97014-46-5

Upstream product

• 94377-06-7 (S)-2-amino-octadecan-3-one; hydrobromide 
• 109-99-9 tetrahydrofuran 
• 60-29-7 diethyl ether 
• 64-17-5 ethanol 
• 193222-34-3 1-deoxy-D-erythro-sphingosine 
• 109555-73-9 Spinulosine 285 
• 1258429-18-3 (2S,3R)-2-azido-3-hydroxyoctadecyl 4-methylbenzenesulfonate 
• 629-80-1 n-hexadecylaldehyde 
• 1392130-35-6 (2S,3R)-2-nitrooctadecan-3-ol 
• 378755-38-5 (4S,5R)-4-methyl-5-pentadecyloxazolidin-2-one 
• 1463439-99-7 dibenzyl 1-((2S,3R,E)-3-hydroxydodec-5-en-2-yl)hydrazine-1,2-dicarboxylate 
• 1463439-97-5 dibenzyl 1-((2S,3R)-3-hydroxyhex-5-en-2-yl)hydrazine-1,2-dicarboxylate 
• 158021-50-2 (2S,3R)-2-azido-1,3-octadecanediol 
• 263558-70-9 ethyl (2R,3R)-2-azido-3-hydroxyoctadecanoate 

Downstream Products

• 103044-87-7 D_s-threo-2-benzoylamino-octadecan-3-ol 

Relevant academic research and scientific papers

Asymmetric synthesis of ES-285, an anticancer agent isolated from marine sources

The asymmetric synthesis of (2S,3R)-2-amino-3-octane-decanol hydrochloride (ES-285-HC1) was achieved in eight steps in ca. 38% overall yield from the N-benzylimine-derived from. (R)-2,3-O-isopropylidene glyceraldehyde, which is easily available on gram sc

Self-assembling nanoparticles of dually hydrophobic prodrugs constructed from camptothecin analogue for cancer therapy

Nanomedicines have shown success in cancer therapy in recent years because of their excellent solubility in aqueous solution and drug accumulation through controlled release in tumor tissues, but the preparation of most nanomedicines still requires ionic materials, surfactants or the amphiphilic structure to maintain nanoparticle stability and function. In this study, we developed a couple of novel dually hydrophobic prodrugs (DHPs) by combining two hydrophobic compounds through different linkers and elaborated their self-assembly mechanisms by virtue of computational simulation. Importantly, without using any excipients, FL-2 NPs exhibited significantly prolonged retention in blood circulation and displayed a remarkable anti-tumor effect at very low concentration in vivo. Both DHPs consisted of camptothecin structural analogue(FL118) and a marine natural product (ES-285). Comparative experiments proved that these compounds could quickly form nanoparticles by way of simple preparation and remained relatively stable for long periods in PBS. FL-2 NPs linked with a disulphide bond could rapidly release bioactive FL118 after being triggered by endogenous reductive stimulus to exert anti-cancer effects. Overall, this study provides a new strategy for design of therapeutic nanomedicines consisting of dually hydrophobic molecules for cancer therapy.

Total synthesis and the anticancer activity of (+)-spisulosine

The total synthesis of the anticancer agent (+)-spisulosine has been accomplished. The strategy involved a substrate-controlled aza-Claisen rearrangement to establish the erythro-configured amino-alcohol motif followed by deoxygenation to create a methyl

Synthesis and identification of unprecedented selective inhibitors of CK1ε

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.

Direct stereoselective synthesis of enantiomerically pure anti -β-amino alcohols

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.

SELECTIVE INHIBITORS AND ALLOSTERIC ACTIVATORS OF SPHINGOSINE KINASE

Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases, such as cancer and vascular remodeling in pulmonary arterial hypertension. Inhibitors of sphingosine kinase 1 and 2 (SK1 and SK2), which catalyze the synthesis of S1P, may be useful anti- proliferative agents. We have synthesized a series of sphingosine-based inhibitors of SK and SK2. Also provided in this invention are compounds that activate SK1 which can be used in diseases such as fibrosis, where intracellular S1P is anti-fibrotic.

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

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.

Straightforward access to spisulosine and 4,5-dehydrospisulosine stereoisomers: Probes for profiling ceramide synthase activities in intact cells

A stereoselective synthesis of spisulosine (ES285) and 4,5- dehydrospisulosine stereoisomers is described. Hydrozirconation of 1-pentadecyne with Schwartz reagent, followed by diastereocontrolled addition to l- or d-alaninal afforded the required 2-amino-1,3-diol framework. The resulting sphingoid bases revealed as excellent probes for the profiling of ceramide synthase activity in intact cells. Among the sphingoid bases described in this work, spisulosine (ES285), RBM1-77, and RBM1-73 were the most suitable ones because of their highest acylation rates. These molecules should prove useful to study the role of the different ceramide synthases and the resulting N-acyl (dihydro)ceramides in cell fate.

Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells

Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases such as cancer and pulmonary arterial hypertension. We have synthesized inhibitors that are selective for the two isoforms of sphingosine kinase (SK1 and SK2) that catalyze the synthesis of S1P. A thiourea adduct of sphinganine (F02) is selective for SK2 whereas the 1-deoxysphinganines 55-21 and 77-7 are selective for SK1. (2S,3R)-1-Deoxysphinganine (55-21) induced the proteasomal degradation of SK1 in human pulmonary arterial smooth muscle cells and inhibited DNA synthesis, while the more potent SK1 inhibitors PF-543 and VPC96091 failed to inhibit DNA synthesis. These findings indicate that moderate potency inhibitors such as 55-21 are likely to have utility in unraveling the functions of SK1 in inflammatory and hyperproliferative disorders.

A Highly anti-selective asymmetric henry reaction catalyzed by a chiral copper complex: Applications to the syntheses of (+)-spisulosine and a pyrroloisoquinoline derivative

A highly anti-selective asymmetric Henry reaction has been developed, affording synthetically versatile β-nitroalcohols in a predominately anti-selective manner (mostly above 15:1) and excellent ee values (mostly above 95 %). Moreover, the anti-selective Henry reaction was carried out in the presence of water for the first time with up to 99 %-ee. The catalytic mechanism was proposed based on the detection of the intermediates by extractive electrospray ionization mass spectrometry (EESI-MS). Furthermore, the anti adducts have been successfully transformed into the biochemically important (+)-spisulosine and a pyrroloisoquinoline derivative. Copyright