Protection of phosphates

Two new sections on the protection of phosphates and the alkyne-CH are included. All other sections of the book have been expanded, some more than others. The section on the protection of alcohols has increased substantially, reflecting the trend of the nineties to synthesize acetate- and propionate-derived natural products. An effort was made to include many more enzymatic methods of protection and deprotection. Most of these are associated with the protection of alcohols as esters and the protection of carboxylic acids. Here we have not attempted to be exhaustive, but hopefully, a sufficient number of cases are provided that illustrate the true power of this technology, so that the reader will examine some of the excellent monographs and review articles cited in the references. The Reactivity Charts in Chapter 10 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first introduced. No attempt was made to update these Charts, not only because of the sheer magnitude of the task, but because it is nearly impossible in... 

The use of phenacyl esters as photolabile protecting groups in organic synthesis is rare save for their use in the protection of phosphates (see section 73 6),... 

Protection of phosphates as 2-(trimethylsilyl)ethyl esters was first developed by the Masamune group as part of their efforts to synthesise Calyculin A with its highly hindered phosphate monoester.77 A diallyi phosphate was evaluated in a model compound, but it was rejected because of incomplete deprotection under Pd(0)-catalysis, The corresponding bis-[2-(trimethylsilyl)ethyl] ester 37 1, on the... 

The H-phosphonate approach for the preparation of 3 -5 - intemucleotidic bonds shows the following advantages protection of phosphate is not required the oxidation reaction is performed by I2 solution at the end of the synthetic cycles the coupling reaction is much faster than the phosphoramidate approach the H-phosphonate units are more stable than... 

Protection of Phosphates and Phosphonates. 2-Hydroxy ethyl phenyl sulfone (1) has been used to differentially protect phosphate esters for nucleotide synthesis. Thus, reaction of the diphosphate (8) with 1 and l-(mesitylene-2-sulfonyl)-3-nitro 1,2,4-trIazole (MSNT) in pyridine afforded the differentially protected phosphate 9 in very good yield (eq 5). The 2-phenylsulfonylethyl phosphate can be cleaved under mild conditions by treatment with triethylamine. 

Protection of phosphate groups is accomplished by reaction of a phosphate monoester with 2-(0 -pyridyl)ethanol and dicyclo-hexylcarbodi-imide (Fig. 6.3). 

The jS-cyanoethyl group has been employed for the protection of phosphate diesters in the synthesis of deoxyribo- [34] and ribo-oligonucleotides [35]. It is introduced using a procedure similar to Fig. 6.11b, and is selectively removed on treatment wdth sodium hydroxide. In the synthesis of ribo-oligonucleotides protection by the phenyl group, also alkali-labile, has been described [36] (Fig. 6.14). It is introduced as in Fig. 6.11a. 

As a new method of protection of phosphate groups during nucleotide synthesis, the 0-2-(arylthio)ethyl group, ArSCHzCHjC)—, is removed by oxidation to the sulphone with N-chlorosuccinimide followed by dilute NaOH this procedure requires a shorter exposure to reagents, and milder alkaline treatment, than the alternative NaI04-2M-Na0H procedure. 

In 1994, Pirrung and Shuey ° reported the protection of phosphates using the dimethoxybenzoin. Resolved ( RjS S -dimethoxybenzoin (optically active) was converted to the phosphoramidite by treatment with diisopropylaminocyanoethoxychlorophosphine. Subsequent reaction with the appropriate primary or secondary alcohol followed by oxidation led to the series of phosphate esters 58a-e in moderate to high yields ... 

Protection of Phosphates. There is one example where the MPM group is used for phosphate protection. It is cleaved with 48% aq HF/MeCN/H20 (eq 8). ... 

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