A new synthesis of L-ascorbic acid from D-galactose

Barili, Pier Luigi; Berti, G.; D’Andrea, Felicia; Bussolo, Valeria Di; Granucci, I.

doi:10.1016/s0040-4020(01)88219-3

Cited by 15 publications

(4 citation statements)

References 22 publications

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“…As the first generation of synthesis suffered in the overall efficiency, primarily due to the poor yield from 17 to 18 , we searched for an alternative synthetic route, resulting in the second-generation synthesis (Scheme ). The regio- and stereoselective introduction of the C10-allyloxy group relied on the work by Berti and co-workers on a similar system …”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of Halistatins 1 and 2

Kumar

Kishi

2020

J. Am. Chem. Soc.

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The first total synthesis of halistatins 1 and 2 has been completed using Cr-mediated coupling reactions for the C11/C12, C17/C18, and C19/C20 bond formation. For the C11/C12 bond formation, a stoichiometric Ni/Cr-mediated reaction is used to couple an α-quaternary aldehyde with a vinyl iodide. The solubilized Cr-reagent, prepared from CrCl2 and a sulfonamide ligand, allows one to perform the coupling with ∼1 equiv of Cr-reagent. Catalytic, asymmetric Co/Cr-mediated iodoallylation is adopted to incorporate the requisite C17–C19 functionality in a stereoselective manner. Asymmetric Ni/Cr-mediated coupling is used to form the C19/C20 bond effectively. Through this study, it has been found that the stereoselectivity of [5,5]-spiroketalization dramatically depends on solvents; p-toluenesulfonic acid (PTSA) in 1:1 methanol–water gave a >20:1 stereoselectivity favoring the natural series. This condition is also effective to isomerize C38-epi-halichondrins into C38 natural halichondrins.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis of Halistatins 1 and 2

Kumar

Kishi

2020

J. Am. Chem. Soc.

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“…Under Zemplén deacetylation conditions, carboxylic ester 62 readily loses acetone to give glycal 63 (Scheme ), which is an intermediate in the synthesis of l -ascorbic acid from d -galactose . Esterification or amidation of carboxylic acid 64 with the Mukaiyama reagent gave the corresponding glycals 65 in a concomitant β-elimination when an excess amount of the reagents was applied. , By using 1 equiv of the reagents the expected carboxylic acid derivatives without elimination were the main products (RXH = BnOH 42%, 2-aminomethylpyridine 59%) .…”

Section: 12-eliminations From Coor-stabilized Anomeric Anionsmentioning

confidence: 99%

“…82 Further transformations of 34 led to glycosidase and glycosyl transferase inhibitors. Aldehyde 35 which needs not be isolated produces glycal 36, 83 an intermediate in a new synthesis of L-ascorbic acid from D-galactose. Ready cleavage of the acetal moiety is probably due to the formation of a stable carbonyl group in the eliminating acetone, as well as to the conjugative stabilization in the R,β-unsaturated aldehyde.…”

Section: Deprotonation Of C-glycosyl Aldehydesmentioning

confidence: 99%

Carbanionic Reactivity of the Anomeric Center in Carbohydrates

Somsák

2001

Chem. Rev.

153

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“…De acordo com a literatura(BARILI et al, 1986), a proteção seletiva e temporária da função álcool com acetona ou seus derivados, através da formação de anéis isopropilideno e 1,3-dioxano, é um procedimento bem estabelecido em síntese orgânica, em particular em química de carboidratos. Apesar da reação ser muito seletiva devido ao impedimento estérico em torno da posição 2 (causado pelo grupo ligado na posição anomérica), alguns subprodutos estruturalmente diferentes podem ser formados a partir de um único açúcar, dependendo do reagente e das condições de reação(BARILI et al, 1986;BARILI et al, 1992). Proteção regiosseletiva da posição 6 do composto 63 fornecendo 64.…”

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Planejamento, síntese e avaliação da atividade biológica de potenciais inibidores da enzima trans-sialidase de Trypanosoma cruzi

Andrade¹

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DE ANDRADE, P. Design, synthesis and biological activity evaluation of potential inhibitors of the Trypanosoma cruzi trans-sialidase enzyme. 2012. 183 f. Thesis (Doctoral). Faculdade de Ciências Farmacêuticas de Ribeirão Preto -Universidade de São Paulo, Ribeirão Preto, 2012.Chagas' disease, also known as American trypanosomiasis, is one of the most devastating tropical diseases and it is caused by the protozoan Trypanosoma cruzi. The parasite expresses a cell surface enzyme, Trypanosoma cruzi trans-sialidase (TcTS), responsible for the transference of sialic acids from host cells to terminal β-galactose molecules present on its glycoprotein surface. The sialylated glycoprotein molecules are involved in the attachment and subsequent penetration of the parasite into host cells. As a result, TcTS plays a key role in the recognition and invasion of host cells. Moreover, the lack of trans-sialidase in humans makes TcTS a potential drug target to be explored, however no strong inhibitors (at nanomolar range) of this enzyme are known to date. Considering the importance of galactose unit and the carboxyl function in sialic acid for interactions in the active site of TcTS, we have focused on the synthesis of galactose derivatives containing succinic acid in different positions of the sugar ring and on their biological evaluation against TcTS. In addition, we have proposed the search for new TcTS inhibitors applying molecular modeling techniques, like virtual screening based on the enzyme´s active site. Commercially available α,β-D-galactose and methyl-β-D-galactopyranoside were treated with suitable reagents to afford some intermediates with just one free hydroxyl group in few steps. Treatment of these compounds with succinic anhydride in pyridine afforded derivatives thereof with succinic acid in all galactosidic ring positions. After deprotection step it was only obtained the derivative containing succinic acid at position 4 (85), which was tested in in vitro TcTS fluorimetric assay for evaluation of its inhibitory activity. In Addition, 85 was tested in in vitro assays for assessment of their trypanocidal activity and cytotoxic. According to the biological assays, compound 85 showed promising inhibitory activity (56%) at 1.0 mM concentration. This preliminary result was important both to show that this type of derivative can act as an inhibitor of TcTS and to guide the synthesis of new derivatives of galactose. The trypanocidal activity value was lower than 40% (0.5 mM) and there was no cytotoxicity at 0.5 mM concentration. The virtual screening studies performed in this work through docking simulations resulted in the selection of the 50 top-ranked molecules, based in the highest score orientation, among 50.000 found at diverset data base. The next step involves new studies to filter the most promising molecules to be tested against TcTS.

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A new synthesis of L-ascorbic acid from D-galactose

Cited by 15 publications

References 22 publications

Total Synthesis of Halistatins 1 and 2

Total Synthesis of Halistatins 1 and 2

Carbanionic Reactivity of the Anomeric Center in Carbohydrates

Planejamento, síntese e avaliação da atividade biológica de potenciais inibidores da enzima trans-sialidase de Trypanosoma cruzi

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