59633-88-4

Upstream product

• 49815-58-9 6,6-dimethyl-2-methyl-1-cyclohexene-1-carboxylic acid methyl ester 
• 432-25-7 2,6,6-trimethylcyclohex-1-enecarbaldehyde 
• 472-20-8 β-cyclogeraniol 
• 60714-17-2 1,1-dimethyl-2,3-bis(methylene)cyclohexane 
• 141-27-5 3,7-dimethyl-2,6-octadienal 
• 79-77-6 (E)-β-ionone 
• 53067-23-5 methyl 7-methyl-3-oxooct-6-enoate 
• 71135-95-0 methyl 2,2-dimethyl-6-oxocyclohexanecarboxylate 
• 870-63-3 prenyl bromide 

Downstream Products

• 3899-20-5 ethyl (all-E)-retinoate 
• 351875-34-8 7-cis-ethyl retinoate 
• 472-68-4 (2,6,6-trimethylcyclohex-1-enyl)acetic acid 
• 514-62-5 (+/-)-ferruginol 
• 3772-54-1 (+/-)-nimbiol methyl ether 
• 113332-25-5 (+/-)-nimbidiol 
• 1187789-82-7 C₂₂H₂₇BrO₄ 
• 1642593-57-4 1-(3,3-dimethyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-1-en-2-yl)-4-methoxybenzene 
• 1642593-76-7 C₂₁H₃₀O₂ 
• 142528-98-1 Acetic acid 3-(2,6,6-trimethyl-cyclohex-1-enyl)-1-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-ethyl]-propyl ester 

Relevant academic research and scientific papers

Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin

Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber's congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin molecules, which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chemical chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analogue 11-cis-6mr-retinal. Following molecular docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new molecules displayed an effect in at least one assay, acting either as chemical chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.

Enantioselective Synthesis Muqubilin and Negombatoperoxides B and C/D

Muqubilin, negombatoperoxide B, and negombatoperoxide C/D were synthesized through enantioselective routes, with the quaternary center derived from a peroxy chiral building block of known absolute configuration. The C-2/C-3 stereogenic centers were introduced by asymmetric aldol condensation, and the 1,2-dioxane ring was constructed via an intramolecular alkylation of a hydroperoxide with a mesylate. The synthetic samples showed physical and spectroscopic data consistent with those reported in the literature and thus verified the configurations of the natural products. A potentially more expeditious enantioselective entry to the 1,2-dioxane-aldol moiety (C-1 to C-6) of such cyclic peroxides was also briefly explored, where the C-2/C-3 stereogenic centers were installed through a [2+2] cycloaddition and the 1,2-dioxane ring was closed via an intramolecular alkylation coupled with an alkyl-oxygen cleavage of a β-lactone.

VISUAL CYCLE MODULATORS

A method of treating an ocular disorder in a subject in need thereof includes administering to the subject a therapeutically effective amount of a retinal sequestering compound of formula (I).

Rational tuning of visual cycle modulator pharmacodynamics

Modulators of the visual cycle have been developed for treatment of various retinal disorders. These agents were designed to inhibit retinoid isomerase [retinal pigment epithelium-specific 65 kDa protein (RPE65)], the rate-limiting enzyme of the visual cy

SUBSTITUTED QUINOLIZINE DERIVATIVES USEFUL AS HIV INTEGRASE INHIBITORS

The present invention relates to Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R1, R2, R3, R4, R5, R9 and R10 are as defined herein. The present invention also relates to compositions comprising at least one Substituted Quinolizine Derivative, and methods of using the Substituted Quinolizine Derivatives for treating or preventing HIV infection in a subject.

Synthesis, antimicrobial and antineoplastic activities for agelasine and agelasimine analogs with a β-cyclocitral derived substituent

Agelasines and agelasimines are antimicrobial and cytotoxic purine derivatives isolated from marine sponges (Agelas sp.). We have synthesized structurally simplified analogs of these natural products starting from β-cyclocitral. The novel compounds were found to be strong inhibitors of a wide variety of pathogenic microorganisms (incl. Mycobacterium tuberculosis) as well as cancer cell lines. The biological activities were generally in the same range as those previously found for the structurally more complex agelasines and agelasimines isolated in small amounts from natural sources. We also report for the first time that agelasine and agelasimine analogs inhibit growth of protozoa (Acanthamoeba castellanii and Acanthamoeba polyphaga). Acanthamoeba keratitis is an increasingly common and severe corneal infection, closely associated with contact lens wear.

Novel domino reactions for diterpene synthesis

New types of concerted domino acylation-cycloalkylation/alkylation- cycloacylation reactions have been described. These processes promoted by methanesulfonic acid-phosphorus pentoxide and concentrated H2SO 4, respectively, provide efficient, elegant, and expeditious routes for biologically active naturally occurring diterpenoids, namely (±)-ferruginol (1), (±)-nimbidiol (2), (±)-nimbiol (3), (±)-totarol (4), and ar-abietatriene (5).

A conjugate addition-radical cyclisation approach to sesquiterpene-phenol natural products

A conjugate addition-radical cyclization approach to sesquiterpenephenol natural products was discussed. The first step involved the conjugate addition of an organocopper species to a chromone-3-carboxylate which resulted in 2,2-disubstituted chroman-4-ones. The second step was the generation of a β-ketoester radical. The last step involved a stereoselective manganese(III) acetate-mediated radical cyclization reaction.

Common synthetic strategy for optically active cyclic terpenoids having a 1,1,5-trimethyl-trans-decalin nucleus: Syntheses of (+)-acuminolide, (-)-spongianolide A, and (+)-scalarenedial

We have developed a simple and practical method for providing enantiomerically pure bi-, tri-, and tetracyclic frameworks having a 1,1,5-trimethyl-trans-decalin nucleus, and demonstrated their utility for terpenoid synthesis. Thus, we achieved the stereocontrolled total syntheses of (+)-acuminolide as a bicyclic, (-)-spongianolide A as a tricyclic, and (+)-scalarenedial as a tetracyclic terpenoid from the corresponding optically pure cyclic β-ketoesters, which were obtained by repeating the same method of the ring construction, including the olefin cyclization with Lewis acid, followed by simple optical resolution using chiral auxiliaries for acetal formation, respectively. This is a general and valuable strategy for the synthesis of enantiomerically pure cyclic terpenoids having the 1,1,5-trimethyl-trans-decalin nucleus.