De Novo Asymmetric Synthesis of 8a-epi-Swainsonine

Abstract

An enantioselective and diastereocontrolled approach to 8a-epi-d-swainsonine has been developed from achiral furfural. The key step to this synthesis was a one-pot procedure for the hydrogenolytic removal of two protecting groups and two intramolecular reductive amination reactions. The absolute stereochemistry was introduced by asymmetric Noyori reduction of furfuryl ketone. This route relies on diastereoselective palladium-catalyzed glycosylation to install the anomeric bond, and Luche reduction, diastereoselective dihydroxylation to set up the manno-stereochemistry of the indolizidine precursor.

Recent Advances in Monosaccharide Synthesis: A Journey into L-Hexose World

“…The versatility of this method has also been proved by the achievement of numerous synthetic tasks (Scheme 17), including deoxysugars [64,65], iminosugars such as swainsonine (144) [66] and 8-epi-D-swainsonine (145) [67] and natural products such as the bioactive pheromone daumone (146) [68]. In addition, quite a few protocols were focused on synthesis of biologically relevant oligosaccharide sequences [69], to demonstrate that de novo methodologies can often represent a better alternative in uncommon oligosaccharide synthesis rather than traditional approaches, starting from natural monosaccharides.…”

Ruthenium-catalyzed coupling reaction of 2,3,5-trisubstituted furans with aryl halides through C–H bond cleavages

“…1). And they are also used as synthetic building blocks [5,6] to construct a variety of substituents with diverse functional groups natural compounds and drugs. Thus, the development of an efficient catalytic activation system for formation of biaryls via CeH activation is an important challenge in organic synthesis.…”

Chiral spiroaminoborate ester as a highly enantioselective and efficient catalyst for the borane reduction of furyl, thiophene, chroman, and thiochroman-containing ketones

“…Recently, enantiomerically pure ( R )-2-furanyl-2-ethanol was used as a building block by O’Doherty and et al to introduce chirality in the synthesis of the anthrax tetrasaccharide produced by Bacillus antharacis 2a. Other furfuryl enantiopure alcohols were used by the same group to obtain iminosugar natural products 2b. Benzofuran carbinols are important units found in chiral drugs such as bufuralols, potent nonselective β-blocker antagonists.…”

“…Benzofuran carbinols are important units found in chiral drugs such as bufuralols, potent nonselective β-blocker antagonists. 2d,e In addition, sulfur heterocycles are important intermediates in the synthesis of chiral biologically active compounds such as the antidepressant Duloxetine 2 (Cymbalta),3 and the carbonic anhydrase inhibitor, MK-0417 3 ,4 used for the treatment of glaucoma (Figure 1). Zileuton 4 from Abbott and other related furan, thiophene and benzofuran 5-lipoxygenase inhibitors have been developed for the treatment of asthma and other inflammatory deseases 5.…”

“…Other limitations of biocatalysts are the lack of generality and difficulties encountered in scaling-up the methods for pharmaceutical production 8. The Noyori asymmetric transfer hydrogenation method, which uses ruthenium diamino complexes, has been successfully applied to the synthesis of heterocyclic enantiopure secondary alcohols 2,9…”