- HPLC and SFC enantioseparation of (±)-Corey lactone diol: Impact of the amylose tris-(3,5-dimethylphenylcarbamate) coating amount on chiral preparation
-
As an important intermediate of prostaglandins and entecavir, optically pure Corey lactone diol (CLD) has great value in the pharmaceutical industry. In this work, the enantioseparation of (±)-CLD was evaluated using high-performance liquid (HPLC) and supercritical fluid chromatography (SFC). In HPLC, the separations of CLD enantiomers on polysaccharide-based chiral stationary phases with both normal phase and polar organic phase were screened. And the conditions for the enantioseparation were optimized in HPLC and SFC, including the selection of mobile phase, temperature, back-pressure, and other conditions. More important, it was found that the chiral resolutions were greatly enhanced by the increase of the coating amount of ADMPC (amylose tris-(3,5-dimethylphenylcarbamate)) under both HPLC and SFC conditions, which can lead to the increase of the productivity and the decrease of the solvent consumption. The preparations of optically pure CLD were evaluated on a semi-preparative (2?×?25?cm) column packed with 30% ADMPC-coated CSP under HPLC and SFC conditions. Preparative performances in terms of kkd are 1.536?kg racemate/kg CSP/day and 1.248?kg racemate/kg CSP/day in HPLC and SFC, respectively.
- Wang, Huiying,Wang, Qiuhua,Wu, Yaling,Cheng, Lingping,Zhu, Lunan,Zhu, Junchen,Ke, Yanxiong
-
-
Read Online
- A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost guided by biocatalytic retrosynthesis
-
Development of efficient and stereoselective synthesis of prostaglandins (PGs) is of utmost importance, owing to their valuable medicinal applications and unique chemical structures. We report here a unified synthesis of PGs cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost from the readily available dichloro-containing bicyclic ketone6aguided by biocatalytic retrosynthesis, in 11-12 steps with 3.8-8.4% overall yields. An unprecedented Baeyer-Villiger monooxygenase (BVMO)-catalyzed stereoselective oxidation of6a(99% ee), and a ketoreductase (KRED)-catalyzed diastereoselective reduction of enones12(87?:?13 to 99?:?1 dr) were utilized in combination for the first time to set the critical stereochemical configurations under mild conditions. Another key transformation was the copper(ii)-catalyzed regioselectivep-phenylbenzoylation of the secondary alcohol of diol10(9.3?:?1 rr). This study not only provides an alternative route to the highly stereoselective synthesis of PGs, but also showcases the usefulness and great potential of biocatalysis in construction of complex molecules.
- Chen, Fener,Huang, Zedu,Jiang, Meifen,Li, Weijian,Tang, Pei,Ye, Baijun,Zhang, Guo-Tai,Zhu, Kejie
-
p. 10362 - 10370
(2021/08/16)
-
- Preparation method corey lactone diol
-
The invention provides a preparation method of corey lactone diol, which has the advantages of easily available raw materials. The method has the characteristics of mild reaction conditions, simple operation, simple synthetic route, high chemical yield, low cost and the like, and is suitable for industrial production.
- -
-
-
- Asymmetric Synthesis of Corey Lactone and Latanoprost
-
Corey lactone was synthesized in a single pot within 152 minutes in a 50 % overall yield via pot and time economical manner. Latanoprost, an antiglaucoma blockbuster drug, was also synthesized via seven pot reaction with five purifications in a 25 % total yield. One of the key reactions is asymmetric domino Michael/Michael reaction, formal [3+2] cycloaddition reaction, of 3-(dimethylphenylsilyl)propenal and ethyl 4-oxo-2-pentenoate, catalyzed by diphenylprolinol silyl ether, which constructed the core substituted cyclopentanone derivative with nearly optically pure form.
- Hayashi, Yujiro,Umekubo, Nariyoshi
-
supporting information
p. 6221 - 6227
(2020/09/21)
-
- A synthesis method of the branch stands lactone diol
-
The invention discloses a method for the branch stands lactone diol (( -) - Corey lactone diol) synthetic method, synthesis method of the invention is to dicyclopentadiene as raw materials, by depolymerization, cyclization, oxidation, dechlorination, open-loop, split, Prins reaction, hydrolysis reaction to obtain the target product. The invention discloses a synthetic route, raw material economic, high separation efficiency, and is suitable for industrial production.
