The Origin of High Stereoselectivity in Di-tert-butylsilylene-Directed α-Galactosylation

Abstract

The origin of the high α(1,2-cis)-stereoselectivity in the reaction of galactosyl and galactosaminyl donors with a di-tert-butylsilylene (DTBS) group with several nucleophiles has been elucidated by means of experimental and computational approaches. DTBS overcomes any other cyclic protecting groups examined to date and the β(1,2-trans)-directing effect due to the neighboring participation by CO groups at C2. Requirements for the α(1,2-cis)-stereoselectivity are as follows: (1) generation of an oxocarbenium ion; (2) a galacto-type glycosyl donor with a cyclic protecting group bridging O4 and O6 to form a six-membered ring; (3) through-space electron donation from O4 and O6 into the empty p-orbital of the anomeric carbon to stabilize the oxocarbenium intermediate; (4) steric hindrance due to bulky alkyl substituents on the cyclic protecting group to prevent nucleophilic attack from the β-face; and (5) a 4,6-O-silylene structure. Furthermore, it was found that the strong stereodirecting effect of the DTBS group was unique and specific among the various cyclic protecting groups examined.

Photoactivated N‐Acyliminoiodinanes Applied to Amination: an ortho‐Methoxymethyl Group Stabilizes Reactive Precursors

“…Thus,t reatment of glycal 18 with 3c under photoirradiation gave an oxazolidine intermediate, [30,31a] which underwent Lewis-acidcatalyzed glycosylation with as eries of alcohols 19 a-c to afford the corresponding aminosugar conjugates 20 a-c in 54-58 %y ields. [32] This type of 1,2-aminoalcoxylation is sometimes difficult using N-sulfonyliminoiodinanes because of the relative instability of the aziridine intermediate, [30,31b,33] whereas conjugation with aminosugars offers apowerful tool for drug discovery. [11,34] In conclusion, we have demonstrated that the coordination of an ortho-methoxymethyl group effectively stabilizes N-acyliminoiodinanes,e nabling the first synthesis and characterization of their structure.T he X-ray structure revealed that the carbonyl oxygen atom coordinates to the iodine atom of the iminoiodinane.A dditionally,t he N-acyliminoiodinane could be activated to react with silyl enol ethers under photoirradiation conditions.T his method was successfully expanded to various N-sulfonyliminoiodinanes.W eb elieve that the present activation method of iodinanes will encourage greener approaches for the introduction of amino groups, and further develop the understanding of hypervalent iodine chemistry.…”

Development of Fluorescently Labeled SSEA-3, SSEA-4, and Globo-H Glycosphingolipids for Elucidating Molecular Interactions in the Cell Membrane

“…The trisaccharide acceptor was synthesized as depicted in Scheme 1. The Galα(1,4)Gal disaccharide 6 was obtained by di-tert-butylsilylene (DTBS)-directed α-galactosylation [29,30]. In this reaction, the formation of an undesirable orthoester was inevitable due to 2-O-Bz of 4.…”

Synthesis of the Highly Branched Hexasaccharide Core of Chlorella Virus N‐Linked Glycans

“…This compound was further glycosylated with 7 under NIS/AgOTf-promoted conditions at À30 8C to generatep entasaccharide 20 in 69 %y ield. Treatment of 20 with 1% TFAi nd ichloromethane resultedi nt he removalo f the PMB group in 88 %y ield generating 21.G lycosylation of 21 with 8 [12] gave the desired hexasaccharide 22 with exclusive a-selectivity [13] in 89 %y ield. The successo ft his "counter-clockwise" approacht oi ntroducing the substituents onto the fucose residue can be rationalized by the need to glycosylate the least reactive (axial) alcohol first, followed by OH-3 andf inally OH-2.…”