Synthesis of `Molecular Asterisks' via Sequential Cross-Metathesis, Sonogashira and Cyclotrimerization Reactions

Abstract

A series of suitably functionalized C-linked carbohydrate derivatives 9-13 were prepared in good yields from alkenyl glycosides 1-4 by cross-metathesis reaction using Grubbs' catalyst [Cl 2 (PCy 3 ) 2 Ru=CHPh]. The reaction was also applied to 6-O-allyl ether 5 and N-Cbz allylamine 6. C-Linked glycopeptide homologue 15 was prepared in 65% yield by cross-metathesis of perbenzylated b-C-allyl mannopyranoside 1 and allyl glycine derivative 8. Finally, amine-ending C-glycoside 11 was subjected to a sequence of deprotection, amidation with p-iodobenzoic acid (EDC, HOBt, DIPEA, r.t., 12 h), Sonogashira reaction [Pd(PPh 3 ) 2 Cl 2 , Et 3 N, 65 °C, 6 h] and treatment with dicobalt octacarbonyl (60 °C, 6 h) to provide a 'molecular asterisk' 21 in 53% yield.

Recent Developments in Olefin Cross‐Metathesis

“…[62] An initial CM reaction between peracetylated a-d-allylgalactopyranoside 70 with protected amine 71 catalyzed by 6 afforded cross-product 72 in moderate yield with complete E selectivity (Scheme 13). The predominance of the E isomer in this CM reaction remains to be explained; CM reactions involving various other sugar derivatives under identical conditions gave selectivity no better than 4:1 in favor of the E form.…”

Recent Advances in the Synthesis of C-linked Glycoconjugates

“…In 2001, Dondoni et al [12] conceived an olefin cross-coupling strategy that gave access to both C-glycosyl arganine and serine analogues. The authors point out that the only previously-reported cross metathesis strategy linked racemic allyl-glycine and a perbenzylated allyl β-D-Cmannoside derivative, as published by Roy and co-workers [13]. Dondoni and co-workers [12] reported that heating a mixture of allyl β-D-C-glucopyranoside 9, with vinyl oxazolidine 10, and the second generation Grubbs' catalyst in CCl 4 at 100 o C afforded the cross-metathesis product 11 in 50% yield as a mixture of E and Z isomers (Scheme (3)).…”

“…In contrast to reactions with organometallic reagents, the α-linked product was formed exclusively. The earliest olefin cross-metathesis approach for the formation of C-glycosyl analogues produced an unnatural amino acid derivative wherein a four-methylene chain connects the amino acid and sugar moieties [13]. Cross coupling of glycosyl derivative 75 and amino acid derivative 76 was carried out using Grubbs' first generation catalyst (Scheme (19)) to provide 77 as a mixture of E and Z isomers in 60% yield.…”

Macromolecules with Сarbohydrate Residues and Their Application in Glycobiology, Biotechnology and Material Science

“…A specific feature of this method is that the final glycosylamino acids can be easily incorporated in peptide-like glycoclusters or glycopeptides. The use of this method for synthesizing glycopeptide (11) and oligoglycine (13) scaffolds, [27] C-glycosyl oligopeptide (16), [28] as well as a synthesis of compounds based on C-fucosylpeptide (17) [29] have been reported. As a result, comparatively powerful P-selectinantagonists were obtained ( Figure 11).…”