- -
-
Paragraph 0085-0088
(2019/06/07)
-
- Access to a Key Building Block for the Prostaglandin Family via Stereocontrolled Organocatalytic Baeyer–Villiger Oxidation
-
A new protocol for the construction of a crucial bicyclic lactone of prostaglandins using a stereocontrolled organocatalytic Baeyer–Villiger (B-V) oxidation was developed. The key B-V oxidation of a racemic cyclobutanone derivative with aqueous hydrogen peroxide has enabled an early-stage construction of a bicyclic lactone skeleton in high enantiomeric excess (up to 95 %). The generated bicyclic lactone is fully primed with two desired stereocenters and enabled the synthesis of the entire family of prostaglandins according to Corey′s route. Furthermore, the reactivity and enantioselectivity of B-V oxidation of racemic bicyclic cyclobutanones were evaluated and 90–99 % ee was obtained, representing one of the most efficient routes to chiral lactones. This study further facilitates the synthesis of prostaglandins and chiral lactone-containing natural products to promote drug discovery.
- Zhu, Kejie,Hu, Sha,Liu, Minjie,Peng, Haihui,Chen, Fen-Er
-
p. 9923 - 9927
(2019/05/16)
-
- Process for Preparing Lubiprostone and Intermediate Therefor
-
The present invention relates to a method for producing lubiprostone and an intermediate product used therefor. According to the present invention, the selective introduction of a protecting group onto corey lactone diol enables the production of lubiprostone in an efficient and economical way.
- -
-
Paragraph 0163; 0164
(2017/05/12)
-
- Transformation of δ-lactone in γ-lactone in the Corey route for synthesis of prostaglandins
-
(Un)substituted benzoate ester protected δ-lactone alcohols are alcoholized in acid catalysis in almost quantitative yield to hydroxyl-halogenoesters. For alkylesters the yield drops to ~70%. After changing the protection between primary and secondary alcohols, the intermediate halogenoesters are transformed into the known γ-lactone alcohols protected as ether, silyl-ether or trityl at the secondary alcohol group. Unprotected δ-lactone alcohol 1 is also quantitatively transformed in chloroester 20. After selective protection of the primary alcohol with bulky ether groups, this is finally transformed into the known Corey γ-lactone alcohol, protected as ester at the secondary alcohol.
- T?nase, Constantin I.,Dr?ghici, Constantin
-
p. 845 - 853
(2015/06/30)
-
- A novel chemoselective cleavage of (tert-butyl)(dimethyl)silyl (TBS) ethers catalyzed by Ce(SO4)2·4 H2O
-
(tert-Butyl)(dimethyl)silyl (tBuMe2Si; TBS) phenyl/alkyl ethers were efficiently cleaved to the corresponding parent hydroxy compounds in good yields using catalytic amounts of Ce(SO4) 2·4 H2O by microwave-assisted or conventional heating in MeOH. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl (iPr3Si; TIPS) and (tert-butyl)(diphenyl)silyl ( tBuPh2Si; TBDPS) ethers. Copyright
- González-Calderón, Davir,González-González, Carlos A.,Fuentes-Benítez, Aydeé,Cuevas-Yá?ez, Erick,Corona-Becerril, David,González-Romero, Carlos
-
p. 965 - 972
(2014/08/05)
-
- Aluminium chloride hexahydrate (AlCl3.6H2o): An efficient, facile, mild, and highly chemoselective catalytic deprotection of tert-butyldimethylsilyl (tbs) ethers
-
tert-Butyldimethylsilyl (TBS) phenyl / alkyl ethers were cleaved to the corresponding efficiently parent hydroxyl compounds in good yields using catalytic amounts of AlCl3.6H2O by conventional or microwave-assisted heating in methanol or isopropanol solution. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl and tert-butyldiphenylsilyl ethers.
- Gonzalez-Calderon, Davir,Benitez-Puebla, Luis J.,Gonzalez-Gonzalez, Carlos A.,Garcia-Eleno, Marco A.,Fuentes-Benitez, Aydee,Cuevas-Yanez, Erick,Corona-Becerril, David,Gonzalez-Romero, Carlos
-
p. 1258 - 1265
(2014/04/17)
-
- Corey lactone as key precursor for a facile synthesis of novel 1,2,3-triazole carbocyclic nucleosides via Click Chemistry
-
Corey lactone (2) and Click Chemistry allowed for an efficient and facile approach to the synthesis of novel 1,2,3-triazole carbocyclic nucleosides (11 and 17) in good overall yields.
