2052-63-3

Basic information

• Product Name: 13-CIS-RETINOL
• Synonyms: 2-CIS-VITAMIN A ALCOHOL;12-CIS-RETINOL;13-CIS-RETINOL;13-DIS-RETINOL;Retinol, 13-cis-;(13Z)-Retinol;13-cis-VitaMin A;neo-Retinol
• CAS NO: 2052-63-3
• Molecular Formula: C₂₀H₃₀O
• Molecular Weight: 286.45
• Mol File: 2052-63-3.mol
• Article Data: 22

Chemical Properties

• Melting Point: 58-60°
• Boiling Point: 421.2 °C at 760 mmHg
• Flash Point: 147.3 °C
• Appearance: /
• Density: 0.954 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.549
• Storage Temp.: ?20°C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• Stability: Light Sensitive, Temperature Sensitive
• CAS DataBase Reference: 13-CIS-RETINOL(CAS DataBase Reference)
• NIST Chemistry Reference: 13-CIS-RETINOL(2052-63-3)
• EPA Substance Registry System: 13-CIS-RETINOL(2052-63-3)

Safety Data

• Hazard Codes: Xi
• Statements: 38
• Safety Statements: 22-36/37
• Hazardous Substances Data: 2052-63-3(Hazardous Substances Data)

Usage

Description

13-CIS-RETINOL, also known as 13-cis-Retinol, is one of the active metabolites of Vitamin A (R252000). It is a yellow, low melting solid with significant biological activities and potential applications in various industries.

Uses

Used in Pharmaceutical Industry:
13-CIS-RETINOL is used as a therapeutic agent for its role in treating various skin conditions and promoting skin health. It is particularly effective in managing acne, psoriasis, and other skin disorders due to its ability to regulate cell growth and differentiation.
Used in Cosmetic Industry:
In the cosmetic industry, 13-CIS-RETINOL is used as an active ingredient in anti-aging and skin rejuvenation products. It helps to reduce the appearance of fine lines, wrinkles, and age spots by stimulating collagen production and promoting skin cell turnover.
Used in Nutritional Supplements:
13-CIS-RETINOL is also used as an additive in nutritional supplements to support overall health and well-being. As a metabolite of Vitamin A, it plays a crucial role in maintaining healthy vision, immune function, and reproductive health.
Used in Research and Development:
Due to its unique chemical properties and biological activities, 13-CIS-RETINOL is utilized in research and development for the discovery of new drugs and therapies. It serves as a valuable tool in studying the mechanisms of cell growth, differentiation, and apoptosis, which can lead to the development of novel treatments for various diseases and conditions.

InChI:InChI=1/C20H30O/c1-16(8-6-9-17(2)13-15-21)11-12-19-18(3)10-7-14-20(19,4)5/h6,8-9,11-13,21H,7,10,14-15H2,1-5H3/b9-6+,12-11+,16-8+,17-13-

Synthetic route

1-acetoxy-3,7-dimethyl-8-(tetrahydropyran-2-yl)oxy-9-phenylsulfonyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2(E),6(E)-nonadiene (103905-07-3) → 2-cis-Vitamin-A (2052-63-3) + 9-cis-retinol (68-26-8, 2052-63-3, 6018-74-2, 17706-49-9, 22737-96-8, 29444-25-5, 34218-73-0, 39815-04-8, 69686-68-6, 69686-69-7, 74743-94-5, 84415-27-0, 84415-28-1, 85354-09-2, 85354-10-5, 93380-02-0, 98462-62-5, 137121-52-9, 22737-97-9) + 11-cis-retinol (22737-96-8) + RETINOL (68-26-8)

Conditions	Yield
With potassium methanolate In cyclohexane at 38℃; for 2h;	A n/a B n/a C n/a D 77%
With potassium methanolate In cyclohexane at 38℃; for 2h; Title compound not separated from byproducts;

9-(2',6',6'-trimethylcyclohex-1'-enyl)-8-acetoxy-3,7-dimethyl-9-(p-tolylsulfonyl)nona-2Z,4E,6E-trien-1-ol (181053-77-0) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
With methanol; potassium dihydrogenphosphate; sodium amalgam In diethyl ether for 0.5h; Ambient temperature;	63%
With potassium dihydrogenphosphate; sodium amalgam In diethyl ether; ethanol at 20℃; for 0.5h;	63%

