333963-40-9

Basic information

• Product Name: lubiprostone
• Synonyms: (2R,4aR,5R,7aR)-2-(1,1-Difluoropentyl)-2-hydroxy-6-oxo-3,4,4a,5,7,7a-hexahydrocyclopenta[b]pyran-5-heptanoic acid;Lubiprostone;Prostan-1-oic acid, 11,15-epoxy-16,16-difluoro-15-hydroxy-9-oxo-, (11alpha,15R)-;Spi 0211;Unii-7662kg2R6k;(2R,4aR,5R,7aR)-2-(1,1-Difluoropentyl)-2-hydroxy-6-oxo-3,4,4a,5,7,7a-hexahydrocyclopenta[b]pyran-5-h;7-((1R,2R,3R)-2-(4,4-difluoro-3-oxooctyl)-3-hydroxy-5-oxocyclopentyl)heptanoic acid;AMitiza Lubiprostone
• CAS NO: 333963-40-9
• Molecular Formula: C₂₀H₃₂F₂O₅
• Molecular Weight: 390.46
• EINECS: 1312995-182-4
• Product Categories: API
• Mol File: 333963-40-9.mol

Chemical Properties

• Boiling Point: 532.3 °C at 760 mmHg
• Flash Point: 275.7 °C
• Appearance: /
• Density: 1.175
• Vapor Pressure: 1.49E-13mmHg at 25°C
• Refractive Index: 1.486
• Storage Temp.: -20°C Freezer
• PKA: 4.77±0.10(Predicted)
• CAS DataBase Reference: lubiprostone(CAS DataBase Reference)
• NIST Chemistry Reference: lubiprostone(333963-40-9)
• EPA Substance Registry System: lubiprostone(333963-40-9)

Safety Data

• Hazardous Substances Data: 333963-40-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Lubiprostone is used as a treatment for chronic idiopathic constipation in adults, addressing the need for novel agents to combat this condition that affects 4-5 million Americans and is often refractory to traditional therapy.
Lubiprostone is used as a treatment for constipation associated with irritable bowel syndrome (IBS-C), providing relief for patients suffering from this condition by increasing intestinal water secretion and chloride ion concentration, which helps to alleviate constipation symptoms.

Originator

Sucampo (US)

Synthesis

Synthesis of lupiprostone started with the tetrahydropyran (THP) protected (-)Corey lactone 30. Desilylation of 30 with TBAF in THF gave free carbinol in 82% yield which was oxidized with oxalyl chloride and DMSO to give corresponding crude aldehyde 31. Aldehyde 31 was condensed with dimethyl 3,3,-difluoro-2-oxoheptylphosphonate (32) in the presence of thallium ethoxide to give unsaturated difluoroketone 33 which was hydrogenated with H2 over Pd/C in ethyl acetate and the resulting ketone was subsequently reduced with sodium borohydride in methanol to give lactone 34 in excellent yield. The lactone 34 was reduced to lactol 35 with DIBAL at -78°C in toluene and the crude lactol 35 was condensed with 4-carboxybutyl triphenylphosphonium bromide (36) in the presence of t-BuOK in THF to yield compound 37. Crude 37 was reacted with benzyl bromide and DBU in dichloromethane (DCM) to give the benzyl ester in 96% yield. Oxidation of the alcohol with Collins reagent and removal of the THP protecting group under acidic conditions gave corresponding prostaglandin E2 benzyl ester 38. Finally, compound 38 was submitted to simultaneous benzyl ester group cleavage and double bond hydrogenation with H2 over Pd/C in ethyl acetate to give lubiprostone (V) in 94% yield.

InChI:InChI=1/C20H32F2O5/c1-2-3-11-19(21,22)20(26)12-10-15-14(16(23)13-17(15)27-20)8-6-4-5-7-9-18(24)25/h14-15,17,26H,2-13H2,1H3,(H,24,25)/t14-,15+,17+,20+/m0/s1

Upstream product

• 136790-79-9 (Z)-7-[(1R,2R,3R)-2-(4,4-difluoro-3-oxooctyl)-3-hydroxy-5-oxocyclopentyl]heptanoic acid-5-enbenzyl ester 
• 1236109-30-0 (2S*/R*,3aR,4S,5R,6aS)-5-benzyloxy-4-[(triisopropylsilyloxy)methyl]hexahydro-2H-cyclopenta[b]furan-2-ol 
• 1236109-31-1 (Z)-7-((1R,2S,3R,5S)-3-(benzyloxy)-5-hydroxy-2-(((triisopropylsilyl)oxy)methyl)cyclopentyl)-5-heptenoic acid 
• 54996-33-7 7-(3R-hydroxy-5-oxo-cyclopent-1-enyl)heptanoic acid 

Downstream Products

• 1372609-11-4 7-((2R,4aR,5R,7aR)-2-(1,1-difluoropentyl)-2-hydroxy-6-oxo-octahydrocyclopenta[b]pyran-5-yl)heptanoate guanidinium 
• 511229-76-8 N₁-ethyl-7-[(2R,4aR,5R,7aR)-2-(1,1-difluoropentyl)-2-hydroxy-6-oxoperhydrocyclopenta[b]pyran-5-yl]heptanamide 

Relevant articles and documents

METHOD OF PRODUCING LUBIPROSTONE

PROBLEM TO BE SOLVED: To provide a method allowing efficient production of lubiprostone. SOLUTION: The invention provides a compound represented by the general formula (I) in the figure, where n represents an integer from 0 to 5, and R1 are identical or different and each represent an alkyl group, aralkyl group, aryl group, halogen atom, hydroxy group, alkoxy group, trifluoromethyl group, nitro group, or amino group. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

