A Sulfuryl Group Transfer Strategy to Selectively Prepare Sulfated Steroids and Isotopically Labelled Derivatives

Alshehri, Jaber Abdullah; Gill, Deborah; Jones, Alan M.

doi:10.3389/fmolb.2021.776900

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…With the exception of the bisalcohol (20) modest to good conversions to the aldehyde was found. It should be noted that in these cases a large disparity between the percentage conversion to the diagnostic aldehyde 1 H NMR spectral signal (9-11 ppm) and the isolated yield was found in all cases, returning at best a 31% isolated yield (18).The low boiling point of the aldehyde led to some losses in isolation (and solvent contamination of the final products), combined with the highly reactive nature of the aldehyde product leading to product degradation. Methods to improve isolation included the use of the sodium bisulfite isolation method [44] and preparative TLC over extensive column chromatography.…”

Section: Resultsmentioning

confidence: 82%

“…[5][6][7][8][9][10][11][12][13][14][15][16] We have recently discovered a novel sulfuryl group transfer reagent with improved organic solubility properties for sulfation of organic substrates, tributylsulfoammonium betaine (TBSAB). [17][18][19][20][21][22][23] We identified TBSAB contains a novel N-S bond (not a dative complex as per Py-SO3) through single crystal X-ray crystallography. [22] The use of TBSAB would be detrimental for purification purposes in this chemistry when not isolating a sulfated intermediate due to its enhanced lipophilicity.…”

Section: Introductionmentioning

confidence: 99%

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A modified all-in-one DMSO-activating and base releasing reagent for the Parikh-Doering-type benzylic oxidation reaction

Xie,

Male,

Jones

2024

Preprint

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The Parikh-Doering reaction, an example of the series of DMSO-mediated selective oxidation named reaction family, finds ongoing use in natural product synthesis when mild oxidative reaction conditions are required. The original conditions require the use of Py-SO3 and NEt3 along with DMSO and DCM. As part of our ongoing interest in sulfating agents, we recently disclosed the novel structure of tributylsulfoammonium betaine (TBSAB) that has a formal N-S bond (not dative) and may indicate that other N(sp3) amine-SO3 complexes have been misassigned. Herein, we explore a commercial sulfating agent, triethylamine-sulfur trioxide complex, as an all-in-one sulfation and base releasing reagent for a modified Parikh-Doering reaction. Single crystal X-ray crystallography further confirms our hypothesis than triethylamine-sulfur trioxide complex exists as triethylsulfoammonium betaine (TESAB). Employing TESAB as an all-in-one reagent, a range of primary and secondary alcohols were screened for competency. Reactivity was observed for the first time with 1) a non Py-SO3 sulfating agent and 2) without the need for additional base. Moderate to good yields of aldehydes and ketones can be prepared in an atom-efficient improvement with concomitant removal of toxic pyridine by-products.

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Section: Resultsmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

A modified all-in-one DMSO-activating and base releasing reagent for the Parikh-Doering-type benzylic oxidation reaction

Xie,

Male,

Jones

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The recently developed sulfation by tributylsulfoammonium betaine (TBSAB; SO 3 ·NBu 3 ) [ 19 ] has proven effective on a variety of phenolic substrates, including steroids [ 34 ] and phenolic acid salts and esters [ 35 ]. A modification of this method uses a SO 3 -pyridine complex, followed by the addition of tributylamine [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis

Kolaříková

Brodsky

Petrásková

et al. 2022

IJMS

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Phenolic acids are known flavonoid metabolites, which typically undergo bioconjugation during phase II of biotransformation, forming sulfates, along with other conjugates. Sulfated derivatives of phenolic acids can be synthesized by two approaches: chemoenzymatically by 3′-phosphoadenosine-5′-phosphosulfate (PAPS)-dependent sulfotransferases or PAPS-independent aryl sulfotransferases such as those from Desulfitobacterium hafniense, or chemically using SO3 complexes. Both approaches were tested with six selected phenolic acids (2-hydroxyphenylacetic acid (2-HPA), 3-hydroxyphenylacetic acid (3-HPA), 4-hydroxyphenylacetic acid (4-HPA), 3,4-dihydroxyphenylacetic acid (DHPA), 3-(4-hydroxyphenyl)propionic acid (4-HPP), and 3,4-dihydroxyphenylpropionic acid (DHPP)) to create a library of sulfated metabolites of phenolic acids. The sulfates of 3-HPA, 4-HPA, 4-HPP, DHPA, and DHPP were all obtained by the methods of chemical synthesis. In contrast, the enzymatic sulfation of monohydroxyphenolic acids failed probably due to enzyme inhibition, whereas the same reaction was successful for dihydroxyphenolic acids (DHPA and DHPP). Special attention was also paid to the counterions of the sulfates, a topic often poorly reported in synthetic works. The products obtained will serve as authentic analytical standards in metabolic studies and to determine their biological activity.

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“…[43][44] TBSAB has also been used for the chemoselective sulfation of steroids affording the corresponding sulfated molecules such as, estrone sulfate, pregnenolone sulfate, and pregnanediol sulfate. [45] TBSAB has also found use as a reagent to install aniline N-sulfamates prior to their intermolecular rearrangement. [46] A summary of the scope and range of sulfated molecules achievable with Bu3NSO3 complex are listed in Table 3.…”

Section: Tributylsulfoammonium Betaine (Tbsab)mentioning

confidence: 99%

Approaches to the Sulfation of Small Molecules: Current Progress and Future Directions

Alshehri,

Jones

2024

Preprint

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Sulfation is one of the most important modifications that occur to a wide range of bioactive small molecules including polysaccharides, proteins, flavonoids, and steroids. In turn, these sulfated molecules have significant biological and pharmacological roles in diverse processes including cell signalling, modulation of immune and inflammation response, anti-coagulation, anti-atherosclerosis, and anti-adhesive properties. This essay summarises the most encountered chemical sulfation methods of small molecules. Sulfation reactions using sulfur trioxide amine/amide complexes are the most used method for alcoholic or phenolic groups in carbohydrates, steroids, proteins, and aliphatic or alicyclic scaffolds. Despite the effectiveness of these methods, they suffer from some issues such as multiple-purification steps, toxicity issues (eg pyridine contamination), purification challenges, stoichiometric excess of reagents which leads to increase of a reaction cost, and intrinsic stability issues of both the reagent and product. Recent advances including SuFEx, the Malins in situ reagent approach and TBSAB show the widespread appeal of novel sulfating approaches that will enable a larger exploration of the field in the years to come by simplifying the purification and isolation to access bespoke sulfated small molecules.

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A Sulfuryl Group Transfer Strategy to Selectively Prepare Sulfated Steroids and Isotopically Labelled Derivatives

Cited by 6 publications

References 26 publications

A modified all-in-one DMSO-activating and base releasing reagent for the Parikh-Doering-type benzylic oxidation reaction

A modified all-in-one DMSO-activating and base releasing reagent for the Parikh-Doering-type benzylic oxidation reaction

Sulfation of Phenolic Acids: Chemoenzymatic vs. Chemical Synthesis

Approaches to the Sulfation of Small Molecules: Current Progress and Future Directions

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