Synthetic Adventures with 2‐C‐Branched Carbohydrates: 4‐C‐Formyl Branched Octoses with Structural Analogy to Bradyrhizose

Abstract

The synthesis of three 4‐C‐formyl branched octoses with variable stereoconfiguration at the C‐2 and C‐3 stereogenic centers is described. This class of compounds is of interest due to potential structural analogies to the naturally occurring bradyrhizose monosaccharide. Branched key sugar intermediates of the synthesis are 2‐C‐(1,2,3‐trihydroxyprop‐1‐yl)‐β‐d‐mannosides. A new mild oxidation protocol using known TEMPO/trichloroisocyanuric acid in ethyl acetate/toluene, buffered with 3‐(N‐morpholino)propanesulfonic acid, is described as a valuable reaction for selective primary alcohol oxidation and, hence, the formation of 2‐(spirofuranose)pyranoses. Upon global deprotection these spirofuranoses give complex mixtures of diverse hemiacetal forms of the liberated 4‐C‐formyl octoses. As revealed by detailed NMR studies, the bradyrhizose‐type annulated forms do not represent the major isomers. For each of the target octoses, these potential neighboured acetal‐hemiacetal‐forms (9,7‐pyranose‐1,9‐pyranoses) seem to be unfavorable, and instead remote bis(hemiacetals) are formed (1,5‐pyranose‐9,7‐pyranoses or 1,4‐furanose‐9,7‐pyranoses) as the major species.