A Ring Expansion–Glycosylation Strategy toward the Synthesis of Septano-oligosaccharides

Abstract

A one-pot ring-expansion-glycosylation reaction was performed using 1,2-cyclopropanated sugars as glycosyl donors and carbohydrate O-nucleophiles as acceptors to provide septanohexose mimics of pyranose and furanose derivatives. The methodology was successfully extended to the synthesis of septano-oligosaccharides by adopting a divergent strategy as well as an iterative protocol.

Synthetic Applications of Carbohydrate‐derived Donor‐Acceptor Cyclopropanes

“…To evaluate this assumption, the configuration at the free hydroxyl group in 62 was inverted using a Mitsunobu reaction to obtain the hydroxy compound 63 which was subjected to the glycosylation reaction with 55 . As expected, diseptanohexose derivative 64 was obtained as a single diastereomer in this reaction in good yield (Scheme ) …”

“…The first one involves the Luche reduction of α,β‐unsaturated ketone 52 , obtained by the hydroxytosyloxyiodobenzene‐mediated oxidation of 3,4,6‐tri‐ O ‐benzyl‐D‐glucal 4a , to give the glucal derivative 53 (Scheme ). Simmons‐Smith cyclopropanation of 53 gave the cyclopropyl alcohol 54 , which on Swern oxidation, provided the cyclopropapyranone derivative 55 as a single diastereomer . On the other hand, syn ‐cyclopropanation of glucal derivatives 56 and 57 , followed by DMP‐mediated oxidation, provided the DA cyclopropanes 58 and 59 , respectively, in good yield (Scheme ) …”

“…When cyclopropane derivative 55 was treated with sugar‐derived O ‐nucleophiles 60a–c in the presence of TMSOTf, it provided the septanohexose derivatives 61a–c , involving ring expansion and glycosylation in a single step. Compound 61a and 61b were found to have α‐configuration at the anomeric position of the septanoside (Scheme ) . With the galactose‐derived primary alcohol 60c as the nucleophile, the reaction resulted in the formation of 61c as an anomeric mixture (7 : 3) in 90 % yield.…”

Ein neues goldenes Zeitalter in der Chemie Donor‐Akzeptor‐substituierter Cyclopropane

“…Zum einen gelang es der Gruppe, die doppelt aktivierten Cyclopropane mit einer Vielzahl unterschiedlicher Phenole unter Einsatz mehrerer ¾quivalente Caesiumcarbonat als Base zur Reaktion zu bringen (Tabelle 1, Nr. [14] 2. [10] Zum anderen konnte durch die Verwendung von primären oder sekundären Aminen (meist Anilin-Derivaten) und katalytischen Mengen der Lewis-Säure Ni(ClO 4 ) 2 die Synthese von Amino-funktionalisierten acyclischen Produkten ausgehend von Enantiomer-angereicherten D-A-Cyclopropanen durchgeführt werden (Tabelle 1, Nr.…”

Synthesis of Highly Functionalized Enantiopure Halocyclopropanes Derived from Carbohydrates

“…[3] Cyclopropanes have been extensively used to introduce a conformational restriction in drugs to enhance their activity and avoid undesired effects. However, although there are several reports on the synthesis of cyclopropane units on the furanosyl and pyranosyl rings of carbohydrates, [7] construction of cyclopropanes on acyclic sugars [8] or in acyclic chains of pyranoses and furanoses, [9] has been much less studied. [4] Moreover, much effort has been devoted to substitution of the cyclopropane moiety by means of either the formation of organometallic cyclopropanes or palladium cross-coupling reactions.…”