40016-25-9

Upstream product

• 54256-51-8 4-octyl-benzoic acid methyl ester 
• 49763-66-8 4-octylbenzaldehyde 
• 3575-31-3 4-octylbenzoic acid 
• 7440-44-0 pyrographite 
• 40016-26-0 1-chloromethyl-4-n-octylbenzene 
• 629-27-6 1-Iodooctane 
• 18282-51-4 4-iodo-benzyl alcohol 
• 99209-58-2 4-(1'-n-octynyl)benzyl alcohol 
• 629-05-0 n-octyne 
• 38841-98-4 n-octylmagnesium chloride 
• 14850-23-8 trans-4-Octene 
• 17049-49-9 octylmagnesium bromide 
• 1126-46-1 Methyl 4-chlorobenzoate 

Downstream Products

• 95902-62-8 ((4-n-Octylphenyl)methyl)triphenylphosphonium bromide 
• 1313876-84-4 5-(N-Cbz-amino)-5-[2-(4-octyloxyphenyl)ethenyl]-2,2-dimethyl-1,3-dioxane 
• 1313876-85-5 2,2-dimethyl-5-[2-(4-octylphenyl)ethyl]-1,3-dioxan-5-amine 
• 40016-26-0 1-chloromethyl-4-n-octylbenzene 
• 885605-36-7 5-(tert-butyloxycarbonylamino)-2,2-dimethyl-5-(4-octylphenethyl)-1,3-dioxane 
• 126156-27-2 2-iodo-4-n-octylbenzoic acid 
• 137476-81-4 (R)-(-)-1,1'-binaphthyl-2,2'-diylbis<(p-octylbenzyl)diphenylphosphonium> dibromide 
• 137476-81-4 (S)-(+)-1,1'-binaphthyl-2,2'-diylbis<(p-octylbenzyl)diphenylphosphonium> dibromide 
• 137476-84-7 [2'-(Diphenyl-phosphinoyl)-[1,1']binaphthalenyl-2-yl]-(4-octyl-benzyl)-diphenyl-phosphonium; bromide 

Relevant academic research and scientific papers

Synthesis of Fingolimod Employing Regioselective Aziridine Ring-Opening Reaction as a Key Step

An efficient and scalable synthesis of the immunomodulating drug fingolimod hydrochloride has been developed with the aziridine regioselective ring-opening reaction as a key step. This manuscript describes design, detailed synthetic route scouting, and optimization study of the aziridine ring-opening reaction. As a starting material for the polar part of the fingolimod molecule, cheap, common, and widely commercially available tris(hydroxymethyl)aminomethane was used. n-Octyl group was introduced into the molecule either via Kumada or Negishi cross-couplings, or alternatively by Sonogashira cross-coupling followed by hydrogenation. The final step consists of a one-pot acidic deprotection both of the acetonide and Boc group, providing thus highly pure fingolimod hydrochloride from the crude reaction mixture directly. The described process is highly effective, is industrially applicable, and has been successfully applied to 500 g scales of the target product.

Terminal-Selective C(sp3)-H Arylation: NiH-Catalyzed Remote Hydroarylation of Unactivated Internal Olefins

A terminal-selective migratory hydroarylation of unactivated olefins has been developed though a NiH-catalyzed alkene isomerization-hydroarylation relay process. This sp3C-H arylation was achieved with a simple pyrox ligand under mild conditions. The practicality and synthetic flexibility of the method is highlighted by the successful regioconvergent conversion of isomeric mixtures of alkenes to value-added linear arylation products on a gram scale.

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 METHOD FOR THE PREPARATION OF FINGOLIMOD

The invention relates to a method of preparation of 2-amino-2-[2-(4-octylphenyl)- ethyl]propane-1,3-diol (I), comprising opening of the aziridine ring of the intermediates (LVI) by the treatment with organometallic compounds, preferably the Grignard reage

Structure-Activity relationships and molecular modeling of sphingosine kinase inhibitors

The design, synthesis, and evaluation of the potency of new isoform-selective inhibitors of sphingosine kinases 1 and 2 (SK1 and SK2), the enzyme that catalyzes the phosphorylation of d-erythro-sphingosine to produce the key signaling lipid, sphingosine 1-phosphate, are described. Recently, we reported that 1-(4-octylphenethyl)piperidin-4-ol (RB-005) is a selective inhibitor of SK1. Here we report the synthesis of 43 new analogues of RB-005, in which the lipophilic tail, polar headgroup, and linker region were modified to extend the structure-activity relationship profile for this lead compound, which we explain using modeling studies with the recently published crystal structure of SK1. We provide a basis for the key residues targeted by our profiled series and provide further evidence for the ability to discriminate between the two isoforms using pharmacological intervention.

A convenient synthesis of the immunosuppressive agent FTY720

This paper describes a practical synthetic approach to preparation of an immunosuppressant, FTY720. The key steps involve an iron-catalyzed cross-coupling reaction and a Wittig reaction. The advantages of this synthesis include readily available starting

S1P RECEPTORS MODULATORS AND THEIR USE THEREOF

The invention relates to novel compounds that have S1P receptor modulating activity. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, autoimmune response. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as autoimmune response.

S1P RECEPTORS MODULATORS

The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.

Nickel-catalyzed reductive cross-coupling of aryl halides with alkyl halides

(Chemical Equation Presented) The direct reductive cross-coupling of alkyl halides with aryl halides is described. The transformation is efficient (equimolar amounts of the starting materials are used), generally high-yielding (all but one between 55 and 88% yield), highly functional-group-tolerant [OH, NHBoc, NHCbz, Bpin, C(O)Me, CO2Et, and CN are all tolerated], and easy to perform (uses only benchtop-stable reagents, tolerates small amounts of water and oxygen, changes color when complete, and uses filtration workup). The reaction appears to avoid the formation of intermediate organomanganese species, and a synergistic effect was found when a mixture of two ligands was employed.

Synthesis and characterization of stilbene derivatives for possible incorporation as smart additives in polymers used as packaging films

Several series of stilbene derivatives for possible use as smart additives in polymers used as packaging films have been prepared and characterized. Differential scanning calorimetry was performed on some of the stilbenes in order to determine any liquid crystal properties. Those compounds which had multiple phase transitions were also shown to have two liquid crystalline phases according to optical microscopy.