- Convergent evolution of bacterial ceramide synthesis
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The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently. [Figure not available: see fulltext.]
- Ashley, Ben,Campopiano, Dominic J.,Chamberlain, Joshua D.,Coleman, Aimiyah,D’Emilia, Rachel,Fu, Larina,Guan, Ziqiang,Hansen, Matthew E. B.,Klein, Eric A.,Mohan, Eric C.,Nguyen, Hung,Stankeviciute, Gabriele,Tang, Peijun
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-
- Short asymmetric syntheses of sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] and its C(2)-epimer
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A short asymmetric synthesis of sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] and its C(2)-epimer is reported. The synthesis of sphinganine employs diastereoselective aminohydroxylation of tert-butyl 2-octadecenoate [conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide, then in situ enolate oxidation with (+)-camphorsulfonyloxaziridine (CSO)] and a stereospecific rearrangement of the resultant anti-α-hydroxy-β-amino ester into the corresponding anti-α-amino-β-hydroxy ester. Final hydrogenolysis and ester reduction completes the synthesis of the sphingoid base target. The synthesis of the C(2)-epimer follows a similar route, incorporating a diastereoselective reduction protocol to transform the anti-α-hydroxy-β-amino ester into its syn-α-hydroxy-β-amino ester counterpart.
- Da Silva Pinto, Solange,Davies, Stephen G.,Fletcher, Ai M.,Newton, Sophie K.,Roberts, Paul M.,Thomson, James E.
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supporting information
(2021/02/09)
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- Development of Asymmetric Transfer Hydrogenation with a Bifunctional Oxo-Tethered Ruthenium Catalyst in Flow for the Synthesis of a Ceramide (D-erythro-CER[NDS])
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The development of an efficient synthetic route for an optically active ceramide compound (d-erythro-CER[NDS]) is described. The route proceeds through asymmetric transfer hydrogenation in a pipes-in-series flow reactor with oxo-tethered ruthenium complex-catalyzed dynamic kinetic resolution. This synthesis was accomplished without any expensive reagents, and none of the intermediates required isolation. This resulted in a robust process that has been successfully run on a production scale.
- Touge, Taichiro,Kuwana, Masahiro,Komatsuki, Yasuhiro,Tanaka, Shigeru,Nara, Hideki,Matsumura, Kazuhiko,Sayo, Noboru,Kashibuchi, Yoshinobu,Saito, Takao
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supporting information
p. 452 - 461
(2019/01/04)
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- Multicomponent cis- and trans-Aziridinatons in the Syntheses of All Four Stereoisomers of Sphinganine
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All four stereoisomers of sphinganine can be synthesized by a multicomponent aziridination of an aldehyde, an amine and an α-diazo carbonyl compound mediated by a BOROX catalyst with high asymmetric induction (≥96% ee). The threo isomers are available from ring-opening of cis-aziridines by an oxygen nucleophile with inversion at the C-3 position and the erythro-isomers are likewise available from trans-aziridines.
- Zhou, Yubai,Mukherjee, Munmun,Gupta, Anil K.,Wulff, William D.
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p. 2230 - 2233
(2017/05/12)
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- 'Chiron' approach to stereoselective synthesis of sphinganine and unnatural safingol, an antineoplastic and antipsoriatic agent
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Highly stereoselective total syntheses of sphingoid bases, natural bioactive ceramide sphinganine 1 (with an overall yield of 33%) and unnatural antineoplastic and antipsoriatic drug safingol 17 (with an overall yield of 38%) starting from chirons 3,4,6-tri-O-benzyl-d-galactal and 3,4,6-tri-O-benzyl-d-glucal respectively have been demonstrated. Mitsunobu reaction and late stage olefin cross metathesis are utilized as important steps in order to complete the total synthesis of these sphingoid molecules.
- Das, Pintu,Kundooru, Somireddy,Shaw, Arun K.
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p. 14505 - 14511
(2016/02/19)
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- Synthesis and identification of unprecedented selective inhibitors of CK1ε
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A small and structure-biased library of enantiopure anti-β-amino alcohols was prepared in a straightforward manner by a simplified version of the Reetz protocol. Antiproliferative activity testing against a panel of five human solid tumor cell lines gave GI50 values in the range 1-20 μM. The reverse screening by computational methods against 58 proteins involved in cancer pointed to kinases as possible therapeutic target candidates. The experimental determination of the interaction with 456 kinases indicated that the compounds behave as selective CK1ε inhibitors. Our results demonstrate that the lead compound represents the first selective CK1ε inhibitor with proven antiproliferative activity in cancer cell lines.
