Expanding the Scope of Aminosugars: Synthesis of 2‐Amino Septanosyl Glycoconjugates Using Septanosyl Fluoride Donors

Abstract

A general strategy amenable to the strerocontrolled synthesis of complex, ring-expanded analogues of natural aminoglycosides has been developed. Central to the method is the utilization of septanosyl fluorides as glycosyl donors in facile and selective glycosylation reactions. The septanosyl fluorides proved to be the best choice for the glycosylations because of their accessibility and the scope of aglycones that they could glycosylate. Moreover, a high degree of stereoselectivity was observed in the glycosylations, exclusively giving 1,2-trans-glycosides. 2-Amino septanosyl fluorides were prepared from D-glucose, D-galactose, and D-mannose. Other routes to the septanosyl glyconjugates, especially with regard to alternate donor types, were systematically investigated. Since routes to the individual donor types were being explored, factors that exert a controlling influence on the acid-mediated cyclization of 1,6-hydroxy-aldehydes were determined. The newly prepared 2-amino septanosyl glycoconjugates illustrate the scope of the reaction and how it may be utilized for the preparation of other ring-expanded analogues of glycosylated natural products.

Formation of and Glycosylation with Per‐O‐Acetyl Septanosyl Halides: Rationalizing Complex Reactivity En Route to p‐Nitrophenyl Septanosides

“…Further, because p ‐nitrophenol is a weak nucleophile, the benzyl ethers would compete as nucleophiles, potentially forming 1,4‐anhydroseptanoses, which we had observed previously . Also, anomeric fluorides such as 15 would likely be prone to formation of α‐linked glycosides only , . Another consideration was the interplay between the C2 stereochemistry and mechanistic pathway of the glycosylation reactions.…”

“…After separation, ozonolysis of 11 yielded hemiacetals like 13 or 14 . The hemiacetal like 13 with a specific C2 configuration, was then converted to glycosyl fluoride 15 , and ultimately glycosides such as 16 , …”

Glycoside Mimics from Glycosylamines: Recent Progress

“…Allylation of the N - p -methoxybenzyl glucosylamine was also exploited by Vankar et al [49] in order to reach an advanced synthetic intermediate in their synthesis of novel hydroxylated indolizidines and pyrrolizidines. The addition of vinyl-magnesium bromide to N -benzyl pentopyranosylamines ( d - xylo , l - arabino ) was a key step in recent work of the Fleet’s group leading to the total synthesis of calystegines B 2 and B 3 [50], as well as of the Peczuh work aiming at amino septanosyl conjugates [51,52]. An improvement of the formation of glycosylamines (i.e., faster reaction times and better yields) using iodine in the presence of imidazole was reported by Chagnault et al [53].…”

A practical and scalable synthesis of carbohydrate based oxepines

“…As had been reported previously, 8 was in equilibrium with the seven-membered ring hemiacetal as observed by NMR spectroscopy. 21,22 To avoid isomerization of the α-hydroxy aldehyde to the corresponding hydroxymethyl ketone, 23 8 was directly acetylated to trap it in its cyclic form, providing di-O-acetyl-tetra-O-benzyl septanoses 9 in 84% yield. Di-O-acetyl septanoses 9 were a relatively complex mixture based on the ratio of stereoisomers at C2 (based on vinyl Grignard addition) and the mixture of anomers.…”