Asymmetric syntheses of α-mercapto carboxylic acid derivatives by dynamic resolution of N-methyl pseudoephedrine α-bromo esters

Nam, Jiyoun; Lee, Sang-kuk; Kim, Kee Yong; Park, Yong Sun

doi:10.1016/s0040-4039(02)02020-8

Cited by 26 publications

(3 citation statements)

References 14 publications

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“…Another product at m/z 1048 was identified as brostallicin-GSH adduct 7 in which bromine is replaced by one phosphate group ( Figure 2C,D,F). GSH-brostallicin R-bromoamido derivative 4 was not detected under these conditions, confirming the hypothesis that brostallicin, after the addition of GSH, forms a highly reactive intermediate which substitutes bromine with other species present in solution (22)(23)(24). However, a long-lived transient species has been observed at m/z 986.…”

Section: Resultssupporting

confidence: 70%

Role of Glutathione Transferases in the Mechanism of Brostallicin Activation

Pezzola

Antonini²,

Geroni

et al. 2009

Biochemistry

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Brostallicin is a novel and unique glutathione transferase-activated pro-drug with promising anticancer activity, currently in phase I and II clinical evaluation. In this work, we show that, in comparison with the parental cell line showing low GST levels, the cytotoxic activity of brostallicin is significantly enhanced in the human breast carcinoma MCF-7 cell line, transfected with either human GST-π or GST-μ. Moreover, we describe in detail the interaction of brostallicin with GSH in the presence of GSTP1-1 and GSTM2-2, the predominant GST isoenzymes found within tumor cells. The experiments reported here indicate that brostallicin binds reversibly to both isoenzymes with K d values in the micromolar range (the affinity being higher for GSTM2-2). Direct evidence that both GSTP1-1 and GSTM2-2 isoenzymes catalyze the Michael addition reaction of GSH to brostallicin has been obtained both by an HPLC-MS technique and by a new fluorometric assay. We also saw the rapid formation of an intermediate reactive species, which is slowly converted into the final products. This intermediate, identified as the R-chloroamido derivative of the GSH-brostallicin adduct, is able to alkylate DNA in a sequence-specific manner and appears to be the active form of the drug. The kinetic behavior of the reaction between brostallicin and GSH, catalyzed by GSTP1-1, has been studied in detail, and a minimum kinetic scheme that suitably describes the experimental data is provided. Overall, these data fully support and extend the findings that brostallicin could be indicated for the treatment of tumor overexpressing the pi or mu class GST.

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Section: Resultssupporting

confidence: 70%

Role of Glutathione Transferases in the Mechanism of Brostallicin Activation

Pezzola

Antonini²,

Geroni

et al. 2009

Biochemistry

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“…Enzymatic and non‐enzymatic dynamic kinetic resolution (DKR) also represents an efficient approach to access enantioenriched α‐thiocarboxylic acids from esters, due to the ability of a C−S stereocentre in alpha to an electron withdrawing group to racemise under specific conditions. Examples of DKR of thioesters using hydrolase enzymes or thiocarboxylic acids using Nocardia diaphanozonaria cells have been reported by Drueckhammer and Otha, respectively, while Birman described a non‐enzymatic DKR of α‐thiocarboxylic acids using homo‐benzotetramisole ( S )‐HBTM . However, despite the excellent conversion and selectivity, all these methods show some limitations in terms of green chemistry, such as the need of additives and bases ( i Pr 2 NEt or trioctylamine) to promote the dynamic racemization of the substrates, the use of ester protecting groups with consequent production of waste in the chemical process and the need of oxygen‐free conditions to avoid the formation of side products.…”

Section: Figurementioning

confidence: 99%

Enantioselective Synthesis of α‐Thiocarboxylic Acids by Nitrilase Biocatalysed Dynamic Kinetic Resolution of α‐Thionitriles

Lauder

Anselmi

Finnigan

et al. 2020

Chemistry A European J

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The enantioselective synthesis of α‐thiocarboxylic acids by biocatalytic dynamic kinetic resolution (DKR) of nitrile precursors exploiting nitrilase enzymes is described. A panel of 35 nitrilase biocatalysts were screened and enzymes Nit27 and Nit34 were found to catalyse the DKR of racemic α‐thionitriles under mild conditions, affording the corresponding carboxylic acids with high conversions and good‐to‐excellent ee. The ammonia produced in situ during the biocatalytic transformation favours the racemization of the nitrile enantiomers and, in turn, the DKR without the need of any external additive base.

