Naturally occurring organic synthesis

Lactic acid [50-21-5] (2-hydroxypropanoic acid), CH CHOHCOOH, is the most widely occurring hydroxycarboxylic acid and thus is the principal topic of this article. It was first discovered ia 1780 by the Swedish chemist Scheele. Lactic acid is a naturally occurring organic acid that can be produced by fermentation or chemical synthesis. It is present ia many foods both naturally or as a product of in situ microbial fermentation, as ia sauerkraut, yogurt, buttermilk, sourdough breads, and many other fermented foods. Lactic acid is also a principal metaboHc iatermediate ia most living organisms, from anaerobic prokaryotes to humans. 

The number of naturally occurring, organic fluorine compounds is very small indeed. Compound 1 is1 a nucleoside antibiotic that contains fluorine attached to the carbohydrate ring, replacing H-4 in the D-ribosyl moiety. The presence of fluorine was shown by -n.m.r.-, 19F-n.m.r.-, and mass-spectral data, and the structure of this compound has been confirmed by independent synthesis.9,10... 

Even though medium-sized carbocycles are structural motifs often encountered in naturally occurring organic substances, richly hydroxylated structures reminiscent of the carbohydrate counterparts are rare, and efforts made to obtain these derivatives via synthesis have not been particularly intense. 

Conjugated polyene fragments occur in a wide variety of naturally occurring organic compounds, such as macrolides, carotenoids, and leukotrienes. The synthesis of all-trans triene 734 is readily accomplished by low-valent titanium-induced reductive elimination of l,6-dibenzoate-2,4-diene 733 [210] (Scheme 97). The requisite cis, c/5-diene geometry is obtained by a stereospecific reduction of diyne 731 with activated zinc—copper couple. 

Enzymatic methods for the synthesis of 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one (kojic acid) esters are reviewed. This naturally occurring organic acid is a fungal secondary metabolite having several biological applications, but its prominent applications are in the cosmetic and skin health industries (13CPA573). 

The chemical structures described in Chapters II and III have been established by organic chemists, not only by means of analysis, but also with the additional control furnished by synthesis. In the case of naturally occurring macromolecules, synthesis is not yet possible for the chemist (although Fraenkel-Conrat, after separating the nucleic acid from the... 

A. Vasconcelos, P.S. Oliveira, M. Ritter, R.A. Freitag, R.L. Romano, F.H. Quina, L. Pizzuti, C.M.P. Pereira, F.M. Stefanello, A.G. Barschak, Antioxidant capacity and environmentally friendly synthesis of dihydropyrimidin-(2fl)-ones promoted by naturally occurring organic acids, J. Biochem. Mol. Toxicol. 26 (2012) 155-161. 

It has been argued that this process leads to compounds, which are identical to the natural compounds, at an economically feasible cost. However, the synthetic material is racemic, contains necessarily (by the nature of organic synthesis) trace amounts of compounds which are alien to natural hops (impurities) and has therefore to be approved by the authorities. In addition to these facts, the price of the starting chemicals, used in the synthesis, already largely exceeds the cost of the hop alpha acids isolated from hops. It can be concluded that, in view of the complexity of the structures of the hop aipha acids, any possible synthetic pathway can not be competitive with the straightforward extraction of the alpha acids from hops. This remark is true for many naturally occurring compounds. 

Clearly, there is a need for techniques which provide access to enantiomerically pure compounds. There are a number of methods by which this goal can be achieved . One can start from naturally occurring enantiomerically pure compounds (the chiral pool). Alternatively, racemic mixtures can be separated via kinetic resolutions or via conversion into diastereomers which can be separated by crystallisation. Finally, enantiomerically pure compounds can be obtained through asymmetric synthesis. One possibility is the use of chiral auxiliaries derived from the chiral pool. The most elegant metliod, however, is enantioselective catalysis. In this method only a catalytic quantity of enantiomerically pure material suffices to convert achiral starting materials into, ideally, enantiomerically pure products. This approach has found application in a large number of organic... 

Some aryl halides occur naturally but most are the products of organic synthesis The methods by which aryl halides are prepared were recalled m Table 23 2... 

There are a large number of naturally occurring molecules which have not yet been obtained by chemical synthesis. A convenient source of information on such compounds is The Dictionary of Organic Compounds, Fifth Addition (1982) and Supplements 1-5, published as a multivolume series by Chapman and Hall, New York and London J. Buckingham, Executive Editor. This compendium contains references to syntheses which are not included in this collection, especially those involving simpler target structures. 

The naturally occurring compound urea, CO(NH,), was first synthesized by Friedrich Wohler in Germany in 1828 by heating ammonium cyanate. This synthesis was a significant event because it was the first time that an organic compound had been produced from an inorganic substance. Urea may also be made by the reaction of carbon dioxide and ammonia ... 

The synthesis of chaparrinone and other quassinoids (naturally occurring substances with antileukemic activity) is another striking example [16a-c]. The key step of synthesis was the Diels-Alder reaction between the a,/l-unsaturated ketoaldehyde 1 (Scheme 6.1) with ethyl 4-methyl-3,5-hexadienoate 2 (R = Et). In benzene, the exo adduct is prevalent but it does not have the desired stereochemistry at C-14. In water, the reaction rate nearly doubles and both the reaction yield and the endo adduct increase considerably. By using the diene acid 2 (R = H) the reaction in water is 10 times faster than in organic solvent and the diastereoselectivity and the yield are satisfactory. The best result was obtained with diene sodium carboxylate 2 (R = Na) when the reaction is conducted 2m in diene the reaction is complete in 5h and the endo adduct is 75% of the diaster-eoisomeric reaction mixture. 

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