Protection-deprotection steps

Another advantage of the synthesis by mixed Kolbe electrolysis is that polar groups in the carboxylic acid are tolerated in radical coupling. This makes additional protection-deprotection steps unneccessary, which are often needed in polar CC-bond forming reactions and can make these approaches less attractive in such cases. 

The synthesis of hyperbranched polymers can often be simplified compared to that of dendrimers as it does not require the use of protection/deprotection steps. This is due to the fact that hyperbranched polymers are allowed to contain some linearly incorporated A B monomers. The most common synthesis route follows a one-pot procedure where A B monomers are condensed in the presence of a catalyst. Another method using a core molecule and an A B monomer has also been described. 

The anticoagulant fondaparinux, a synthetic analogue of the terminal fragment of heparin, is synthesized using multiple protection/deprotection steps that result in a route of up to 50 steps. There is, as yet, no enzymatic system that approaches the capability to make such a molecule." As this modified pentasaccharide is a natural product, it should, in theory, be accessible through a series of biotransformations, but we currently lack the biocatalytic tools to achieve more than a few steps and would stiU need to use some protection steps to avoid multiple products. Enzymatic synthesis in vivo depends largely on the levels and selectivities of glycosylating enzymes to achieve multistep reactions, a situation that has been mimicked in vitro for simpler systems." ... 

One of the most attractive biocatalytic options is the nitrilase-catalysed enantioselective hydrolysis of the racemic cyanohydrin. The hydroxyacid is produced directly without need for protection/deprotection steps and cyanohydrins racemize spontaneously at neutral or... 

Bromo- and iodoanihnes, -phenols and -benzoic acids are first deprotonated in situ by an excess of the organomagnesinm reagent and then coupled (PdCl2(dppf), 1 mol%, THF, 25 °C, 3 h) with organomagnesium halides, thus avoiding tedious protection-deprotection steps . Iron(in) salts can also serve as appropriate catalysts for varions cross-coupling... 

Possible extension to solid-phase synthesis of glycosides, avoiding protection-deprotection steps... 

Clearly, an improved synthesis of L-ascorbic acid would result from the direct oxidation of L-sorbose (25) to L-xy/o-2-hexulosonie acid (28), thus eliminating the protecting-deprotecting steps currently required in the Reichstein-Griissner synthesis (see Scheme 4). Efforts to perform this oxidation may be divided into two categories, namely, chemical and fermentative. The results of each method will be summarized. 

The direct conversion of raw sugars without additional expensive and time-consuming protection/deprotection steps hold obvious advantages, but comes with considerable challenges regarding selectivity. Reactions are typically run in aqueous solution, using water-soluble phosphines such as TPPTS, but examples in organic solvents such as acetonitrile or DMF are also known. 

As mentioned, fermentation is used to provide the core structure of simvastatin, and hydrolysis is used to remove the 2-methylbutyrate sidechain the dimethylbutyric acid sidechain is introduced by coupling (Scheme 31.6).70-73 Chemical methylation to form the quaternary dimethylated center in the sidechain has been achieved on synthetic intermediates.7475 The chemical approach has to differentiate two hydroxy groups, and this requires protection-deprotection steps.76-86... 

Recently, series of carbon-sulfur [n]helicenes substituted with w-octyl groups at the a-positions of the terminal thiophene rings were prepared (Fig. 15.16) [64, 87]. The helical structures of [7]helicene 44 and [ll]helicene 45 were confirmed by X-ray crystallography. Multiple short S-S contacts were found, especially for racemic [ll]helicene 45. Asymmetric synthesis of [ll]helicene 45 provided enantiomeric excess of either the (-)- or the (+)-enantiomer for the monoannelation or, unprecedented, triannelation approach (Fig. 15.16). Also, selective diannelation of octathiophene 47, followed by monoannelation of decathiophene 46, provided an efficient synthetic route to (-)-[ll]helicene 45, avoiding protection/deprotection steps [64],... 

Different authors tried to perform directly the hydrosilylation of unprotected sugars. It would avoid time-consuming protection-deprotection steps. It would avoid also the risk of equilibration of the silicone backbone occuring under the acid or basic deprotection conditions. Usually the sugar hydroxyl groups react with hydrosilanes to form silylethers, namely Si-O-C bonds in the presence of a hydrosilylation catalyst. This dehydrocondensation side reaction has to be controlled in order to avoid cross-linking, by using selected solvents and catalysts. 

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