One-pot Synthesis of Penta- and Hepta-saccharides from Monomeric Mannose Building Blocks Using the Principles of Orthogonality and Reactivity Tuning

Abstract

Employment of the butane-2,3-diacetal protecting group allowed the reactivity tuning of glycosyl fluorides in the one-pot sequential glycosidation of up to five different components affording both linear and branched penta-and heptasaccharides.

A Catalytic and Stereoselective Glycosylation withβ-Glycosyl Fluorides

“…In 1988, Fraser-Reid and co-workers introduced the so-called armed-disarmed chemoselective glycosylation strategy; that is, a C(2)-ether-protected pentenyl glyco- side was chemoselectively coupled with a benzoylated pentenyl glycoside [22]. Chemoselective glycosylations have also been developed for other types of glycosides, for example, thioglycosides, selenoglycosides, glycals, and 2,6-anhydro-2-thiosugars; as concerns glycosyl fluorides, it was firstly reported by Castillon and co-workers a chemoselective glycosylation with glycosyl fluorides by using [HfCl 2 (Cp) 2 ]/AgX (X OTf, ClO 4 ) promoter system [23] to give the corresponding disaccharide in a good yield, and later, Ley and co-workers reported a successful chemoselective glycosylation based on their cyclic acetal protecting-group strategy [24]. We decided to study the application of the TrB(C 6 F 5 ) 4 -catalyzed glycosylation reaction to the ordinary armed-disarmed glycosylation strategy.…”

Thio-arylglycosides with various aglyconpara-substituents: a probe for studying chemical glycosylation reactions

“…In the programmable reactivity based chemoselective glycosylation, RRVs methanol were utilized as a quantitative measure to guide building block selection 2, 5, 6, 10, 11, 14, 15. However, in some cases, glycosylation yields were lower than those indicated based on RRV methanol differentials,11, 40 which could be due to the decrease of chemoselectivity resulting from glycosylating a less reactive carbohydrate acceptor.…”

“…Donors bearing electron donating protective groups have much higher anomeric reactivities towards a promoter than those bearing electron withdrawing and conformational restricting protective groups. This phenomenon was first observed with the glycosyl halides,3 which has been subsequently found to be general for a variety of donors including pentenyl glycosides,4 thioglycosides,2, 5, 6 glycosyl fluorides,7 glycosyl thioimidates8 and glycosyl sulfoxides 9. The understanding of protective group effect on glycosylation rate led to the development of reactivity based chemoselective glycosylation method, where a thioglycoside donor with higher anomeric reactivity (armed) is mixed together with a less reactive (disarmed) thioglycosyl acceptor 2, 6.…”

“…The newly formed thioglycosyl disaccharide, in turn can be further activated as a donor leading to a more convergent synthesis of oligosaccharides. Multiple sequential chemoselective glycosylations can be carried out in the sequence of decreasing order of anomeric reactivities in one single reaction flask 2, 5, 6, 10, 11…”

Formation of the Glycosidic Linkage

“…This concept has proven to be of great value to the synthetic chemist: 179,180 It has been suggested that iodine may be a useful promoter of 'armed' thioglycosides 181 and that 2-O-pivalyl thioglycosides seem particularly suited for the preparation of 1,2-trans glycosides. 190 In the matter of cyclic protecting groups, Ley has made something of an art form out of the use of various glycosyl donors, including thioglycosides, and the concepts of 'torsional control/reactivity tuning' for glycoside synthesis; [39][40][41]191 other workers have used cyclic esters and cyclic acetals, across O2/O3 and O4/O6, in a similar manner. 190 In the matter of cyclic protecting groups, Ley has made something of an art form out of the use of various glycosyl donors, including thioglycosides, and the concepts of 'torsional control/reactivity tuning' for glycoside synthesis; [39][40][41]191 other workers have used cyclic esters and cyclic acetals, across O2/O3 and O4/O6, in a similar manner.…”