A simplified synthesis of 8-substituted purine nucleosides via lithiation of 6-chloro-9-(2,3-O-isopropylidene-.BETA.-D-ribofuranosyl)purine.

A New Entry to 2-Substituted Purine Nucleosides Based on Lithiation-Mediated Stannyl Transfer of 6-Chloropurine Nucleosides

“…When lithiation of 2 was carried out with LDA (1.2 equiv) in THF below −70 °C and the resulting lithiated species quenched by adding CH 3 OD, deuterium was incorporated solely into the 8-position to the extent of 89% (98% recovery). This is fully in accord with the previous result obtained by using 1 . Additional evidence to support the exclusive 8-lithiation of 2 came from the fact that quenching with iodine gave the 8-iodo derivative 3 in 93% yield.…”

“…Lithiation (hydrogen−lithium exchange) of purine nucleosides started with the finding by Barton et al that 8-alkylation of N -methyl derivatives of 2‘,3‘- O -isopropylideneadenosine can be achieved by way of lithiation with butyllithium followed by alkylation. , Later, in 1983, we reported an improved method for the synthesis of 8-carbon-substituted purine nucleosides in which 6-chloro-9-(2,3- O -isopropylidene-β- d -ribofuranosyl)purine ( 1 ) was used as a substrate for lithiation .…”

First Evident Generation of Purin-2-yllithium: Lithiation of an 8-Silyl-Protected 6-Chloropurine Riboside as a Key Step for the Synthesis of 2-Carbon-Substituted Adenosines

“…As the hydroxyl-protecting groups of the sugar portion of 6-chloropurine riboside, isopropylidene, and trityl groups were selected. Compound 6 was prepared in 95% yield by tritylation (TrCl/Et 3 N/CH 2 Cl 2 , reflux for 18 h) of 6-chloro-9-(2,3- O -isopropylidene-β- d -ribofuranosyl)purine . Introduction of the 8-TIPS group to 6 was carried out by using LHMDS and TIPSCl as mentioned in the preparation of 3 , which gave 7 in 99% yield (Scheme ).…”

“…Lithiation of purine nucleosides started with the finding that N 6 -methylated 2‘,3‘- O -isopropylideneadenosine undergoes exclusive deprotonation at the 8-position with BuLi . This regiochemical outcome has been observed for a series of lithiation studies of adenosine, inosine, and 6-chloropurine riboside, in which LDA (lithium diisopropylamide) was used as a lithiating agent. , …”

Photochemical Synthesis of 6-Aryluridines1)

“…Our recent publications on the lithiation of nucleosides [2][3][4][5][6][7] have proved the effectiveness of this tactic for the modification of base moieties both in terms of simplicity and generality. Thus, various types of 6-substituted uridines were prepared by the metallation of 2',3'-0-iso--propylidene-5'-0-methoxymethyluridine -(1) -with lithium diisopropylamide (LDA) and successive reactions with electrophiles.…”