- González-González, Carlos A.,Fuentes-Benítez, Aydeé,Cuevas-Yá?ez, Erick,Corona-Becerril, David,González-Romero, Carlos,González-Calderón, Davir
-
supporting information
p. 2726 - 2728
(2013/06/26)
-
- PREPARATION OF LUBIPROSTONE
-
Aspects of the present application relate to process for the preparation of lubiprostone.
- -
-
Paragraph 0112
(2013/07/25)
-
- Selective deprotection of TBDMS alkyl ethers in the presence of TIPS or TBDPS phenyl ethers by catalytic CuSO4·5H2O in methanol
-
TBDMS alkyl ethers are efficiently cleaved to the corresponding hydroxyl compounds upon heating (conventional or microwave) in methanol solution containing 20 mol % CuSO4·5H2O. Intramolecular chemoselective experiments showed that TBDMS alkyl ethers are selectively cleaved in the presence of TIPS or TBDPS aryl ethers. Competition experiments also showed that TBDMS alkyl ethers were selectively cleaved in the presence of TBDPS alkyl ethers.
- González-Calderón, Davir,Benítez-Puebla, Luis J.,González-González, Carlos A.,Assad-Hernández, Salomón,Fuentes-Benítez, Aydeé,Cuevas-Yá?ez, Erick,Corona-Becerril, David,González-Romero, Carlos
-
p. 5130 - 5132
(2013/08/28)
-
- PROSTAGLANDIN SYNTHESIS AND INTERMEDIATES FOR USE THEREIN
-
Fused cyclopentane—4-substituted 3,5-dioxalane lactone compounds useful as an intermediate in the synthesis of prostaglandin analogs are provided. The compounds have the formula A: wherein R represents an aryl group such as p-methoxyphenyl. This compound can be reacted with a lower alkyl aluminum compound to open the dioxalane ring and reduce the lactone to lactol, without over-reducing to diol. The resulting compound can be functionalized to insert chemical side groups of target prostaglandins, adding the required α-side chain and then the required ω-side chain sequentially and independently of each other. The compounds and process are particularly suitable for preparing lubiprostone.
- -
-
Page/Page column 3
(2010/04/23)
-
- Silyl group deprotection by Pd/C/H2. A facile and selective method
-
An easy, high yield, RT, short-reaction-time Pd/C hydrogenation of silyl groups is described. This includes TES, TPS, TBS, TBDMS, TIPS, and TBDPS. The relative selectivity of the process has been investigated and we can show, for example, that TES, TPS, TBS, and TBDMS removal can be performed in the presence of TIPS and TBDPS.
- Kim, Seongjin,Jacobo, Sheila Marie,Chang, Chih-Tsung,Bellone, Sophie,Powell, William S.,Rokach, Joshua
-
p. 1973 - 1976
(2007/10/03)
-
- Total synthesis of prostaglandin F(2α) using nickel-catalyzed stereoselective cyclization of 1,3-diene and tethered aldehyde via transmetalation of nickelacycle with diisobutylaluminum acetylacetonate
-
Total synthesis of prostaglandin F(2α) utilizing a nickel(0)-catalyzed cyclization of 1,3-diene and tethered aldehyde was achieved. The cyclization proceeded via a transmetalation of nickelacycle with dilsobutylaluminum acetylacetonate ((i)Bu2-ALAC). Thus, the reaction of 19, having a side chain corresponding to the α-chain in PGF(2α) with Ni(cod)2 (10 mol %), PPh3 (20 mol %), and 1,3-cyclohexadiene (25 mol %) in the presence of (i)Bu2-ALAC (1.5 eq) proceeded stereoselectively to give the cyclized product 26 in 54% yield. During the cyclization of 19, the Z-olefin at C-5 in the side chain completely retained its geometry, and the four contiguous chiral carbon centers in PGF(2α) were stereoselectively constructed. Transformation of the key intermediate 19 into PGF(2α) was successfully achieved.
- Sato,Takimoto,Mori
-
p. 1753 - 1760
(2007/10/03)
-
- The isoprostanes, a new class of natural products: Synthesis and biosynthesis
-
A new class of natural products called isoprostanes are formed in humans as a result of non-enzymatic free-radical-catalyzed lipid peroxidation. Isoprostanes possess biological activity and can be used as an index of five- radical lipid peroxidation and as a marker of oxidative stress. We report here a new and general synthetic methodology for the syntheses of isoprostanes, using the four key lactones which are constructed from D- and L-glucose by a thionocarbonate-mediated radical cyclization reaction. These lactose possess the required stereochemistry and the right functional groups for the syntheses of isoprostanes.
