Action of toluene-p-thiol and triethylamine on fully protected thymidylyl-(3′→ 5′)-thymidine. Possible occurrence of thiolate ion-promoted internucleotide cleavage in the synthesis of oligonucleotides by the phosphotriester approach

Abstract

Das aus den Verbindungen (I) und (II) erhältliche Nucleotidsalz (III) wird mit dem (bekannten) Thymidinderivat (IV) zum Dinucleosidphosphat (V) umgesetzt; dieses wird bei der Behandlung mit dem Thiol (VII) unter Bildung der Produkte (VIII) und (IX) gespalten.

Synthesis of Unsymmetrical Difluoromethylene Bisphosphonates

“…Deprotection of 19 was achieved by removal of the ethyl esters using thiophenol in MeCN/TEA, desilylation with hydrogen fluoride in pyridine, and finally, cleavage of the acetyl esters and adenine benzoyl groups using aqueous ammonia providing ADPr analogue 21 . However, partial cleavage of the ribose- and adenosine phosphonate linkages was observed, and the resulting side products could not be separated from the target compound 21 . We therefore purified partially deprotected ADPr after the desilylation step using preparative high-performance liquid chromatography (HPLC) to afford compound 20 in 48% yield.…”

“…However, partial cleavage of the ribose- and adenosine phosphonate linkages was observed, and the resulting side products could not be separated from the target compound 21 . 28 We therefore purified partially deprotected ADPr after the desilylation step using preparative high-performance liquid chromatography (HPLC) to afford compound 20 in 48% yield. Subsequent deacylation then provided ADPr isostere 21 in 85% yield after isolation by gel filtration.…”