Esters of Glucose-2-Phosphate: Occurrence and Chemistry

Abstract

Phosphodiesters of glucose-2-phosphate (G2P) are found only in few natural compounds such as agrocinopine D and agrocin 84. Agrocinopine D is a G2P phosphodiester produced by plants infected by Agrobacterium fabrum C58 and recognized by the bacterial periplasmic binding protein AccA for being transported into the bacteria before cleavage by the phosphodiesterase AccF, releasing G2P, which promotes virulence by binding the repressor protein AccR. The G2P amide agrocin 84 is a natural antibiotic produced by the non-pathogenic Agrobacterium radiobacter K84 strain used as a biocontrol agent by competing with Agrobacterium fabrum C58. G2P esters are also found in irregular glycogen structures. The rare glucopyranosyl-2-phophoryl moiety found in agrocin 84 is the key structural signature enabling its action as a natural antibiotic. Likewise, G2P and G2P esters can also dupe the Agrobacterium agrocinopine catabolism cascade. Such observations illustrate the importance of G2P esters on which we have recently focused our interest. After a brief review of the reported phosphorylation coupling methods and the choice of carbohydrate building blocks used in G2P chemistry, a flexible access to glucose-2-phosphate esters using the phosphoramidite route is proposed.

The phosphate ester group in secondary metabolites

“…A stepwise strategy featuring benzyl as the protecting group for the phosphite and phosphate intermediates was employed by Queneau, Faure and Moréra in their synthesis of agrocinopine A ( 92 ). 252,277 A three-step sequence was followed by the authors to keep the phosphate moiety protected until the last stage of the synthesis in order to ease purification of the intermediates (Scheme 6). Arabinose derivative 166 was functionalized to compound 167 using benzyloxy phosphanediamine (BnO)P[N( i -Pr) 2 ] 2 in the presence of diisopropylammonium tetrazolide (formed in situ ) as a mild hindered activator to prevent double diisopropyl displacement.…”

“…Agrocinopine D ( 95 ) was synthetized by Queneau group following the phosphoramidite/oxidation procedure (Scheme 7). 252 The authors took advantage of the inherent symmetry of the natural product and performed the reaction in a one-pot process to obtain perbenzylated 171 from 170. Subsequent hydrogenation with Pd/C and treatment with an ion exchange resin delivered agrocinopine D ( 95 ) as the ammonium salt, which showed identical spectroscopic data as the synthetic derivative obtained by Lindberg and Oscarson. 254 Queneau and collaborators reviewed previous synthetic methodologies employed in the synthesis of the agrocinopine family and related glucose-2-phosphate esters.…”

“…254 Queneau and collaborators reviewed previous synthetic methodologies employed in the synthesis of the agrocinopine family and related glucose-2-phosphate esters. 252…”

“…254 The strategies to the syntheses of agrocinopines and related compounds have been recently reviewed. 252…”

“…254 Queneau and collaborators reviewed previous synthetic methodologies employed in the synthesis of the agrocinopine family and related glucose-2-phosphate esters. 252 In 2002, Waldmann employed bis(9-uorenylmethyl)-N,Ndiisopropylphosphoramidite, (FmO) 2 PN(i-Pr) 2 , 240b,i in the presence of 1H-tetrazole, followed by addition of I 2 , to introduce the phosphate group as the bis-uorenylmethyl ester derivative during the synthesis of cytostatin (7) to solve a series of misfortunate phosphate manipulation. 37,40 They rst attempted to phosphorylate iodoalkyne 172 by using bis(b-cyanoethyl)-N,Ndiisopropylphosphoramidite, (b-CE) 2 PN(i-Pr) 2 , and 1H-tetrazole followed with H 2 O 2 or I 2 treatment, but instead of obtaining the…”