Regio/Stereoselective Glycosylation of Diol and Polyol Acceptors in Efficient Synthesis of Neu5Ac‐α‐2,3‐LacNPhth Trisaccharide

Abstract

Ac oncise approach to aN eu5Ac-a-2,3-LacNPhth trisaccharide derivativew as developed. First, the regio/stereoselective glycosylation between glycoside donors and glucoNPhth diol acceptors was investigated. It was found that the regioselectivityd epends not only on the steric hindrance of the C2-NPhth group and the C6-OH protecting group of the glucosamine acceptors, but also on the leaving group and protecting group of the glycoside donors. Under optimized conditions, LacNPhth derivatives were synthesized in up to 92 %y ield through aregio/stereoselective glycosylation between peracetylated-a-galactopyranosyl trichloroacetimidate and p-methoxyphenyl 6-O-tert-butyldiphenylsilyl-2-deoxy-2-phthalimido-b-d-glucopyranoside, avoiding the formation of glycosylated orthoesters and anomeric aglycon transfer.T hen, the LacNPhth derivative was deacylated and then protected on the primary position by TBDPS to form a LacNPhth polyol acceptor. Finally,t he Neu5Ac-a-2,3-LacNPhth derivativew as synthesized in 48 %y ield through the regio/stereoselective glycosylationb etween the LacNPhth polyol acceptora nd as ialyl phosphite donor. Startingf rom d-glucosamine hydrochloride, the target Neu5Ac-a-2,3-LacNPhthd erivativew as synthesized in at otal yield of 18.5 %o ver only 10 steps. Figure 1. Structure of the Neu5Ac-a-2,3 LacNAc (3'SLN).

A One-Pot Method for Removal of Thioacetyl Group via Desulfurization under Ultraviolet Light To Synthesize Deoxyglycosides

“…The synthesis of deoxy sugars, especially the synthesis of 2-deoxyglycosides and their derivatives, has drawn increasing attention from carbohydrate chemists because many bioactive natural products have deoxyglycosides as the main constituents of glycosidic chains that play significant roles in bioactivity. − Usually, these deoxy carbohydrate derivatives were synthesized through the reduction of glycals, glyco-epoxides, glycosides with halides, − and glycosides with a thiocarbonyl group − and thioacetate group. , Recently, we have developed a method to obtain the deoxyglycosides through desulfurization of glycoside thiols under ultraviolet light (Scheme a) in order to overcome the shortcomings of Raney nickel catalyzed reduction of a thioacetate group. , In this method, the acylated substrates have to be deprotected in the first step to form glycosyl thiols, which is then desulfurized in the second step to form unprotected deoxy glycosides. This method may be limited in many applications in which acylated deoxyglycoside derivatives are key intermediates (Scheme b). − ,, Therefore, we wondered if we could develop a method for removal of a thioacetyl group via desulfurization under UV light to obtain acylated deoxyglycoside derivatives.…”

Synthesis of 6′-galactosyllactose, a deviant human milk oligosaccharide, with the aid of Candida antarctica lipase-B

“…Procedure from literature: 53 thiophenyl donor 28 (0.395 mmol, 287.9 mg, 1.32 equiv. ), acceptor 26 (0.3 mmol, 104.5 mg) and activated 4 Å molecular sieves in dry DCM (3 mL) was stirred at room temperature under argon for 1 h and then cooled to −20 °C.…”

“…The reaction was followed by TLC -PE : EtOAc 1 : 1, R f = 0.35; mp 72-75 °C (from DCM); [α] 20 D -10.9 (CHCl 3 , c 0.13); 1 H NMR (400 MHz, CDCl 3 ) δ 7.44-7.52 (m, 2H), 7.28-7.36 (m, 3H), 5.40 (d, J = 2.8 Hz, 1H, H-4), 5.36 (d, J = 2.9 Hz, 1H, H′-4), 5.23 (t, J = 10.0 Hz, 1H, H-2), 5.17 (dd, J = 8.2, 10.3 Hz, 1H, H′-2), 5.03 (dd, J = 3.2, 9.9 Hz, 1H, H-3), 4.96 (dd, J = 3.3, 10.4 Hz, 1H, H′-3), 4.74 (d, J = 10.0 Hz, 1H, H-1), 4.49 (d, J = 8.0 Hz, 1H, H′-1), 4.15 (dd, J = 6.7, 11.3 Hz, 1H, H′-6a/6b), 4.10 (dd, J = 6.9, 11.4 Hz, 1H, H′-6a/6b), 3.93 (t, J = 5.7 Hz, 1H, H-5), 3.87 (t, J = 6.5 Hz, 1H, H′-5), 3.81 (dd, J = 4.9, 11.0 Hz, 1H, H-6a/6b), 3.76 (dd, J = 7.4, 10.7 Hz, 1H, H-6a/6b), 2.15 (s, 3H), 2.12 (s, 3H), 2.08 (s, 3H), 2.05 (s, 3H), 1.97 (s, 3H), 1.96 (s, 3H), 1.96 (s, 3H); 13 (29). Procedure from literature: 53 thiophenyl donor 28 (0.395 mmol, 287.9 mg, 1.32 equiv. ), acceptor 26 (0.3 mmol, 104.5 mg) and activated 4 Å molecular sieves in dry DCM (3 mL) was stirred at room temperature under argon for 1 h and then cooled to −20 °C.…”

SnCl4 Promoted Efficient Cleavage of Acetal/Ketal Groups with the Assistance of Water in CH2Cl2

“…Orthogonally protected glycosyl building blocks play key roles in the synthesis of oligosaccharides, whose preparation usually requires multiple steps of selective protection and deprotection [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Acetalation is a routine manipulation for protecting the 4- and 6-hydroxyl groups of glycosides in the synthesis of glycosyl building blocks [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], and thus methods for removing 4,6-arylidene acetals were extensively reported [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”