(2Z,4E,6E,8E)-methyl 3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoate (16760-45-5) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
With lithium aluminium tetrahydride; diethyl ether at -50℃;

triethylsilyl ether of 13-cis-retinol (118304-60-2) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
With pyridine hydrogenfluoride; sodium fluoride Ambient temperature; Yield given;
With pyridine hydrogenfluoride; sodium fluoride In tetrahydrofuran; acetonitrile for 5h; Ambient temperature;

Acetic acid (2Z,6E)-9-benzenesulfonyl-3,7-dimethyl-8-(tetrahydro-pyran-2-yloxy)-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,6-dienyl ester (103905-07-3, 105615-50-7) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
With potassium methanolate In cyclohexane at 38℃; for 2h;

Acetic acid (2Z,6E)-9-benzenesulfonyl-3,7-dimethyl-8-(tetrahydro-pyran-2-yloxy)-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,6-dienyl ester (103905-07-3, 105615-50-7) → 2-cis-Vitamin-A (2052-63-3) + 11,13-Di-cis-vitamin A (17706-49-9) + (9Z,13Z)-retinol (29444-25-5) + RETINOL (68-26-8)

Conditions	Yield
With potassium methanolate In cyclohexane at 38℃; for 2h; Yield given. Title compound not separated from byproducts;
With potassium methanolate In cyclohexane at 38℃; for 2h; Title compound not separated from byproducts;

O-all-trans-retinol → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
With iodine; benzene Einwirkung von Tageslicht;

ethyl (2E,4E,6Z)-8-hydroxy-2,6-dimethylocta-2,4,6-trienoate (181053-78-1) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: 98 percent / imidazole / dimethylformamide / 1 h / 20 °C 2.1: 96 percent / LiAlH4; AlCl3 / diethyl ether / 3 h / 0 °C 3.1: 100 percent / MnO2 / hexane; CHCl3 / 12 h / 20 °C 4.1: n-BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 4.2: tetrahydrofuran; hexane / 3 h / -78 °C 5.1: 118.2 mg / tetrahydrofuran; hexane / -78 - 20 °C 6.1: 99 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 7.1: 63 percent / KH2PO4; Na/Hg / ethanol; diethyl ether / 0.5 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1: 98 percent 2: 96 percent / AlCl3, LiAlH4 3: 100 percent / MnO2 4: 1.) nBuLi 5: n-Bu4NF 6: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

ethyl (2E,4E,6Z)-8-tert-butyldimethylsiloxy-2,6-dimethylocta-2,4,6-trienoate (181053-73-6) → 2-cis-Vitamin-A (2052-63-3)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: TBAF / tetrahydrofuran / 0.5 h / 20 °C 2.1: 98 percent / imidazole / dimethylformamide / 1 h / 20 °C 3.1: 96 percent / LiAlH4; AlCl3 / diethyl ether / 3 h / 0 °C 4.1: 100 percent / MnO2 / hexane; CHCl3 / 12 h / 20 °C 5.1: n-BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 5.2: tetrahydrofuran; hexane / 3 h / -78 °C 6.1: 118.2 mg / tetrahydrofuran; hexane / -78 - 20 °C 7.1: 99 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 8.1: 63 percent / KH2PO4; Na/Hg / ethanol; diethyl ether / 0.5 h / 20 °C View Scheme

(3E,6Z)-8-(tert-Butyl-dimethyl-silanyloxy)-2-(N,N-dimethyl-aminooxy)-2,6-dimethyl-octa-3,6-dienoic acid ethyl ester (181053-74-7) → 2-cis-Vitamin-A (2052-63-3)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: methanol / 72 h / 20 °C 2.1: TBAF / tetrahydrofuran / 0.5 h / 20 °C 3.1: 98 percent / imidazole / dimethylformamide / 1 h / 20 °C 4.1: 96 percent / LiAlH4; AlCl3 / diethyl ether / 3 h / 0 °C 5.1: 100 percent / MnO2 / hexane; CHCl3 / 12 h / 20 °C 6.1: n-BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 6.2: tetrahydrofuran; hexane / 3 h / -78 °C 7.1: 118.2 mg / tetrahydrofuran; hexane / -78 - 20 °C 8.1: 99 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 9.1: 63 percent / KH2PO4; Na/Hg / ethanol; diethyl ether / 0.5 h / 20 °C View Scheme

