Direct Chemical Synthesis of the β-d-Mannans: The β-(1→2) and β-(1→4) Series

Abstract

The direct syntheses of a beta-(1-->2)-mannooctaose and of a beta-(1-->4)-mannohexaose are reported by means of 4,6-O-benzylidene-protected beta-mannosyl donors. The synthesis of the (1-->2)-mannan was achieved by means of the sulfoxide coupling protocol, whereas the (1-->4)-mannan was prepared using the analogous thioglycoside/sulfinamide methodology. In the synthesis of the (1-->4)-mannan, the glycosylation yields and stereoselectivities remain approximately constant with increasing chain length, whereas those for the (1-->2)-mannan consist of two groups with the formation of the tetra- and higher saccharides giving yields and selectivities consistently lower than those of the lower homologues. The decrease in yield after the trisaccharide in the (1-->2)-mannan synthesis is attributed to steric interference by the n-3 residue and is consistent with the collapsed, disordered structure predicted by early computational work. The consistently high yields and selectivities seen in the synthesis of the (1-->4)-mannan are congruent with the more open, ordered structure originally predicted for this polymer. The lack of order in the structure of the (1-->2)-mannan, as compared to the high degree of order in the (1-->4)-mannan, is also evident from a comparison of the NMR spectra of the two polymers and even from their physical nature: the (1-->2)-mannan is a gum and the (1-->4)-mannan is a high melting solid.

Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry

“…For instance, the direct syntheses of β-(1 → 2)- and β-(1 → 4)-mannans represent the power of this technique. 74 As depicted in Scheme 7, synthesis of the (1 → 2)-mannan was achieved by means of the sulfoxide coupling protocol. Thus, 2- O -paramethoxybenzyl protected sulfoxide donor 63 was reacted with cyclohexanol 64 in the presence of triflic anhydride and 2,4,6-tri- tert -butylpyrimidine (TTBP) to afford β-mannoside 65 ( n = 1) in 77% yield.…”

Improved Synthesis of 1‐Benzenesulfinyl Piperidine and Analogs for the Activation of Thioglycosides in Conjunction with Trifluoromethanesulfonic Anhydride*

“…[1,2] In designing the sulfinamide activating system we set several criteria, the most important of which was the need for a stable, crystalline reagent capable, in combination with triflic anhydride, of rapidly activating a wide range of armed and disarmed thioglycosides at low temperature. [1] BSP met these criteria admirably and activates most thioglycosides for coupling in a matter of minutes at −60 °C as demonstrated in a series of subsequent synthetic endeavors from this [3][4][5][6][7] and other laboratories. [8][9][10][11][12][13] The highly crystalline nature of BSP, however, limits its solubility below −60 °C, which explains the choice of this temperature for coupling reactions as opposed to the more convenient −78 °C achieved with dry ice/acetone cooling baths.…”

Evaluation of Immunostimulatory Activities of Synthetic Mannose-Containing Structures Mimicking the β-(1→2)-Linked Cell Wall Mannans of Candida albicans

“…1A, 2A, 3A, and 4A), were prepared by applying and further modifying the recently developed methodologies for construction of ␤-(1¡2)-mannosidic linkages by Crich and others (7). The synthesis procedures have been published previously by us (9,10,28).…”