- Rokach,Khanapure,Hwang,Adiyaman,Schio,FitzGerald
-
p. 569 - 580
(2007/10/03)
-
- Prostanoids: Synthesis of enantiomers of 15-deoxy-16-hydroxy-16-methylprostaglandin E1
-
Four optically pure isomers of methyl 11,16-dihydroxy-16-methyl-9-oxoprost-13-enoate (1a-1d) were synthesized using an approach reverse to the classical Corey procedure, the key intermediates being the easily accessible (-)- and (+)-enantiomers of the Corey lactone, 2a and 2b.
- Terinek, Miroslav,Kozmik, Vaclav,Palecek, Jaroslav
-
p. 1325 - 1341
(2007/10/03)
-
- Total Synthesis of 12-epi-PGF2α
-
A novel synthesis of 12-epi-PGF2α 5 is described. The key synthon 11, which has been used as a starting point for the synthesis, is produced by a radical cyclization process using thionocarbonate 9a. The radical cyclization of 9a to 11 has been studied in some detail.
- Hwang, Seong-Woo,Adiyaman, Mustafa,Khanapure, Subhash P.,Rokach, Joshua
-
p. 779 - 782
(2007/10/03)
-
- A Free Radical Route to Syn Lactones and other Prostanoid Intermediates in Isoprostaglandin Synthesis.
-
The hex-5-enyl radical cyclization methodology was applied to the formation of optical active prostanoid intermediates 7,8,9 with readily available diacetone-D-glucose as starting material.This result should lead to isoprostaglandins, a novel class of arachidonic acid metabolites obtained by a non-cyclooxygenase mechanism involving free radical-catalysed peroxidation of arachidonic acid.
- Rondot, Benoit,Durand, Thierry,Girard, Jean Pierre,Rossi, Jean Claude,Schio, Laurent,et al.
-
p. 8245 - 8248
(2007/10/02)
-
- Prins Reaction of 2-Oxabicyclooct-6-en-3-one and Related Derivatives
-
Reaction of formaldehyde with the title olefinic lactone in acetic acid affords diacetate of 1,3-diol (2a) as the main product in 50-60percent yield via regioselective trans-addition.Less favourable results were obtained with related bicyclic derivatives.
- Toemoeskoezi, Istvan,Gruber, Lajos,Baitz-Gacs, Eszter
-
p. 10345 - 10352
(2007/10/02)
-
- Enzymes in Organic Synthesis, 8: Synthesis of Enantiomerically Pure Prostaglandin Intermediates by Enzymatic Transesterification of (1S*,5R*,6R*,7R*)-(+/-)-7-Hydroxy-6-hydroxymethyl-2-oxabicyclooctan-3-one
-
Lipase Amano PS is a suitable biocatalyst for the highly regio- and enantioselective transesterification of the racemic prostaglandin building block (1S*,5R*,6R*,7R*)-(+/-)-7-hydroxy-6-hydroxymethyl-2-oxabicyclooctan-3-one (rac-1) yielding (1S,5R,6R,7R)-(-)-6-acetoxymethyl-7-hydroxy-2-oxabicyclooctan-3-one (2) and the unreacted (1R,5S,6S,7S)-(+)-enantiomer ent-1.Key Words: Prostaglandin intermediates / Enzymatic transformations / Lipases in organic solvents
- Weidner, Judith,Theil, Fritz,Kunath, Annamarie,Schick, Hans
-
p. 1301 - 1304
(2007/10/02)
-
- PREPARATION OF OPTICALLY PURE ENANTIOMERS OF COREY LACTONE BY RESOLUTION OF THE RACEMATE
-
Racemic hydrogen butanedioates (IIa, IIb) and hydrogen pentanedioates (IIIa, IIIb), prepared by reaction of racemic Corey alcohol Ia, Ib with the corresponding acid anhydride, were resolved by optically active bases to give the optically pure diastereoisomeric salts from which the individual enantiomers of hydrogen butanedioate IIa and IIb and hydrogen pentanedioate IIIa and IIIb were liberated.Acid-catalyzed transesterification with methanol converted these optically pure enantiomers into the pure (-)-enantiomer Ia and (+)-enantiomer Ib of the Corey lactone.