(2E,4E,6Z)-8-tert-butyldiphenylsiloxy-2,6-dimethylocta-2,4,6-trien-1-ol (181053-80-5) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 100 percent / MnO2 / hexane; CHCl3 / 12 h / 20 °C 2.1: n-BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 2.2: tetrahydrofuran; hexane / 3 h / -78 °C 3.1: 118.2 mg / tetrahydrofuran; hexane / -78 - 20 °C 4.1: 99 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 5.1: 63 percent / KH2PO4; Na/Hg / ethanol; diethyl ether / 0.5 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: 100 percent / MnO2 2: 1.) nBuLi 3: n-Bu4NF 4: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

(2E,4E,6Z)-8-tert-butyldiphenylsiloxy-2,6-dimethylocta-2,4,6-trienal (181053-76-9) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 1.2: tetrahydrofuran; hexane / 3 h / -78 °C 2.1: 118.2 mg / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 99 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 4.1: 63 percent / KH2PO4; Na/Hg / ethanol; diethyl ether / 0.5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 1.) nBuLi 2: n-Bu4NF 3: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

ethyl (2E,4E,6Z)-8-tert-butyldiphenylsiloxy-2,6-dimethylocta-2,4,6-trienoate (181053-79-2) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 96 percent / LiAlH4; AlCl3 / diethyl ether / 3 h / 0 °C 2.1: 100 percent / MnO2 / hexane; CHCl3 / 12 h / 20 °C 3.1: n-BuLi / tetrahydrofuran; hexane / 1 h / -78 °C 3.2: tetrahydrofuran; hexane / 3 h / -78 °C 4.1: 118.2 mg / tetrahydrofuran; hexane / -78 - 20 °C 5.1: 99 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 6.1: 63 percent / KH2PO4; Na/Hg / ethanol; diethyl ether / 0.5 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1: 96 percent / AlCl3, LiAlH4 2: 100 percent / MnO2 3: 1.) nBuLi 4: n-Bu4NF 5: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

9-(2',6',6'-trimethylcyclohex-1'-enyl)-8-acetoxy-1-tert-butyldiphenylsiloxy-3,7-dimethyl-9-(p-tolylsulfonyl)nona-2Z,4E,6E-triene (463302-50-3) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 2: 63 percent / KH2PO4; Na/Hg / ethanol; diethyl ether / 0.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: n-Bu4NF 2: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

(3E,5E,7Z)-9-(tert-Butyl-diphenyl-silanyloxy)-3,7-dimethyl-1-(toluene-4-sulfonyl)-1-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-3,5,7-trien-2-ol → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 118.2 mg / tetrahydrofuran; hexane / -78 - 20 °C 2: 99 percent / TBAF / tetrahydrofuran / 0.5 h / 20 °C 3: 63 percent / KH2PO4; Na/Hg / ethanol; diethyl ether / 0.5 h / 20 °C View Scheme

β-cyclogeranyl p-tolyl sulfone → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) nBuLi 2: n-Bu4NF 3: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

C20H39NO4Si (181053-72-5) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 100 percent / n-Bu4NF 2: 98 percent 3: 96 percent / AlCl3, LiAlH4 4: 100 percent / MnO2 5: 1.) nBuLi 6: n-Bu4NF 7: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

[(2E)-3-ethoxycarbonylbut-2-enyl][1-isopropenyl-2-(tert-butyldimethylsiloxy)ethyl]dimethylammonium bromide → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: KOEt / ethanol / 5 h / -70 °C 2: peracetic acid, Na2CO3 / CH2Cl2 / -60 °C 3: 100 percent / n-Bu4NF 4: 98 percent 5: 96 percent / AlCl3, LiAlH4 6: 100 percent / MnO2 7: 1.) nBuLi 8: n-Bu4NF 9: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

(2E,6Z)-8-(tert-Butyl-dimethyl-silanyloxy)-4-dimethylamino-2,6-dimethyl-octa-2,6-dienoic acid ethyl ester (181053-71-4) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 8 steps 1: peracetic acid, Na2CO3 / CH2Cl2 / -60 °C 2: 100 percent / n-Bu4NF 3: 98 percent 4: 96 percent / AlCl3, LiAlH4 5: 100 percent / MnO2 6: 1.) nBuLi 7: n-Bu4NF 8: 63 percent / Na/Hg, KH2PO4, MeOH / diethyl ether / 0.5 h / Ambient temperature View Scheme

neryl acetate (141-12-8) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: SeO2, salicylic acid, tert-butyl hydroperoxide / CH2Cl2 / 27 h / Ambient temperature 2: PDC / CH2Cl2 / 10 h / Ambient temperature 3: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 4: p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 5: MeOK / cyclohexane / 2 h / 38 °C View Scheme
Multi-step reaction with 4 steps 1: SeO2, salicylic acid, tert-butyl hydroperoxide / CH2Cl2 / 27 h / Ambient temperature 2: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 3: p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 4: MeOK / cyclohexane / 2 h / 38 °C View Scheme