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“…There are another noticeable synthetic studies leading to chiral 2‐sulfanylpropanoic acid (unless otherwise noted), which are listed in chronologic order: (i) solid‐phase Mitsunobu inversion followed by NH 4 OH hydrolysis, (ii) S N 2 displacement of 2‐bromosuccinic acids derived from chiral aspartic acids specifically leading to 2‐sulfanylsuccinic acid, (iii) esterase‐catalyzed hydrolysis of 2‐( S ‐acetylsulfanyl)propanoate, (iv) S N 2 displacement using tritylthiol followed by reductive deprotection, (v) dynamic resolution method using N ‐methyl pseudoephedrine 2‐bromoesters leading to 2‐sulfanylpropane amide, (vi) Cu‐chiral spiro(bisoxazoline) complex‐catalyzed enantioselective carbenoid insertion into S–H bonds, and (vii) Rh 2 complexes and chiral spiro phosphoric acid‐catalyzed enantioselective S–H bond insertion …”

Section: Introductionmentioning

confidence: 99%

Chiral syntheses of methyl (R)‐2‐Sulfanylcarboxylic esters and acids with optical purity determination using HPLC

Sasaki

Tanabe

2018

Chirality

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Accessible chiral syntheses of 3 types of (R)-2-sulfanylcarboxylic esters and acids were performed: (R)-2-sulfanylpropanoic (thiolactic) ester (53%, 98%ee) and acid (39%, 96%ee), (R)-2-sulfanylsucciinic diester (59%, 96%ee), and (R)-2-mandelic ester (78%, 90%ee) and acid (59%, 96%ee). The present practical and robust method involves (i) clean S 2 displacement of methanesulfonates of (S)-2-hydroxyesters by using commercially available AcSK with tris(2-[2-methoxyethoxy])ethylamine and (ii) sufficiently mild deacetylation. The optical purity was determined by the corresponding (2R,5R)-trans-thiazolidin-4-one and (2S,5R)-cis-thiazolidin-4-one derivatives based on accurate high-performance liquid chromatography analysis with high-resolution efficiency. Compared with the reported method utilizing AcSCs (generated from AcSH and CsCO ), the present method has several advantages, that is, the use of odorless AcCOSK reagent, reasonable reaction velocity, isolation procedure, and accurate, reliable optical purity determination. The use of accessible AcSK has advantages because of easy-to-handle odorless and hygroscopic solid that can be used in a bench-top procedure. The Ti(OiPr) catalyst promoted smooth trans-cyclo-condensation to afford (2R,5R)-trans-thiazolidin-4-one formation of (R)-2-sulfanylcarboxylic esters with available N-(benzylidene)methylamine under neutral conditions without any racemization, whereas (2S,5R)-cis-thiazollidin-4-ones were obtained via cis-cyclo-condensation and no catalysts. Direct high-performance liquid chromatography analysis of methyl (R)-mandelate was also performed; however, the resolution efficiency was inferior to that of the thaizolidin-4-one derivatizations.

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Asymmetric syntheses of α-mercapto carboxylic acid derivatives by dynamic resolution of N-methyl pseudoephedrine α-bromo esters

Cited by 26 publications

References 14 publications

Role of Glutathione Transferases in the Mechanism of Brostallicin Activation

Role of Glutathione Transferases in the Mechanism of Brostallicin Activation

Enantioselective Synthesis of α‐Thiocarboxylic Acids by Nitrilase Biocatalysed Dynamic Kinetic Resolution of α‐Thionitriles

Chiral syntheses of methyl (R)‐2‐Sulfanylcarboxylic esters and acids with optical purity determination using HPLC

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