Synthetic Optimizations for Gram-Scale Preparation of 1-<i>O</i>-Methyl <span style="font-variant: small-caps">d</span>-<i>Glycero</i>-α-<span style="font-variant: small-caps">d</span>-<i>gluco</i>-heptoside 7-Phosphate from <span style="font-variant: small-caps">d</span>-Glucose

Abstract

Heptose phosphates—unique linkers between endotoxic lipid A and O-antigen in the bacterial membrane—are pathogen-associated molecular patterns recognized by the receptors of the innate immune system. Understanding the mechanisms of immune system activation is important for the development of therapeutic agents to combat infectious diseases and overcome antibiotic resistance. However, in practice, it is difficult to obtain a substantial amount of heptose phosphates for biological studies due to the narrow scope of the reported synthetic procedures. We have optimized and developed an inexpensive and convenient synthesis for the first performed gram-scale production of 1-O-methyl d-glycero-α-d-gluco-heptoside 7-phosphate from readily available d-glucose. Scaling up to such amounts of the product, we have increased the efficiency of the synthesis and reduced the number of steps of the classical route through the direct phosphorylation of the O6,O7-unprotected heptose. The refined method could be of practical value for further biological screening of heptose phosphate derivatives.

Keywords

• heptose phosphates
• silylation
• phosphorylation
• bacterial LPS
• PAMPs