- Silveira-Dorta, Gastón,Sousa, Inês J.,Fernandes, Miguel X.,Martín, Victor S.,Padrón, José M.
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p. 308 - 317
(2015/04/27)
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- Pd-catalyzed intramolecular aminohydroxylation of alkenes with hydrogen peroxide as oxidant and water as nucleophile
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A palladium-catalyzed intramolecular aminohydroxylation of alkenes was developed, in which H2O2 was applied as the sole oxidant. A variety of related alkyl alcohols could be successfully obtained with good yields and excellent diastereoselectivities, which directly derived from oxidation cleavage of alkyl C-Pd bond by H2O2. Facile transformation of these products provided a powerful tool toward the synthesis of 2-amino-1,3-diols and 3-ol amino acids. Preliminary mechanistic studies revealed that major nucleophilic attack of water (SN2 type) at high-valent Pd center contributes to the final C-O(H) bond formation.
- Zhu, Haitao,Chen, Pinhong,Liu, Guosheng
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supporting information
p. 1766 - 1769
(2014/03/21)
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- METHOD FOR PRODUCING HIGH-PURITY CERAMIDE
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Provided is a method for producing an optically active ceramide by an N-acylation (amidation) reaction of an optically active aminodiol, wherein a crude ceramide produced therein is purified by an industrially advantageous process. Namely, provided is a method for producing a high-purity ceramide that has high diastereo purity with high yield. A high-purity ceramide is produced by: a step wherein a ceramide represented by general formula (1) is produced by reacting an aminodiol with an alkyl ester having 1-5 carbon atoms of an aliphatic carboxylic acid having 12-24 carbon atoms, said aliphatic carboxylic acid optionally having a hydroxyl group, in a hydrocarbon solvent having 5-10 carbon atoms; and a step wherein an alcohol having 1-3 carbon atoms is added into the reaction mixture obtained in the preceding step, thereby causing crystals to precipitate. (In the formula, R1 represents an alkyl group which has 13-17 carbon atoms and optionally has a carbon-carbon unsaturated bond; R2 represents an alkyl group which has 11-23 carbon atoms and optionally has a hydroxyl group; and * represents an optically active state.)
- -
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Paragraph 0050
(2014/11/13)
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- Direct stereoselective synthesis of enantiomerically pure anti -β-amino alcohols
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Enantiomerically pure anti-β-amino alcohols were synthesized from optically pure α-(N,N-dibenzylamino)benzyl esters, derived from α-amino acids, by the sequential reduction to aldehyde with DIBAL-H at -78 °C and subsequent in situ addition of Grignard reagents. Besides anti-β-amino alcohols, anti-2-amino-1,3-diols and anti-3-amino-1,4-diols were obtained in good yields (60-95%) and excellent stereoselectivity (de > 95%). Our technique is compatible with free hydroxyl groups present in the substrate. To demonstrate the versatility of the method, spisulosine and sphinganine were synthesized in two steps from the appropriate N,N-dibenzyl-l-aminobenzyl ester in 42% and 45% yield, respectively.
- Silveira-Dorta, Gastón,Donadel, Osvaldo J.,Martín, Víctor S.,Padrón, José M.
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p. 6775 - 6782
(2014/08/18)
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- Synthesis of D-erythro-sphinganine through serine-derived α-amino epoxides
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A total synthesis of d-erythro-sphinganine [(2S,3R)-2-aminooctadecane-1,3- diol] starting from commercial N-tert-butyloxycarbonyl-l-serine methyl ester is described. The approach is based on the completely stereoselective preparation of an α-amino epoxide obtained by treating a protected l-serinal derivative with dimethylsulfoxonium methylide. The oxirane synthon is obtained with an anti configuration fitting the (2S,3R) stereochemistry of the 2-amino-1,3-diol polar head of d-erythro-sphinganine. The synthetic procedure afforded the target compound in a 68% overall yield based on the initial amount of the starting l-serine material.
