- Synthesis method of paclitaxel side chain and analogs thereof (by machine translation)
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The invention discloses a synthesis method of a taxol side chain ((4S, 5R) -3 - benzoyl -2 - (4 - methoxyphenyl) -4 - phenyl -5 - oxazoline carboxylic acid) shown as a formula (f) and a series of reactions such as epoxidation, methyl esterification, ammonolysis, ester hydrolysis, condensation, configuration overturning, condensation and hydrolysis as well as analogues thereof. The invention discloses a synthesis method of the taxol side chain ((4S 5R) -3 -benzoyl -2 - (4 - methoxyphenyl) -4 - phenyl -5 - oxazoline carboxylic acid) and the like. The method has the advantages of short reaction time, high yield, good chiral selectivity, suitability for industrial production and the like. (by machine translation)
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- Preparation method of paclitaxel oxazole ring side chain intermediate
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The invention provides a preparation method of a paclitaxel oxazole ring side chain intermediate, which can effectively enhance the single-step yield, thereby enhancing the total yield of the paclitaxel oxazole ring side chain and lowering the preparation cost. According to the method, suction filtration and concentration are directly carried out on a product (1) in a hydrogenation reduction stepin a process for synthesizing docetaxel by a four-step purification method, the product is used for a subsequent substitution reaction, and the product is subjected to a reaction in an organic solventwith a solvent polarity parameter of less than or equal to 4.5 to prepare a substitution product (2), so that the problem of low yield caused by incomplete extraction during hydrogenation reduction reaction post-treatment is solved.
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Paragraph 0026-0029
(2020/05/14)
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- Method for preparing optically active alpha-hydroxy-beta-amino acid compounds
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The invention discloses a method for preparing optically active N-acyl-beta-hydroxy-amino ester compounds of formula II from alpha-acyloxy-beta-enamine ester compounds through a one-pot process. The method uses novel six-membered cyclic pyridinecarboxamid
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Paragraph 0046-0051
(2019/10/01)
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- Chemoselective esterification of α-hydroxyacids catalyzed by salicylaldehyde through induced intramolecularity
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A new, direct and chemoselective esterification of α-hydroxyacids was developed using a reversible covalent-binding strategy. By taking advantage of acetal chemistry, simple aldehydes can be used to efficiently catalyze the esterification of α-hydroxy carboxylic acids in the presence of β-hydroxyacid moieties or other carboxylic acids in amounts equal to or in excess of the alcohols. A diverse array of α-aryl, α-alkyl, α-heteroaryl, and functionalized α-hydroxyacids were smoothly esterified with 1° and 2° alcohols catalyzed by 10 mol% inexpensive and commercially available salicylaldehyde, furnishing the resultant esterification products in 83-95% yields after a simple basic aqueous workup to remove the unreacted hydroxyacids. In addition, the salicylaldehyde can be recovered through vacuum distillation or silica gel purification, thereby meeting the standards of green chemistry. A mechanistic study proved that the formation of covalent adduct III during our proposed catalytic cycle (Scheme 1A) is responsible for the real catalysis.
- Weng, Shiue-Shien,Li, Hsin-Chun,Yang, Teng-Mao
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p. 1976 - 1986
(2013/03/13)
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- Efficient enantioselective synthesis of α-hydroxy-β-amino acids using the Claisen and Curtius rearrangements
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Highly enantioselective and facile synthesis of α-hydroxy-β- amino acids has been achieved using the Claisen and Curtius rearrangements as key reactions. Chiral allylic alcohols were employed, which can be prepared by asymmetric catalysis in both E- and Z
- Jung, Doo Young,Kang, Sol,Chang, Sukbok,Kim, Yong Hae
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- A practical and stereoselective synthesis of taxol side chain
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Apractical and efficient synthesis of taxol C-13 side chain from cheap and easily available starting material is described.
- Zhou, Zhongqiang,Mei, Xingguo
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p. 723 - 728
(2007/10/03)
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- A practical diastereoselective synthesis of β-amino-α-hydroxy carboxylates
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Practical synthetic routes to β-amino-α-hydroxy carboxylates (AHC) have been developed from amino acids. Reduction of β-amino-α- keto esters 6 with NaBH4 was found to give anti-AHCs 7 in high de, which were efficiently converted to the corresponding syn-AHCs 8 via oxazolidine ring 10 formation.
