Caruthers

The disadvantage of this method is that the dichloridites and monochloridites are sensitive to water and thus could not be used readily in automated oligonucleotide synthesis. This problem was overcome by Beaucage and Caruthers, who developed the phosphoramidite approach. In this method, derivatives of the form R 0P(NR2)2 react with one equivalent of an alcohol (catalyzed by species such as l//-tetrazole) to form diesters, R OP(OR")NR2, which usually are stable, easily handled solids. These phosphoroamidites are easily converted to phosphite triesters by reaction with a second alcohol (catalyzed by l//-tetrazole). Here, again, oxidation of the phosphite triester with aqueous iodine affords the phosphate triester. Over the years, numerous protective groups and amines have been examined for use in this approach. Much of the work has been reviewed. ... 

Davos, 15th-19th May 1995, paper 18. 8(13) CHEMICAL RECYCLING DILEMMA Caruthers W C Amoco Corp. 

Caruthers, M. H., Synthesis of oligonucleotides and oligonucleotide analogues, in Oligodeoxynucleotides — Antisense Inhibitors of Gene Expression, Cohen, J. S., Ed., CRC Press, Boca Raton, FL, 1989, 7. 

Succinylated derivatives of nucleic acids may be prepared by reaction of the anhydride with available —OH groups. The reaction forms relatively stable ester derivatives that create car-boxylates on the nucleotide for further conjugation or modification (Figure 1.83). This method has been used in nucleic acid synthesis (Matteucci and Caruthers, 1980) and to derivatize nucleotide analogs such as AZT (Tadayoni et al., 1993). 

Caruthers, J. M. and McKay, D. B. Helicase structure and mechanism. Curr. Opin. Struct. Biol. 12 123-133, 2002. 

For a review on peptides see Atherton, E., and Sheppard, R. C., Solid Phase Peptide Synthesis A Practical Approach, IRL Press, Oxford Univ. Press, Oxford, England, 1989, p. 203 for nucleotides, see Caruthers, M. H., Science 230, 281-285 (1985). 

Caruthers, M.H. Gene synthesis machines DNA chemistry and its uses. Science 1985, 230(4723), 281-285. 

Example 41 based upon the early observation that the 0-chlorophenoxy group can be selectively eliminated from a dinucleoside 0-arylphosphite triester [75], Caruthers and associates have used 0-arylphosphoroamidites in the synthesis of dinucleoside ET-phosphonates [76]. 

Example 59 Caruthers and his associates have synthesized esterified acetic acids phosphonodiamidites under Reformatsky reaction conditions [96]. 

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