Synthesis of ω-(methoxycarbonyl)alkyl and 9-(methoxycarbonyl)-3,6-dioxanonyl glycopyranosides for the preparation of carbohydrate-protein conjugates

Sugawara, Tamio; Irie, Kunihiko; Iwasawa, Hiroyuki; Yoshikawa, Tomohiro; Okuno, Satoshi; Watanabe, Hiroshi; Kato, Takashi; Shibukawa, Mitsuru; Ito, Yukio

doi:10.1016/s0008-6215(00)90517-2

Cited by 12 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The α/β assignment was attested by comparison of these NMR signals with those collected for pure 4 α , 5 α , and anomeric 4 α , β or 5 α , β mixtures (see Table ) and by comparison with the 1 H ( − ) and 13 C NMR data for similar derivatives ( 55 , 56 , 58 ). For instance, the α and β configurations of 4 are confirmed by the anomeric H-1α and H-1β singlets at 4.96 and 4.89 ppm, respectively, the C-13α and C-13β resonances determined by 2D experiments being at 97.9 and 98.9 ppm, respectively ( , ). The variations of α:β ratios of the various protected and deprotected PI prodrugs were essentially due to the purification steps which were performed by column chromatography.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and in Vitro Biological Evaluation of Mannose-Containing Prodrugs Derived from Clinically Used HIV-Protease Inhibitors with Improved Transepithelial Transport

et al. 2006

View full text Add to dashboard Cite

In an approach to improve the pharmacological properties, safety and pharmacokinetic profiles, and their penetration into HIV reservoirs or sanctuaries, and consequently, the therapeutic potential of the current protease inhibitors (PIs) used in clinics, we investigated the synthesis of various mannose-substituted saquinavir, nelfinavir, and indinavir prodrugs, their in vitro stability with respect to hydrolysis, anti-HIV activity, cytotoxicity, and permeation through a monolayer of Caco-2 cells used as a model of the intestinal barrier. Mannose-derived conjugates were prepared in two steps, in good yields, by condensing an acid derivative of a protected mannose with the PIs, followed by deprotection of the sugar protecting group. With respect to hydrolysis, these PI prodrugs are chemically stable with half-life times in the 50-60 h range that are compatible with an in vivo utilization aimed at improving the absorption/penetration or accumulation of the prodrug in specific cells/tissues and liberation of the active free drug inside HIV-infected cells. These stabilities correlate closely with the low in vitro anti-HIV activity measured for those prodrugs wherein the coupling of mannose to the PIs was performed through the peptidomimetic PI's hydroxyl. Importantly, mannose conjugation to the PIs was further found to improve the absorptive transepithelial transport of saquinavir and indinavir but not of nelfinavir across Caco-2 cell monolayers, by contrast to glucose conjugation which had the opposite effect. The mannose-linked prodrugs of saquinavir and indinavir display therefore a most promising therapeutic potential provided that bioavailability, penetration into the HIV infected macrophages, and HIV-reservoirs of these PIs are improved.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and in Vitro Biological Evaluation of Mannose-Containing Prodrugs Derived from Clinically Used HIV-Protease Inhibitors with Improved Transepithelial Transport

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Conjugates containing several types of spacer arms, such as a nine-carbon chain (1 1 -14), and chains containing dioxa (1 5-17), amide (1 8), thioether (1 9-23), phenylthiourea (24), or (7-N-acryloylphenyl (25) functional groups, have been prepared. Four-, seven-, twelve-, and fifteen-carbon spacer a m s have also been employed (26). Here we describe the synthesis of a conjugate of the trisaccharide and bovine serum albumin (BSA) by using a 12-carbon spacer arm.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of O-α-D-Rhap-(1 → 3)-O-α-D-Rhap-(1 → 2)-O-α-D-Rhap-(1 → 12)-oxydodecanoyl-bovine serum albumin

Zou¹,

Sen²,

Szarek³

et al. 1993

Can. J. Chem.

View full text Add to dashboard Cite

. Can. J . Chenl. 71, 2194Chenl. 71, (1993. The title compound (191, a conjugate of a trisaccharide based upon the repeating trisaccharide of a-D-rhamnose, which comprises the polysaccharide portion of "A-band" lipopolysaccharide from a mutant (AK1401) of Pselldornotlns nerugitlosn, strain PAOI, with bovine serum albumin (BSA) was synthesized starting with methyl a-D-mannopyranoside. Suitably protected D-rharnnose derivatives, namely, ethyl 3,4-di-0-benzyl-I-thio-a-D-rharnnopyranoside (11) and 3-0-acetyl-2,4-di-0-benzyl-cu-o-rhamnopyranos chloride (12), were used as the glycosyl acceptor and donor, respectively, in the synthesis of disaccharide 13. 0-Deacetylation of 13 gave 14, a glycosyl acceptor that reacted with 12 to yield the trisaccharide 15. N-Iodosu~cinimide -tritluoroinethanesulfonic acid was used as an activator of the thioglycoside in the synthesis of 16 and 17 from 15. Compound 16 was converted into the hydrazide 18 by treatment with hydrazine. The conjugation was achieved by coupling of the intermediate acyl azide derivative of 18 with BSA.

show abstract

“…Column chro matography gave 0.849 g (67%) of tribenzoate 5 identical to that obtained by method A, [α] D + 4.5 (lit 28 : [α] D +4.9). 1,3 Di O acetyl 2,4,6 tri O benzoyl α α α α α D mannopyranose (3). A cooled solution of conc.…”

mentioning

confidence: 99%

Synthesis of a derivative of a pentasaccharide repeating unit of the O-antigenic polysaccharide of the bacterium Klebsiella pneumoniae O3 as a benzoylated 2-methoxycarbonylethyl thioglycoside

et al. 2009

View full text Add to dashboard Cite

show abstract

Synthesis of ω-(methoxycarbonyl)alkyl and 9-(methoxycarbonyl)-3,6-dioxanonyl glycopyranosides for the preparation of carbohydrate-protein conjugates

Cited by 12 publications

References 38 publications

Synthesis and in Vitro Biological Evaluation of Mannose-Containing Prodrugs Derived from Clinically Used HIV-Protease Inhibitors with Improved Transepithelial Transport

Synthesis and in Vitro Biological Evaluation of Mannose-Containing Prodrugs Derived from Clinically Used HIV-Protease Inhibitors with Improved Transepithelial Transport

Synthesis of O-α-D-Rhap-(1 → 3)-O-α-D-Rhap-(1 → 2)-O-α-D-Rhap-(1 → 12)-oxydodecanoyl-bovine serum albumin

Synthesis of a derivative of a pentasaccharide repeating unit of the O-antigenic polysaccharide of the bacterium Klebsiella pneumoniae O3 as a benzoylated 2-methoxycarbonylethyl thioglycoside

Contact Info

Product

Resources

About