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A short enantioselective synthetic route to the cytotoxic marine natural product jaspine B has been developed. A chiral non-racemic primary α-allenol, obtained from pentadecanal, gave access to an enantioenriched 2-tetradecyl-2,5-dihydrofuran as key intermediate. A stereodivergent functionalization of this dihydrofuran allowed access in a few steps to jaspine B and its 4-epimer.

By utilizing an l -serine-derived bicyclic lactone as an advanced chiral building block, a short synthetic route to the cytotoxic marine natural product jaspine B has been developed. Targeting structure–activity relationship investigations, the synthetic route has also been utilized for the synthesis and cytotoxicity evaluation of strategically modified jaspine B analogues. In addition, a previously reported synthesis of the title natural product from our research has been reinvestigated to clarify the sterochemical assignment.

The practical syntheses of pachastrissamine (jaspine B), 2-epi-pachastrissamine, and the 2-epimer of the pyrrolidine analogue were accomplished via the stereoselective reduction of an allylketone derived from commercially available diethyl D-tartrate and the cross-metathesis of an allyltetrahydrofuran or allypyrrolidine with 1-tridecene as key steps.

A versatile synthetic procedure for a sulfur analogue of pachastrissamine (jaspine B), which involves the tandem thiolation-cyclization of a 1,4-ditosylate to construct a tetrahydrothiophene ring, was developed. Nucleophilic amino substitution of a tetrahydrothiophene-4-sulfonate with unexpected retention of the configuration afforded the sulfur analogue of 4-epi-pachastrissamine.

The first biologically relevant clickable probe related to the antitumor marine lipid jaspine B is reported. The concise synthetic route to both enantiomers relied on the supercritical fluid chromatography (SFC) enantiomeric resolution of racemic materials. The eutomeric dextrogyre derivative represents the first jaspine B analogue with enhanced cytotoxicity with IC50 down to 30 nm. These enantiomeric probes revealed a chiralitydependent cytoplasmic imaging of U2OS cancer cells by in situ click labeling.

A short, 8-step synthesis of the marine natural product pachastrissamine has been developed that relies on a diastereoselective aldol reaction between a suitably protected hydantoin and an optically enriched α-chloroaldehyde. This synthetic route provides new opportunities for exploring structure activity relationships within this family of natural products.

The stereoselective synthesis of Jaspine B has been achieved from easily available ( S )-Garner’s aldehyde. The trisubstituted tetrahydrofuran core of Jaspine B was constructed by utilizing a diastereoselective iodocyclization as the key step. Deiodination and debenzylation were performed in a single step by using n -Bu 3 SnH and ABCN as a conjugate catalyst system. The in vitro cytotoxicity of compounds 1 and 1a against 3 human cancer cell lines-A549 (lung), MCF7 (breast), and KB (oral); and a non-cancer cell line (NIH3T3) was determined by sulphorhodamine B based assay.

Conformationally constrained sphingolipids such as anhydrophytosphingosines represented by jaspine B (also known as pachastrissamine) and its stereoisomers have become an attractive and timely target for total synthesis due to their significant biological activity as well as the unique structures. This review article describes the biological activity and chemistry of the natural jaspine B and its seven stereoisomers.

(R)-tert-butyl 4-formyl-2,2-dimethylthiazolidine-3-carboxylate is an imntermediate of S-jaspine B known as a potential substitution of pachastrissamine (jaspine B) which shows effective biological activity. Herein we describe an elegant straightforward synthetic path for this attractive molecule intermediate. Introduction Jaspine B (1) (showed in Figure 1) is a natural occurring product with three chiral centers in a tetrahydrofuran ring. Since jaspine B has been firstly isolated form Okinawan marine sponge Pachastrissa sp. in 2002 by Higa and coworkers [1], many investigations has been attached to this attractive molecule and its analogs [2-4]. Jaspine B was observed to display remarkable cytotoxicity against several kinds of cancer cell lines. Andrieu-Abadie and co-workers reported that jaspine B induces apoptotic cell death in melanoma cells through a caspase-dependent pathway [5]. A lot of literatures have reported the syntheses of jaspine B [6-9].

Efficient, stereochemically unambiguous, total syntheses of pachastrissamine and its 2- epi -congener from the readily available common precursor (1 R )-1-{(4 S ,5 S )-2-oxo-4-[(trityl­oxy)methyl]-1,3-oxazolidin-5-yl}pentadecyl methanesulfonate are reported. Syntheses of (3a S ,6 R ,6a R )- and (3a S ,6 S ,6a R )-6-tetradecylhexahydro-2 H -cyclopenta[ d ][1,3]oxazol-2-one by this route have unambiguously resolved a dispute over the structures of these products.