PREPARATION METHODE OF 5-PHENYL PENTYL HEXAHYDRO CYCLOPENTAFURAN COMPOUNDS AND CYCLOHEPTANOATE COMPOUNDS

A producing method of a 5-phenylpentyl hexahydrocyclopentafuran compound comprises: a step (a) of preparing a 5-phenylfe-1-tenyl hexahydrocyclopentafuran compound which is a compound of chemical formula 1; and a step (b) of producing a 5-phenylpentyl hexahydrocyclopentafuran compound which is a compound of chemical formula 2 by a hydrogenation transition reaction of the compound of chemical formula 1 in the presence of a hydrogenation catalyst, a hydrogen donor and a solvent. In chemical formula 1 and chemical formula 2, R1 is any one selected from a group consisting of hydrogen and hydroxy. The producing method by the present invention enables mass production.COPYRIGHT KIPO 2020

Process for the preparation of Lubiprostone and intermediates thereof

The present invention relates to a novel process for preparing Lubiprostone and novel intermediates prepared from the process. The process of the present invention does not generate hydrogenated by-products that are difficult to be removed, and thus enables the production of Lubiprostone in an efficient and economical way.

Method for synthesizing 1R,2R,3R-substituted cyclopentanone compound

The invention relates to a method for synthesizing a 1R,2R,3R-substituted cyclopentanone compound. The method comprises: carrying out a reaction on a compound 1 and a halogenated alkane in an organicsolvent under the actions of a strong alkali and a cuprous salt to obtain a compound 3, carrying out ester hydrolysis on the compound 3 under the action of an alkali or pancreatin, and carrying out deprotection by using a fluorine reagent to obtain the product. According to the present invention, the synthesis method has characteristics of high yield, high product purity, good diastereoselectivity, easy reaction control and simple post-treatment, is suitable for industrial production, and can synthesize high-purity and high-yield alprostadil, lubiprostone, and the analogs of misoprostol and limaprost. The compound 1 is defined in the specification.

A process for the preparation of intermediates useful in the ruby's forefront, preparation method thereof and through its preparation ruby's forefront method

The invention relates to an intermediate for preparing lubiprostone, a preparation method of the intermediate and a method for preparing the lubiprostone through the intermediate, in particular to a compound as shown in a formula V for preparing the lubiprostone (as shown in a formula I), a preparation method of the compound and a method for preparing the lubiprostone through the compound. The method comprises the following steps: performing reduction treatment on the compound as shown in the formula V, performing selective deprotection and hydroxyl oxidation to obtain a compound as shown in a formula II, and performing hydroxyl deprotection on the compound as shown in the formula II to prepare the lubiprostone as shown in the formula I. The method is easy and convenient to operate, high in synthetic yield and suitable for large-scale production.

The preparation method of the ruby's forefront

The invention relates to a preparation method of lubiprostone, and concretely relates to a preparation method of highly pure lubiprostone represented by formula (I). The method comprises the steps of reducing an initial compound, oxidizing, and hydrolyzing in order to obtain a target compound. Compared with other methods, the method provided by the invention has the advantages of good process reappearance, simple operation, high yield, low cost, high purity of the above obtained product, suitableness for industrialized production, and very high economic benefit.

Ruby's forefront method for preparing or intermediates (by machine translation)

The invention discloses a novel method for preparing a lubiprostone midbody as shown in the formula 7. The method comprises the following steps: (1), a compound as shown in the formula 1 reacts with tert-butyldimethylsilyl chloride to selectively protect a primary hydroxyl group, thereby obtaining a compound shown in the formula 2; (2), a protecting group is applied to the compound 2 under the action of a catalyst, thereby obtaining a compound shown in the formula 3; (3), after the compound 3 is reduced through diisobutylaluminium hydride, a Wittig reaction is carried out on the compound 3, thereby obtaining carboxylic acid shown in the formula 4; (4), the compound 4 is protected in an acetonitrile solvent through a protecting group, thereby obtaining a compound shown in the formula 5; (5), the compound 5 is treated by using the tert-Butyldimethylsilane for removing the protecting group, thereby obtaining a compound shown in the formula 6; and (6), the compound 6 is oxidized by an oxidant and then reacts with a compound shown in the formula (10), thereby obtaining the higher-purity compound shown in the formula 7.

High-purity lubiprostone compound and preparation method thereof

The invention belongs to the technical field of medicine, and provides a high-purity lubiprostone compound and a preparation method thereof. According to the method, a LB-2 is taken as a raw material, then is subjected to oxidation and hydrogenation reactions, and then is processed to obtain the high-purity lubiprostone compound, wherein the oxidation reaction employs a dess-martin oxidizing agent, and the hydrogenation reaction is one-step hydrogenation. According to the invention, the production process is simplified, overall yield of the reaction is high, and the high-purity lubiprostone compound is prepared.

PROCESSES FOR PREPARATION OF LUBIPROSTONE

PROBLEM TO BE SOLVED: To provide new processes for preparing and purifying lubiprostone. SOLUTION: A process involves 1,4-conjugate addition of a higher order cuprate compound to a protected cyclopentenone intermediate as an important preparation step. Obtained lubiprostone is converted into a guanidine salt derivative that possesses a different melting point and solubility than lubiprostone, and thereby lubiprostone is refined. A novel synthetic intermediate is also present. COPYRIGHT: (C)2015,JPOandINPIT

PREPARATION OF LUBIPROSTONE

Aspects of the present application relate to process for the preparation of lubiprostone.