104872-06-2

Basic information

• Product Name: (3S,4S)-3-HEXYL-4-[(R)-2-(HYDROXYTRIDECYL)]OXETAN-2-ONE
• Synonyms: (3S,4S)-3-Hexyl-4-[(2R)-2-hydroxytridecyl]-2-oxetanone;Orlistat Related Compound A (25 mg) ((3S,4S)-3-hexyl-4-[(R)-2-hydroxytridecyl]-2-oxetanone);[3S-[3α,4β(S*)]]-3-Hexyl-4-(2-hydroxytridecyl)-2-oxetanone;Orlistat USP RC A;Orlistat Related CoMpound A;2-Oxetanone,3-hexyl-4-[(2R)-2-hydroxytridecyl]-, (3S,4S)-;Orlistat USP Related Compound A;(3S,4S)-3-HEXYL-4-[(R)-2-(HYDROXYTRIDECYL)]OXETAN-2-ONE
• CAS NO: 104872-06-2
• Molecular Formula: C₂₂H₄₂O₃
• Molecular Weight: 354.57
• EINECS: 418-650-2
• Mol File: 104872-06-2.mol

Chemical Properties

• Melting Point: 61-62 °C
• Boiling Point: 467.9 °C at 760 mmHg
• Flash Point: 176.2 °C
• Appearance: /
• Density: 0.935
• Vapor Pressure: 1.01E-10mmHg at 25°C
• Refractive Index: 1.467
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 14.71±0.20(Predicted)
• CAS DataBase Reference: (3S,4S)-3-HEXYL-4-[(R)-2-(HYDROXYTRIDECYL)]OXETAN-2-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: (3S,4S)-3-HEXYL-4-[(R)-2-(HYDROXYTRIDECYL)]OXETAN-2-ONE(104872-06-2)
• EPA Substance Registry System: (3S,4S)-3-HEXYL-4-[(R)-2-(HYDROXYTRIDECYL)]OXETAN-2-ONE(104872-06-2)

Safety Data

• Hazard Codes: N
• Statements: 50/53
• Safety Statements: 60-61
• Hazardous Substances Data: 104872-06-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(3S,4S)-3-HEXYL-4-[(R)-2-(HYDROXYTRIDECYL)]OXETAN-2-ONE is used as an intermediate in the preparation of Orlistat (O686500) for its role in inhibiting the hydrolysis of endocannabinoid 2-arachidonoylglycerol (2-AG). This application is significant in the development of medications targeting weight management and obesity-related conditions.
Used in Research and Development:
As an analog of Tetrahydrolipstatin, (3S,4S)-3-HEXYL-4-[(R)-2-(HYDROXYTRIDECYL)]OXETAN-2-ONE is utilized in research and development for understanding the mechanisms of endocannabinoid hydrolysis and its implications in various physiological processes. This knowledge can lead to the discovery of new therapeutic approaches and treatments for a range of health conditions.

InChI:InChI=1/C22H42O3/c1-3-5-7-9-10-11-12-13-14-16-19(23)18-21-20(22(24)25-21)17-15-8-6-4-2/h19-21,23H,3-18H2,1-2H3/t19-,20+,21+/m1/s1

Upstream product

• 68711-31-9 tetrahydroesterastin 
• 134453-13-7 (2S,3S,5S)-5-(benzyloxy)-2-hexyl-3-hydroxyhexadecanoic acid 
• 134453-14-8 (3S,4S,2'S)-3-hexyl-4-(2'-benzyloxytridec-1'-yl)oxetan-2-one 
• 239136-79-9 (S)-3-(2-methoxyprop-2-oxy)tetradecanal 
• 658075-64-0 (2S,3E,5S)-2-hexyl-5-hydroxyhexadec-3-enoic acid 
• 112-54-9 Dodecanal 
• 250138-58-0 (1S,4S,6S)-4-Undecyl-3,7-dioxa-bicyclo[4.1.0]heptan-2-one 
• 250138-62-6 (2S,3S,5S)-2-Hexyl-3-hydroxy-5-(tetrahydro-pyran-2-yloxy)-hexadecanoic acid methyl ester 
• 81017-06-3 (6RS)-6-undecyl-5,6-dihydro-2-pyranone 
• 130645-86-2 (E)-1-dimethyl(phenyl)silyltridec-1-ene 
• 214683-72-4 (Z)-(2R,3S)-3-(Dimethyl-phenyl-silanyl)-2-hexyl-hexadec-4-en-1-ol 
• 130625-77-3 ({(Z)-(S)-1-[(R)-1-(tert-Butyl-dimethyl-silanyloxymethyl)-heptyl]-tetradec-2-enyl}-dimethyl-silanyl)-benzene 
• 130625-75-1 (Z)-3-(Dimethyl-phenyl-silanyl)-hexadec-4-enoic acid benzyl ester 
• 130625-78-4 (7R,8S,10S)-7-(tert-Butyl-dimethyl-silanyloxymethyl)-8-(dimethyl-phenyl-silanyl)-henicosan-10-ol 

