•Two series of NHC-Au(I)X complexes are reported.•All compounds are fully characterized chemically.•All compounds are tested on the NCI 60 cancer cell panel.•Two compounds show promising anticancer activity.The synthesis and biological evaluation of three gold pseudohalides and three gold thiolates, stabilised by the NHC ligand 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene (NHC*), in order to form stable gold(I) complexes is reported. Two separate procedures have been developed for the synthesis; the one for the pseudohalide complexes employs the use of a biphasic medium while the one for the thiolate complexes requires higher temperature for their formation. The gold complexes have been prepared in varying yields (44–81%) from the corresponding NHC*-Au-Cl precursor. One thiolate and two pseudohalide gold complexes were characterized by single crystal X-ray diffraction and showed the expected monomeric nature of all derivatives. All six complexes were submitted to the NCI 60 cancer cell panel for cytotoxicity tests; most of the complexes showed activity in the medium to low micromolar region, while the NHC*-Au-SCN derivative was superior exhibiting nanomolar anticancer activity.Six NHC-Au(I) pseudohalides and thiolates were synthesized and tested as anticancer drug candidates.Download high-res image (191KB)Download full-size image

•Stereoselective synthesis of α-S-linked galactosylceramide.•Synthetic strategy is applicable to the synthesis of other α-S-GalCer analogues.•The synthesized α-S-glycolipid is a potential immunostimulant.Synthesis of a glucosylated α-S-galactosylceramide (1), a potential immunostimulant, was achieved starting from D-galactose. Both O- and S-glycosidic linkages were constructed in highly stereoselective way, and the synthetic strategy could be extended to the synthesis of other α-S-GalCer analogues.Download high-res image (79KB)Download full-size image

The influence of anomeric configuration upon thioglycoside donors remains relatively unexplored. Utilizing methodology developed for the stereoselective and high-yielding synthesis of α-glycosyl thiols, a series of α-thioglycosides were synthesized, and their reactivity was compared to that of their β-counterparts. The highly selective activation observed for anomeric pairs containing a 2-O-acyl moiety and additional findings are reported. Application of a pair of “superarmed” thioglycosides to a one-pot oligosaccharide system is also described, in which selectivity is a result of configuration-based orthogonal activation.

A new sialyl thioimidate donor 6 was prepared in high yields from the known sialyl hemiketal 1 over five steps. Under the action of catalytic TMSOTf, 6 exhibited excellent reactivity using a series of primary alcohols to give the desired sialylation products in high to excellent yields. Chemoselective activation of 6 in the presence of thioglycosides was also demonstrated.

•Expedient and stereoselective synthesis of α-glycosyl azides.•In some cases, α-only selectivity and generally high yields achieved.•Applicable to substrates with various protecting groups and oligosaccharides.•The synthesized α-glycosyl azides is of great utility and potential.We describe here an expedient and highly stereoselective procedure for the synthesis of α-glycosyl azides. Treatment of 1,6-anhydrosugars with trimethylsilyl azide in the presence of trimethylsilyl triflate led to the formation of α-glycosyl azides. All the reactions were highly stereoselective and afforded the α-glycosyl azides in good to excellent yields.

Thioperoxide (1) in combination with trimethylsilyl trifluoromethanesulfonate (TMSOTf) provides a powerful thiophilic promoter system, capable of activating different thioglycosides. Both armed and disarmed thioglycosides were activated effectively in the presence of different glycosyl acceptors, giving glycosidation products in high to excellent yields. A plausible activation pathway was also proposed and supported by isolating side-products trifluoromethylphenyl disulfide (CF3SSPh) and alkene (42).

An α-S-(1→6)-linked pentaglucosyl thiol has been synthesized in a convenient and stereoselective way. Key steps of the synthesis involved thioglycosylation of 6-iodinated sugars with α-glycosyl thiols under phase transfer conditions. The α-configuration of glycosidic linkages was thus introduced prior to the coupling steps, and relied on the intrinsic configurational stability of α-glycosyl thiols. This work also demonstrated the great utility of MMTr as an effective anomeric S-protecting group.

•The first total synthesis of Calocybe indica var. APK2 polysaccharide repeating unit.•A high overall synthetic yield achieved with a convergent [3+2] strategy.•The target pentasaccharide is of potential immunostimulatory activity.The first total synthesis of p-methoxyphenyl α-l-fucopyranosyl-(1→6)-α-d-galactopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside (2) was achieved starting from five monosaccharide building blocks. This structure represents the repeating unit of the polysaccharide isolated from edible mushroom Calocybe indica var. APK2, and was synthesized in high overall yield via a convergent ‘3+2’ glycosylation strategy.

