203381-39-9

Upstream product

• 108-86-1 bromobenzene 
• 95763-58-9 3,7-dimethyl-8-<(tetrahydro-2H-pyran-2-yl)oxy>-2E,6E-octadien-1-ol 
• 100-58-3 phenylmagnesium bromide 
• 221656-69-5 1,8-dihydroxy-2,6-dimethyl-1-phenyl-2(E),6(E)-octadiene 
• 105-87-3 3,7-dimethyl-2E,6-octadien-1-yl acetate 
• 37905-03-6 8-hydroxygeranyl acetate 
• 37905-02-5 (2E,6E)-3,7-dimethyl-8-oxoocta-2,6-dien-1-yl acetate 
• 95575-96-5 (2E,6E)-3-methyl-7-((tetrahydro-2H-pyran-2-yloxy)methyl)octa-2,6-dienyl acetate 

Downstream Products

• 221656-71-9 3,7-dimethyl-8-phenyl-2(E),6(E)-octadienyl bromide 
• 1310065-53-2 C₂₇H₂₈O₂ 
• 221656-72-0 N,N,3,7-tetramethyl-8-phenyl-2(E),6(E)-octadienylamine 

Relevant academic research and scientific papers

Preparation of aromatic farnesol analogues via a Cu(I)-mediated Grignard coupling of THP ethers

A Cu(I)-mediated reaction of aromatic Grignard reagents with allylic tetrahydropyranyl ethers results in formation of the coupled products in good yields. This methodology allows facile synthetic manipulation of compounds with two reactive allylic positio

Synthetic Small Molecules Derived from Natural Vitamin K Homologues that Induce Selective Neuronal Differentiation of Neuronal Progenitor Cells

We synthesized new vitamin K2 analogues with ω-terminal modifications of the side chain and evaluated their selective differentiation of neuronal progenitor cells into neurons in vitro. The result of the assay showed that the menaquinone-3 analogue modified with the m-methylphenyl group had the most potent activity, which was twice as great as the control. This finding indicated that it is possible to obtain much more potent compounds with modification of the structure of vitamin K2.

Synthesis of novel vitamin K2 analogues with modification at the Ω-terminal position and their biological evaluation as potent steroid and xenobiotic receptor (SXR) agonists

Vitamin K2 is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. We synthesized vitamin K2 analogues with hydroxyl or phenyl groups at the Ω-terminal of the side chain. The up-regulation of SXR-mediated transcription of the target gene by the analogues was dependent on the length of the side chain and the hydrophobicity of the Ω-terminal residues. Phenyl analogue menaquinone-3 was as active as the known SXR ligand rifampicin.

Synthesis and antimicrobial evaluation of farnesyl diphosphate mimetics

The synthesis and first antimicrobial evaluation of farnesyl diphosphate mimetics are described. Several analogues (10, 12, 13, and 20) are inhibitors of Candida albicans, Shizosaccharomyces pombe, and Saccharomyces cerevisiae. The activities of analogues 10, 12, and 13, which contain a ω-phenyl moiety and a diphosphate isostere, are not attributable to inhibition of sterol biosynthesis via squalene synthase. Two geranyl phenylsulphones (14 and 15) are potent inhibitors of Escherichia coli. Analogue 15 exhibits potent activity towards Salmonella typhimurium and Pseudomonas aeruginosa (MIC - 2μg/mL) and represents the first type of semi-synthetic terpenoid allylic sulphone active against these bacteria.

Zwitterionic sulfobetaine inhibitors of squalene synthase

A substantial number of sulfobetaines (e.g., 10) have been synthesized and evaluated as inhibitors of squalene synthase (SS) on the basis of the idea that their zwitterionic structure would have properties conducive both to binding in the active site and to passage through cell membranes. When the simple sulfobetaine moiety is incorporated into compounds containing hydrophobic portions like those in farnesyl diphosphate (1) or presqualene diphosphate (2), inhibition of SS in a rat liver microsomal assay was indeed observed. For example, farnesylated sulfobetaine 10 has IC50 = 10 μM and aromatic derivative 35 has IC50 = 2 μM for SS inhibition. A wide variety of structural modifications, exemplified by compounds 43, 52, 76, 85, 91, 99, 111, and 115, was investigated. Unfortunately, no inhibitors in the submicromolar range were discovered, and exploration of a different type of zwitterion seems necessary if this appealing approach to inhibition of SS is going to provide a potential antihypercholesterolemic agent.

Synthesis of Farnesol Analogues through Cu(I)-Mediated Displacements of Allylic THP Ethers by Grignard Reagents

The synthesis of a family of farnesol analogues, incorporating aromatic rings, has been achieved in high yields through the development of a regioselective coupling of allylic tetrahydropyranyl ethers with organometallic reagents. The allylic THP group is displaced readily by Grignard reagents in the presence of Cu(I) halides but is stable in the absence of added copper. Thus, an allylic THP group can fulfill its traditional role as a protecting group or serve as a leaving group depending on reaction conditions. An improved synthesis of (2E,6E)-10,11-dihydrofarnesol also has been accomplished using this methodology, and some preliminary studies on the reactivity and regioselectivity of THP ether displacements were conducted. The farnesol analogues reported herein may be useful probes of the importance of nonbonding interactions in enzymatic recognition of the farnesyl chain and allow development of more potent competitive inhibitors of enzymes such as farnesyl protein transferase.