- Siciliano, Carlo,Barattucci, Anna,Bonaccorsi, Paola,Di Gioia, Maria Luisa,Leggio, Antonella,Minuti, Lucio,Romio, Emanuela,Temperini, Andrea
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p. 5320 - 5326
(2014/06/23)
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- A general synthesis of sphinganines through multicomponent catalytic asymmetric aziridination
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A catalytic asymmetric synthesis of all four stereoisomers of sphinganine is described starting from hexadecanal. Utilizing either the (R) or (S) enantiomer of a BOROX catalyst, a multicomponent reaction of this aldehyde with an amine and ethyl diazoacetate gives rise to enantiomeric aziridine-2- carboxylates. Access to all diastereomers of sphinganine is realized upon ring opening of the enantiopure aziridine-2-carboxylate at the C-3 position by direct SN2 attack of an oxygen nucleophile, which occurs with inversion of configuration and by ring expansion of an N-acyl aziridine to an oxazolidinone and then hydrolysis. Overall, this process results in the formal ring opening of the aziridine with an oxygen nucleophile with retention of configuration. The synthesis of all four stereoisomers of sphinganine was achieved by multi-component asymmetric aziridination of hexadecanal. Complete stereocontrol is realized with the proper choice of the chirality of the BOROX catalyst and the introduction of an oxygen substituent at the 3-position of the aziridine with either retention or inversion. MEDAM = tetramethyldianisylmethyl. Copyright
- Mukherjee, Munmun,Zhou, Yubai,Gupta, Anil K.,Guan, Yong,Wulff, William D.
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supporting information
p. 1386 - 1390
(2014/03/21)
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- A General Synthesis of Sphinganines through Multicomponent Catalytic Asymmetric Aziridination
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A catalytic asymmetric synthesis of all four stereoisomers of sphinganine is described starting from hexadecanal. Utilizing either the (R) or (S) enantiomer of a BOROX catalyst, a multicomponent reaction of this aldehyde with an amine and ethyl diazoacetate gives rise to enantiomeric aziridine-2-carboxylates. Access to all diastereomers of sphinganine is realized upon ring opening of the enantiopure aziridine-2-carboxylate at the C-3 position by direct SN2 attack of an oxygen nucleophile, which occurs with inversion of configuration and by ring expansion of an N-acyl aziridine to an oxazolidinone and then hydrolysis. Overall, this process results in the formal ring opening of the aziridine with an oxygen nucleophile with retention of configuration.
- Mukherjee, Munmun,Zhou, Yubai,Gupta, Anil K.,Guan, Yong,Wulff, William D.
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supporting information
p. 1386 - 1390
(2015/10/05)
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- A highly concise and practical route to clavaminols, sphinganine and (+)-spisulosine via indium mediated allylation of α-hydrazino aldehyde and a theoretical insight into the stereochemical aspects of the reaction
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A conceptually different approach has been employed for the synthesis of 1,2-amino alcohols by proline-catalyzed α-amination of aldehyde and one-pot indium mediated allylation of the crude α-hydrazino aldehydes. DFT based quantum chemical calculations have been performed to obtain a quantitative explanation of the stereoselectivity of the reaction. The Royal Society of Chemistry 2013.
- Pandey, Menaka,Chowdhury, Partha Sarathi,Dutta, Achintya Kumar,Kumar, Pradeep,Pal, Sourav
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p. 15442 - 15448
(2013/09/02)
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- A stereocontrolled route to d-ribo-phytosphingosine and sphinganine from an achiral secondary homoallylic alcohol using Sharpless kinetic resolution
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A facile and efficient enantioselective route for the synthesis of d-ribo-phytosphingosine (1a) and sphinganine (1b) has been developed employing commercially available and cheap starting material trans-cinnamaldehyde 2. The synthetic strategy features the Sharpless kinetic resolution, regioselective epoxide opening and Wittig olefination as the key steps.
- Devi, Thongam Joymati,Saikia, Bishwajit,Barua, Nabin C.
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p. 3817 - 3822
(2013/06/27)
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- Stereoselective synthesis of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine via chiral tricyclic iminolactone
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The stereoselective syntheses of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine are described. The two continuous chiral centers within three target molecules were constructed through aldol reaction of chiral tricyclic iminolactone and aldehyde. Concise and efficient syntheses of (-)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine have been accomplished in practical four or three steps. The synthetic route featured in an aldol reaction between iminolactone 1a and 1b with aldehyde, which introduced the two continuous chiral centers within three target molecules. Copyright
- Li, Qiong,Zhang, Hongbo,Li, Chenguang,Xu, Pengfei
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supporting information
p. 149 - 153
(2013/08/24)
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- Stereoselective synthesis of N,O,O,O-tetraacetyl-D-ribo-phytosphingosine, N,O,O-triacetyl-D-erythro-sphingosine and N,O,O-triacetyl sphingonine from a common chiral intermediate derived from D-mannitol
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An efficient protocol for the stereoselective synthesis of tetraacetyl-D-ribo-hytosphingosine, triacetyl-D-erythro-sphingosine and triacetyl sphinganine has been devised from a common chiral intermediate derived from commercially available D-mannitol. The key steps involved are Sharpless epoxidation, Miyashita C(2) selective endo mode azide opening of 2,3-epoxy alcohol, and selective E-Wittig olefination. ARKAT-USA, Inc.
