Efficient Synthesis of Deazaguanosine‐Derived tRNA Nucleosides PreQ₀, PreQ₁, and Archaeosine Using the Turbo‐Grignard Method

Abstract

The natural products PreQ1, PreQ0, and archaeosine are deazaguanosine‐derived natural products of immense biological importance. All three are critical components of tRNAs and, as such, are involved in decoding genetic information. We were able to consolidate and shorten the syntheses of all three compounds by using a novel Turbo‐Grignard‐based approach. The reported iodine/magnesium exchange followed by a Grignard reaction with the deazaguanosine skeleton showed a high tolerance towards important functional groups such as esters and amides.

Progress and developments in the turbo Grignard reagent i-PrMgCl·LiCl: a ten-year journey

“…[28][29][30][31][32] Besides the classical functional groups mentioned above (e. g., alkyl, alkoxyl, CN, halides and carboxylic esters), substrates with many other sensitive or reactive functional groups can also undergo the halogen-magnesium exchange successfully employing the turbo Grignard reagent. For example, using the protocol of a stepwise deprotonation and exchange reaction, Knochel and co-workers described the generation of organomagnesium reagents from unprotected aromatic and heteroaromatic alcohols 28 and carboxylic acid derivatives 29 (top,Scheme 12).…”

“…27 Scheme 12 Exchange in the presence of acidic groups. [28][29][30][31][32] Scheme 13 Preparation of the (hetero)aryl boronic esters. 33 temperatures.…”

Synthesis of a 3′-C-ethynyl-β-d-ribofuranose purine nucleoside library: Discovery of C7-deazapurine analogs as potent antiproliferative nucleosides

“…Staudinger reduction furnished the corresponding 6-amino derivatives. Deprotection afforded the final compounds (31,32,33,34). To dehalogenate the 7-iodo intermediate 26, it was subjected to I/Mg exchange using Knochel's iPrMgCl.LiCl [26,31], and the magnesiated intermediate was quenched with aqueous acid to give 35 in good yield.…”

Iron/Copper Co-Catalyzed Cross-Coupling Reaction for the Synthesis of 6-Substituted 7-Deazapurines and the Corresponding Nucleosides

“…Compound 8 was obtained according to the literature reported by Seela et al Deiodination of 8 was achieved by iodine–magnesium exchange reaction using Knochel’s Turbo-Grignard reagent , ( i PrMgCl·LiCl) and subsequent hydrolysis of the magnesium intermediate to give 2′,3′,5′-tri- O -benzoyl-6-chloro-9-β- d -ribofuranosyl-7-desazapurine ( 9 ) in 71% yield.…”