- Lee, Jae-Mok,Lim, Hyun-Suk,Seo, Kyung-Chang,Chung, Sung-Kee
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p. 3639 - 3641
(2007/10/03)
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- Chemoenzymatic synthesis of the C-13 side chain of paclitaxel (Taxol) and docetaxel (Taxotere)
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Reduction of methyl 3-chloro-2-oxo-3-phenylpropanoate with various reducing agents gave syn- and anti-3-chloro-2-hydroxy-3-phenylpropanoates 3, which underwent an efficient lipase-catalyzed resolution. All four diastereomers were subsequently converted to N-benzoyl-(2R,3S)-3-phenylisoserine methyl ester, C-13 side chain analogues of paclitaxel (Taxol).
- Hamamoto, Hiromi,Mamedov, Vakhid A.,Kitamoto, Makiko,Hayashi, Nobuyuki,Tsuboi, Sadao
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p. 4485 - 4497
(2007/10/03)
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- Stereocontrolled Synthesis of the Taxol C-13 Side Chain: Methyl (2R,3S)-3-Benzoylamino-2-hydroxy-3-phenylpropanoate
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Addition of lithiated methoxyallene 5 to literature-known amino aldehyde 3 followed by ozonolysis provided syn-configurated α-hydroxy-β-amino ester 6 in moderate overall yield and with an ee of 90%. The predominant formation of syn-compounds may be due to a chelate controlled addition step.
- Schade, Wolfgang,Reissig, Hans-Ulrich
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p. 685 - 686
(2007/10/03)
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- Totally stereocontrolled nitrone-ketene acetal based synthesis of (2S,3S)-N-benzoyl-and N-boc-phenylisoserine
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A novel, nitrone-ketene acetal based approach to enantiopure (2S,3S)-N- benzoyl- and N-boc-phenylisoserine has been realized. The convergent approach, which involves the intermediacy of isoxazolidinones, proceeds in up to 59% overall yield and requires only three operations from the starting nitrones.
- Jost,Gimbert,Greene
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p. 6672 - 6677
(2007/10/03)
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- 4-Isopropyl-2-oxazolin-5-one anion as masked umpoled synthon for both formyl and hydroxycarbonyl anions: Generation, reactivity and synthetic applications
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The anion of the title compound, simply generated in the presence of catalytic amount of triethylamine, reacts with both common electrophilic olefins and aldehydes to give moderate to good yield of Michael or aldol adducts respectively. Mild acid treatment of these adducts at ambient temperature serves to demask the aldehyde function, allowing one to consider the anion of 1 as a nucleophilic acylating equivalent of formaldehyde. On the other hand, the same anion of 1 may act as a masked umpoled synthon for a hydroxycarbonyl anion since its aldol adducts with aldehydes undersent concomitant isomerization and ring cleavage under mild basic conditions producing dipeptides which could be hydrolyzed to give the corresponding carboxylic acids. Synthetic applications of this chemistry in the area of sugar, aminosugar and non-proteinogenic aminoacid derivatives are discussed.
- Barco, Achille,Benetti, Simonetta,De Risi, Carmela,Pollini, Gian P.,Spalluto, Giampiero,Zanirato, Vinicio
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p. 4719 - 4734
(2007/10/03)
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- Asymmetric synthesis of taxol and taxotere side chains by enolate hydroxylation
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We report an asymmetric synthesis of the taxol and taxotere side chains by hydroxylation of enolates derived from N-substituted methyl 3-amino-3-phenyl propionate with the oxodiperoxymolybdenum (pyridine) (hexamethyl phosphoric triamide) complex (MoOPH). We report an asymmetric synthesis of the taxol and taxotere side chains by hydroxylation of enolates derived from N-substituted methyl 3-amino-3-phenyl propionate with the oxodiperoxymolybdenum (pyridine) (hexamethyl phosphoric triamide) complex (MoOPH).