- Mettu, Ravinder,Thatikonda, Narendar Reddy,Olusegun, Oladoye Sunday,Vishvakarma, Ramesh,Vaidya, Jayathirtha Rao
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p. 421 - 436
(2013/11/06)
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- A highly stereoselective synthesis of glycidic amides based on a new class of chiral sulfonium salts: Applications in asymmetric synthesis
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A new type of chiral sulfonium salts that are characterized by a bicyclic system has been designed and synthesized from α-amino acids. Their corresponding ylides, which were prepared by basic treatment of the sulfonium salts, reacted smoothly with a broad array of simple and chiral aldehydes to provide trans-epoxy amides in reasonable to very good yields and excellent stereoselectivities (>98 %). The obtained epoxy amides were found to be useful as synthetic building blocks. Thus, they were reduced into their corresponding epoxy alcohols and subjected to oxirane-ring-opening reactions with different types of nucleophiles.
- Sarabia, Francisco,Vivar-García, Carlos,García-Castro, Miguel,García-Ruiz, Cristina,Martín-Gálvez, Francisca,Sánchez-Ruiz, Antonio,Chammaa, Samy
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supporting information
p. 15190 - 15201
(2013/01/15)
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- Total synthesis of symbioramide: A flexible approach for the efficient preparation of structural isomers
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A concise, enantioselective total synthesis of symbioramide, starting from simple achiral compounds and racemic α-amino-β-keto ester derivatives is reported. This highly flexible strategy allowed the efficient preparation of seven structural isomers of the natural product as well. The synthesis relies on a convergent route that involves the efficient stereoselective reduction of a α-keto-β-yne ester, and the dynamic kinetic resolution of an α-amino-β-keto ester through ruthenium-mediated asymmetric hydrogenation. Copyright
- Prevost, Sebastien,Ayad, Tahar,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie
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experimental part
p. 3213 - 3226
(2012/01/03)
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- Asymmetric synthesis of vicinal amino alcohols: Xestoaminol C, sphinganine and sphingosine
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The highly diastereoselective anti-aminohydroxylation of α,β-unsaturated esters, via conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide and subsequent in situ enolate oxidation with (+)-(camphorsulfonyl)oxaziridine, has been used as the key step in the asymmetric synthesis of N,O-diacetyl xestoaminol C (41% yield over 8 steps), N,O,O-triacetyl sphinganine (30% yield over 8 steps) and N,O,O-triacetyl sphingosine (30% yield over 7 steps). The Royal Society of Chemistry 2008.
- Abraham, Elin,Davies, Stephen G.,Millican, Nicholas L.,Nicholson, Rebecca L.,Roberts, Paul M.,Smith, Andrew D.
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supporting information; experimental part
p. 1655 - 1664
(2008/10/09)
-
- Stereoselective synthesis of safingol and its natural stereoisomer from d-glycals
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Efficient and convenient syntheses of (2S,3S)-safingol and its natural (2S,3R)-isomer have been developed from 3,4,6-tri-O-benzyl glycals. The key step is the one-pot reduction of an azide, saturation of the double bonds and debenzylation under catalytic hydrogenation.
- Kokatla, Hari Prasad,Sagar, Ram,Vankar, Yashwant D.
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p. 4728 - 4730
(2008/12/21)
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- Structural confirmation of the dihydrosphinganine and fatty acid constituents of the dental pathogen Porphyromonas gingivalis
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Porphyromonas gingivalis, a recognized periodontal pathogen, is a source of sphinganine bases, fatty acids, free ceramides as well as complex lipids that potentiate interleukin-1b-mediated secretory responses in gingival fibroblasts. The purpose of this study is the structural verification of the sphinganine bases and fatty acids that had been proposed as major components of the complex lipids found in P. gingivalis. The putative C17, C18, and C19 sphinganine bases were prepared from Garner's aldehyde (1) or from a protected serine Weinreb's amide (2). We confirmed that isobranched sphinganine bases are the major structural feature of the ceramides observed from P. gingivalis. We also prepared a C17 unsaturated fatty acid, along with an isobranched C17 3-hydroxy fatty acid, and determined that the major component of the active lipids was the latter. The Royal Society of Chemistry 2007.
