Synthesis of the Fungal Lipo‐Chitooligosaccharide Myc‐IV (C16:0, S), Symbiotic Signal of Arbuscular Mycorrhiza

Abstract

A new synthesis of the fungal lipo‐chitooligosaccharide Myc‐IV (C16:0, S), which was recently reported to be a major symbiotic signalling molecule in arbuscular mycorrhiza, is described. Key steps include the oxidative cleavage of a 4,6‐O‐benzylidene acetal to prepare a disaccharidic glycosyl acceptor, and stereoselective glycosylations with 2‐methyl‐5‐tert‐butylphenyl thioglycosyl donors.

Chitooligosaccharide Synthesis Using an Ionic Tag

“…At this stage, HPLC‐MS analysis showed that the Cbz (benzyloxycarbonyl) group survived the two steps. For comparison, the analogous tetrasaccharide lacking an ITag (i.e., 23 ) gave, without complication, chitotetrasaccharide 24 in 84 % yield, as reported previously18a (Table 2, entry 3). Furthermore, monosaccharide 10a was transformed into ITagged N ‐acetyl glucosamine derivative 21 , which was easily purified by simple organic solvent washes (82 % yield; Table 2, entry 2).…”

“…We chose to attach the ITag to the glycosyl acceptor with a linker derived from 4 or 5 (Scheme ) connected to the C‐1 position by a stable benzyl glycoside linkage, and removable by hydrogenolysis 13b,17a,17c,20. Glycosylation of benzyl alcohol 4 with donor 3 18a prepared from the nonmalodorous 2‐methyl‐5‐ tert ‐butylphenylthiol (HSMbp),21 followed by halide displacement at the benzylic position provided ITagged glycosyl acceptor precursor 6 in moderate yield (44 %) 22. This sequence was preferred over direct glycosylation of a benzyl alcohol already bearing the ITag23 (viscous liquid) for practical reasons, even though the overall yield was similar.…”

“…Selective removal of the Fmoc group by triethylamine gave alcohol 17 in high yield (90 %; Table 1). Glycosylation of ITagged alcohol 17 with an excess of disaccharide donor 18 18a in the presence of the NIS ( N ‐iodosuccinimide)/TfOH promoter provided protected ITagged tetrasaccharide 19 in 83 % yield (Scheme ). In some experiments, a KPF 6 treatment was used to correct the triflate/hexafluorophosphate counterion mixture resulting from the glycosylation step, which complicated the 1 H NMR spectra.…”

“…4‐(1‐Methyl‐3‐methylimidazolium)benzyl 3‐ O ‐Acetyl‐6‐ O ‐benzyl‐2‐deoxy‐2‐phthalimido‐β ‐ D ‐glucopyranoside Hexafluorophosphate (10a): Thioglucoside 7 18a (100 mg, 0.17 mmol, 1.0 equiv.) and 4‐(chloromethyl)benzyl alcohol 4 (33.5 mg, 0.22 mmol, 1.3 equiv.)…”

“…2‐Methyl‐5‐( tert ‐butyl)phenyl 3‐ O ‐Acetyl‐6‐ O ‐benzyl‐2‐deoxy‐4‐ O ‐fluorenylmethyloxycarbonyl‐2‐phthalimido‐1‐thio‐β‐ D ‐glucopyranoside (15): Thioglucoside 7 18a (710 mg, 1.18 mmol, 1.0 equiv.) and FmocCl (609 mg, 2.36 mmol, 2.0 equiv.)…”