5352-74-9

Usage

Uses

Used in Pharmaceutical Industry:
9,13-Retinoic acid is used as a therapeutic agent for the treatment of liver fibrosis. Its application is based on its ability to activate latent transforming growth factor-β, which is a key player in the development of liver fibrosis. By modulating this process, 9,13-Retinoic acid can potentially help in managing and treating this condition.
Additionally, due to its role in cell growth and differentiation, 9,13-Retinoic acid may also have potential applications in other areas of medicine, such as cancer therapy or regenerative medicine. However, further research would be required to explore these possibilities and establish their efficacy and safety.

InChI:InChI=1/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8-,16-14-

Upstream product

• 638-10-8 ethyl 3-methylbut-2-enoate 
• 54226-17-4 (2Z,4E)-3-methyl-5-[2,6,6-trimethylcyclohex-1-enyl]penta-2,4-dienal 
• 302-79-4 9,13-di-cis-retinoic acid 
• 41891-54-7 diethyl 3-(ethoxycarbonyl)-3-methylprop-2-en-yl phosphate 
• 20110-08-1 methyl (2Z,4E)-3-methyl-5-(2,6,6-trimethylcyclohex-1-enyl)penta-2,4-dienoate 
• 86708-67-0 ethyl (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoate 
• 24519-09-3 (2E,4E,6Z,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid ethyl ester 
• 58526-50-4 [7t,9c,11t,13t]retinoic acid methyl ester 
• 62054-49-3 ethyl (E)-3-formyl-2-butenoate 
• 68-26-8 9-cis-retinol 
• 514-85-2 9-cis vitamin A aldehyde 
• 2408-37-9 2,2,6-trimethylcyclohexan-1-one 
• 189633-82-7 2,2,6-trimethyl-cyclohexanone hydrazone 
• 189633-81-6 2‐iodo‐1,3,3‐trimethylcyclohex‐1‐ene 

Downstream Products

• 58526-50-4 [7t,9c,11t,13t]retinoic acid methyl ester 
• 53839-60-4 retinoyl chloride 
• 302-79-4 9-cis-retinoic acid 
• 68070-33-7 [7t,9c,11t,13c]retinoic acid methyl ester 
• 4759-48-2 13-cis-retinoic acid 
• 302-79-4 all-trans-retinoic-acid 
• 187836-80-2 potassium all-trans-retinoate 

Relevant academic research and scientific papers

Catalytic synthesis of 9-cis-retinoids: Mechanistic insights

The regioselective Z-isomerization of thermodynamically stable all-trans retinoids remains challenging, and ultimately limits the availability of much needed therapeutics for the treatment of human diseases. We present here a novel, straightforward approach for the catalytic Z-isomerization of retinoids using conventional heat treatment or microwave irradiation. A screen of 20 transition metal-based catalysts identified an optimal approach for the regioselective production of Z-retinoids. The most effective catalytic system was comprised of a palladium complex with labile ligands. Several mechanistic studies, including isotopic H/D exchange and state-of-the-art quantum chemical calculations using coupled cluster methods indicate that the isomerization is initiated by catalyst dimerization followed by the formation of a cyclic, six-membered chloropalladate catalyst-substrate adduct, which eventually opens to produce the desired Z-isomer. The synthetic development described here, combined with thorough mechanistic analysis of the underlying chemistry, highlights the use of readily available transition metal-based catalysts in straightforward formats for gram-scale drug synthesis.

Z -isomerization of retinoids through combination of monochromatic photoisomerization and metal catalysis

Catalytic Z-isomerization of retinoids to their thermodynamically less stable Z-isomer remains a challenge. In this report, we present a photochemical approach for the catalytic Z-isomerization of retinoids using monochromatic wavelength UV irradiation treatment. We have developed a straightforward approach for the synthesis of Z-retinoids in high yield, overcoming common obstacles normally associated with their synthesis. Calculations based on density functional theory (DFT) have allowed us to correlate the experimentally observed Z-isomer distribution of retinoids with the energies of chemically important intermediates, which include ground- and excited-state potential energy surfaces. We also demonstrate the application of the current method by synthesizing gram-scale quantities of 9-cis-retinyl acetate 9Z-a. Operational simplicity and gram-scale ability make this chemistry a very practical solution to the problem of Z-isomer retinoid synthesis.

