Orthogonally Protected Furanoid Sugar Diamino Acids for Solid-Phase Synthesis of Oligosaccharide Mimetics

Abstract

Sugar diamino acids (SDAs), which differ from the widely used sugar amino acids in the presence of a second amino group connected to the carbohydrate core, share structural features of both amino acids and carbohydrates. They can be used for the preparation of linear and branched amide-linked oligosaccharide mimetics. Such oligomers carry free amino groups, which are positively charged at neutral pH, in a spatially defined way and, thus, represent a potential class of aminoglycoside mimetics. We report here the first examples of orthogonally protected furanoid SDAs and their use in solid-phase synthesis. Starting from d-glucose, we developed a divergent synthetic route to three derivatives of 3,5-diamino-3,5-dideoxy-d-ribofuranose. These building blocks are compatible with solid-phase peptide synthesis following the 9-fluorenylmethoxycarbonyl (Fmoc) strategy, which we demonstrate by the synthesis of an SDA tetramer.

Origin of problems related to Staudinger reduction in carbopeptoid syntheses

“…To our great surprise the phosphinimino group on the furanoid building block of cis (and only cis) conforma-tion proved unexpectedly stable. Although recently John and Wittmann (2015) published the reduction of a 3-azido-3-deoxy-ribofuranoid building block in a tetrapeptide with Me 3 P, the unexpected stability of the intermediate phos-phinimino group demands explanation. We present a model based on X-ray diffraction, spectroscopic and theoretical (QM) data and describe multiple routes that allow efficient synthesis of α/β-heterooligopeptides in solid phase.…”

Novel synthetic aromatic thiourea derivatives and investigations on their cytotoxic potential efficacy

“…Many eukaryotic proteins are post translationally modified with phosphoethanolamines at C‐6 mannose sugar unit to anchor proteins 21 . Reduction of azides and Gabriel's phathalimide synthesis are examples of synthetic procedures to obtain primary amines 22 . A two‐step one‐pot synthesis of primary amine with carbon disulfide via dithiocarbamic acid salt through in situ desulfuration using propane phosphonic anhydride (T 3 P) was adopted 23 .…”

“…21 Reduction of azides and Gabriel's phathalimide synthesis are examples of synthetic procedures to obtain primary amines. 22 A two-step one-pot synthesis of primary amine with carbon disulfide via dithiocarbamic acid salt through in situ desulfuration using propane phosphonic anhydride (T 3 P) was adopted. 23 T 3 P is a peptide coupling "green" reagent which is stable and non-toxic.…”