Colin B. Reese

Dibenzoyl tetrasulphide - A rapid sulphur transfer agent in the synthesis of phosphorothioate analogues of oligonucleotides

Dibenzoyl tetrasulphide (6), an easily prepared crystalline solid, has been found to be a fast and efficient sulphur-transfer agent in the solid phase synthesis of phosphorothioate analogues of oligodeoxyribonucleotides from phosphoramidite building blocks.

An acetal group suitable for the protection of 2'-hydroxy functions in rapid oligoribonucleotide synthesis

Abstract The 1-[(2-chloro-4-methyl)phenyl]-4-methoxypiperidin-4-yl [Ctmp, as in ( 14a )] has an acid lability similar to that of the 4-methoxytetrahydropyran-4-yl (Mthp) protecting group under mild hydrolytic conditions [pH 2–3]; however, under the relatively more drastic conditions required for the complete removal of a 9-phenylxanthen-9-yl (Px) group, the Ctmp protecting group remains virtually intact.

Synthesis of D-myo-inositol 1,4,5-triphosphate

The conversion of myo-inositol into the ammonium salts both of racemic and enantiomerically pure D-myo-inositol 1,4,5-trisphosphate (6) is described. The n.m.r. spectroscopic properties and biological activity of synthetic and naturally-isolated (6) are virtually identical.

Uridylyl-(3′ → 5′)-(5′-thiouridine). An exceptionally base-labile di-ribonucleoside phosphate analogue

Like uridylyl-(3′→5′)-uridine (UpU), uridylyl-(3′→5′)-(5′-thiouridine) 2 both undergoes hydrolysis and isomerizes in aqueous acidic solution; however, it is very much more susceptible to hydrolysis than UpU under neutral and mildly basic conditions.

Nucleoside phosphonodithioates as intermediates in the preparation of dinucleoside phosphorodithioates and phosphorothioates

Abstract 5′-O-(9-Phenylxanthen-9-yl)thymidine ( 1 ) is converted into the triethylammonium salt of its 3′-phosphonodithioate ( 2a ) in good yield; the latter compound is converted into a dinucleoside phosphonothioate ( 4a ) and thence into a dinucleoside phosphorodithioate ( 6a ) in good overall yield.

The chemical synthesis of oligo- and poly-nucleotides: a personal commentary

In October 1953, I began my research career as a Ph.D. student in the laboratory of Alexander Todd (who became Sir Alexander Todd in 1954 and then Lord Todd of Trumpington in 1962), after having graduated from Cambridge University earlier that year. Nineteen fiftythree was of course a momentous year in the history of nucleic acid chemistry. Some six months or so before I started my Ph.D. course, J. D. Watson and F. H. C. Crick had assembled their DNA model in the old Cavendish Physics Laboratory that was almost literally within striking distance of the old University Chemical Laboratory where I was to carry out my Ph.D. studies. I believe that I was very fortunate indeed to start working in what was then most probably the main nucleic acid chemistry laboratory in the world and at a time just before the first ever synthesis of an oligonucleotide with a natural 30!50-internucleotide linkage (see below) was to be carried out in that laboratory. As I myself have been actively engaged in oligonucleotide synthesis for the past 40 years, I have been able to follow the development of this field from, so to speak, its birth to its present state. In this Commentary, I shall attempt to highlight what I personally consider to have been significant developments in this field throughout the whole of this period. I shall not attempt to present a comprehensive review of the whole field.

Solid phase synthesis of the 3′-terminal nonadecaribonucleoside octadecaphosphate sequence of yeast alanine transfer ribonucleic acid

Abstract The rapid synthesis of the 3′-terminal decaribonucleoside nonaphosphate and nonadecaribonucleoside octadecaphosphate sequences of yeast tRNA Ala by the phosphoramidite approach on controlled pore glass is described; the synthetic products were found to be identical to the authentic oligoribonucleotides, prepared by the phosphotriester approach in solution.

3′- Thiouridylyl - (3′→5′) - uridine

Abstract 3′-Thiouridylyl-(3′→5′)-uridine 3 undergoes base-catalysed hydrolysis more rapidly than UpU 1a ; it also undergoes cleavage more rapidly than UpU in glacial acetic acid solution, but shows much less (if any) tendency to isomerize.

Use of the 2,4-dinitrobenzyl protecting group in the synthesis of phosphorodithioate analogues of oligodeoxyribonucleotides

The putative intermediate bis(1,2,4-triazolide) derivative (5) is used in the stepwise synthesis in solution of the phosphorodithioate analogue (10) of thymidylyl-(3′→5′)-thymidylyl-(3′→5′)-thymidine; the 2,4-dinitrobenzyl (Dnb) group is used to protect phosphorodithioate internucleotide linkages.

Preparation of 2-(2-cyanoethyl)sulfanyl-1H-isoindole-1,3-(2H)-dione and related sulfur-transfer agents

Abstract The title compound 3 and 4-[(2-cyanoethyl)sulfanyl]morpholine-3,5-dione 12 are both conveniently prepared in good yield from 2-cyanoethyl disulfide, which itself is readily prepared in one step from S -(2-cyanoethyl)isothiouronium chloride 4 . In the same way, dimethyl and diphenyl disulfides are converted into 2-methylsulfanyl- and 2-phenylsulfanyl-1 H -isoindole-1,3-(2 H )-diones 8a and 8b , respectively, also in good yields.