- A facile regioselective synthesis of sphingosine 1-phosphate and ceramide 1-phosphate
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A novel regioselective synthesis of D-erythro-sphingosine 1-phosphate and D-erythro-ceramide 1-phosphate is described. The synthesis is based upon (1) in situ oxidative phosphorylation of the primary hydroxyl group in N-Boc-D-erythro-sphingosine utilizing trimethyl phosphite and carbon tetrabromide in pyridine, (2) chemoselective deprotection of the 1-O-phosphate and/or 2-amino groups with trimethylsilyl bromide or chloride, and (3) introduction of the fatty acid moiety into sphingosine 1-phosphate dimethyl ester via base-catalyzed N-acylation. (C) 2000 Elsevier Science Ltd.
- Szulc,Hannun,Bielawska
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Read Online
- 4'-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.
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Page/Page column 309-310
(2021/07/10)
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- 4'-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.
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(2019/10/01)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 67; 68
(2017/07/14)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 145
(2017/09/27)
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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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- NUCLEOTIDE AND NUCLEOSIDE COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 214
(2015/03/28)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to halogenated nucleosides optionally conjugated to a phosphorus oxide or pharmaceutically acceptable salts thereof. In certain embodiments, the disclosure relates to conjugate compounds or pharmaceutically acceptable salts thereof comprising an amino acid ester or a sphingolipid or derivative linked by a phosphorus oxide to a nucleotide or nucleoside. In certain embodiments, the disclosure contemplates pharmaceutical compositions comprising these compounds for uses in treating infectious diseases, viral infections, and cancer.
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Page/Page column 182-183
(2014/08/20)
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- Practical syntheses of sphingosine-1-phosphate and analogues
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Sphingosine-1-phosphate (S1P, 1) is a bioactive sphin- golipid metabolite involved in a variety of critical cellular processes including proliferation, survival, and migration. For this reason the stereoselective syntheses of S1P and analogues are of great interest. Based on L-serine as source of chirality we achieved practical routes to prepare S1P (1) and the aryl group containing analogues 3 and 4 in fair amounts. The crucial stages of the syntheses are: introduction of the required side chain by addition of appropriate organometal- lics to Garner's aldehyde and conversion of the primary alcohols into the corresponding phosphates. Georg Thieme Verlag Stuttgart.
- Blot, Virginie,Jacquemard, Ulrich,Reissig, Hans-Ulrich,Kleuser, Burkhard
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experimental part
p. 759 - 766
(2009/07/19)
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- A concise and scalable synthesis of high enantiopurity (-)-d-erythro- sphingosine using peptidyl thiol ester-boronic acid cross-coupling
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A short and efficient synthesis of high enantiopurity (-)-D-erythro- sphingosine has been achieved in 71% yield over 6 steps from N-BOC-L-serine. The key steps are high yield, racemization-free, palladium-catalyzed, copper(I)-mediated coupling of the thiophenyl ester of N-Boc-O-TBS L-serine with E-1-pentadecenyl boronic acid and the highly diastereoselective reduction of the resulting peptidyl ketone with LiAI(O-t-Bu)3H. By using this concise route (-)-D-erythro-sphingosine can be prepared on large scale and in high enantio- and diastereopurity (ee >99%, de up to 99%).
- Yang, Hao,Liebeskind, Lanny S.
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p. 2993 - 2995
(2008/02/09)
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- Versatile synthetic method for sphingolipids and functionalized sphingosine derivatives via olefin cross metathesis
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A highly efficient and versatile method for the synthesis of various sphingolipids, such as sphingomyelin, ceramide, sphingosine, sphingosine 1-phosphate, and functionalized sphingosine derivatives, was established by two types of combinations of the olefin cross metathesis reaction. One reaction was between the same olefin part and appropriate amino alcohols, which were prepared starting from N-Boc-L-serine, and the other was between appropriate olefins and the same amino alcohol.
- Yamamoto, Tetsuya,Hasegawa, Hiroko,Hakogi, Toshikazu,Katsumura, Shigeo
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p. 5569 - 5572
(2007/10/03)
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- SPHINGOMYELIN, INTERMEDIATES THEREOF AND METHODS FOR PREPARATION OF SAME
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The invention concerns novel oxazaphospholanes, cyclic and acyclic, and to their use in the synthesis of sphingomyelin and sphingomyelin analogous as well as to synthetic sphingomyelins obtained therefrom. One group of oxazaphospholane according to the invention has the general formula (1) disclosed herein. Specifically, the invention provides the 2S, 3R stereoisomers of the disclosed oxazaphospholanes and sphingomyelins and synthetic methods for their preparation.
