Synthesis of a non-natural glucose-2-phosphate ester able to dupe the acc system of Agrobacterium fabrum

Abstract

Novel non-natural G2P ester G2LP can enter A. fabrum and serve as nutrient. Binding to AccA and activity vs. AccF is fully demonstrated.

Esters of Glucose-2-Phosphate: Occurrence and Chemistry

“…In the chemistry of agrocinopines A and B [ 20 ], which involve an arabinose building block instead of a glucose one in agrocinopines C and D, Thiem and coworkers used trichloroethyl phosphorodichloridate with 1,2,4-triazole in pyridine as coupling reagent. More recently, our team has used the convenient phosphoramidite strategy for constructing the phosphodiester both in the arabinose and glucose series [ 6 , 7 ]. This method combines easiness and flexibility for a diversity-oriented strategy towards a variety of agrocinopine analogs from various sugars and alcohols.…”

“…They relied on a 5 steps synthesis starting from tetra- O -acetyl-α- d -glucopyranosyl bromide, formation of the 1,2-orthoester, Zemplén deacetylation followed by Williamson etherification using benzyl bromide to the tri- O -benzyl orthoester, then HgBr 2 -mediated glycosylation with benzyl alcohol and deacetylation to tetrabenzyl derivative 1 ( Scheme 3 a). The α anomer benzyl 3,4,6- tri - O -benzyl-α- d -glucopyranoside 2 can be made from endo -type 1,2- O -benzylidene acetal [ 26 ] or using the elegant reductive selective 2- O- debenzylation promoted by triisobutyl aluminum (TIBAL) [ 27 ] of perbenzyl glucose [ 6 , 7 ] ( Scheme 3 b,c). However, this latter debenzylation step only proceeds on the α anomer, limiting significantly the overall yield when mixtures of anomers are used as substrate as all the β anomer remains untransformed.…”

“…Its structure was fully identified as a glucopyranosyl-2-phosphoryl derivative after X-ray crystallography diffraction studies of its complex with AccA [ 6 ]. The ability of G2P esters to dupe the acc cascade of Agrobacterium fabrum was also confirmed using the G2P lactic acid ester (G2LP) found to be the first non-natural G2P ester to mimic the role of natural agrocinopine A [ 7 ].…”

Sequential In Situ-Formed Kukhtin–Ramirez Adduct and P(NMe2)3-Catalyzed O-Phosphination of α-Dicarbonyls with P(O)–H

“…Organophosphorus compounds are common motifs in natural products and pharmaceutical molecules as well as versatile ingredients in organic synthesis, catalysis, and materials science . Among them, α-phosphoryloxy carbonyls attract special interest due to their key roles in material applications and biological significance . Common methods for the synthesis of α-phosphoryloxy carbonyls remain severely limited to sensitive and hazardous agents, such as chlorophosphine or chlorophosphine oxide (Scheme a), and excess base and/or strict conditions are intensively required.…”