- Mun, JiYoung,Onorato, Amber,Nichols, Frank C.,Morton, Martha D.,Saleh, Abdullah I.,Welzel, Morgan,Smith, Michael B.
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p. 3826 - 3833
(2008/10/09)
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- A general, efficient and stereospecific route to sphingosine, sphinganines, phytosphingosines and their analogs
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Sphingosine, sphinganines and phytosphingosines and their analogs were synthesized by an aldol condensation between an iminoglycinate bearing a (+)-(1R,2R,5R)-2-hydroxy-3-pinanone group as chiral auxiliary and an appropriate aldehyde. All condensations proceeded with excellent enantioselectivity to generate the (2S,3R)-d-erythro structures in good yields. The Royal Society of Chemistry 2006.
- Cai, Ye,Ling, Chang-Chun,Bundle, David R.
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p. 1140 - 1146
(2008/02/03)
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- CATIONIC CERAMIDES, AND ANALOGS THEREOF, AND THEIR USE FOR PREVENTING OR TREATING CANCER
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The present invention relates to cationic ceramides, their dihydro-analogs and aromatic analogs and their derivatives, comprising a pyridinium group. Also provided are methods for making cationic ceramides comprising a pyridinium group, and their use for treating or preventing diseases associated with cell overproliferation and sphingolipid signal transduction, such as cancer, inflammation, and stenosis. The compounds are also useful as mitochondritropic agents that are localized to mitochondria carrying with them chemical cargoes, such as drugs, or signaling molecules, such as fluorophores for probing organelle structure and functions.
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Page/Page column 71
(2008/06/13)
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- A highly efficient and direct approach for synthesis of enantiopure β-amino alcohols by reductive cross-coupling of chiral N-tert- butanesulfinyl imines with aldehydes
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A highly efficient and practical approach for the synthesis of optically pure β-amino alcohols by the SmI2-induced reductive cross-coupling of chiral N-tert-butanesulfinyl imines with aldehydes was developed. This method allows the preparation of a broad range of chiral β-amino alcohols, including functionalized ones under mild conditions. It provides a straightforward access to enantiopure β-amino alcohols that are widely applicable in asymmetric synthesis. Copyright
- Zhong, Yu-Wu,Dong, Yi-Zhou,Fang, Kai,Izumi, Kenji,Xu, Ming-Hua,Lin, Guo-Qiang
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p. 11956 - 11957
(2007/10/03)
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- Straightforward Synthesis of Sphinganines via a Serine-derived Weinreb Amide
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Sphinganines can be synthesized in just three steps from easily prepared serine-derived Weinreb amide 4. Pre-deprotonation of the acidic (N-H and O-H) protons of 4 allows for its efficient conversion to amino ketones 5. Such ketones can be selectively reduced to either erythro- or threo-sphinganines. Partially protected sphinganines 11 are also readily accessible in five steps from 4. Thus, Weinreb amide 4 represents one of the most versatile templates described to date for sphinganine synthesis.
- So, Regina C.,Ndonye, Rachel,Izmirian, Douglas P.,Richardson, Stewart K.,Guerrera, Robyn L.,Howell, Amy R.
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p. 3233 - 3235
(2007/10/03)
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- Synthesis of D-erythro-dihydrosphingosine and D-xylo-phytosphingosine from a serine-derived 1,5-dioxaspiro[3.2]hexane template
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Matrix presented A serine-derived 1,5-dioxaspiro[3.2]hexane template is shown to be a useful precursor for both aminodiol and aminotriol sphingoid bases by its conversion to D-erythro-dihydrosphingosine and D-xylo-phytoshingosine.
- Ndakala, Albert J.,Hashemzadeh, Mehrnoosh,So, Regina C.,Howell, Amy R.
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p. 1719 - 1722
(2007/10/03)
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- Antifungal activity of bifunctional sphingolipids. Intramolecular synergism within long-chain alpha,omega-bis-aminoalcohols.
