An Efficient Deprotection of N-Trimethylsilylethoxymethyl (SEM) Groups From Dinucleosides and Dinucleotides

Abstract

A convenient and efficient method for deprotection of N-(trimethyl)silylethoxymethyl (SEM) groups from thymidine dinucleoside and dinucleotide has been achieved. The SEM groups were easily removed in excellent yields from protected nucleosides, dinucleosides, and dinucleotides.

Synthesis and bioluminescence of electronically modified and rotationally restricted colour-shifting infraluciferin analogues

“…Therefore 22 was protected using the SEM group as there is literature precedent of it being cleaved from sensitive biological substrates. 30 We observed that the SEM group protected each tautomer of the benzimidazole (23a:23b, 1:1) and these were separated in 41% and 40% isolated yields respectively. Both isomers were separated by column chromatography and each was carried forward in the synthetic route.…”

“…Cyclisation to the thiazoline (28a 65%, 28b 67%) was achieved by treating thioamides 27a,b with DAST at -78 C. Finally, the SEM group was cleaved with Tin (IV) chloride 30 to give the methyl ester 29 in 95% yield. The ester was found to be unstable in base (LiOH) and so was hydrolysed with porcine liver esterase 17 to give BIiLH2 (13).…”

Synthesis of [2H5]baricitinib via [2H5]ethanesulfonyl chloride

“…The following step, a nucleophilic addition reaction between compound 4 and commercially available 4‐(1 H ‐pyrazol‐4‐yl)‐7‐((2‐(trimethylsilyl)ethoxy)methyl)‐7 H ‐pyrrolo[2,3‐ d ]pyrimidine ( 6 ), based on the procedure published in the patent literature, 20 proceeded in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) at r.t., resulting in the formation of 7 in quantitative yield. SEM deprotection of 7 was attempted unsuccessfully with LiBF 4 /MeCN, 21,22 TFA/ethylene diamine 23 and BF 3 ·Et 2 O, 24 before complete deprotection was achieved by reaction with a 1 M solution of tin(IV) chloride at room temperature followed by a basic workup at 0°C 25 forming 2 in 66% yield. This approach was employed thenceforth.…”

Synthesis and Properties of Oligonucleotides Having Ethynylphosphonate Linkages

“…A palladium-catalyzed cross-coupling of H -phosphonate and dibromoalkene was performed and is a key reaction in the dimer synthesis . First, the imide at the nucleobase of starting material 1 was protected with a 2-(trimethylsilyl)­ethoxymethyl (SEM) group, and the dimethoxytrityl (DMTr) group was removed under acidic conditions. An oxidation of the primary alcohol of 2 using Dess–Martin periodinane, followed by the conversion of the resulting aldehyde into 1,1-dibromoalkene by a Corey–Fuchs reaction, gave 3 in 85% yield over 2 steps.…”

“…An oxidation of the primary alcohol of 2 using Dess–Martin periodinane, followed by the conversion of the resulting aldehyde into 1,1-dibromoalkene by a Corey–Fuchs reaction, gave 3 in 85% yield over 2 steps. The SEM group was then removed with tin­(IV) tetrachloride, and the TBDPS group was subsequently deprotected by treatment with TBAF. This step-by-step approach afforded 4 in 97% yield.…”