3,7-dimethyl-2E,6-octadien-1-yl acetate (105-87-3) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: SeO2, salicylic acid, tert-butyl hydroperoxide / CH2Cl2 / 27 h / Ambient temperature 2: PDC / CH2Cl2 / 10 h / Ambient temperature 3: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 4: 99 percent / p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 5: MeOK / cyclohexane / 2 h / 38 °C View Scheme
Multi-step reaction with 4 steps 1: SeO2, salicylic acid, tert-butyl hydroperoxide / CH2Cl2 / 27 h / Ambient temperature 2: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 3: 99 percent / p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 4: MeOK / cyclohexane / 2 h / 38 °C View Scheme

8-hydroxygeranyl acetate (37905-03-6) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: PDC / CH2Cl2 / 10 h / Ambient temperature 2: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 3: 99 percent / p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 4: MeOK / cyclohexane / 2 h / 38 °C View Scheme

(2E,6E)-3,7-dimethyl-8-oxoocta-2,6-dien-1-yl acetate (37905-02-5) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 2: 99 percent / p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 3: MeOK / cyclohexane / 2 h / 38 °C View Scheme

(2'Z,6'E)-Essigsaeure-(8'-hydroxy-3',7'-dimethyl-2',6'-octadien-1'-yl)ester (70238-37-8) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: PDC / CH2Cl2 / 10 h / Ambient temperature 2: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 3: p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 4: MeOK / cyclohexane / 2 h / 38 °C View Scheme

{[(2,6,6-trimethyl-1-cyclohexen-1-yl)methyl]sulfonyl}benzene (56691-74-8) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 2: 99 percent / p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 3: MeOK / cyclohexane / 2 h / 38 °C View Scheme
Multi-step reaction with 3 steps 1: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 2: p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 3: MeOK / cyclohexane / 2 h / 38 °C View Scheme
Multi-step reaction with 3 steps 1: n-BuLi / tetrahydrofuran / 5 h / -78 °C 2: p-toluenesulfonic acid / CH2Cl2 3: MeOK / cyclohexane / 2 h / 38 °C View Scheme

(2Z,6E)-3,7-dimethyl-8-oxoocta-2,6-dien-1-yl acetate (94853-00-6) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) n-BuLi / 1.) THF, -78 deg C, 2 h, 2.) THF, -78 deg C, 3 h 2: p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 3: MeOK / cyclohexane / 2 h / 38 °C View Scheme
Multi-step reaction with 3 steps 1: n-BuLi / tetrahydrofuran / 5 h / -78 °C 2: p-toluenesulfonic acid / CH2Cl2 3: MeOK / cyclohexane / 2 h / 38 °C View Scheme

Acetic acid (2Z,6E)-9-benzenesulfonyl-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,6-dienyl ester (105615-49-4) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 2: MeOK / cyclohexane / 2 h / 38 °C View Scheme
Multi-step reaction with 2 steps 1: p-toluenesulfonic acid / CH2Cl2 2: MeOK / cyclohexane / 2 h / 38 °C View Scheme

1-acetoxy-8-hydroxy-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-9-(phenylsulfonyl)-2(E),6(E)-nonadiene (103905-01-7) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / p-toluenesulfonic acid / CH2Cl2 / 3 h / Ambient temperature 2: MeOK / cyclohexane / 2 h / 38 °C View Scheme