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The in vitro antifungal activity of a series of alpha,omega-bifunctionalized aminoalcohols against Candida glabrata was measured. The dimeric bi-functionalized lipids exhibited activity about approximately 10-fold higher higher than D-sphingosine, which is a larger factor than expected from the simple additive effects of vicinal aminoalcohols groups.
- Nicholas, Gillian M,Li, Ronghua,MacMillan, John B,Molinski, Tadeusz F
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p. 2159 - 2162
(2007/10/03)
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- Stereoselective synthesis of D-erythro- and L-threo-sphinganines via palladium-catalyzed equilibration and Suzuki coupling
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The Pd-catalyzed isomerization of 5-vinyloxazolines was utilized for the stereoselective synthesis of D-erythro- and L-threo-spinganine triacetate. A hydroboration/Suzuki coupling sequence was employed to elongate the hydrophobic chain.
- Cook, Gregory R.,Pararajasingham, Ketheeswaran
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p. 9027 - 9029
(2007/10/03)
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- A highly efficient and versatile synthesis of D- and L-erythro-sphinganine
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An expedient convergent synthesis of naturally occurring C18-erythro-sphinganine (dihydrosphingosine, 1) is presented. Chiral protected 2-amino-1,3,4-butanetriol 6 is readily transformed into oxazolinyl oxirane building block 9, which is alkylated by a copper mediated SN2 type nucleophilic substitution with tetradecylmagnesium chloride. This method promises to be suited for largescale syntheses and for rapid access to sphinganine analogues modified in the backbone.
- Hertweck,Sebek,Svato?
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p. 1965 - 1967
(2007/10/03)
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- A stereoselective synthesis of dihydrosphingosine
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A highly enantioselective synthesis of D-(+)-erythro-dihydrosphingosine (sphinganine) as its triacetate derivative 10, starting from palmityl alcohol (3) and employing the Sharpless asymmetric dihydroxylation as the key step, is described.
- Fernandes, Rodney A.,Kumar, Pradeep
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p. 3447 - 3449
(2007/10/03)
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- Enantiodivergent biosynthesis of the dimeric sphingolipid oceanapiside from the marine sponge Oceanapia phillipensis. Determination of remote stereochemistry
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The absolute stereochemistry of oceanapiside, an antifungal α,ω-bis- aminohydroxylipid with four stereogenic centers from the marine sponge Oceanapia phillipensis Dendy, 1895, has been obtained as 2S,3R,26R,27R from development and application of a general CD method based on superposition of additive exciton couplings in perbenzoyl derivatives of bis-amino alcohols. The method allows simultaneous determination of the local relative configuration at each of the termini of the long chain bis-aminolipid and also relates the absolute configuration of the two remote termini. Oceanapiside contains erythro and threo relative configurations at C1,2 and C26,27, respectively, but opposite absolute configurations at the amino substituted carbons C2 and C27 which implies an enantiodivergent biogenesis formally derived from both D- and L-amino acids.
- Nicholas, Gillian M.,Molinski, Tadeusz F.
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p. 4011 - 4019
(2007/10/03)
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- A Stereocontrolled, Efficient Synthetic Route to Bioactive Sphingolipids: Synthesis of Phytosphingosine and Phytoceramides from Unsaturated Ester Precursors via Cyclic Sulfate Intermediates
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An efficient and highly enantioselective method for the preparation of D-ribo- and L-lyxo-phytosphingosines (1a,b, respectively) and phytoceramides (2a,b) has been developed. The key steps in the syntheses are as follows: (i) osmium-catalyzed asymmetric dihydroxylation of 4-O-protected (E)-α,β-unsaturated ester 5 (generated by dihydroxylation of 1-hexadecene, followed by oxidation to the aldehyde and Horner-Wadsworth-Emmons olefination), (ii) conversion to cyclic sulfate intermediate 7, and (iii) regioselective α-azidation of 7. Reduction of 4-O-protected 2-azido ester 8 via α-azidolactone 9 afforded phytosphingosine 1a. Staudinger reduction of the azido group of 8, followed by in situ N-acylation in aqueous media and reduction of the ester functionality with NaBH4/LiBr, provided phytoceramide 2a. By using a similar approach, phytosphingosine 1b was synthesized. D-erythro-4,5-Dihydrosphingosine 1c and D-erythro-4,5-dihydroceramide 2c were synthesized in high yield from 1-hexadecanol via cyclic sulfate intermediate 15. The desired configurations at C-2, C-3, and C-4 of the sphingoid chain can be accessed readily by the route described here.
