Synthetic approaches

In nature, complex functional molecules such as en2ymes ate produced by using the chemical synthetic approach outlined above (13). The molecules... 

The types of molecules synthesized by biotechnological techniques are restricted to those biomolecules whose stmctures can be encoded in the DNA of organisms capable of translating them into functional nanomaterials. Other types of molecules and nanomaterials can be synthesized by chemical synthetic approaches, such as covalent syntheses and molecular self-assembly of molecular units. 

Alkyl hahdes in the presence of silver oxide react with alkyl malates to yield alkoxy derivatives of succinic acid, eg, 2-ethoxysuccinic acid, H00CCH2CH(0C2H )C00H (12,13). A synthetic approach to produce ethers of malic acid is the reaction of malic esters and sodium alkoxides which affords 2-alkoxysuccinic esters (14). 

The first synthetic route for isocyanates was reported in 1848 (10,11)- Subsequent efforts by Hofmann, Curtius, and Hentschel pioneered alternative synthetic approaches (12). These efforts highlighted the phosgene—amine approach. Staudinger presented the stmctural similarities between isocyanates and ketenes and stimulated interest in this class of compounds (13). However, it was not until 1945, when the world was pressed for an alternative to natural mbber, that synthetic routes to isocyanates became an area of great importance. Several excellent review articles covering the synthesis and chemistry of isocyanates have been presented (1 9). 

Phosphorothioates. All three synthetic approaches appHcable to unmodified oligonucleotides can be adapted for synthesis of phosphorothioates (11) (33,46). If all of the phosphodiester linkages in an oligonucleotide are to be replaced with phosphorothioates, the ff-phosphonate method for coupling, followed by oxidation with Sg in carbon disulfide and triethylamine in the final step, is the most straightforward method. 

ISlew Synthetic Approaches. There have been a number of efforts to prepare quinolines by routes quite different from the traditional methods. In one, the cyclization of 3-ariiino-3-phenyl-2-alkerLiniines (18) using alkah metals leads to modest yields of various 4-arylaminoqurnolines (54). Because this stmcture is found in many natural products and few syntheses of it exist, the method merits further investigation. 

The reddish brown pentachloride, uranium pentachloride [13470-21 -8], UCl, has been prepared in a similar fashion to UCl [10026-10-5] by reduction—chlorination of UO [1344-58-7] under flowing CCl, but at a lower temperature. Another synthetic approach which has been used is the oxidation of UCl by CI2. The pentachloride has been stmcturaHy characterized and consists of an edge-sharing bioctahedral dimer, U2CI2Q. The pentachloride decomposes in H2O and acid, is soluble in anhydrous alcohols, and insoluble in benzene and ethers. 

Other approaches to direct C2Q couplings have been reported (9,30—35). Based on their knowledge of sulfone chemistry, Rhc ne-Poulenc has patented many syntheses of P-carotene which use this olefination chemistry (36—41). Homer-Emmons chemistry has also been employed for this purpose (42). The synthetic approaches to the carotenoids have been reviewed (43). 

The first synthesis of vitamin IQ was reported by several workers ia the late 1930s and the synthetic approaches have been reviewed (22). Vitamin IQ was prepared by the reaction of menadione with phytyl bromide ia the preseace of 2iac (23). 

In the period up to 1970 most P-lactam research was concerned with the penicillin and cephalosporin group of antibiotics (1). Since that time, however, a wide variety of new mono- and bicychc P-lactam stmctures have been described. The carbapenems, characterized by the presence of the bicychc ting systems (1, X = CH2) originated from natural sources the penem ring (1, X = S) and its derivatives are the products of the chemical synthetic approach to new antibiotics. The chemical names are 7-oxo-(R)-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxyhc acid [78854-41-8] CyH NO, and 7-oxo-(R)-4-thia-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxylic a.cid [69126-94-9], C H NO S, respectively. 

Also, the cost of dyeing cotton with natural vegetable dyes is 31—77/kg compared to a synthetic approach costing 35 cents /kg. In short, the use of natural vegetable dyes to color the world s textiles is both environmentally and logisticaHy impossible (4). 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Furans, thiophenes and pyrroles have all been obtained by addition of alkynic dienophiles to a variety of other five-membered heterocycles, as illustrated in Scheme 104. As the alkynic moiety provides carbons 3 and 4 of the resulting heterocycle, this synthetic approach provides an attractive way of introducing carbonyl containing substituents at these positions, especially as many of the heterocyclic substrates are readily generated. Such reactions do... 

Thus, reaction of a 1,2-binucleophile with a 1,3-bielectrophile would lead to a five-membered heterocycle, as would the reaction of a 1,4-binucleophile with a 1,1-bielectrophile. Considering the reactions in this manner has several advantages and provides a convenient framework for considering synthetic approaches to target heterocycles. 

The previously described penem syntheses from 6-APA-derived starting materials have been inefficient in the sense that the C(2) and C(3) atoms of the penam are lost during the sequence. Scheme 71 shows a route in which C(2) and C(3) of the penam become C(2) and C(3) of the penem (79CC665). The major product of this sequence is the (55) enantiomer. A related synthetic approach, starting with the natural product clavulanic acid, has been described (79CC663). 

Due to the very flexible synthetic approach, imprinted layers are highly suitable for sensor measurements in complex mixtures Sensor coatings consisting of a carbonic-acid-imprinted sol-gel material e.g. incorporate oxidative degradation products from engine oil leading to a chemical lubricant sensor. 

Estrone (54, Chart 6) contains a full retron for the o-quinonemethide-Diels-Alder transform which can be directly applied to give 55. This situation, in which the Diels-Alder transform is used early in the retrosynthetic analysis, contrasts with the case of ibogamine (above), or, for example, gibberellic acid (section 6.4), and a Diels-Alder pathway is relatively easy to find and to evaluate. As indicated in Chart 6, retrosynthetic conversion of estrone to 55 produces an intermediate which is subject to further rapid simplification. This general synthetic approach has successfully been applied to estrone and various analogs. ... 

In Pedersen s first full paper on the synthesis of macrocyclic polyethers, he reported the synthesis of thirty-three macrocycles having a variety of ring sizes and substituents. These compounds were prepared by a variety of routes and Pedersen offered a scheme in which he generalized the synthetic approaches he used. He designated the four principal methods V , W , X , and Y . The methods are diseussed individually. 

A large number of chiral crowns have been prepared by numerous groups. The reader is directed to the tables at the end of this chapter to obtain an overview of these structures. It would not be useful to try to recount the synthetic approaches used in the preparation of all of these compounds we have chosen rather to subdivide this mass of compounds into three principal groups. The groups are (1) Cram s chiral binaphthyl systems (2) chiral crowns based on the tartaric acid unit and (3) crowns incorporating sugar subunits. These are discussed in turn, below. 

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