An Improved Approach to the Direct Construction of 2‐Deoxy‐β‐Linked Sugars: Applications to Oligosaccharide Synthesis

Abstract

A next-generation reagent-controlled approach for the synthesis of 2,6-dideoxy and 2,3,6-trideoxy sugar donors in good yield and high β-selectivity is reported. The use of p-toluenesulfonyl chloride and potassium hexamethyldisilazide (KHMDS) greatly simplifies deoxy-sugar glycoside construction, and can be used for gram-scale glycosylation reactions. The development of this approach and its application to the construction of β-linked deoxy-sugar oligosaccharides are described.

Asymmetric Total Synthesis of the Complex Polycyclic Xanthone FD‐594

“…The same group also used this strategy in their total syntheses of TAN‐1085, PD‐116740, and pradimicinone . Recently, Bennett and co‐workers reported the stereoselective formation of the β‐linked trisaccharide unit through a reagent‐controlled strategy in which the dideoxy‐sugar donors are activated using p ‐toluenesulfonyl chloride …”

Asymmetric Total Synthesis of the Complex Polycyclic Xanthone FD‐594

“…[14] Recently, Bennett and co-workers reported the stereoselective formation of the b-linked trisaccharide unit through a reagentcontrolled strategy in which the dideoxy-sugar donors are activated using p-toluenesulfonyl chloride. [15] We aimed to achieve the first total synthesis of FD-594 (1) as part of our on-going interest in the total synthesis of bioactive polycyclic natural products and their medicinal chemistry. [16] In previous work, we constructed tetrahydroxanthones using photo-induced CÀO bond formation, [17] and synthesized dimeric xanthone ascherxanthone A [18] as well as polycyclic xanthone kibdelone C (4).…”

“…[21] We adopted the reagent-controlled strategy developed by Bennett and co-workers, in which the dideoxy-sugar donors are activated using p-toluenesulfonyl chloride in the presence of 2,4,6-tri-tert-butylpyrimidine (TTBP). [15,22] This generates a reactive a-glycosyl tosylate species that interacts with acceptors through an S N 2 process that shows excellent bselectivity. [22,23] Following the reliable glycosylation as described by Bennett and co-workers, [15,22] we prepared the blinked trisaccharide fragments on a gram scale (see the Supporting Information for details).…”

“…We then attempted to activate the sugar donor using p-toluenesulfonyl chloride as described by Bennetts group. [15,22] Compound 34 a was transformed into the corresponding a-glycosyl tosylate species, which reacted with acceptor 33 in the presence of KHMDS to afford the desired b-linked glycoside 35 as the major product in 61 % yield (dr = 7:1). The same reaction conditions were used to couple trisaccharide 36 with 33, furnishing the b-linked glycoside 37 in 55 % yield and stereoselectivity of b/a = 2.2:1.…”

A Convergent Synthetic Strategy towards Oligosaccharides containing 2,3,6‐Trideoxypyranoglycosides

“…These problems are most pronounced in 2,3,6-trideoxypyranoglycosides.Infact, many of the stereoselective (substratecontrolled) methods recently developed for 2,6-dideoxyglycoside resulted in ap oorer outcome for 2,3,6-trideoxyglycosides. [11] Due to these problems,c lassical syntheses of 2deoxyoligosaccharides rely heavily on the use of removable electron-withdrawing groups at the 2'-position. [12] Thus,g eneral and flexible approaches that can provide various 2deoxyoligosaccharides,p articularly those possessing 2,3,6trideoxyglycosides,remainunderdeveloped.…”