Synthesis of the thiazoline-based siderophore (S)-desferrithiocin

Mulqueen, G. C.; Pattenden, Gerald; Whiting, Donald A.

doi:10.1016/s0040-4020(01)82385-1

Cited by 54 publications

(21 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1). [10][11][12] Desferrithiocin, a tridentate chelator, forms a 2:1 complex with Fe(III) (K f = 4 × 10 29 M −1 ); 13,14 the thiazoline nitrogen, the phenolic oxygen, and the carboxylate comprise the donor groups. In all of these examples Fe(III) forms hexacoordinate octahedral complexes with these ligands.…”

mentioning

confidence: 99%

Iron chelation promoted by desazadesferrithiocin analogs: An enantioselective barrier

et al. 2003

View full text Add to dashboard Cite

For patients who require lifelong blood transfusions, there is no efficient means, unless chelation therapy is employed, for elimination of excess iron. Alternatives to desferrioxamine, the currently accepted treatment for transfusional iron overload, are being investigated. The current article focuses on an enantiomeric pair of analogs of desferrithiocin, (+)-(S)- and (-)-(R)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid (4'-hydroxydesazadesferrithiocin). The crystal structure corroborated the absolute configuration of the two compounds, (+) and (-) for the (S)- and (R)-enantiomers, respectively. Job's plots established the tridentate nature of both analogs and circular dichroism spectra confirmed the ligands' antipodal relationship. (+)-(S)-4'-Hydroxydesazadesferrithiocin is a more efficient deferration agent than is the (-)-(R)-enantiomer in a Cebus apella model of iron overload. Pharmacokinetic analyses and IC(50) measurements in L1210 murine leukemia cells were undertaken in an effort to account for the contrast in efficacy between the two enantiomers. Some differences exist in the plasma pharmacokinetic parameters between the two analogs. However, a more plausible explanation may be the apparent differences in transport across the cell membrane; the IC(50) value in L1210 cells of the (+)-(S)-enantiomer was at least 5-fold lower than that of the (-)-(R)-compound.

show abstract

mentioning

confidence: 99%

Iron chelation promoted by desazadesferrithiocin analogs: An enantioselective barrier

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Although (R)-2-methylcysteine methyl ester hydrochloride 5 [9] has been obtained by Donald A. Whiting using the Seebach's 'Self-regeneration of stereocenters' protocol, we prepared it by an improved method [10] of using NaHMDS instead of LDA in the alkylation step (Scheme 2). Substituting the LDA with the NaHMDS in our experiment led significant improvement in the yield from 56 to 90%.…”

Section: Resultsmentioning

confidence: 99%

Concise total synthesis of largazole

Xiao

Wang

Jiao

et al. 2010

Journal of Asian Natural Products Research

View full text Add to dashboard Cite

show abstract

“…Consequently, a variety of methods have been reported for the synthesis of thiazoline building blocks, for example (i) the condensation of aminothiols with nitriles [10], esters [11], iminoethers [12], or imino triflates [13], (ii) from N-acyl-2-aminoethanols [14] and (R)-hydroxy thioamides [15], (iii) by the multi-step conversion from oxazolines [16] and (iv) by the microwave irradiation of N-acylbenzotriazoles with 2-aminoethanethiol hydrochloride [17]. However, these reactions generally require drastic reaction conditions, such as the use of triisobutyl aluminium.…”

Section: Introductionmentioning

confidence: 99%

“…However, these reactions generally require drastic reaction conditions, such as the use of triisobutyl aluminium. Furthermore when nitriles are employed, a Lewis acid is required along with higher temperatures for the elimination of ammonia [10]. Other methods employ complex reagents [15b] or strongly acidic conditions.…”

Section: Introductionmentioning

confidence: 99%