Synthesis of l-Pyranosides by Hydroboration of Hex-5-enopyranosides Revisited

Abstract

Extensive study of the diastereoselective synthesis of l-pyranosides utilizing hydroboration of substituted exo-glucals (5-enopyranosides) obtained from d-sugars is presented. On the basis of this study we present the empirical rules describing the reaction stereoselectivity and the correlation between the yield of the l-ido product and the size of protecting groups used. Application of these guidelines revealed that the hydroboration of methyl 2,3-O-methyl-6-deoxy-α-d-xylo-hex-5-enopyranoside resulted in exclusive formation of l-ido product with high yield. This method can be successfully applied to the synthesis of l-iduronic acid being an essential component of anticoagulant drugs with diastereoselectivity superior to previously published protocols.

Rapid Synthesis of l‐Idosyl Glycosyl Donors from α‐Thioglucosides for the Preparation of Heparin Disaccharides

“…As expected, the corresponding d ‐glucoside 1 was formed as the major product, nevertheless, the desired l ‐ ido thioglycoside 4 was also obtained in 32 % isolated yield. Recently, Łopatkiewicz and Mlynarski have demonstrated that hydroboration stereoselectivity can be substantially influenced by the C4 protective group . They have found that small C4‐substituents or free 4‐OH group are favorable, while bulky C‐4 substituents are unfavorable for l ‐idose isomer formation.…”

Synthesis of Four Orthogonally Protected Rare l-Hexose Thioglycosides from d-Mannose by C-5 and C-4 Epimerization

“…The C-5 epimerization of 26 was performed by hydroboration with BH 3 ·THF complex followed by oxidation with H 2 O 2 under previously optimized conditions, using 10 equiv. of the borane reagent [ 25 , 26 , 65 , 66 , 67 ]. Although the yield of the expected l - gulo -configured product 28 was only 53%, a sufficiently high l -guloside: d -mannoside ratio was observed ( 28 : 24 ~5:1), so it was considered worthwhile to investigate the C-5 epimerization of 1-thiomannoside alkenes having other protecting group patterns.…”

“…Therefore, it is important to produce l -sugars from common carbohydrates by cost-effective and high-yielding synthetic routes. To meet the demand of l -sugars, various strategies have been developed for their synthesis [ 20 , 21 , 22 , 23 , 24 ], including C-5 epimerization of readily available d -sugars [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], homologation of carbohydrates with shorter chains [ 38 , 39 , 40 , 41 , 42 ], de novo synthetic routes [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ], head to tail inversion [ 51 , 52 , 53 , 54 , 55 , 56 ], site selective epimerization [ 57 , 58 ], C-H activation [ 59 , 60 ], and enzymatic synthesis [ 61 , 62 ]. However, there are very few approaches that provide the l -sugars as glycosyl donors, e.g., in form of thioglycosides, ready for glycosylation [ 60 , 63 , 64 , 65 , …”

“…The synthesis of l -sugars by hydroboration/oxidation of d -sugar-derived 5-enopyranosides has been extensively studied on α- O -glycosides, focusing mainly on d -glucosides, and to a lesser extent also on sugars of other configurations. ( Scheme 1 A) [ 25 , 26 , 67 ]. Recently, we have successfully extended the scope of this method to thioglycosides derived from d -glucose, thus giving direct, rapid access to l -idose glycosyl donors.…”

“…While the hydroboration of d -glucoside-derived enopyranosides has been studied extensively [ 25 , 26 , 75 , 76 , 77 ], only two publications have so far addressed the hydroboration of the corresponding mannosides [ 25 , 67 ]. The BH 3 ·THF-mediated C-5 epimerization of 5-enomannoside 8 was reported to proceed with moderate diastereoselectivity [ 25 ], probably due to the steric hindrance by the C-2 substituent which hampers attack of the reagent from the β-face ( Scheme 1 A).…”