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Page/Page column 21-22
(2010/02/13)
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- Synthesis and biological properties of novel sphingosine derivatives
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Sphingosine-1-phosphate (S-1P) derivatives such as threo-(2S,3S)-analogues, which are C-3 stereoisomers of natural erythro-(2S,3R)-S-1P, have been synthesized starting from l-serine or (1S,2S)-2-amino-1-aryl-1,3-propanediols (6). threo-(1S,2R)-2-Amino-1-aryl-3-bromopropanols (HBr salt) have also been prepared from 6. The threo-S-1Ps and the threo-amino-bromide derivatives have shown potent inhibitory activity against Ca2+ ion mobilization in HL60 cells induced by erythro-S-1P, suggesting that these compounds would compete with cell surface EDG/S1P receptors.
- Murakami, Teiichi,Furusawa, Kiyotaka,Tamai, Tadakazu,Yoshikai, Kazuyoshi,Nishikawa, Masazumi
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p. 1115 - 1119
(2007/10/03)
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- Syntheses of sphingosine-1-phosphate stereoisomers and analogues and their interaction with EDG receptors.
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Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding affinities to EDG-1, -3, and -5.
- Lim, Hyun Suk,Oh, Yong Seok,Suh, Pann Ghill,Chung, Sung Kee
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p. 237 - 240
(2007/10/03)
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- Synthesis and evaluation of a photolyzable derivative of sphingosine 1-phosphate-caged SPP
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The synthesis of a photolyzable sphingosine 1-phosphate derivative is reported via the reaction of N-(tert-butoxycarbonyl)-2-N,3-O-isopropylidenesphingosine 7 and bis(α-methyl-o-nitrobenzyl) N,N-diisopropylphosphoramidite. Stimulation of DNA synthesis upon illumination of caged SPP-loaded cells is also described.
- Qiao, Lixin,Kozikowski, Alan P.,Olivera, Ana,Spiegel, Sarah
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p. 711 - 714
(2007/10/03)
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- Enzymatic Preparation of Sphingosine 1-Phosphate
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Sphingosine 1-phosphate was prepared from sphingosine by two steps involving conversion of sphingosine to phosphatidylsphingosine catalyzed by phospholipase D and enzymatic hydrolysis of the intermediate to a diacyglycerol and sphingosine 1-phosphate with phospholipase C.
- Morigaki, Eiji,Miura, Yoshie,Takahata, Kyoya,Tada, Mikiro,Nakajima, Shuhei,Baba, Naomichi
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p. 774 - 775
(2007/10/03)
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- Efficient Synthesis of Sphingosine-1-phosphate, Ceramide-1-phosphate, Lysosphingomyelin, and Sphingomyelin
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Readily available D-erythro-azidosphingosine is transformed into 3-O-silyl-protected derivative 6.Reduction of the azido group afforded 3-O-silyl-protected sphingosine 7 which was either converted into N-Fmoc-protected derivative 8 or via N-acylation into ceramide derivatives 16 and 17, respectively.Treatment of 6, 8, and 16 with bis(2-cyanoethoxy)(diisopropylamino)phosphane as monofunctional phsophitylating agent, subsequent oxidation and then removal of the protective groups furnished azidosphingosine-1-phosphate (11), sphingosine-1-phosphate (2), and ceramide-1-phosphate (4), respectively.Treatment of 8 and 17 with bis(diisopropylamino)(2-cyanoethoxy)phosphane as bifunctional phosphitylating agent and then with choline afforded after oxidation and subsequent deprotection lysosphingomyelin (3) and sphingomyelin (1), respectively in high overall yields.All final products are sterochemically pure and possess D-erythro configuration in the sphingosine moiety. - Key Words: Phosphosphingolipids, synthesis of/ Azidosphingosine/ Azidosphingosine-1-phosphate/ Phosphitylation/ Sphingosine phosphates
- Kratzer, Bernd,Schmidt, Richard R.
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p. 957 - 964
(2007/10/02)
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- An efficient synthesis of sphingosine-1-phosphate
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The total synthesis of D-erythro-sphingosine-1-phosphate (2) via the phosphoramidite approach, starting from 3-O-TBDMS-protected D-erythro-azidosphingosine 3 is described.
- Kratzer, Bernd,Schmidt, Richard R.
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p. 1761 - 1764
(2007/10/02)
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