Chemistry and biochemistry of 1-desoxysphinganine 1-phosphonate (dihydrosphingosine-1-phosphonate)

Stoffel, Wilhelm; Grol, Michael

doi:10.1016/0009-3084(74)90011-5

Cited by 34 publications

(17 citation statements)

References 36 publications

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“…Therefore, we planned to synthesize the corresponding phosphonate 5, which is formally a derivative of 1-deoxysphingosine. Considering the distance between the func-nide led to the same C 19 cyclic urethane as obtained in the first route. Similarly, the C 18 cyclic urethane led to the other target molecule, namely sphingosine-1-phosphonate.…”

Section: Introductionmentioning

confidence: 76%

“…However, it was found that first reduction of the aldehyde group in 12 (Ǟ 5-deoxy-hexitol 13) and then 1,2-diol cleavage, which provides 3-O-unprotected 4-deoxypentaose 15, gives better results in the following chain extension. The (E)-selective Wittig reaction with 14 and (triphenyl)tetradecylphosphonium bromide with phenyllithium as base in the presence of lithium bromide gave C 19 Activation of the 3-OH group for azide introduction was carried out by O-mesylation (Ǟ 17). Treatment with sodium azide gave the 3-azido compound 18 (Scheme 3), which had the desired d-erythro-configuration of homosphingosine.…”

Section: Resultsmentioning

confidence: 99%

“…[16Ϫ18] The sphinganine analogue of 5 has been previously synthesized as racemic mixture [19] and also the syn-thesis of a protected derivative of 5 has been reported. [20] Syntheses of homosphinganine and homophytosphingosine analogs of 6 have also been recently reported.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Sphingosine‐1‐phosphonate and Homosphingosine‐1‐phosphonate

et al. 2005

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In the first approach to homosphingosine‐1‐phosphonate, D‐glucofuranose was selectively deoxygenated at C‐5. Bond cleavage between C‐1 and C‐2 afforded a 5‐deoxy‐D‐threo‐pentose intermediate. (E)‐Selective Wittig reaction with a C14‐chain gave a C19‐intermediate, which was readily transformed into homosphingosine. Formation of a cyclic urethane containing the 3‐amino and the 4‐hydroxy group of the C19‐intermediate permitted regioselective introduction of the phosphonate group at C‐1, thus affording the target molecule after deprotection. In a second and shorter route, C18‐sphingosine was converted to a cyclic urethane containing the 2‐amino and the 3‐hydroxy group of the C18‐chain. C1‐Chain extension by a hydroxymethyl group by introduction of cyanide led to the same C19 cyclic urethane as obtained in the first route. Similarly, the C18 cyclic urethane led to the other target molecule, namely sphingosine‐1‐phosphonate. The third and shortest route to homosphingosine‐1‐phosphonate could be based on regioselective 1‐O‐tosylation of 1,2,3‐(trihydroxy)octadec‐4‐ene. Transformation into a 1,2‐epoxide, then combination of C1‐chain extension and introduction of a phosphonate group with methylphosphonate as reagent, and finally azide introduction, led after functional group liberation to the target molecule. As shown, also truncated derivatives are readily accessible by this route. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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Section: Introductionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

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Synthesis of Sphingosine‐1‐phosphonate and Homosphingosine‐1‐phosphonate

et al. 2005

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“…Due to the rather high molecular mass of the investigated compounds resulting in additional molecular ion peaks, [4,5-2D]sphinganine-phosphate (M-l of PTC-derivative of 5 17 m/z) does not seem to be a good choice, but sphinganine-phosphonate (M-l of PTC-derivative of 499 m/z), first synthesized by Stoffel and Grol [22], might be a good candidate. Nevertheless, a rough estimation was obtained by spiking a duplicate biological extract with 2 nmoles of phosphorylated bases (1.6 nmol of sphingenine-phosphate plus 0.4 nmol of sphinganine-phosphate) and normalising the intensities of the m/z 513 peaks to that of other prominent peaks, representing one of the acyl-or alk(en)ylglycerophosphoethanolamines-derivatives.…”

Section: Resultsmentioning

confidence: 99%

On the presence of phosphorylated sphingoid bases in rat tissues A mass‐spectrometric approach

Veldhoven¹,

Ceuster²,

Rozenberg³

et al. 1994

FEBS Letters

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A simple and straightforward procedure to analyze phosphorylated sphingoid bases has been developed. After phase separation of lipid extracts under alkaline conditions, the compounds were quantitatively recovered in the aqueous upper phase. Following a clean-up of the aqueous phase on C18-solid phase extraction columns, the amino-group of the bases was derivatized by means of phenylisothiocyanate addition. FAB-MS of the phenylthiocarbamate derivatives of sphingenine-and sphinganine-phosphate in the negative mode revealed the expected pseudo-molecular ions (M-l) at 513 m/z and 515 m/z, respectively. Moreover, a typical fragmentation pattern, characterized by the loss of the phenylthiocarbamate moiety (m/z = 135), was observed. When applied to rat tissues, the presence of sphingenine-phosphate in brain, kidney and liver could easily be demonstrated. Highest levels, amounting to 5 nmol/g of wet weight, were present in brain.

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“…Recently, cis-4-methylsphingosine has been identified as a prodrug of a metabolically stable sphingosine-1-phosphate analogue (Section 4.1). Stoffel and Grol [217] have prepared a deoxysphinganine-1-phosphonate, which is a competitive inhibitor of the lyase (K i 5 mm, K m 16 mm). This extremely toxic compound is actually cleaved by the lyase, but at a rate that is slower by a factor of 10 than the natural phosphate.…”

Section: Inhibitors Of Sphingosine-1-phosphate Lyasementioning

confidence: 99%