Facile Solid‐Phase Synthesis of AICAR 5′‐Monophosphate (ZMP) and Its 4‐N‐Alkyl Derivatives

Abstract

We report herein a facile, solid-phase synthesis of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide-5Ј-monophosphate (ZMP), a biosynthetic precursor of purine nucleotides, as well as a small collection of its 4-N-alkyl derivatives. The very difficult, direct, chemical phosphorylation of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICAR) was circumvented by installing a suitable, fully protected, phos-

Synthesis and Evaluation of the Antitumor Properties of a Small Collection of PtII Complexes with 7‐Deazaadenosine as Scaffold

“…General Procedure for the Preparation of Compounds 14a–e‐( R ) and 14a–e‐( S ): In a typical experiment, compound 13b ‐( R ) [or 13b ‐( S )] (50 mg, 0.082 mmol) was dissolved in CH 2 Cl 2 (0.5 mL) and the solution cooled to 0 °C. TFA (0.5 mL) was added in one portion . The reaction was then warmed to room temp.…”

Synthesis of 13C‐labeled 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐[13C5] ribofuranosyl 5′‐monophosphate

“…8 However, this paper cited low yields of 11% to 16% from the inosinic acid derivative. 9,11 Our approach (Scheme 1) started with C-13 labeled adenosine, which was converted to inosine enzymatically, followed by ribose protection, inosine ring activation and cleavage to generate a 2′3′-protected acadesine derivative. Similarly, Oliviero, et al developed a solid-phase synthesis that conducts the phosphorylation on an inosine derivative on a small scale.…”

“…The purity and isolation of the final compound were also unclear. [7][8][9]11,12 We then developed a direct and scalable chemical route from 2′3′-protected acadesine to AICAR-PO 3 H 2 that will provide a valuable standard for the metabolomics community. 9 Shaw et al synthesized AICAR-PO 3 H 2 by phosphorylating an acadesine derivative containing a methyl ester on the imidazole ring which was later converted to the necessary amide.…”

“…Similarly, Oliviero, et al developed a solid-phase synthesis that conducts the phosphorylation on an inosine derivative on a small scale. 9 Shaw et al synthesized AICAR-PO 3 H 2 by phosphorylating an acadesine derivative containing a methyl ester on the imidazole ring which was later converted to the necessary amide. 10 A direct phosphorylation of the acadesine nucleoside core (AICAR) would be ideal.…”

“…However, this reaction has been noted in the literature as challenging and has only been done enzymatically with adenosine kinase on a 2.4 mg scale. 9,11 Our approach (Scheme 1) started with C-13 labeled adenosine, which was converted to inosine enzymatically, followed by ribose protection, inosine ring activation and cleavage to generate a 2′3′-protected acadesine derivative. [7][8][9]11,12 We then developed a direct and scalable chemical route from 2′3′-protected acadesine to AICAR-PO 3 H 2 that will provide a valuable standard for the metabolomics community.…”