A wide range of symmetrical and unsymmetrical glycosyl disulfides is synthesized with focus on the use of α-glycosyl thiols. Oxidation of α-glycosyl thiols with iodine leads to symmetrical α,α-glycosyl disulfides, while unsymmetrical disulfides are readily synthesized from α- and β-glycosyl thiols under the action of DDQ. Thus, glycosyl disulfides containing at least one α-glycosidic linkage are made available.Both symmetrical and unsymmetrical glycosyl disulfides containing α-glycosidic linkages were synthesized readily from the corresponding glycosyl thiols by oxidation with I2 or DDQ.

We describe here the first synthesis of thioglycoside analogues of maradolipid, based on a new procedure for the synthesis of 1-thiotrehalose developed recently in our laboratories. The challenging α,α-(1→1′) thioglycosidic linkage was constructed by Schmidt’s inverse procedure in very high yield and excellent stereoselectivity. Subsequent protecting group manipulation and coupling with different fatty acids led smoothly to a group of symmetrical and unsymmetrical thiomaradolipids which would be of high value for biological studies.

A facile and highly stereoselective synthesis of 1-thiotrehalose, that is, α,α-S-linked trehalose, is described. Glycosylation of configurationally pure α-glucosyl thiol 5 with glucosyl trichloroacetimidate 6 or glucosyl thioimidate 9 followed by deprotection afforded 1-thiotrehalose in excellent α-stereoselectivity and high yield. A different synthetic route to the key building block, α-glucosyl thiol 5, was also investigated in this report.Glycosylation of configurationally pure α-glucosyl thiol 5 with glucosyl trichloroacetimidate 6 or glucosyl thioimidate 9 followed by deprotection afforded 1-thiotrehalose in excellent α-stereoselectivity and high yield.

We present here a convenient synthesis of the truncated sphingoid iodide 15 from d-galactose, in which Mitsunobu reaction was utilized to retrieve successfully an unwanted intermediate, thereby increasing greatly the synthetic efficiency. Subsequent reaction of 15 with the pre-prepared α-galactosyl thiol 16 led smoothly to the desired thioglycoside 17 in good yield, from which the catabolically stable thioglycoside analogs of OCH 4 and 22 were synthesized.Two thioglycoside analogs of α-galactosylceramide with a truncated sphingoid chain were synthesized as potential immunomodulating agents.

Treatment of 1,6-anhydrosugars with commercially available bis(trimethylsilyl) sulfide in the presence of trimethylsilyl triflate led to the formation of α-glycosyl thiols. All the reactions were highly stereoselective and afforded the α-glycosyl thiols in good to excellent yields. By this procedure, a variety of 1,6-anhydrosugars, differing in their sugar units, glycosidic linkages, and protecting group pattern, were converted smoothly into the corresponding α-glycosyl thiols, which could be of great utility in thioglycoside chemistry. It is noteworthy that 1,6-anhydrosugars carrying the 2-O-acyl group and 1,6-anhydrosugar-containing oligosaccharides could also be ring-opened stereospecifically under the same conditions to give rise to the corresponding 1-thiosugars in high yields. Thus, a very concise and efficient access to α-glycosyl thiols of great value was established.

A new simple method for the synthesis of α-glycosyl thiols is described. Ring-opening of 1,6-anhydrosugars with commercially available bis(trimethylsilyl)sulfide under the action of catalytic amounts of TMSOTf smoothly afforded α-glycosyl thiols in very high yields and in a stereospecific way.

A new simple method for the synthesis of α-glycosyl thiols is described. Ring-opening of 1,6-anhydrosugars with commercially available bis(trimethylsilyl)sulfide under the action of catalytic amounts of TMSOTf smoothly afforded α-glycosyl thiols in very high yields and in a stereospecific way.

An α-S-(1→6)-linked pentaglucosyl thiol has been synthesized in a convenient and stereoselective way. Key steps of the synthesis involved thioglycosylation of 6-iodinated sugars with α-glycosyl thiols under phase transfer conditions. The α-configuration of glycosidic linkages was thus introduced prior to the coupling steps, and relied on the intrinsic configurational stability of α-glycosyl thiols. This work also demonstrated the great utility of MMTr as an effective anomeric S-protecting group.