Stereodirecting Effect of C5-Carboxylate Substituents on the Glycosylation Stereochemistry of 3-Deoxy-d-manno-oct-2-ulosonic Acid (Kdo) Thioglycoside Donors: Stereoselective Synthesis of α- and β-Kdo Glycosides

Abstract

The stereodirecting effect of C5-ester functions on the glycosylation stereoselectivity of 3-deoxy-d- manno-oct-2-ulosonic acid (Kdo) ethyl thioglycoside donors is presented. The coupling of 5- O-arylcarbonyl or acetyl protected Kdo thioglycosides with acceptors proceeds in an α-selective and high-yielding manner, leading to formation of α-linked Kdo glycosides products. On the other hand, the glycosylation stereoselectivity of the 5- O-2-quinolinecarbonyl (Quin) or 4-nitropicoloyl substituted Kdo thioglycoside donors is switchable: (1) The glycosylation of the 5- O-Quin carrying Kdo donors with primary glycosyl acceptors shows complete β-stereoselectivity, furnishing the corresponding β-glycosides in good-to-excellent yield. (2) The stereochemical outcome of the secondary acceptors with these Kdo donors is determined mainly by the stereoelectronic nature of the acceptor. Only or predominant α anomeric products are obtained when the Kdo donors couple with the disarmed or highly crowded secondary carbohydrate acceptors, while the selectivity may switch to predominant β in the glycosylation of the 5- O-4-nitropicoloyl carrying donor with more reactive secondary alcohols. The synthetic use of the newly developed Kdo donors 1c and 7b has been demonstrated by facile preparation of a structurally unique trisaccharide motif 19 which possesses both α- and β-Kdo glycosidic bonds.

Divergent Synthesis of 3‐Deoxy‐d‐manno‐oct‐2‐ulosonic Acid (Kdo) Glycosides Containing α‐(2→4)‐Linked Kdo‐Kdo Unit

“…Importantly,n ob-anomeric byproduct was observed under theser eactionc onditions. Analysis of the undecoupled 13 CNMR spectra of 8 unambiguously indicated the a-configuration of each Kdo glycosidicb ond ( 3 J C-1/H-3ax < 1.5 Hz for each Kdo unit). The global deprotection of 8 was achieved in the followingo rder:d eprotection of the TBS ether and DTBS acetals with triethylamine-trihydrofluoride complex (Et 3 N·3HF) [16] in tetrahydrofuran( THF), removalo fa ll the ester groupsa nd release of the carboxylic groups through saponification with sodium hydroxide (NaOH) in aM eOH/H 2 O( 2:1) cosolvent, and finally cleavage of the Nap ether ands imultaneous reduction of the azide to amine by catalytic hydrogenolysis over 10 %P d/C in am ixture of MeOH and H 2 O.…”

“…Upon activation with 1.2 equivalents of tris(4-bromophenyl)ammoniumylh exachloroantimonate (TBPA) [14] at À20 to 0 8Cf or 3h in acetonitrile (MeCN), Kdo 3-azidopropyl glycoside acceptor 4 was glycosylated efficiently and a-stereoselectively with glycosyl donor 1 (see the Supporting Information) to give the corresponding 3 in 73 %y ield without formation of the b-anomeric product. The anomeric configuration of aK do glycoside can be determined by the coupling constant between the axial protona t the C3 positiona nd the carbon at the C1 positiono ft he Kdo ring in the undecoupled 13 CNMR spectra. [10h,15] For the a-Kdo anomer, the 3 J C-1/H-3ax value is less than 1.5 Hz, whereas for the b-anomer,t he 3 J C-1/H-3ax value is about 5.0-6.0 Hz.…”

“…The structurea nd stereochemistry of 17 and 19 were unambiguously confirmed by NMR and electrospray ionization mass spectrometry (ESIMS) analysis. Take trimer 17 for instance, the a-anomeric configurations of every Kdo residue were evident from the un-decoupled 13 CNMR spectroscopy ( 3 J C-1/H-3ax < 1.5 Hz for each Kdo unit). Its structure was furthers upported by the high-resolution MS data, which provided an (MÀH) À signal at m/z = 734.2359(calcd 734.2355).…”

“…[12] The means allows av ariety of acceptors to be used, giving a-linked Kdo glycosides in high chemical yields with complete a-selectivity.M ore recently,w ed isclosed the stereodirecting effect of 5-O-ester functionalities on the glycosylationc hemistry of Kdo thioglycoside donors. [13] The5 -O-arylcarbonyl or acetyls ubstituted Kdo thioglycosides were found to exhibit excellent astereocontrolling ability in the coupling with variousa cceptors. On the other hand, the stereochemical outcomeo f5 -O-2-quinolinecarbonyl or 4-nitropicoloyl protected Kdo thioglycosides was switchable.…”

“…O-benzoyl-5,7-O-isopropylidene-8-O-(2-methylnaphthyl)-3-deoxy-a-d-manno-oct-2-ulopyranosyl]onate-(2!4)-methyl (3-azidopropyl 7,8-O-isopropylidene-3-deoxya-d-manno-oct-2-ulopyranosid)onate(13) …”