- Hanessian,Sanceau
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p. 621 - 624
(2007/10/03)
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- Synthesis of α-hydroxy-β-amino acids from chiral cyanohydrins
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(-)-(R,E)-2-hydroxy-3-pentenenitrile 1, obtained by R-oxynitrilase catalyzed addition of HCN to 2-butenal, was shown to be an excellent chiral starting material for the synthesis of α-hydroxy-β-amino acids of high enantiomeric and diastereomeric purity. T
- Warmerdam, Erwin G.J.C.,Van Rijn, Rachel D.,Brussee, Johannes,Kruse, Chris G.,Van Der Gen, Arne
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p. 1723 - 1732
(2007/10/03)
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- Semisynthese von Taxol: eine hochenantio- und -diastereoselektive Synthese der Seitenkette und eine neue Methode zur Esterbildung an C13 unter Verwendung von Thioestern
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Keywords: Asymmetrische Synthesen; Enolate; Imine; Taxol; Thioester
- Gennari, Cesare,Vulpetti, Anna,Donghi, Monica,Mongelli, Nicola,Vanotti, Ermes
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p. 1809 - 1812
(2007/10/03)
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- A chemoenzymatic approach to chiral phenylisoserinates using 4-isopropyl-2-oxazolin-5-one as masked umpoled synthon for hydroxycarbonyl anion
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The aldol adduct between the anion of 4-isopropyl-2-oxazolin-5-one with racemic N-(tertbutoxycarbonyl)-phenylglycinal underwent concomitant isomerization and ring cleavage under mild basic conditions producing the racemic dipeptide N-Boc-phenylisoserine-v
- Barco, Achille,Benetti, Simonetta,De Risi, Carmela,Pollini, Gian P.,Romagnoli, Romeo,Zanirato, Vinicio
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p. 9289 - 9292
(2007/10/02)
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- N-Benzoyl-(2R,3S)-3-Phenylisoserine Methyl Ester; A Facile and Convenient Synthesis and Resolution by Entrainment
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The importance of N-benzoyl (2R,3S)-phenylisoserine (3), also known as the "taxol side chain", for the strong antitumor activity of taxol (1), a potent anticancer drug, has prompted numerous efforts towards the development of a practical taxol side chain synthesis.Here we describe a highly practical and inexpensive synthesis of the taxol side chain methyl ester 4 and resolution via entrainment based on the observation that compound 4 exhibits conglomerate crystal structure.
- Srivastava, Ranjan P.,Zjawiony, Jordan K.,Peterson, John R.,McChesney, James D.
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p. 1683 - 1688
(2007/10/02)
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- Asymmetric Synthesis of the Taxol and Taxotere C-13 Side Chains
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A practical and efficient asymmetric synthesis of the 3-benzoylamino-2-hydroxy-3-phenylpropionic acid derived side chain of the important anticancer agent taxol is described.The pivotal synthetic transformation relies upon the highly diastereoselective tandem lithium amide conjugate addition-electrophilic hydroxylation of tert-butyl cinnamate 4.The resultant anti β-amino-α-hydroxy acid derivative is readily converted to the anti diastereomer of the taxol side chain methyl ester, from which the naturally occuring syn configuration is secured by a simple Mitsunobu inversion sequence via a dihydrooxazole intermediate.Under optimal conditions, this straightforward approach provides the taxol side chain methyl ester (-)-15 (natural enantiomer) in four steps and 60percent yield from tert-butyl cinnamate 4.The protocol is applied to the preparation of all four taxol side chain stereoisomers and is extended to allow for the synthesis of the side chain of taxotere, a potent taxol analogue.
- Bunnage, Mark E.,Davies, Stephen G.,Goodwin, Christopher J.
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p. 2385 - 2392
(2007/10/02)
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- Highly stereocontrolled asymmetric syntheses of taxol and taxotere C-13 side chain analogues
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Asymmetric aldol reaction of (+)-tricarbonyl(η6-2-trimethylsilylbenzaldehyde)chromium(0) complex (4) with titanium enolate of S-tert-butyl benzyloxyethanethioate (10) provided, after consecutive desilylation and decomplexation, anti-aldol product 15 in a highly stereo selective manner. Anti-product 15 was subsequently converted to (2R,3S)-N-benzoyl- and N-tert-butoxycarbonyl-3-phenylisoserine methyl esters (23 and 24), C-13 side chain analogues of taxol (1) and taxotere (2).
- Mukai, Chisato,Kim, In Jong,Furu, Etsuko,Hanaoka, Miyoji
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p. 8323 - 8336
(2007/10/02)
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- Asymmetric Synthesis of Sulfinimines: Applications to the Synthesis of Nonracemic β-Amino Acids and α-Hydroxy-β-amino Acids
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Asymmetric oxidation of sulfenimines 1 affords sulfinimines 2 (88-90percent ee) which are chiral ammonia imine synthons useful in the enantioselective synthesis of β-amino acids and α-hydroxy-β-amino acids such as the C-13 side chain of taxol (2R,3S)-7.
- Davis, Franklin A.,Reddy, R. Thimma,Reddy, Rajarathnam E.
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p. 6387 - 6389
(2007/10/02)
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- Highly stereoselective synthesis of α-hydroxy β-amino acids through β-lactams: Application to the synthesis of the taxol and bestatin side chains and related systems
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Formation of α-hydroxy β-lactams, followed by chemical elaboration at C4 and further β-lactam cleavage afforded functionalised α-hydroxy β-amino acids or their derivatives in a highly stereoselective manner.
- Palomo,Arrieta,Cossio,Aizpurua,Mielgo,Aurrekoetxea
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p. 6429 - 6432
(2007/10/02)
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