Concise and efficient syntheses of d - lyxo -phytosphingosine and pachastrissamine were achieved utilizing a chiral oxazine. The key features in these strategies are the stereoselective intramolecular oxazine formation catalyzed by palladium(0), and intermolecular olefin cross-metathesis.

The highly stereoselective Grignard addition on chiralimine 8 and opening of chiral epoxide 9 with Grignard reagent have been used as key steps in the stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B) and N , O , O , O -tetra-acetyl d - lyxo -phytosphingosine.

The total synthesis of the enantiomer of the tetrahydrofuran containing natural product Jaspine B is reported. The key reactions in the synthesis include formation of the tetrahydrofuran unit by an acid mediated Williamson etherification and a subsequent elaboration with an olefin cross metathesis reaction.

( R )-2,3-Cyclohexylideneglyceraldehyde 1 has been found to be a good substrate for nitroaldol reaction both in anhydrous and aqueous conditions. In both cases, the reaction took place with good substrate-controlled anti -selectivity. The major nitroaldol product 2b has been exploited to develop a simple and stereoselective synthesis of jaspine B X . Also, beginning with nitroaldol reaction of 1 , this route presents a simple approach for the stereoselective preparation of ( anti – anti - 5 , 7 )- and ( syn – syn - 9 , 11 , 12 )-1,2,3,4-alkanetetrols, each possessing three contiguous oxygenated stereocenters.

The synthesis of the C2 and C3 epimer and also the enantiomer of jaspine B from D-glucose is reported. The cytotoxicity of these isomers along withjaspine B and its C2 epimer on MCF7 cells has been correlated with commercially available anticancer drug Epirubicin.

The synthesis of isomeric jaspines (anhydro phytosphingosines), arising from intramolecular cyclization of the corresponding phytosphingosines with different configurations at C3 and C4 positions of the sphingoid backbone, is reported. Natural jaspine B is the most cytotoxic isomer on A549 cells and it induces cell death in a dose-dependent manner. The cytotoxicity of jaspine B has been correlated with a significant increase of intracellular dihydroceramides, which seem to play an active role in autophagy.

A new route for the synthesis of the cytotoxic anhydrosphingosine pachastrissamine has been developed. [3.3] Sigmatropic rearrangement of an allyl cyanate was employed to construct the allyl amine moiety in 2 from the chiral C-4 unit 3. Oxidative cleavage of the double bond in 2, followed by THF ring formation furnished the target pachastrissamine.

The asymmetric synthesis of jaspine B (pachastrissamine) using a (R)-proline-catalyzed enantioselective aldol reaction as key step is described. Jaspine B was synthesized from the commercially available and inexpensive 1-pentadecanal and the dihydroxyacetone equivalent 2,2-dimethyl-1,3-dioxan-5-one in nine steps, good overall yield (23.6%) and excellent stereoselectivity (de >98%, ee = 95%).

A short total synthesis of the cytotoxic natural product pachastrissamine is described. The synthesis includes eight steps starting from Garner’s aldehyde and proceeds in 20% overall yield. Pd(0)-mediated intramolecular cyclisation and Ru-mediated cross-metathesis are the key reactions in this sequence.

A novel stereoselective synthesis of pachastrissamine (jaspine B), starting from commercially available 1-pentadecanol is described. Sharpless asymmetric dihydroxylation and a chelation controlled vinyl Grignard reaction are the key steps in this synthetic strategy.

A practically efficient stereoselective synthesis of pachastrissamine (jaspine B) is described starting from 3,4,6-tri-O-benzyl- d -galactal in eight steps and 11% overall yield.

Synthesis of both enantiomers of pachastrissamine is described from a common chiral template. The stereoselective construction of the central tetrahydrofuran units was based on the pseudodesymmetrization of a pentodialdo-1,4-furanose derivative taking advantage of the latent symmetry present.

A series of carbocyclic analogues of naturally-occurring marine sphingolipid pachastrissamine were prepared and biologically evaluated. The analogues were efficiently synthesized via a tandem enyne/diene-ene metathesis reaction as a key step. We found that the analogue 4b exhibited comparable cytotoxicity and more potent inhibitory activity against sphingosine kinases, compared to pachastrissamine. Molecular modeling studies were conducted to provide more detailed insight into the binding mode of 4b in sphingosine kinase. In our docking model, pachastrissamine and 4b were able to effectively bind to the binding pocket of sphingosine kinase 1 as co-crystalized sphingosine. However, 4b showed a hydrophobic interaction with Phe192, which suggests that it contributes to its increased inhibitory activity against sphingosine kinase 1.

