Highly Alpha‐Selective Sialyl Phosphate Donors for Efficient Preparation of Natural Sialosides

Hsu, Che‐Chang; Chu, Kuo-Ching; Lin, Yih‐Shyan; Han, Jeng‐Liang; Peng, Yu‐Shiang; Ren, Chien‐Tai; Wu, Chung‐Yi; Wong, Chi‐Huey

doi:10.1002/chem.200903035

Cited by 157 publications

(94 citation statements)

References 81 publications

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“…The results of the expression profile studies identified SSEA4 as another important antibreast cancer target because of its high expression level not only on general breast cancer cells but also on BCSCs. Thus, we used the programmable one-pot strategy (46) to synthesize SSEA4 that bears the aminopentanyl spacer arm suitable for protein conjugation (Scheme 2). To conjugate carrier protein DT to SSEA4, our first attempt was to use the same homobifunctional linker strategy, but the yield was very low.…”

Section: Expression Profiles Of Gh-related Structures In Breast Cancementioning

confidence: 99%

Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer

Huang

Hung

Cheung

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Globo H (GH) is a hexasaccharide specifically overexpressed on a variety of cancer cells and therefore, a good candidate for cancer vaccine development. To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked GH to a carrier protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, and BSA, and combined with an adjuvant, and it was administered to mice for the study of immune response. Glycan microarray analysis of the antiserum obtained indicated that the combination of GH-DT adjuvanted with the α-galactosylceramide C34 has the highest enhancement of anti-GH IgG. Compared with the phase III clinical trial vaccine, GHkeyhole limpet hemocyanion/QS21, the GH-DT/C34 vaccine elicited more IgG antibodies, which are more selective for GH and the GHrelated epitopes, stage-specific embryonic antigen 3 (SSEA3) and SSEA4, all of which were specifically overexpressed on breast cancer cells and breast cancer stem cells with SSEA4 at the highest level (>90%). We, therefore, further developed SSEA4-DT/C34 as a vaccine candidate, and after immunization, it was found that the elicited antibodies are also IgG-dominant and very specific for SSEA4.carbohydrate vaccine | diphtheria toxin

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Section: Expression Profiles Of Gh-related Structures In Breast Cancementioning

confidence: 99%

Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer

Huang

Hung

Cheung

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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141

150

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“…In addition, no participating group on C-3 can be used to direct the stereochemistry at the anomeric carbon (C-2) [2]. Efficient chemical sialylation reactions utilize the cyclic 4 O ,5 N -oxazolidinone protecting group [12–15], where the trans -fused cyclic protecting group in the glycosylation transition state likely stabilizes the positive charge on the intermediate acetonitrile adduct and decreases the generation of a positive charge at the anomeric center by their strong dipole moment [2,16–17]. …”

Section: Resultsmentioning

confidence: 99%

“…Installation of O -chloroacetyl groups on C-7 and C-8 for better α-stereoselectivity [12] produced 3 . An α-anomeric phosphate leaving group was chosen since it had previously shown high reactivity [14,18] and selectivity [15]. Building block 4 was obtained in 54% yield over three steps from 1 .…”

Section: Resultsmentioning

confidence: 99%

Automated solid-phase synthesis of oligosaccharides containing sialic acids

Lai¹,

Hahm²,

Liang³

et al. 2015

Beilstein J. Org. Chem.

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“…On the other hand, N-acetyl-5-N,4-O-carbonyl-protected sialyl donor enables transformation of the glycosylated products to the N-acetyl sialic acids by hydrolysis (Crich and Li 2007). The N-acetyl-5-N,4-O-carbonyl-protected sialyl phosphate 13 undergo a-sialylation of the C8 and C9 hydroxy groups of sialic acids 14 and 16 to provide the disialyl glycosyl donors 15 and 17 in good yields (Scheme 2: Hsu et al 2010). The 5-N,4-O-carbonylprotected sialic acids enabled the synthesis of the complex oligosaccharides containing di-and oligosialic acids such as the a(2,8) and a(2,9) tetrasialic acids 18 and 19 and the GP1c epitope 20 containing five sialic acids (Fig.…”

Section: A-sialylation With 5-n4-o-carbonyl-protected Sialyl Donorsmentioning

confidence: 97%

Chemical Synthesis of Oligosialic Acid by Using 5-N,4-O-Carbonyl-Protected Sialyl Donors

Tanaka

2014

Glycoscience: Biology and Medicine

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Synthesis of oligosialic acids using 5-N,4-O-carbonyl-protected sialyl donors is described. The cyclic protection of sialyl donor enables an efficient a-sialylation of various acceptors in non-coordinating solvents such as CH 2 Cl 2 . The protection is also effective for improving the reactivity of the hydroxy group at the eight position. In addition, protecting groups of the alcohol in exocyclic side chain affected not only their reactivity towards sialylation but also selectivity in glycosidation. The 7,8 dichloroacetyl-protected donor was effective for glycosylation of the primary alcohols and the C8 hydroxy group of sialic acid. Cyclic acetal protection of the 7,8 dihydroxy groups is effective for a-sialylation of galactoside at the three position. The sialyl phosphonate underwent chemoselective glycosylation of thiosialoside and would be effective for convergent synthesis of complex oligosaccharides.

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Highly Alpha‐Selective Sialyl Phosphate Donors for Efficient Preparation of Natural Sialosides

Cited by 157 publications

References 81 publications

Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer

Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer

Automated solid-phase synthesis of oligosaccharides containing sialic acids

Chemical Synthesis of Oligosialic Acid by Using 5-N,4-O-Carbonyl-Protected Sialyl Donors

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