96829-59-3

Basic information

• Product Name: Lipstatin
• Synonyms: N-Formyl-L-leucine (1S,3Z,6Z)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]-3,6-dodecadien-1-yl ester;(-)-Lipstatin N-Formyl-L-leucine (1S,3Z,6Z)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]-3,6-dodecadien-1-yl ester;Orlistat Tetradehydro Impurity;Lipstatin;L-Leucine, N-formyl-,(1S,3Z,6Z)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]-3,6-dodecadien-1-ylester;(2S-(2alpha(1R*,3Z,6Z),3beta))-N-Formyl-L-leucine 1-((3-hexyl-4-oxo-2-oxetanyl)methyl)-3,6-dodecadienyl ester;Lipstatin Solution, 100ppm
• CAS NO: 96829-59-3
• Molecular Formula: C₂₉H₄₉NO₅
• Molecular Weight: 491.708
• EINECS: 1308068-626-2
• Product Categories: Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Amino Acids & Derivatives
• Mol File: 96829-59-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 627.402 °C at 760 mmHg
• Flash Point: 333.241 °C
• Appearance: /
• Density: 0.993
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.485
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• PKA: 14.57±0.23(Predicted)
• CAS DataBase Reference: Lipstatin(CAS DataBase Reference)
• NIST Chemistry Reference: Lipstatin(96829-59-3)
• EPA Substance Registry System: Lipstatin(96829-59-3)

Safety Data

• Hazardous Substances Data: 96829-59-3(Hazardous Substances Data)

Usage

Description

Lipstatin, also known as Orlistat, is a potent and irreversible inhibitor of pancreatic lipase, an enzyme responsible for the breakdown of dietary fats. It is produced by the bacterium Streptomyces toxytricini and was first reported in 1987. Lipstatin works by blocking the absorption of triglycerides in the gastrointestinal tract, while still allowing the absorption of essential fatty acids. This mechanism of action makes it a promising candidate for the treatment and prevention of obesity and related diseases.

Uses

Used in Pharmaceutical Industry:
Lipstatin is used as an anti-obesity drug for the treatment and prevention of obesity and related diseases. It functions by inhibiting pancreatic lipase, which in turn reduces the absorption of dietary fats and caloric intake, promoting weight loss and management.
Used in Weight Management:
Lipstatin is used as a weight management aid to help individuals reduce their body weight and maintain a healthy lifestyle. By inhibiting the absorption of triglycerides, it helps to decrease overall caloric intake and supports weight loss efforts.
Used in Treatment of Obesity-Related Diseases:
Lipstatin is used as a therapeutic agent for the treatment of obesity-related diseases, such as type 2 diabetes, hypertension, and cardiovascular diseases. By reducing the absorption of dietary fats and promoting weight loss, it can help improve the overall health and well-being of individuals suffering from these conditions.
Used in Development of Orlistat:
The tetrahydro analogue of lipstatin, known as orlistat, was developed as a less potent but more suitable alternative for the treatment of obesity. Orlistat has been approved for use in various countries and is available as a prescription medication or over-the-counter weight loss aid. It offers a more convenient and accessible option for individuals seeking to manage their weight and improve their health.

InChI:InChI=1/C29H49NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h12-13,15-16,22-27H,5-11,14,17-21H2,1-4H3,(H,30,31)/b13-12-,16-15-/t24-,25-,26-,27-/m0/s1

Synthetic route

N-formyl-L-leucine (5338-45-4, 44978-39-4, 89921-44-8, 6113-61-7) + 4-<(4Z,7Z)-2-hydroxytrideca-4,7-dienyl>-3-hexyloxetan-2-one (108102-73-4) → (-)-lipstatin (96829-59-3)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran for 1.5h; 0 deg C to RT;	50%

(Z)-non-3-en-1-ol (10340-23-5) → (-)-lipstatin (96829-59-3)

Conditions

Yield

Multi-step reaction with 8 steps 1: 90 percent / PPh3Br2, pyridine / acetonitrile / 1 h / -7 to RT 2: 100 percent / acetonitrile / 48 h / Heating 3: 86 percent / NaN(SiMe3)2 / tetrahydrofuran / 12 h / -100 deg C to RT 4: 93 percent / DIBAH / CH2Cl2 / 1 h / -90 °C 5: 81 percent / EtAlCl2 / diethyl ether; hexane / 2.5 h / -40 to -20 deg C 6: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 7: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 8: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