A short and efficient stereoselective synthesis of truncated pachastrissamine and its enantiomer have been achieved using the Wittig olefination, azidation through imidazole sulfonate ester and one-pot reductive hydrogenation as the key steps.

Enantioselective total synthesis of anhydrophytosphingosine pachastrissamine (jaspin B) was achieved using Sharpless asymmetric dihydroxylation and dirhodium(II)-catalyzed C-H amination as key steps.

The synthesis of the natural anhydrophytosphingosine pachastrissamine (jaspine B) 1a from Garner’s aldehyde is described.

The 5-endo-tet cyclization/ring opening of aziridine (I) proceeds smoothly in the presence of HF/MeCN to afford tetrahydrofuran (II), which in turn is further elaborated to ent-(-)-pachastrissamine (IV).

(+)-Pachastrissamine 3, also known as jaspine B, induces apoptosis in melanoma cells by a caspase-dependent pathway. Nobutaka Fujii and Hiroaki Ohno of Kyoyo University developed (J. Org. Chem. 2010, 75, 3831) a practical route to 3 based on the Pd-mediated cyclization of 1 to 2. Thomas G. Minehan of California State University, Northridge, optimized (Organic Lett. 2010, 12, 1580) the condensation of 5 with the bis-pivalate 4. This opened a general route to C-aryl glycosides, including aspalathin 6. (+)-Varitriol 11 is vinylogously related to 7. A key step in the synthesis of 11 reported (J. Org. Chem. 2010, 75, 2107) by Subhash Ghosh of the Indian Institute of Chemical Technology was the intermolecular Heck coupling of 8 with 9. Aspercyclide A 14 and its more stable methyl ether are promising lead compounds for the treatment of asthma. In the course of a synthesis of 14, Alan C. Spivey of Imperial College developed (Chem. Commun. 2010, 1824) the intramolecular Heck cyclization of 12 to 13. In a bold synthesis of etnangien 17, Dirk Menche of Ruprecht-Karls-Universität Heidelberg showed (J. Org. Chem. 2010, 75, 2429) that the intramolecular Heck coupling of 15 to 16 proceeded efficiently. The substituents on 15 may be favoring conformations that lead to cyclization.

Aminohydroxylation of prochiral divinylcarbinol and subsequent Pd(II)-catalysed oxy-/amidocarbonylation of aminopentenediols is reported. The method was applied to the preparation of useful building blocks for syntheses of cytotoxic jaspines and glycosidase inhibitor DLX-homologues. The key intermediates, tetrahydrofuranolactones (l-arabino-II) and pyrrolidinolactones (l-arabino-IX and l-xylo-IX), were prepared in a short 2-step sequence from divinylcarbinol.

Pachastrissamine (Ia) and its epimers (Ib) and (II) are prepared to investigate structure—activity relationships.

Jaspine B (pachastrissamine), which was isolated in 2002, is a naturally occurring anhydrophytosphingosine which displays potent biological activity, and as such has attracted much attention from synthetic chemists in recent years, with 14 syntheses reported to date. This review delineates the isolation of jaspine B, and laboratory total syntheses of jaspine B, 2-epi-jaspine B and analogues, which serves to confirm their structure and stereochemistry.

Jaspine B (pachastrissamine), which was isolated in 2002, is a naturally occurring anhydrophytosphingosine which displays potent biological activity, and as such has attracted much attention from synthetic chemists in recent years, with 14 syntheses reported to date. This review delineates the isolation of jaspine B, and laboratory total syntheses of jaspine B, 2-epi-jaspine B and analogues, which serves to confirm their structure and stereochemistry. © 2008 Elsevier Ltd. All rights reserved.

Enantioselective total synthesis of anhydrophytosphingosine pachastrissamine (jaspin B) was achieved using Sharpless asymmetric dihydroxylation and dirhodium(II)-catalyzed C-H amination as key steps.

The highly diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to a γ-silyloxy-α,β-unsaturated ester and in situ enolate oxidation with (+)-(camphorsulfonyl)oxaziridine has been used as the key step in the asymmetric synthesis of N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine, jaspine B (pachastrissamine) and its C(2)-epimer. © 2007 Elsevier Ltd. All rights reserved.

A practical stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B) was achieved in 48% overall yield from D-(-)-tartaric acid. Key features of the sequence include the diastereoselective formation of a tetrol with three contiguous chiral centers, which was further elaborated to pachastrissamine. The synthetic route is operationally simple, diastereoselective and is amenable for the synthesis of a number of analogues of pachastrissamine.