333963-40-9 Usage
Description
Chronic constipation is an affliction affecting 4–5 million Americans alone.
When no specific cause is identified, it is classified as idiopathic. Dietary and
lifestyle modifications are the first-line conventional approaches followed by the
administration of laxatives. Unfortunately, chronic idiopathic constipation is frequently
refractory to traditional therapy; thus, the need for novel agents exists.
Lubiprostone is a bicyclic fatty acid with a novel mechanism of action. Without
affecting sodium and potassium ion concentrations, lubiprostone activates
intestinal chloride ion channels, thereby, increasing intestinal water secretion
and intestinal fluid chloride ion concentration. In basolateral membranepermeabilized
T84 gastrointestinal epithelial cells under chloride gradient conditions,
lubiprostone concentration-dependently increased short-circuit current
with an EC50 of approximately 20 nM.
Originator
Sucampo (US)
Uses
Lubiprostone (Ring Closed) is a bicyclic fatty acid used for the treatment of chronic constipation and constipation associated irritable bowel syndrome (IBS-C).
Brand name
Amitiza
General Description
This product is marketed as Amitiza bySucampo Pharmaceuticals, Inc. and Takeda PharmaceuticalsAmerica, Inc. to relieve chronic idiopathic constipation inadults. The recommended oral dosage is 24 μg 2 times a daywith food. Precautions and side effects are similar to thosefor other prostaglandin-derived products.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 333963-40-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,3,3,9,6 and 3 respectively; the second part has 2 digits, 4 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 333963-40:
(8*3)+(7*3)+(6*3)+(5*9)+(4*6)+(3*3)+(2*4)+(1*0)=149
149 % 10 = 9
So 333963-40-9 is a valid CAS Registry Number.
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
333963-40-9Relevant articles and documents
PREPARATION METHODE OF 5-PHENYL PENTYL HEXAHYDRO CYCLOPENTAFURAN COMPOUNDS AND CYCLOHEPTANOATE COMPOUNDS
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Page/Page column 12-13, (2020/04/17)
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
METHOD OF PRODUCING LUBIPROSTONE
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Paragraph 0087, (2019/08/27)
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
The preparation method of the ruby's forefront
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, (2018/04/01)
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.