Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov St., 119991 Moscow, Russia.
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Avenue, 119991 Moscow, Russia.
Molecules. 2022 Nov 3;27(21):7534. doi: 10.3390/molecules27217534.
Heptose phosphates-unique linkers between endotoxic lipid A and -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--methyl d--α-d--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 ,-unprotected heptose. The refined method could be of practical value for further biological screening of heptose phosphate derivatives.
七糖磷酸酯是细菌膜中内毒素脂 A 和 -抗原之间的独特连接物，是先天免疫系统受体识别的病原体相关分子模式。了解免疫系统激活的机制对于开发治疗传染病和克服抗生素耐药性的治疗剂非常重要。然而，在实践中，由于报道的合成方法范围狭窄，难以获得大量的七糖磷酸酯用于生物学研究。我们已经对其进行了优化和开发，以从易得的 D-葡萄糖首次进行大规模生产 1--甲基 D--α-D--庚糖 7-磷酸酯。扩大到如此大量的产物，我们通过直接磷酸化未保护的庚糖，提高了合成效率并减少了经典路线的步骤数。这种改进的方法对于进一步进行七糖磷酸酯衍生物的生物学筛选可能具有实际价值。