Stereospecific synthesis process for tretinoin compounds

A stereospecific synthesis process for tretinoin compounds comprises the following steps: using substituted triphenyl phosphine salt and β-formyl crotonic acid as raw material to carry out WITTIG reaction under the action of alkali; then adjusting the pH of the reaction liquid to 5-10; adding palladium compound or rhodium compound to carry out isomerization directly and obtain tretinoin compounds with desired configuration. The product yield of the process is high and the intermediate product in the reaction dose not need to be separated. The process is easy to operate and can save the production cost and as well is suitable for industrial production.

Synthesis of 11C-labeled retinoic acid, [11C]ATRA, via an alkenylboron precursor by Pd(0)-mediated rapid C-[11C] methylation

Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized 11C-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of 11C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[11C] methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [11C]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [11C]Tamibarotene (artificial retinoid).

A sensitive and specific method for measurement of multiple retinoids in human serum with UHPLC-MS/MS

Retinol (vitamin A) circulates at 1-4 μM concentration and is easily measured in serum. However, retinol is biologically inactive. Its metabolite, retinoic acid (RA), is believed to be responsible for biological effects of vitamin A, and hence the measurement of retinol concentrations is of limited value. A UHPLC-MS/MS method using isotope-labeled internal standards was developed and validated for quantitative analysis of endogenous RA isomers and metabolites. The method was used to measure retinoids in serum samples from 20 healthy men. In the fed state, the measured concentrations were 3.1 ± 0.2 nM for at RA, 0.1 ± 0.02 nM for 9-cisRA, 5.3 ± 1.3 nM for 13-cisRA, 0.4 ± 0.4 nM for 9,13-dicisRA, and 17.2 ± 6.8 nM for 4oxo-13-cisRA. The concentrations of the retinoids were not significantly different when measured after an overnight fast (3.0 ± 0.1 nM for atRA, 0.09 ± 0.01nM for 9-cisRA, 3.9 ± 0.2 nM for 13-cisRA, 0.3 ± 0.1 nM for 9,13-dicisRA, and 11.9 ± 1.6 nM for 4oxo-13-cisRA). 11-cisRA and 4OH-RA were not detected in human serum. The high sensitivity of the MS/MS method combined with the UHPLC separation power allowed detection of endogenous 9-cis RA and 4oxo-atRA for the first time in human serum. Copyright

PROCESS FOR PREPARATION OF HIGHLY PURE ISOTRETINOIN

The present invention relates to a process for preparation of isotretinoin and more specifically, to a purification process for obtaining highly pure isotretinoin that is useful as a keratolytic agent, particularly useful for the treatment of acne. The process involves treating isotretinoin containing metal contamination and/or other impurities with a base in a suitable solvent to form a solution of isotretinoin, followed by adsorption, precipiation, and filtration or centrifugation

Caesium fluoride-promoted Stille coupling reaction: An efficient synthesis of 9Z-retinoic acid and its analogues using a practical building block

A highly efficient and rapid total synthesis of 9Z-retinoic acid was accomplished by caesium fluoride-promoted Stille coupling reaction; using a common building block, 9Z-retinoic acid analogues were also prepared by the same method without isomerisation of the Z-double bond. The Royal Society of Chemistry 2008.

A caged retinoic acid for one- and two-photon excitation in zebrafish embryos

(Chemical Equation Presented) Escaping the cage: Retinoic acid (RA), a crucial signaling molecule for the embryogenesis of vertebrates, can be photoreleased from a simple caged derivative (cRA) upon illumination. In zebrafish embryos, cRA causes RA-induced phenotypes with one- and two-photon excitation (see picture), which opens a route to the noninvasive generation of controlled RA concentration patterns in vivo.

All-Trans-Retinol: All-Trans-13,14-Dihydroretinol Saturase and Methods of Its Use

Compositions of all-trans-retinol: all-trans-13,14-dihydroretinal saturase and methods of use thereof are provided.

Preparation and biological activity of 13-substituted retinoic acids

13-Demethyl or 13-substituted all-E- and 9Z-retinoic acids were synthesized using a palladium-catalyzed coupling reaction of enol triflates and tributylstannylolefins. Their biological activities were then measured. The 13-ethyl analogs exhibited approximately one-half of the antiproliferative and differentiation-inducing activity of ATRA in HL-60 cells. In contrast, in the 9Z-derivatives, all analogs, except for the 13-butyl derivatives, showed apoptosis-inducing activity.