Downstream Products

• 68711-41-1 (S,E)-Henicos-7-en-10-ol 
• 104872-04-0 Orlistat 
• 1072902-86-3 N-[(phenylmethoxy)carbonyl]-β-alanine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 
• 1072902-85-2 N-[(phenylmethoxy)carbonyl]-L-alanine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 
• 1072902-87-4 N-[(phenylmethoxy)carbonyl]-L-valine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 
• 1072902-69-2 N-[(phenylmethoxy)carbonyl]-D-leucine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 
• 1072902-79-4 N-[(phenylmethoxy)carbonyl]-L-phenylalanine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 
• 1072902-88-5 N-[(phenylmethoxy)carbonyl]-L-isoleucine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 
• 1072902-72-7 N-[(phenylmethoxy)carbonyl]-glycine-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 
• 1072902-89-6 N-[(phenylmethoxy)carbonyl]-L-proline-(1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester 
• 1310352-51-2 (S)-1-((2S,3S)-3-hexyl-4-oxooxetan-2-yl)tridecan-2-yl 4-fluorobenzoate 
• 1310352-62-5 C₃₅H₅₅NO₆ 
• 1398817-33-8 C₃₄H₅₅NO₆ 
• 1398816-88-0 C₃₆H₅₉NO₆ 

Relevant articles and documents

One-step modification to identify dual-inhibitors targeting both pancreatic triglyceride lipase and Niemann-Pick C1-like 1

Pancreatic triglyceride lipase (PTL) and Niemann-Pick C1-like 1 (NPC1L1) have been identified as attractive therapeutic targets for obesity and hypercholesteremia, respectively. Obesity and hypercholesteremia usually co-exist, however no dual-inhibitors against PTL and NPC1L1 were reported for the treatment of obesity patients with hypercholesteremia so far. In this work, molecular hybridization-based one-step modification screening identified a potent dual-inhibitor against PTL and NPC1L1. Compound P1-11 has IC50 values of 2.1 μM against PTL through covalent binding, as well as significantly reduces cholesterol absorption in a non-competitive inhibitory manner. Molecule docking and molecular dynamics studies revealed the reason of its activity to both PTL and NPC1L1. Moreover, the gene and protein expression levels of PTL and NPC1L1 were also determined respectively after the treatment of P1-11. Development of dual-inhibitors against PTL and NPC1L1 could provide novel treatment options for obesity patients with hypercholesteremia. The results of current research would great support the development of dual-inhibitors against PTL and NPC1L1.

Refining method for key intermediate of orlistat

The invention discloses a refining method for a key intermediate of orlistat as well as key intermediate impurities and a preparation method thereof. The refining method comprises the step that a compound I is recrystallized in an organic solvent or a mixed organic solvent to remove impurities 1-5 which are difficult to remove in a process. The method has good selectivity on the impurities 1-5, and is simple and convenient to operate, low in cost and suitable for industrial production. The invention also provides an impurity 3 and a preparation method thereof, and application of the impurity 3 as an impurity reference substance of an orlistat key intermediate (3S,4S)-3-hexyl-4-[(R)-2-(hydroxytridecyl)]oxetan-2-one (the compound I).

Total Synthesis of Tetrahydrolipstatin, Its Derivatives, and Evaluation of Their Ability to Potentiate Multiple Antibiotic Classes against Mycobacterium Species

Tetrahydrolipstatin (THL, 1a) has been shown to inhibit both mammalian and bacterial α/β hydrolases. In the case of bacterial systems, THL is a known inhibitor of several Mycobacterium tuberculosis hydrolases involved in mycomembrane biosynthesis. Herein we report a highly efficient eight-step asymmetric synthesis of THL using a route that allows modification of the THL α-chain substituent to afford compounds 1a through 1e. The key transformation in the synthesis was use of a (TPP)CrCl/Co2(CO)8-catalyzed regioselective and stereospecific carbonylation on an advanced epoxide intermediate to yield a trans-β-lactone. These compounds are modest inhibitors of Ag85A and Ag85C, two α/β hydrolases of M. tuberculosis involved in the biosynthesis of the mycomembrane. Among these compounds, 10d showed the highest inhibitory effect on Ag85A (34 ± 22 μM) and Ag85C (66 ± 8 μM), and its X-ray structure was solved in complex with Ag85C to 2.5 ? resolution. In contrast, compound 1e exhibited the best-in-class MICs of 50 μM (25 μg/mL) and 16 μM (8.4 μg/mL) against M. smegmatis and M. tuberculosis H37Ra, respectively, using a microtiter assay plate. Combination of 1e with 13 well-established antibiotics synergistically enhanced the potency of few of these antibiotics in M. smegmatis and M. tuberculosis H37Ra. Compound 1e applied at concentrations 4-fold lower than its MIC enhanced the MIC of the synergistic antibiotic by 2-256-fold. In addition to observing synergy with first-line drugs, rifamycin and isoniazid, the MIC of vancomycin against M. tuberculosis H37Ra was 65 μg/mL; however, the MIC was lowered to 0.25 μg/mL in the presence of 2.1 μg/mL 1e demonstrating the potential of targeting mycobacterial hydrolases involved in mycomembrane and peptidoglycan biosynthesis.

