Convenient Synthesis of 3,4-Dichloro-5-hydroxy-2(5H)-Furanone Glycoconjugates

Edyta Gondela,Krzysztof Z Walczak

doi:10.3390/molecules16021011

Edyta Gondela, Krzysztof Z Walczak

Open Access

https://doi.org/10.3390/molecules16021011

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Journal: Molecules	Publication Date: Jan 25, 2011
Citations: 22	License type: CC BY 4.0

Affiliation: Silesian University of Technology

Abstract

3,4-Dichloro-5-hydroxy-2(5H)-furanone treated with methyl chloroformate in the presence of diisopropylethylamine (Hünig’s base) gave the corresponding carbonate. The labile methoxycarbonyloxy group smoothly undergoes substitution by amino alcohols. The obtained 5-(ω-hydroxyalkylamino) mucochloric acid derivatives reacted with peracetylated glucals using triphenylphosphine hydrobromide as a catalyst to give the title muchloric acid glycoconjugates.

Highlights

Mucochloric acid (3,4-dichloro-5-hydroxy-2(5H)-furanone, MCA, 1) is a highly functionalized molecule possessing a hydroxyl group, two chlorine atoms and a lactone-like structure
As a part of our investigation we report our initial trials of the synthesis of MCA conjugates
The hydrophilic part can be represented by a sugar ring or an acyclic linker bearing hydroxyl or carboxylic groups

Summary

Introduction

Mucochloric acid (3,4-dichloro-5-hydroxy-2(5H)-furanone, MCA, 1) is a highly functionalized molecule possessing a hydroxyl group, two chlorine atoms and a lactone-like structure. 5-Methoxycarbonyloxy-3,4-dichloro-2(5H)-furanone reacts with secondary amines at room temperature in toluene giving the corresponding 5-amino derivatives in yields of 61–79% [7]. O-Protected mucochloric acid reacted with appropriate amines giving 1,4-addition/elimination products [12, 13]. E.g. DMSO, the 4-substituted derivative of MCA is formed – formally, it is a product of addition/elimination reaction. Unsubstituted MCA condenses with racemic 2-amino-3-mercapto-3-methylbutanoic acid forming a bicyclic β-lactam [16], whereas with formamides the products of substitution at carbon C4 of the 2-(5H)-furanone moiety are obtained [17]. Further improvements of the leading structure furnished 3,4dichloro-5-(oxiran-2-ylmethoxy)-2(5H)-furanone derivatives with cytotoxicity in the nanomolar range on the same cancer cell lines [5]. As a part of our investigation we report our initial trials of the synthesis of MCA conjugates

Results and Discussion

General

General procedure for the synthesis of compounds 6a-g

Conclusions