Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. Stny. 1/A, Budapest, 1117, Hungary.
György Hevesy Doctoral School of Chemistry, Eötvös Loránd University, Budapest, Hungary.
Amino Acids. 2023 Aug;55(8):969-979. doi: 10.1007/s00726-023-03278-1. Epub 2023 Jun 21.
The synthesis of D-glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and Fmoc-GlcAPC(Ac)-OH, β-SAAs consisting of only 4-5 synthetic steps. Their active ester and amide bond formation with glycine methyl ester (H-Gly-OMe) was completed and monitored by H NMR. The stability of the pyranoid OHs protecting the acetyl groups was investigated under three different Fmoc cleavage conditions and was found to be satisfactory even at high piperidine concentration (e.g. 40%). We designed a SPPS protocol using Fmoc-GlcAPC(Ac)-OH to produce model peptides Gly-β-SAA-Gly as well as Gly-β-SAA-β-SAA-Gly with high coupling efficiency. The products were deacetylated using the Zemplén method, which allows the hydrophilicity of a building block and/or chimera to be fine-tuned, even after the polypeptide chain has already been synthesized.
D-葡萄糖胺-1-羧酸基β-糖氨基酸（β-SAAs）的合成通常需要经过九步连续反应，通过效率低下的 OAc→Br→CN 转化方案，总收率低。在这里，我们提出了一种改进的、更有效的方法，通过 4-5 步合成步骤，可分别合成 Fmoc-GlcAPC-OH 和 Fmoc-GlcAPC(Ac)-OH，这两种β-SAAs。通过 1H NMR 对其与甘氨酸甲酯（H-Gly-OMe）的活性酯和酰胺键形成进行了监测。研究了在三种不同的 Fmoc 脱保护条件下，保护乙酰基的吡喃糖基 OH 的稳定性，即使在高哌啶浓度（例如 40%）下，稳定性也令人满意。我们设计了一种使用 Fmoc-GlcAPC(Ac)-OH 的 SPPS 方案，以高产率合成模型肽 Gly-β-SAA-Gly 以及 Gly-β-SAA-β-SAA-Gly。使用 Zemplén 方法对产物进行脱乙酰化，即使在多肽链已经合成之后，也可以对构建块和/或嵌合体的亲水性进行微调。
