- Chiral combinatorial preparation and biological evaluation of unique ceramides for inhibition of sphingomyelin synthase
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Enantiomers or diastereomers of chiral bioactive compounds often exhibit different biological and toxicological properties. Here, we report the efficient synthesis of four stereoisomers of sphingosine and derivatization of unique chiral ceramides through a combinatorial chemistry by solid-phase activated resin ester. In addition, to test the effectivity of stereochemistry of ceramide, we demonstrated a cell-based assay of sphingomyelin synthase inhibition in the presence ofchiral unique ceramides, which suggested that libraries of this sort will be a rich source of biologically active synthetic molecules.
- Koolath, Sajeer,Monde, Kenji,Murai, Yuta,Suga, Yoshiko
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supporting information
(2020/02/04)
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- A diversity oriented synthesis of D-erythro-sphingosine and siblings
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An efficient building block-based synthetic protocol has been developed for the synthesis of 3-ketosphingoids with various chain lengths using cross metathesis of a Garner's aldehyde-derived α,β-unsaturated ketone as the key step. Stereoselective reduction of the biomimetic precursors thus obtained provided D-erythro-sphingosine and truncated anaogues in good overall yields.
- Ghosh, Amrita,Chattopadhyay, Shital K.
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p. 1139 - 1143
(2017/09/15)
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- Studies on the inhibition of sphingosine-1-phosphate lyase by stabilized reaction intermediates and stereodefined azido phosphates
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Two kinds of inhibitors of the PLP-dependent enzyme sphingosine-1-phosphate lyase have been designed and tested on the bacterial (StS1PL) and the human (hS1PL) enzymes. Amino phosphates 1, 12, and 32, mimicking the intermediate aldimines of the catalytic process, were weak inhibitors on both enzyme sources. On the other hand, a series of stereodefined azido phosphates, resulting from the replacement of the amino group of the natural substrates with an azido group, afforded competitive inhibitors in the low micromolar range on both enzyme sources. This similar behavior represents an experimental evidence of the reported structural similarities for both enzymes at their active site level. Interestingly, the anti-isomers of the non-natural enantiomeric series where the most potent inhibitors on hS1PL.
- Sanllehí, Pol,Abad, José-Luís,Bujons, Jordi,Casas, Josefina,Delgado, Antonio
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supporting information
p. 905 - 915
(2016/08/24)
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- METHODS FOR THE SYNTHESIS OF SPHINGOMYELINS AND DIHYDROSPHINGOMYELINS
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The present invention includes methods for the synthesis of sphingomyelins and dihydrosphingomyelins. The present invention also includes methods for the synthesis of sphingosines and dihydrosphingosines. The present invention further includes methods for the synthesis of ceramides and dihydroceramides.
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- METHODS FOR THE SYNTHESIS OF SPHINGOMYELINS AND DIHYDROSPHINGOMYELINS
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The present invention includes methods for the synthesis of sphingomyelins and dihydrosphingomyelins. The present invention also includes methods for the synthesis of sphingosines and dihydrosphingosines. The present invention further includes methods for the synthesis of ceramides and dihydroceramides.
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