Functional groups, protection and deprotection

Enzymes are the catalyst per excellence for reactions in water, which is their natural habitat. Moreover, the use of enzymes often circumvents the need for functional group protection and deprotection steps. For example, enzymatic hydrolysis of penicillin G to 6-APA (Fig. 2.30) proceeds in one step at ambient temperature while chemical deacylation requires three steps, a temperature of - 40 C and various stoichiometric reagents, leading to a high E factor. 

Another method for deallylation of ally esters is the transfer of the allyl group to reactive nucleophiles. Amines such as morpholine are used[415-417], Potassium salts of higher carboxylic acids are used as an accepter of the allyl group[418]. The method is applied to the protection and deprotection of the acid function in rather unstable /f-lactam 664[419,420]. 

Advantages of the Stille reaction include neutral conditions under which the reaction takes place, often with full retention of stereochemistry, and compatibility with nearly all functional groups thus eliminating additional steps required for protection and deprotection. Conversely, a highly undesirable drawback is the use of toxic tin compounds and the ensuing difficult removal of these from the reaction mixture. 

Despite impressive advances in the design of highly selective reagents, protection and deprotection of functional groups is still very... 

Functional Group Interconversion by Substitution, Including Protection and Deprotection... 

Because they are readily available from natural sources in enantiomerically pure form, carbohydrates are very useful starting materials for the synthesis of other enantiomerically pure substances. However, the high number of similar functional groups present in the carbohydrates requires versatile techniques for protection and deprotection. Show how appropriate manipulation of protecting groups and other selective reactions could be employed to effect the following transformations. 

Synthetic efficiency. In many organic syntheses, it may be possible to eliminate the need for the protection and deprotection of functional groups, and save many synthetic steps. Water-soluble substrates can be used directly. This will be especially useful in carbohydrate and protein chemistry. 

The chemistry of A3-phosphorins which are substituted at the ring carbon atoms by functional groups is still an open field and very few derivatives are known. One promising reaction for such syntheses involves initial protection of the reactive phosphorus atom, then introduction of the functional group followed by deprotection. Some preliminary experiments in this direction were recently performed with two OMe groups on the phosphorus, which were subsequently removed by hydrolysis and Ph2SiH2 reduction (equation 28) (83UP11700). 

Guibe and co-workers took advantage of this high reactivity to use N,N -dimethylbarbituric acid 231 (Scheme 47) as an efficient nucleophilic reagent in the deprotection of functional groups protected with allyl radicals. The recovery of benzylamine from its diallyl derivative 232 is one example (93JOC6109). 

Biocatalysis has many advantages in the context of green chemistry, e.g. mild reaction conditions and often fewer steps than conventional chemical procedures because protection and deprotection of functional groups are often not required. Consequently, classical chemical procedures are increasingly being replaced by cleaner biocatalytic alternatives in the fine chemicals industry (see later). 

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