5-hydroxy-4-methyl-5H-furan-2-one (40834-42-2) → 2-cis-Vitamin-A (2052-63-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 1.) NaH / 1.) HMPA, 0 deg C, 1 h, 2.) 20 min 2: 1.) ethylmagnesium bromide / 1.) THF, room temperature, 1 h, 2.) 15 min 3: 75 percent / DIBAH / tetrahydrofuran; toluene / 0.5 h / -78 °C 4: 90 percent / H2 / Lindlar catalyst / methanol / 24 h 5: 80 percent / imidazole / dimethylformamide / 18 h / Ambient temperature 6: 90 percent / LiAlH4, TiCl3 / tetrahydrofuran / 0.5 h / Ambient temperature 7: sodium fluoride, pyridinium fluoride / tetrahydrofuran; acetonitrile / 5 h / Ambient temperature View Scheme
Multi-step reaction with 7 steps 1: 85 percent / NaH / hexamethylphosphoric acid triamide 2: 90 percent / EtMgBr 3: 75 percent / DIBAL 4: 80 percent 5: 90 percent / H2 / Lindlar catalist 6: 90 percent / LiAlH4,TiCl3 / tetrahydrofuran / 0.5 h / Ambient temperature 7: NaF, pyridiniumfluoride / Ambient temperature View Scheme

pyridine (110-86-1) + 2-cis-Vitamin-A (2052-63-3) + acetyl chloride (75-36-5) → (7E,9E,11E,13Z)-retinyl acetate (34356-31-5)

Conditions	Yield
With 1,2-dichloro-ethane

pyridine (110-86-1) + 2-cis-Vitamin-A (2052-63-3) + n-hexadecanoyl chloride (112-67-4) → 9-Palmitoyloxy-3.7-dimethyl-1t-(2.2.6-trimethyl-cyclohexen-(6)-yl)-nonatetraen-(1.3t.5t.7c) (26771-20-0)

Conditions	Yield
With 1,2-dichloro-ethane

2-cis-Vitamin-A (2052-63-3) → 13-cis-vitamin A aldehyde (472-86-6)

Conditions	Yield
With manganese(IV) oxide; Petroleum ether unter Lichtausschluss;
With manganese(IV) oxide
With manganese(IV) oxide In tetrachloromethane for 0.5h;

4-phenylazobenzoyl chloride (104-24-5) + 2-cis-Vitamin-A (2052-63-3) → 9-(4-Phenylazo-benzoyloxy)-3.7-dimethyl-1t-(2.2.6-trimethyl-cyclohexen-(6)-yl)-nonatetraen-(1.3t.5t.7c) (50696-24-7, 50837-87-1, 105616-34-0)

2-cis-Vitamin-A (2052-63-3) + anthraquinone-2-carbonyl chloride (6470-87-7) → O-(9.10-dioxo-9.10-dihydro-anthracenecarbonyl-(2))-[7t.9t.11t.13c]retinol (107892-29-5)

Conditions	Yield
With pyridine; dichloromethane

2-cis-Vitamin-A (2052-63-3) + acetic anhydride (108-24-7) → 9-cis-retinol (68-26-8, 2052-63-3, 6018-74-2, 17706-49-9, 22737-96-8, 29444-25-5, 34218-73-0, 39815-04-8, 69686-68-6, 69686-69-7, 74743-94-5, 84415-27-0, 84415-28-1, 85354-09-2, 85354-10-5, 93380-02-0, 98462-62-5, 137121-52-9, 22737-97-9) + 9cis,13cis-retinyl acetate (29444-27-7) + (7E,9E,11E,13Z)-retinyl acetate (34356-31-5) + 11,13-di-cis-Vitamin-A-acetat (63568-38-7)

Conditions	Yield
With triethylamine In hexane Yield given;

2-cis-Vitamin-A (2052-63-3) + acetic anhydride (108-24-7) → 9cis,13cis-retinyl acetate (29444-27-7) + (7E,9E,11E,13Z)-retinyl acetate (34356-31-5) + 11,13-di-cis-Vitamin-A-acetat (63568-38-7)

Conditions	Yield
With triethylamine In hexane Yield given;

2-cis-Vitamin-A (2052-63-3) + propargyl bromide (106-96-7) → 2-((1E,3E,5E,7Z)-3,7-Dimethyl-9-prop-2-ynyloxy-nona-1,3,5,7-tetraenyl)-1,3,3-trimethyl-cyclohexene (173010-18-9)

Conditions	Yield
With n-butyllithium 1.) benzene, hexane, 20 deg C, 5 min, 2.) benzene, DMF, hexane, RT, 4 h; Yield given. Multistep reaction;

hydrogenchloride (7647-01-0) + 2-cis-Vitamin-A (2052-63-3) → anhydrovitamin-A1

Conditions	Yield
Kinetics; Dehydratisierung;

2-cis-Vitamin-A (2052-63-3) + iodine (7553-56-2) + benzene (71-43-2) → O--derivative of all-trans-retinol

