxane has provided the bicyclo[3.3.0]octanol (34), a central precursor to the monoterpene iridomyrmecin (35 equation 13). In studies of the biomimetic synthesis of the natural tri-quinanes capnellene (37 equation 14) and pentalenene (40 equation IS) Pattenden et al. have shown that both molecules can be produced from appropriate cycloocta-l,S-diene precursors, i.e. (36) and (39) [or indeed their corresponding positional isomers (38) and (41), respectively] by treatment with boron trifluoride. Mehta et al. have described an alternative transannulation approach to the triquinane unit found in pentalenene, i.e. (42) - (43 equation 16), and also to the ring system (44 equation 17) found... 

P-Lactams.1 A biomimetic synthesis of /3-lactams from chiral amino acids such as L-serine has been developed by Mattingly and co-workers. The protected amino acid (1) is first converted into the O-alkyl or O-acyl hydroxamate (2), which undergoes cyclization to derivatives of l-hydroxy-2-azetidinones on treatment with triphenylphosphine-carbon tetrachloride. This cyclization is also possible with triphenylphosphine-diethyl azodicarboxylate.2 The final step involves reduction of the N—OH group with TiClj.3 The advantage of this method over that of Wasserman (9,428), which involves cyclization of /3-haloamides, is that a strong base such as NaH is not required. 

H.Y. (2006) Carbon nanotubes assisted biomimetic synthesis of hydroxyapatite from simulated body fluid. Mater. Sci. Eng. A, 426, 202-207. 

A significant study of the synthesis of chiral chromans by the Pd-catalysed intramolecular asymmetric allylic alkylation of readily available phenol allyl carbonates has established the optimum conditions for this highly efficient method and demonstrated its value by the total syntheses of (+)-clusifoliol and (-)-siccanin (Scheme 6) <04JA11966>. A biomimetic enantioselective synthesis of (-)-siccanin also features this approach to the chroman moiety <04JA12565>. 

A biomimetic synthesis of the tobacco alkaloid anatabine (1,2,3,6-tetrahydro-2,3 -bipyridine) (69) has been reported starting from 1,2,3,6-tetrahydropyridine-2-carboxylic acid (68) labelled with carbon-13 and deuterium at C-2 (Scheme 15).9" ... 

The same cyclization behavior of the p-polycarbonyl chain—not to fold in the middle, as postulated for the alkaloid biosynthesis (see Scheme 3), but to roll up from an unprotected end—was also observed for the parent compound, the free 3-pentaketone 30, itself, which led in vitro directly to doubly cyclized products like 49 (52). This type of chemical cyclization is sometimes used by nature, as well, and thus could be exploited biomimetically (50,51,53) for a first total synthesis of the aloenin aglycon (52), a natural product from Aloe ar-borescens var. natalensis, in which the carbon chain is similarly folded. The same type of cyclization, using the (3-polycarbonyl chain in its complete, non-decarboxylated form 55, could achieve a still shorter synthesis of 52 (Scheme 9), being even more closely oriented to the biosynthesis (50,51). 

In addition, Trauner and co-workers recently presented the short total synthesis of racemic merochlorin B by means of this biomimetic [3+2] cationic condensation between phenol ring carbons and the internal nucleophilic alkene moiety mediated by hypervalent iodine reagents (Scheme 20) [107]. 

A very short synthesis of rac-incarviditone and rac-incarvilleatone was reported in 2012 by Lawrence and co-workers [147], who first prepared on a multigram scale rengyolone in three steps from tyrosol via a DIB-mediated hydroxylative dearomatization into the para-quinol 287 and an oxa-Michael addition. The resulting (zh)-rengyolone was then biomimetically dimerized under mildly basic conditions simply using a catalytic amount of potassium carbonate to furnish ( )-incarviditone in 19% yield via a homochiral oxa-Michael/Michael domino reaction, and ( )-incarvilleatone in 23% yield via a heterochiral oxa-Michael/ Michael/aldol domino reaction (Fig. 70) [147]. 

A biomimetic synthesis of the strobane carbon skeleton has been achieved using an oxymercuration-demercuration reaction on epimanool (Scheme 41). ... 

The synthesis commences with alkylation of oxindole 120 with spiroaziri-dinium triflate 109, providing the 3,3-disubstituted 121 in 53% yield (cf. Scheme 2.17). Treatment of 121 with boron trifluoride etherate at 100°C in toluene initiates the tandem retro Diels-Alder/intramolecular aza Diels-Alder process, leading to spiro-tetracyclic oxindoles 122 and 123 (1.5/1) in 61% yield. Addition of 2-lithio-l,l-diethoxy-2-propene to oxindole 122 provides carbinolamine 124 (95%). Exposure of 124 to p-toluenesulfonic acid in acetone-water followed by treatment with excess triethylamine in acetonitrile at 80°C effects the biomimetic transformation to adduct 126, which possesses the pentacyclic carbon framework of pseudotabersonine. This unique two-step one-pot transformation generates the inherently unstable dihydropyridine portion of dehydrosecodine 125, which participates in an intramolecular reverse electron-demand Diels-Alder reaction, providing 126 in 50% yield. The total synthesis is completed by transformation of the formyl group into the requisite carbomethoxy unit followed by N-benzyl deprotection (Scheme 2.19). 

The most recent foray into the group 3 biomimetic approach launched by Brooks, Grothaus and Mazdiyasni (27) has resulted in the first synthesis of the cytostatic agent anguidine (9). Importantly, this work also represented the first chiral synthesis of a trichothecene metabolite, as their sequence opened with an enantioselective microbial reduction (26) of dione (174) shown in Scheme 16. The fact that this reduction yielded the unnatural configuration at the carbon destined to be C-4 in the trichothecene skeleton is easily rectified by an alcohol inversion sequence furnishing, after suitable protection, the optically pure cyclopentane (175). Further elaboration of this chiral synthon, as reported in a preliminary communication 28), led to the heavily substituted oxabicyclo[3.2.1]octane (176). 

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