Protected Sphingosine from Phytosphingosine as an Efficient Acceptor in Glycosylation Reaction

Abstract

A convenient, simple, and high-yielding five-step synthesis of a sphingosine acceptor from phytosphingosine is reported, and its behavior in glycosylation reactions is described. Different synthetic paths to sphingosine acceptors using tetrachlorophthalimide as a protecting group for the sphingosine amino function and different glycosylation methods have been explored. Among the acceptors tested, the easiest accessible acceptor, unprotected on the two hydroxyl groups in positions 1 and 3, was regioselectively glycosylated on the primary position, the regioselectivity depending on the donor used.

Highly efficient chemoenzymatic synthesis and facile purification of α-Gal pentasaccharyl ceramide Galα3nLc4βCer

“…According to several previous reports 30-32 for the synthesis of glucosyl, galactosyl, or lactosyl sphingosine, the azido-derivative of sphingosine was a better acceptor than other N -protected sphingosine derivatives for glycosylation with trichloroacetimidate glycosylation donors. For example, our attempts for glycosylation using N -tetrachlorophthaloyl (N-TCP) protected acceptor 30 and lactosyl trichloroacetimidate led to very low yields.…”

“…For example, our attempts for glycosylation using N -tetrachlorophthaloyl (N-TCP) protected acceptor 30 and lactosyl trichloroacetimidate led to very low yields. In addition to using the azido protecting group, benzoyl protection of the secondary alcohol in sphingosine was designed to improve the regioselectivity of glycosylation.…”

Total synthesis of ceramides and β-O-glucosylceramides via intramolecular fatty acyl group migration

“…Synthesis of acceptor sphingosine-1-ol (2) was obtained from a commercially available phytosphingosine in eight steps adopted from the previously reported procedure (Scheme 1). 27 Initially phytosphingosine amine was blocked with tetrachlorophthalic anhydride (TCPA) and the resulting compound was then dried and reacted with p-methoxy-dimethylacetal in the presence of a catalytic amount of camphorsulfonic acid (CSA). The C-4 secondary hydroxyl group was substituted with iodide by reaction with triphenylphosphine (PPh 3 ), imidazole and molecular I 2 followed by iodide elimination using 1,8diazabicyclo[5.4.0]undec-7-ene (DBU), then removal of PMB acetal yielded sphingosine-1,3-diol.…”

“…However, its further reaction with 1 M TBAF in DMF and acetic acid in DMF, yielded the desired benzoyl protected sphingosine-1-ol 2 (Scheme 1), (Di Benedetto et al, 2014). 27 The trichloroacetimidate 7 was prepared from pentaacetyl b-D-glucose 6 by the reported method. 22,28 With both intermediates 2 and 7 in our hand, we then coupled the sphingosine acceptor (2) and excess of imidate donor (7) in a glycosylation reaction using TMSOTf as a promoter at À40 1C, resulting in a nonseparable glycosylated product, along with un-reacted glucosyl donor.…”

An Efficient and Concise Synthesis of α-Galactosylceramide

“…Accordingly, commercial phytosphingosine was converted into the tetrachlorophthalimido derivative 2 as previously described. 8 The protection of the 3,4-hydroxyl groups was performed using an excess of 2,2-dimethoxypropane under acid catalysis. Not unespectedly, 9 the reaction gave a minor amount of the desired 3,4-acetal and a main product containing, besides the 3,4acetonide, a mixed 2-methoxyisopropyl (MIP) acetal arising Template for SYNLETT © Thieme Stuttgart • New York 2020-10-20 page 2 of 4 from the reaction of dimethoxypropane with the primary hydroxyl group.…”