- He, Linli,Byun, Hoe-Sup,Bittman, Robert
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p. 7618 - 7626
(2007/10/03)
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- A short and efficient stereoselective synthesis of dihydrosphingosine triacetate
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A highly enantiocontrolled synthesis of D-(+)-erythro-dihydrosphingosine (sphinganine) triacetate is described using the Sharpless asymmetric dihydroxylation and the regiospecific nucleophilic opening of a cyclic sulfite as key steps. (C) 2000 Elsevier Science Ltd.
- Fernandes, Rodney A.,Kumar, Pradeep
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p. 4797 - 4802
(2007/10/03)
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- Use of heterocycles as chiral ligands and auxiliaries in asymmetric syntheses of sphingosine, sphingofungins B and F
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D-erythro-Sphingosine and its derivatives (dihydrosphingosine, cissphingosine, etc.), sphingofungins B and F have been synthesized from simple achiral compounds using heterocyclic compounds as key chiral ligands and auxiliaries. 5-Benzyloxy-4-ethynyl-2,2-dimethyl-1,3-dioxane (5 or 5- ent), a key intermediate for the synthesis of sphingosine family, was prepared from 1-trimethylsilylpropinal and ketene silyl acetal 4 using a Sn(OTf)2-chiral ligand 1 or 1-ent-catalyzed asymmetric aldol reaction. Sphingosine and its derivatives were readily prepared from 5 according to standard transformation. The chiral hydrophobic side chain (6) of sphingofungin B was synthesized using a catalytic asymmetric aldol reaction using chiral ligand 1-ent. Another key step in the total synthesis of sphingofungin B was a condensation of chiral aldehyde 7 and chiral heterocycle 2. Similarly, the reaction of chiral aldehyde 8 with heterocycle 3 was a key step for the synthesis of sphingofungin F. Highly diastereoselective reactions proceeded smoothly in both cases to afford the corresponding adducts in high yields.
- Kobayashi, Shu,Furuta, Takayuki
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p. 10275 - 10294
(2007/10/03)
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- Stereoselective synthesis of sphinganine by means of modified asymmetric borane reduction
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Efficient stereoselective synthesis of sphinganine by the asymmetric borane reduction of α-oxoketoxime trityl ethers is described. Both threo and erythro sphinganine could be obtained with high enantioselectivities by using borane-N,N-diethylaniline complex as a reducing agent.
- Masui, Moriyasu,Shioiri, Takayuki
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p. 5199 - 5200
(2007/10/03)
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- Synthesis of Sphingosines, 11 - Convenient Synthesis of Phytosphingosine and Sphinganine from D-Galactal and D-Arabitol
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3,4,6-Tri-O-benzyl-D-galactal (3) was directly converted into 3,4,6-tri-O-benzyl-2-deoxy-D-galactose (5).Wittig reaction of 5 with alkyltriphenylphosphonium salts in the presence of n-butyllithium as the base afforded olefins 6a, b which could be readily transformed into phytosphingosines 1a, b via different routes; (i) at first group introduction and then double bond and protective group removal, and azido group generation via hydrogenation; (ii) 2-O-mesylation, then double bond and benzyl group removal via hydrogenation, and finally nitrogen introduction; (iii) selective double bond hydrogenation, then nitrogen introduction, and finally benzyl group removal and amino group generation via hydrogenation.Wittig reaction of 5 with alkyltriphenylphosphonium salt in the presence of potassium tert-butoxide as the base afforded diene 7a which proved to be a convenient precursor for sphinganine syntheses; thus, 2-O-mesylation, then double bond and benzyl group removal via hydrogenation and 1,3-O-acetylation, and finally nitrogen introduction and de-O-acetylation afforded 23a.Based on the convenient transformation of D-arabitol into the 1,3-O-benzylidene derivative 25 a further phytosphingosine synthesis is outlined. - Key Words: Phytosphingosine / Sphinganine / Galactal / 2-Deoxy-D-galactose / D-Arabitol / Carbohydrates
- Wild, Robert,Schmidt, Richard R.
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p. 755 - 764
(2007/10/02)
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- Synthesis of Sphingosine Relatives, XIV. A New Synthesis of Symbioramide, a Ca(++)-ATPase Activator from Symbiodinium sp.