(Z)-3-nonenal (31823-43-5) → (-)-lipstatin (96829-59-3)

Conditions

Yield

Multi-step reaction with 9 steps 1: LiAlH4 / tetrahydrofuran / 2.5 h / -90 to -20 deg C 2: 90 percent / PPh3Br2, pyridine / acetonitrile / 1 h / -7 to RT 3: 100 percent / acetonitrile / 48 h / Heating 4: 86 percent / NaN(SiMe3)2 / tetrahydrofuran / 12 h / -100 deg C to RT 5: 93 percent / DIBAH / CH2Cl2 / 1 h / -90 °C 6: 81 percent / EtAlCl2 / diethyl ether; hexane / 2.5 h / -40 to -20 deg C 7: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 8: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 9: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

(3Z)-1-bromo-3-nonene (136695-81-3, 60705-54-6) → (-)-lipstatin (96829-59-3)

Conditions

Yield

Multi-step reaction with 7 steps 1: 100 percent / acetonitrile / 48 h / Heating 2: 86 percent / NaN(SiMe3)2 / tetrahydrofuran / 12 h / -100 deg C to RT 3: 93 percent / DIBAH / CH2Cl2 / 1 h / -90 °C 4: 81 percent / EtAlCl2 / diethyl ether; hexane / 2.5 h / -40 to -20 deg C 5: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 6: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 7: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

(Z)-3-nonenal diisopropyl acetal (120018-49-7) → (-)-lipstatin (96829-59-3)

Conditions

Yield

Multi-step reaction with 10 steps 1: p-TsOH / H2O; tetrahydrofuran / 0.17 h / Heating 2: LiAlH4 / tetrahydrofuran / 2.5 h / -90 to -20 deg C 3: 90 percent / PPh3Br2, pyridine / acetonitrile / 1 h / -7 to RT 4: 100 percent / acetonitrile / 48 h / Heating 5: 86 percent / NaN(SiMe3)2 / tetrahydrofuran / 12 h / -100 deg C to RT 6: 93 percent / DIBAH / CH2Cl2 / 1 h / -90 °C 7: 81 percent / EtAlCl2 / diethyl ether; hexane / 2.5 h / -40 to -20 deg C 8: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 9: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 10: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

[(3Z)-3-nonen-1-yl]triphenylphosphonium bromide (85924-42-1) → (-)-lipstatin (96829-59-3)

Conditions

Yield

Multi-step reaction with 6 steps 1: 86 percent / NaN(SiMe3)2 / tetrahydrofuran / 12 h / -100 deg C to RT 2: 93 percent / DIBAH / CH2Cl2 / 1 h / -90 °C 3: 81 percent / EtAlCl2 / diethyl ether; hexane / 2.5 h / -40 to -20 deg C 4: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 5: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 6: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

hexanal (66-25-1) → (-)-lipstatin (96829-59-3)

Conditions

Yield

Multi-step reaction with 11 steps 1: 100 percent / NaN(SiMe3)2 / tetrahydrofuran / 12 h / -100 deg C to RT 2: p-TsOH / H2O; tetrahydrofuran / 0.17 h / Heating 3: LiAlH4 / tetrahydrofuran / 2.5 h / -90 to -20 deg C 4: 90 percent / PPh3Br2, pyridine / acetonitrile / 1 h / -7 to RT 5: 100 percent / acetonitrile / 48 h / Heating 6: 86 percent / NaN(SiMe3)2 / tetrahydrofuran / 12 h / -100 deg C to RT 7: 93 percent / DIBAH / CH2Cl2 / 1 h / -90 °C 8: 81 percent / EtAlCl2 / diethyl ether; hexane / 2.5 h / -40 to -20 deg C 9: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 10: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 11: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

(R)-(Z,Z)-3-<(tert-Butyldimethylsilyl)oxy>-5,8-tetradecadienal (151509-74-9) → (-)-lipstatin (96829-59-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 81 percent / EtAlCl2 / diethyl ether; hexane / 2.5 h / -40 to -20 deg C 2: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 3: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 4: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

