Stereoselective synthesis of 1,2-cis glycosides is one of the most challenging issues in the chemical synthesis of glycans [1,2,3,4,5,6,7]. Various 1,2-cis glycosides in nature have been found as α-glucoside and β-mannoside in glycoproteins, glycolipids, proteoglycans, microbial polysaccharides, and bioactive natural products. In the structure of polysaccharides such as α-glucan, 1,2-cis α-glucosides were found to be the major linkage between the glucopyranosides. Various regioisomeric linkages, 1→3, 1→4, and 1→6 for backbone structure, and 1→2/3/4/6 for branching in the polysaccharide as well as in the oligosaccharides were identified.

α-D-glucan is a homopolysaccharide and a simple polymer of α-D-glucopyranoside (α-D-Glcp) [8,9]. D-Glucose, the component of the D-glucans, is photosynthesized in plants and widespread in nature and exists in its D-glucopyranose form in α-D-glucans [10]. The most common and linear example of α-D-glucan is (1→4)-α-D-glucan (amylose), which plays an essential role as an energy source for metabolism [11]. The chain length of amylose is known to be in the order of 500–6000 glucose units, depending on its botanical origin. Three crystalline forms of amylose, A-, B-, and C- (a mixture of A and B) granules [12], containing random and short helical segments, have been reported. Crystallized structures were found in the V form [13,14,15], and each segment composed of six glucose residues formed a left-handed, single-stranded helical structure [16]. Branched (1→4)-α-D-glucans are called amylopectin and glycogen, the analogues of starch for energy storage in plants and animals, fungi, and bacteria, respectively. The structures of amylopectin and glycogen are well known to be more compact than that of linear amylose. (1→4)-α-D-glucan is biologically synthesized by glucosyltransferase [17,18,19,20] and amylosucrase (sucrose-1,4-α-glucan glucosyltransferase [21,22,23,24] and (1→4)-α-D-glucan branching enzymes [25,26,27,28,29,30]).

α-D-glucans also have extremely complex structural diversity according to various regioisomers, making non-branched and branched α-D-glucans with (1→6)-, (1→4)-, (1→3)-, and (1→2)-glycosidic linkages and molecular masses according to the degree of polymerization (Figure 1). The α-D-glucans have been obtained from various species, listed in Table 1 [31,32,33,34,35,36].

Regioisomeric linear (1→6)-α-D-glucans (isomaltosides) were isolated from Amillariella tabescens and Sarcodon aspratus [37,38,39]. A dextran [40] obtained from lactic acid bacteria, such as Lactobacillus, Leuconostoc, Weissella, and Streptococcus, has a (1→6)-α-D-glucan backbone with up to 50% branching as α-(1→3), α-(1→4), or α-(1→2) linkages. Several glucosyl transferase (Gtf) enzymes synthesize dextrans with [41,42] and without branching [43,44,45,46,47,48]. The complex branched structures make the dextrans effective energy storage molecules that release D-glucose slowly via enzymatic hydrolysis [49,50,51,52,53].

Linear (1→3)-α-D-glucan (pseudonigan) was identified from Aspergillus niger [48] as a storage polysaccharide [54]. To the best of our knowledge, a linear (1→2)-α-D-glucan has not yet been identified. The (1→3)-α-D-glucans are major components of the cell wall of filamentous fungi [55,56,57] and dimorphic yeasts [58,59,60,61] and are synthesized via the primer for (1→3)-α-D-glucans by intracellular amylases. The structural analysis of (1→3)-α-D-glucan was reported and it was mentioned that three crystalline forms I–III of (1→3)-α-D-glucan were detected and interconverted via dehydration and hydration reactions [32,62]. Various biological functions of (1→3)-α-D-glucan were investigated such as immunological activity via Toll-like receptor 4 (TLR4) [63,64,65], which has been shown in the case of (1→4)-α-D-glucans as well as β-D-glucans [66].

More complex branching structures have been discovered in various linear glucans [33,67,68]. From dextran, NRRL B1397, an α-D-Glc-(1→2)-α-D-Glc-(1→6)-D-Glc structure [69,70,71,72,73] was identified and the D-Glc-(1→2)-branching moiety was found to be an α-glucoside to tricholomal (1→4)-α-D-glucan [74].

The most common and linear example of a stereoisomeric β-D-glucans is cellulose, composed of β-D-Glcp, which plays a fundamental role as a structural component of the cell wall [75,76]. As physiologically active biological response modifiers (BRMs), the structure of glucans and the biological activity relationship of β-D-glucans have been reported to be adjuvants in bacterial, viral, or protozoan infections, and potent antitumor drugs, depending on the molecular weight, degree of branching, conformation, and intermolecular associations of glucans [76,77,78,79,80,81]. In the case of the synthesis of β-D-glucans, a common methodology such as stereoselective β-D-glucopyranosylation via the effect of neighboring group participation from the 2-O-acyl group can be effectively used [82,83,84].

2. 1,2-cis glycosylation