- Zak, Bohumil,Vesely, Ivan,Neumitka, Karel,Palecek, Jaroslav
-
p. 1690 - 1700
(2007/10/02)
-
- PROSTANOIDS. XXXII. SYNTHESIS OF (+)-PROSTAGLANDIN F2α
-
Natural prostaglandin F2α was obtained from cyclopentadiene monoxide.The key stages of the synthesis included the following: Optical resolution of (+/-)-trans-2-carboxymethylcyclopent-3-en-1-ol with the transformation of its (-)-enantiomer into (-)-cis-2-oxabicyclooct-6-en-3-one and then into (-)-7α-triethylsilyloxy-6β-triethylsilyloxymethyl-cis-2-oxabicyclooctan-3-one; selective oxidation of the latter by the DMSO-(COCl)2 system; condensation of the intermediate (-)-7α-triethylsilyloxy-6β-formyl-cis-2-oxabicyclooctan-3-one with dimethyl 2-oxoheptylphosphonate under the conditions of phase-transfer catalysis with the production of (-)-7α-hydroxy-6β-(3-oxo-1E-octenyl)-cis-2-oxabicyclooctan-3-one; conversion of the latter into (+)-PGF2α by standard methods.
- Miftakhov, M. S.,Adler, M. E.,Komissarova, N. G.,Tolstikov, G. A.
-
p. 1274 - 1280
(2007/10/02)
-
- Enzymes in Organic Synthesis. 2. Synthesis of Enantiomerically Pure Prostaglandin Intermediates by Enzymatic Hydrolysis of (1SR, 5RS, 6RS, 7RS)-7-Acetoxy-6-acetoxymethyl-2-oxabicyclooctan-3-one
-
Subtilisin DY as well as alkaline protease from Bacillus licheniformis 41 p catalyze the hydrolysis of (1SR, 5RS, 6RS, 7RS)-7-acetoxy-6-acetoxymethyl-2-oxabicyclooctan-3-one (rac-1) with practically useful enantio- and regioselectivity.Under the hitherto found optimal conditions (1S, 5R, 6R, 7R)-7-hydroxy-6-hydroxymethyl-2-oxabicyclooctan-3-one (4), an important intermediate in prostaglandine syntheses, could be prepared in a yield of 16percent with an enantiomeric excess of 99percent.The enantiomer (ent-4) was obtained with the same enantiomeric excess in 20percent yield.The chemical yields are related to the racemic starting material rac-1.
- Theil, Fritz,Schick, Hans,Nedkov, Peter,Boehme, Monika,Haefner, Barbara,Schwarz, Sigfrid
-
p. 893 - 899
(2007/10/02)
-
- BF3-MEDIATED REACTION OF A SULPHONE WITH ALDEHYDES. A METHOD FOR STEREOSPECIFIC CONSTRUCTION OF PROSTAGLANDIN ω-CHAIN
-
A new method for stereospecific construction of the allylic alcohol moiety of prostaglandins, based on application of optically active α-hydroxy aldehydes, is described.In the presence of BF3*Et2O, lithiated sulphones 1 prepared from Corey aldehyde, and carbonyl compounds 2 give the corresponding adducts 3 in moderate to excellent yields, while in the absence of the Lewis acid either no products or only their traces were formed.The addition products 3, in the form of benzoates, mesylates or free alcohols, were subjected to reductive elimination by means of sodium amalgam to give the alkenes 4.Compounds 4d and 4f were transformed into racemic and natural PGF2α, respectively, in line with the known method.
- Achmatowicz, B.,Baranowska, E.,Daniewski, A. R.,Pankowski, J.,Wicha, J.
-
p. 4989 - 4998
(2007/10/02)
-
- STEREOSPECIFIC NITROMETHANE CONJUGATE ADDITION TO 4-OXYGENATED-2-SUBSTITUTED-CYCLOPENT-2-ENONES: A SIMPLE APPROACH TO PROSTAGLANDINS
-
The compatibility of nitromethane conjugate addition to 2-cyclopentenones bearing a 4-oxygenated function has been illustrated through a short and practical synthesis of the Corey aldehyde, a key intermediate in prostaglandin synthesis, in both racemic and optically active form.A new synthesis of PGF2α featuring the introduction of the ω-chain via cycloaddition has been also described.
- Baraldi, P. G.,Barco, A.,Benetti, S.,Pollini, G. P.,Simoni, D.,Zanirato, V.
-
p. 4669 - 4678
(2007/10/02)
-