Synthesis of isobemisiose, neosartose, and fischerose: three α-1,6-linked trehalose-based oligosaccharides identified from Neosartorya fischeri

Abstract

Three complex α-1,6-linked trehalose-based oligosaccharides with unique preservation properties, isobemisiose, neosartose, and fischerose, were recently identified from the extreme stress-tolerant ascospores of Neosartorya fischeri. Herein, we report the first concise, scalable, and iterative chemical synthesis of these oligosaccharides from a differentially protected thioglycoside donor and a selectively protected, asymmetric trehalose acceptor. This work constitutes an improved synthesis of isobemisiose, and is also the first reported synthesis of neosartose, a tetrasaccharide, and fischerose, a pentasaccharide, in good yield. Importantly, in-depth studies of biological function are enabled by this synthetic platform.

Fig. 1. The structures of trehalose and representative derivatives of biological importance, with the trehalose core highlighted in red.

Fig. 2. Trehalose-containing oligosaccharides with preservation capabilities identified in Neosartorya fischeri (Aspergillus fischeri).

Fig. 3. Iterative oligosaccharide synthesis by incorporation of a bifunctional glycosyl linchpin.

Scheme 1. Synthesis of α-1,6-linked oligosaccharides.