Activated esters in the field of polynucleotides and coenzymes

Abstract

The 1- ethoxyvinyl esters of a variety of acids have been prepared, and isolated in some cases. In other cases their presence was demonstrated by their spectra and chemical properties. Thus 1-ethoxyvinyl thiolates and sulphonates were isolated , characterised and were found to be readily attacked by nucleophiles. Monoesters of sulphuric acid reacted with ethoxyacetylene to give 1- ethoxyvinyl sulphates, attempts to purify these compounds being unsuccessful. They were, however, successfully used to prepare the coenzyme analogue adenosine-5'-sulphatophosphate in up to 45% yield.
The 1-ethoxyvinyl esters of pyruvic and oxalic acids were prepared and found to undergo rearrangement on heating to 70 degrees. Carbon monoxide and B-keto esters were the products. A five centre rearrangement in the first case, and a five centre followed by a four centre rearrangement in the second case has been suggested for the mechanisms of these rearrangements.
Although the diethoxyvinyl esters of phthalic acid could not be isolated (although this was possible when terephthalic acid was used) phthaloyl protected amino acids and esters were prepared by activation of phthalic acid using ethoxyaoetylene in the presence of a free amino acid or its ester. The reaction was conducted successfully in aqueous and non-aqueous solvents, and when an optically active aminoacid was used, no racemisation was detected. This method holds potentialities both for protection and for end group labelling of peptide hydrolysis fragments.
Polynucleotides containing thymidylate and deoadenylate residues were synthesised using DCC as the condensing reagent. One of the mononucleotides was labelled with 32P so that nearest-neighbour base sequence analyses could be conducted on the polymeric products. The results of these analyses suggest that the base sequence is essentially random, but that thymidylate residues predominate over deoxyadenylute residues in the ratio of 27.5 in the polymers. Reasons for this predominance have been suggested.
The chemistry of alkolkynes and of enol esters has been reviewed and a survey has been made of recent techniques of polynucleotide synthesis. The structure, biosynthesis and properties of nucleic acids and coenzymes have also been reviewed.