C‐Linked Disaccharide Analogue of the Thomsen–Friedenreich (T)‐Epitope α‐O‐Conjugated to L‐Serine

Abstract

Condensation of a silylated beta-D-galactopyranosylaldehyde (3) with isolevoglucosenone (4) in the presence of Et(2)AlI provided bicyclic enone 5. Subsequent addition of BnNHOMe gave adduct 6, which was converted into 4-O-acetyl-1,6-anhydro-3-C-[(1 R)-1,3,4,5,7-penta-O-acetyl-2,6-anhydro-D-glycero-L-manno-heptitol-1-C-yl]-2-azido-2,3-dideoxy-beta-D-galacto-hexopyranose after liberation of the 2-amino group, its transformation into a 2-azido moiety, desilylation, and peracetylation. Ring-opening of the 1,6-anhydro galactopyranosyl unit and O-glycosidation with Fmoc-Ser-O-tBu afforded a 5:1 mixture of alpha- and beta-galactosides. Treatment with CH(3)COSH gave pure N-[(9H-fluoren-9-ylmethoxy)carbonyl]-{4,6-di-O-acetyl-3-C-[(1 R)-2,6-anhydro 1,3,4,5,7-penta-O-acetyl-D-glycero-L-manno-heptitol-1-C-yl]-2-[(N-acetyl)amino]-2,3-dideoxy-alpha-D-galactopyranosyl}-l-serine tert-butyl ester (2), a protected form of a C-disaccharide analogue of the Thomsen-Friedenreich (or T) epitope (beta-D-Galp-(1-->3)-alpha-D-GalNAcp) alpha-O-conjugated to L-serine.

Synthesis of chemical tools to improve water solubility and promote the delivery of salinomycin to cancer cells

“…2B). A known aldehyde 4 (25,(29)(30)(31)(32)(33)(34)(35)(36)(37) was treated under Henry reaction conditions (38) with nitromethane, in the presence of ammonium acetate to form the dehydrated product 5. The crude product 5 was subsequently treated with sodium borohydride in the presence of double distilled water and methanol for complete reduction in order to produce the amine form 6, which was treated with trifluoromethanesulfonyl azide in order to convert it to the azido sugar 7.…”

Silyl methallylsulfinates: efficient and powerful agents for the chemoselective silylation of alcohols, polyols, phenols and carboxylic acids

“…The usefulness of our new silylating reagents is demonstrated once more in the case of unreactive, sterically hindered alcohols 9 18 and 10. 19 The semi-protected C-linked disaccharide precursor 9 possesses a secondary alcohol moiety that refused to be silylated to the triethylsilyl ether applying known techniques [e.g. : Et 3 SiOTf/ lutidine/CH 2 Cl 2 , 2 days or Et 3 SiOTf/pyridine/4-(Me 2 N)-pyridine, 2 days].…”

Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates

“…[α] 25 (20). To a stirred solution of 19 (58.0 mg, 0.12 mmol) and AcOH (65.8 μL, 1.25 mmol) in THF (3.2 mL) was added TBAF•3H 2 O (157.7 mg, 0.50 mmol) at 0 °C under an atmosphere of argon.…”

“…15 Recently, some more TACAs were modified in different ways, proving the validity of this protocol. [16][17][18][19][20][21][22][23][24][25][26][27][28] STn antigen 1 (Fig. 1), an O-linked disaccharide [NeuAcα- (2)(3)(4)(5)(6)GalNAc], is expressed on a wide range of tumor cells such as breast, prostate, and ovarian carcinomas but has rarely been observed in normal tissues.…”