(Ley)3-peptide-Pam3Cys

合成路线:The protected pentasaccharide (I) was converted to the corresponding thioglycoside by epoxidation with dimethyldioxirane followed by epoxide opening with ethanethiol in the presence of trifluoroacetic acid.Subsequent acylation of the free hydroxyl group with benzoyl chloride afforded the thioglycoside benzoate (II).Alternatively,treatment of (I) with dimethyldioxirane in the presence of 4-penten-1-ol and ZnCl2 and subsequent O-benzoylation furnished the pentenyl benzoate (III).Condensation of either the thioethyl donor (II) or the pentenyl donor (III) with the protected serine glycoside acceptor (IV) using N-iodosuccinimide and triflic acid afforded the coupled product (V).

合成路线:Desilylation of (V) with tetrabutylammonium fluoride followed by acetylation of the free hydroxyl groups provided the fully acylated compound (VI).Reductive acetylation of the azido group of (VI) using a 1:1 mixture of thioacetic acid and pyridine gave rise to the acetamide (VII).The benzyl ester of (VII) was then cleaved by hydrogenolysis over Pd/C to yield the carboxylic acid (VIII).

合成路线:Coupling of the protected serine O-hexasaccharide (VIII) with the tetrapeptide ester Ala-Val-Ala-Val-OBn (A) by means of HATU afforded the Fmoc-pentapeptide O-hexasaccharide (IX).The Fmoc group of (IX) was then deprotected by treatment with morpholine,and the deprotected amine was coupled with a second unit of Fmoc-Ser(O-hexasaccharide) (VIII) to produce adduct (X).

合成路线:A further deprotection and coupling cycle of (X) with the serine derivative (VIII) furnished (XI).

合成路线:The Fmoc protecting group of (XI) was removed by means of morpholine and the resulting amine was acylated with Ac2O to give acetamide (XII).

合成路线:Hydrogenolysis of the benzyl ester group of (XII) and subsequent hydrazinolysis of the acetate and benzoate esters afforded the fully deprotected product,which was finally coupled with tripalmitoyl S-glyceryl-Cys-Ser-N-(3-aminopropyl)amide (XIII) to furnish the title compound.

参考文献标题:Design and synthesis of Le(y)-bearing glycopeptides that mimic cell surface Le(y) mucin glycoprotein architecture
文献作者:Glunz,P.W.; et al.
参考来源:J Am Chem Soc 2000,122(30),7273


合成路线:The protected pentasaccharide (I) was converted to the corresponding thioglycoside by epoxidation with dimethyldioxirane followed by epoxide opening with ethanethiol in the presence of trifluoroacetic acid.Subsequent acylation of the free hydroxyl group with benzoyl chloride afforded the thioglycoside benzoate (II).Alternatively,treatment of (I) with dimethyldioxirane in the presence of 4-penten-1-ol and ZnCl2 and subsequent O-benzoylation furnished the pentenyl benzoate (III).Condensation of either the thioethyl donor (II) or the pentenyl donor (III) with the protected serine glycoside acceptor (IV) using N-iodosuccinimide and triflic acid afforded the coupled product (V).

合成路线:Desilylation of (V) with tetrabutylammonium fluoride followed by acetylation of the free hydroxyl groups provided the fully acylated compound (VI).Reductive acetylation of the azido group of (VI) using a 1:1 mixture of thioacetic acid and pyridine gave rise to the acetamide (VII).The benzyl ester of (VII) was then cleaved by hydrogenolysis over Pd/C to yield the carboxylic acid (VIII).

合成路线:Coupling of the protected serine O-hexasaccharide (VIII) with the tetrapeptide ester Ala-Val-Ala-Val-OBn (A) by means of HATU afforded the Fmoc-pentapeptide O-hexasaccharide (IX).The Fmoc group of (IX) was then deprotected by treatment with morpholine,and the deprotected amine was coupled with a second unit of Fmoc-Ser(O-hexasaccharide) (VIII) to produce adduct (X).

合成路线:A further deprotection and coupling cycle of (X) with the serine derivative (VIII) furnished (XI).

合成路线:The Fmoc protecting group of (XI) was removed by means of morpholine and the resulting amine was acylated with Ac2O to give acetamide (XII).

合成路线:Hydrogenolysis of the benzyl ester group of (XII) and subsequent hydrazinolysis of the acetate and benzoate esters afforded the fully deprotected product,which was finally coupled with tripalmitoyl S-glyceryl-Cys-Ser-N-(3-aminopropyl)amide (XIII) to furnish the title compound.
参考文献标题:Probing cell surface "glyco-architecture" through total synthesis.Immunological consequences of a human blood group determinant in a clustered mucin-like context
文献作者:Glunz,P.W.; et al.
参考来源:J Am Chem Soc 1999,121(45),10636