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Symbioramide was synthesized from D-erythro-dihydrosphingosine (19) and (R,E)-2'-tert-butyldimethylsilyloxy-3'-octadecenoic acid (14), which was prepared from (E)-2-octadecen-1-ol (4) by employing the Sharpless asymmetric epoxidation.The (2S,2'S,3R,3'E)-isomer 28 of 1 was also synthesized to further confirm the structure of 1. - Key Words: Ca(++)-ATPase activator / Ceramides / Marine natural products / Sphingosines / Symbioramide
- Mori, Kenji,Uenishi, Keiji
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- Total Synthesis of Symbioramide, a Novel Ca(2+)-ATPase Activator from Symbiodinium sp.
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The first total synthesis of symbioramide 1 has been accomplished by the coupling of D-erythro-dihydrosphingosine with an unusual, chiral α-hydroxy-β,γ-unsaturated fatty acid prepared from L-ascorbic acid, and simultaneously established the complete stereostructure of 1 to be (2S,2'R,3R,3'E)-N-(2'-hydroxyoctadec-3'-enoyl)dihydrosphingosine.
- Yoshida, Jun,Nakagawa, Masako,Seki, Hiroko,Hino, Tohru
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p. 343 - 350
(2007/10/02)
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- Syntheses of two pairs of enantiomeric C18-sphingosines and a palmitoyl analogue of gaucher spleen glucocerebroside
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Sixteen kinds of chiral C4-epoxides [(-)-10a-d,(+)-10a-d,(-)-11a-d,(+)-11a-d], which are synthons in our synthetic strategy for complex lipids, have been prepared from (2Z)-2-butene-1,4-diol (6) by employing a Sharpless asymmetric epoxidation. By using the chiral C4-epoxides [(+)-10a,(-)-10a,(-)-11a,(+)-11a] as starting compounds, two pairs of enantiomeric (D-erythro, L-erythro, D-threo, and L-threo)-C18-sphingosines (1, 2, 3, 4) have been synthesized via a regioselective ring-opening of the epoxide ring with azide anion followed by reduction of the azide group to an amino group and a Wittig reaction. Furthermore, D-erythro-C18-sphingosine (1) has been converted to a palmitoyl analogue (5a) of Gaucher spleen glucocerebroside (5) through a reaction pathway including successive condensations with palmitic acid and D-glucose.
- Shibuya,Kawashima,Narita,Ikeda,Kitagawa
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p. 1154 - 1165
(2007/10/02)
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- First Total Synthesis of Symbioramide, a Novel Ca2+-ATPase Activator from Symbiodinium sp.
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The first total synthesis of symbioramide (1) is described and simultaneously established the complete stereostructure of 1 to be (2S,3R,2'R,3'E)-N-(2'-hydroxy-3'-octadecenoyl)-dihydrosphingosine.
- Nakagawa, Masako,Yoshida, Jun,Hino, Tohru
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p. 1407 - 1410
(2007/10/02)
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- Directed Openings of 2,3-Epoxy Alcohols via Reactions with Isocyanates: Synthesis of (+)-erythro-Dihydrosphingosine
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Two methods for the synthesis of 2-(N-alkylamino) 1,3-diols from 2,3-epoxy alcohols are described.In one procedure (method A) an epoxyurethane (5, 8, 11, 14, 16) prepared from the corresponding epoxy alcohol by standard procedures is cyclized to a 2-oxazolidinone derivative (6, 9, 12, 15, 17) in 81-90percent yield by treatment with NaH in THF or NaOMe in MeOH.The second procedure (method B) involves treatment of the epoxy alcohol (4, 7, 10, 13, 24) with benzyl isocyanate, an NH3 synthetic equivalent, and NaH in THF at reflux.Hydrolysis of the crude isoxazolidinones by exposure to LiOH in EtOH at reflux smoothly affords 2-(N-benzylamino) 1,3-diols (22, 23, 30, 31) in 68-72percent overall yield.These procedures are highly regioselective; products resulting from intramolecular addition of the urethane nitrogen atom to the epoxide β-position were not detected.This methodology was applied to a short, highly stereoselective synthesis of (+)-erythro-dihydrosphingosine (26) from palmitic aldehyde ( 47-54percent overall yield).
- Roush, William R.,Adam, Michael A.
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p. 3752 - 3757
(2007/10/02)
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- Synthesis of Dihydrosphingosine
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A conversion of (S)-3-acetoxy-2-phthalimidopropanal into dihydrosphingosine is described.
- Saitoh, Yutaka,Moryama, Yoshihiko,Hirota, Hiroshi,Takahashi, Takeyoshi
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p. 1783 - 1784
(2007/10/02)
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