Conditions	Yield
Gleichgewichtsgemisch mit dem O--Derivat unter der Einwirkung von Tageslicht;

Upstream product

• 16760-45-5 (2Z,4E,6E,8E)-methyl 3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoate 
• 103905-07-3 Acetic acid (2Z,6E)-9-benzenesulfonyl-3,7-dimethyl-8-(tetrahydro-pyran-2-yloxy)-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,6-dienyl ester 
• 103905-07-3 1-acetoxy-3,7-dimethyl-8-(tetrahydropyran-2-yl)oxy-9-phenylsulfonyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2(E),6(E)-nonadiene 
• 37905-03-6 8-hydroxygeranyl acetate 
• 37905-02-5 (2E,6E)-3,7-dimethyl-8-oxoocta-2,6-dien-1-yl acetate 
• 116-31-4 all-trans-Retinal 
• 68-26-8 RETINOL 
• 58526-50-4 [7t,9c,11t,13t]retinoic acid methyl ester 
• 108-24-7 acetic anhydride 
• 210700-52-0 tert-butyldimethylsilyl (7E,9Z,11E,13E)-retinyl ether 
• 79-81-2 retinyl palmitate 
• 3917-41-7 (2E,4E)-3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienal 
• 111724-05-1 <(2E)-4-hydroxy-2-methyl-2-butenyl>triphenylphosphonium bromide 
• 29443-88-7 (2E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,6,8-trien-4-yn-1-ol 

Downstream Products

• 34356-31-5 (7E,9E,11E,13Z)-retinyl acetate 
• 26771-20-0 9-Palmitoyloxy-3.7-dimethyl-1t-(2.2.6-trimethyl-cyclohexen-⁽⁶⁾-yl)-nonatetraen-(1.3t.5t.7c) 
• 472-86-6 13-cis-vitamin A aldehyde 
• 514-85-2 9-cis vitamin A aldehyde 
• 107892-29-5 O-(9.10-dioxo-9.10-dihydro-anthracenecarbonyl-⁽²⁾)-[7t.9t.11t.13c]retinol 
• 3899-20-5 ethyl retinoate 
• 68-26-8 9-cis-retinol 
• 29444-27-7 9cis,13cis-retinyl acetate 
• 63568-38-7 11,13-di-cis-Vitamin-A-acetat 
• 564-87-4 (11Z)-retinal 
• 56085-55-3 7-cis,9-cis,13-cis-retinal 
• 116-31-4 7-cis,9-cis,11-cis-retinal 
• 173010-18-9 2-((1E,3E,5E,7Z)-3,7-Dimethyl-9-prop-2-ynyloxy-nona-1,3,5,7-tetraenyl)-1,3,3-trimethyl-cyclohexene 
• 302-79-4 9-cis-retinoic acid 

Relevant articles and documents

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.

Substrate specificity and subcellular localization of the aldehyde-Alcohol redox-Coupling reaction in carp cones

Our previous study suggested the presence of a novel conespecific redox reaction that generates 11-cis-retinal from 11-cisretinol in the carp retina. This reaction is unique in that 1) both 11-cis-retinol and all-trans-retinal were required to produce 11-cis-retinal; 2) together with 11-cis-retinal, all-trans-retinol was produced at a 1:1 ratio; and 3) the addition of enzyme cofactors such as NADP(H) was not necessary. This reaction is probably part of the reactions in a cone-specific retinoid cycle required for cone visual pigment regeneration with the use of 11-cis-retinol supplied from Mueller cells. In this study, using purified carp cone membrane preparations, we first confirmed that the reaction is a redox-coupling reaction between retinals and retinols. We further examined the substrate specificity, reaction mechanism, and subcellular localization of this reaction. Oxidation was specific for 11-cis-retinol and 9-cis-retinol. In contrast, reduction showed low specificity: many aldehydes, including all-trans-, 9-cis-, 11-cis-, and 13-cis-retinals and even benzaldehyde, supported the reaction. On the basis of kinetic studies of this reaction (aldehyde-alcohol redox-coupling reaction), we found that formation of a ternary complex of a retinol, an aldehyde, and a postulated enzyme seemed to be necessary, which suggested the presence of both the retinol- and aldehydebinding sites in this enzyme. A subcellular fractionation study showed that the activity is present almost exclusively in the cone inner segment. These results suggest the presence of an effective production mechanism of 11-cis-retinal in the cone inner segment to regenerate visual pigment.