COMPOUNDS FOR THE REDUCING LIPOTOXIC DAMAGE

Provided herein are novel lipase inhibitors and methods for using the same to treat inflammation, multisystem organ failure, necrotic pancreatic acinar cell death, acute pancreatitis, sepsis (e.g., culture negative sepsis), burns, and acne. For example, provided herein are two novel lipase inhibitors useful in the methods described herein: (I) (II) or a pharmaceutically acceptable salt thereof.

Orlistat derivatives

The invention relates to orlistat derivatives. In particular, the invention relates to the general formula (I) compound of formula, wherein R such as specification and defined in the claims. The general formula (I) indicated by the compounds can be used as anti-tumor and inhibit lipase activity of the drug.

Asymmetric syntheses of the lactone core of tetrahydrolipstatin and tetrahydroesterastin and of the oriental hornet Vespa Orientalis pheromone

Abstract A synthetic approach to the lactone core of the anti-obesity drugs tetrahydrolipstatin and tetrahydroesterastin has been developed starting from readily accessible methyl (5S)-5-{[tert-butyl(dimethyl)silyl]-oxy}-3-oxohexadecanoate. (6S)-6-Undecyltetrahydro-2H-pyran-2-one, the oriental hornet Vespa Orientalis pheromone, has also been synthesized. A formal synthesis of (3S,4R,6S)-dihydroxy-6-undecyltetrahydro-2H-pyran-2-one (metabolite of a fungus separated from mangrove seeds) has been proposed.

Total synthesis of tetrahydrolipstatin and stereoisomers via a highly regio- and diastereoselective carbonylation of epoxyhomoallylic alcohols

A concise enantioselective synthesis of tetrahydrolipstatin (THL) and seven stereoisomers has been achieved. The synthesis of THL was accomplished in 10 steps and 31% overall yield from an achiral ynone. Key to the success of the approach is the use of a bimetallic [Lewis acid]+[Co(CO)4]- catalyst for a late-stage regioselective carbonylation of an enantiomerically pure cis-epoxide to a trans-β-lactone. The success of this route to THL and its stereoisomers also demonstrated the practicality of the carbonylation catalyst for complex molecule synthesis as well as its functional group compatibility.

MNBA-mediated β-lactone formation: Mechanistic studies and application for the asymmetric total synthesis of tetrahydrolipstatin

Various β-lactones were prepared from β-hydroxycarboxylic acids by intramolecular dehydration condensation using MNBA, an effective coupling reagent, along with a nucleophilic catalyst. The transition state that provides the desired 4-membered ring model system is disclosed by density functional theory (DFT) calculations, and the structural features of the transition form are discussed. This method was successfully applied to the asymmetric total synthesis of tetrahydrolipstatin (THL), an antiobestic drug used in clinical treatment to inhibit the activity of pancreatic lipase.

THE PREPARATION METHOD OF (3S,4S)-3-HEXYL-4-((R)-2-HYDROXYTRIDECYL)-OXETAN-2-ONE AND THE PRODUCT OF THAT METHOD

The present invention relates to a method for the preparation of (3S,4S)-3-hexyl-4-((R)-2-hydroxytridecyl)-oxetan-2-one and a product of the method. The method includes the following steps: a) reducing a substance represented by formula (II) to obtain a substance represented by formula (III), and then oxidizing the substance represented by formula (III) to form a substance represented by formula (IV); b) acylating n-octanoic acid to obtain n-octanoyl chloride using thionyl dichloride, then condensing the obtained n-octanoyl chloride with 2-mercapto-pyridine under basic condition to form a substance represented by formula (V), and then converting the substance represented by formula (V) to a substance represented by formula (VI); c) reacting the substance obtained in the step a) with the substance obtained in the step b) under catalytic condition of Lewis acid to generate a substance represented by formula (VII), and then reacting with a Lewis acid. The meanings of the signs in these formulas are the same as those in the description.

Inhibitors of an essential mycobacterial cell wall lipase (Rv3802c) as tuberculosis drug leads

The first targeted inhibitors of an essential M. tuberculosis cell wall lipase, Rv3802c, are described. Lead compounds exhibited nanomolar inhibition of the enzyme, and encouraging antibacterial activity against M. tuberculosis in vitro, supporting Rv3802c as a novel TB drug target.