Methyl (R)-(Z,Z)-3-<(tert-butyldimethylsilyl)oxy>-5,8-tetradecadienoate (151509-75-0) → (-)-lipstatin (96829-59-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 93 percent / DIBAH / CH2Cl2 / 1 h / -90 °C 2: 81 percent / EtAlCl2 / diethyl ether; hexane / 2.5 h / -40 to -20 deg C 3: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 4: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 5: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

3-Hexyl-4-((4Z,7Z)-(R)-2-hydroxy-trideca-4,7-dienyl)-3-trimethylsilanyl-oxetan-2-one → (-)-lipstatin (96829-59-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 2: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

4-((4Z,7Z)-2-<1,1-dimethylethyl(dimethyl)silyloxy>trideca-4,7-dienyl)-3-trimethylsilyl-3-hexyloxetan-2-one → (-)-lipstatin (96829-59-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 77 percent / 40percent aq. HF / acetonitrile / 12 h / 0 deg C to RT 2: 70 percent / Bu4NF / tetrahydrofuran / 0.25 h / -90 °C 3: 50 percent / PPh3, diethyl azodicarboxylate / tetrahydrofuran / 1.5 h / 0 deg C to RT View Scheme

(-)-lipstatin (96829-59-3) → Orlistat (104872-04-0, 104872-27-7, 104872-28-8, 111466-61-6, 111466-62-7, 111466-63-8, 130193-40-7, 130193-41-8, 130193-42-9, 130193-43-0, 96829-58-2)

Conditions	Yield
With sodium tetrahydroborate; (R,R)-(-)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine cobalt; copper(l) chloride In acetonitrile at 15℃; Temperature; Reagent/catalyst; Inert atmosphere;	95.2%
carbon palladium In ethanol

(-)-lipstatin (96829-59-3) → 1-(3-hexyl-4-oxo-oxetan-2-yl)tridecan-2-yl 2-formylamino-4-methylpentanoate

Conditions	Yield
Stage #1: (-)-lipstatin With pyrographite In methanol; H20 for 0.5h; Stage #2: With hydrogen; palladium 10% on activated carbon In methanol; water under 3677.86 Torr; for 8h;
Stage #1: (-)-lipstatin With pyrographite In H20; isopropyl alcohol for 0.5h; Stage #2: With hydrogen; palladium 10% on activated carbon In methanol; water under 2942.29 Torr; for 6h;
Stage #1: (-)-lipstatin With pyrographite In H20; ethanol for 0.5h; Stage #2: With hydrogen; palladium 10% on activated carbon In methanol; water under 2206.72 Torr; for 5h;

Upstream product

• 5338-45-4 N-formyl-L-leucine 
• 108102-73-4 4-<(4Z,7Z)-2-hydroxytrideca-4,7-dienyl>-3-hexyloxetan-2-one 
• 10340-23-5 (Z)-non-3-en-1-ol 
• 31823-43-5 (Z)-3-nonenal 
• 136695-81-3 1-bromo-non-3-cis-ene 
• 151509-75-0 Methyl (R)-(Z,Z)-3-<(tert-butyldimethylsilyl)oxy>-5,8-tetradecadienoate 
• 151509-74-9 (R)-(Z,Z)-3-<(tert-Butyldimethylsilyl)oxy>-5,8-tetradecadienal 
• 66-25-1 hexanal 
• 85924-42-1 [(3Z)-3-nonen-1-yl]triphenylphosphonium bromide 
• 120018-49-7 (Z)-3-nonenal diisopropyl acetal 

Downstream Products

• 104872-04-0 Orlistat 
• 1225451-00-2 orlistat 

Relevant articles and documents

An Approach to the Syntheiss of (-)-Lipstatin by Wittig Reaction and Lewis Acid-promoted Cycloaddition

The β-lactone moiety of (-)-lipstatin 1, a potent inhibitor of pancreatic lipase, is prepared via a Lewis acid-promoted cycloaddition between hexyltrimethylsilyl ketene 3 and the (Z,Z)-dienic aldehyde 4, obtained from hexenal by two stereoselective Wittig reactions.