- METHOD FOR PRODUCING THIOLACTONE COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for producing a thiolactone compound at high yield. SOLUTION: A method for producing a thiolactone compound includes bringing a lactone compound, in which S in a compound of the formula (II) is replaced with O, into contact with acetic acid alkali metal salt in a first organic solvent to make a first mixture; and bringing the first mixture into contact with a thiocarboxylic acid to make a second mixture including the thiolactone compound of the formula (II) [R1 and R2 each denote H, a benzyl group, or a substituted benzyl group]. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
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Paragraph 0086-0091; 0096-0102
(2021/10/02)
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- Practical Synthesis of (+)-Biotin Key Intermediate by Calcium Borohydride Reduction and Temperature-Dependent Purity Upgrade during Crystallization
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An expedient synthesis of a key intermediate for (+)-biotin has been accomplished through high-yielding reduction of chiral imide with calcium borohydride and efficient isolation of the desired isomer by crystallization at a specific temperature where only undesired isomer was converted to soluble anhydrate while the desired isomer kept unchanged as a less soluble monohydrate.
- Seki, Masahiko,Takahashi, Yusuke
-
p. 1950 - 1959
(2021/08/03)
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- METHOD FOR PRODUCING THIOLACTONE COMPOUND
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To provide a production method for obtaining a high-purity thiolactone compound at good yields.SOLUTION: A method for producing a thiolactone compound includes crystallizing and extracting a thiolactone compound of the following formula in an alcohol solvent with a boiling point of 85°C or higher, where R1 and R2 each denote H or a ureine protection group such as a benzyl group.SELECTED DRAWING: None
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Paragraph 0101-0103
(2021/02/26)
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- Preparation method of sodium thioacetate and method for preparing thiolactone by using sodium thioacetate
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The invention relates to the field of organic chemistry, and discloses a preparation method of sodium thioacetate and a method for preparing thiolactone from sodium thioacetate, which are characterized in that the method comprises the following steps: in the presence of a first solvent, reacting RONa with thioacetic acid; wherein R is an alkyl group of C1 to C4, preferably an alkyl group of C1 toC2. The method has the advantages of simple process, cheap and easily available raw materials and high product yield, and provides convenience for industrial production of sodium thioacetate. The thiolactone prepared from the sodium thioacetate prepared by the method has the advantages of high reaction yield, few side reactions and high product purity.
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Paragraph 0046; 0063-0084
(2020/12/05)
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- ESTER DERIVATIVE, AND METHOD FOR PRODUCING THIOLACTONE DERIVATIVE
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PROBLEM TO BE SOLVED: To provide an ester derivative, that is a novel intermediate for producing thiolactone derivative from a lactone derivative, and a method for producing thiolactone derivative. SOLUTION: The ester derivative (2) is obtained via halogenation and esterification of a lactone derivative (1). (In the formula, R1 and R2 represent benzyl. R3 is alkyl and X is halogen.). SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
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Paragraph 0080-0083
(2020/10/03)
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- Amide derivatives, the amide derivative and (by machine translation)
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[Problem] amide derivative useful as an intermediate for synthesis of biotin, and method for producing an amide derivative. [Solution] the corresponding alcohol derivative, mesyl agent, such as agent manufactured by reacting sulfonyl, an amide derivative represented by the formula. (In the formula R1 And R2 The, same or different, substituted or unsubstituted benzyl group, R3 Is, substituted or unsubstituted phenyl group, X is, thiol groups, [meshirokishi[meshirokishi] group, a trifluoromethanesulfonyloxy group, p - [toshirokishi[toshirokishi] groups, such as halogen groups are selected from the group. )[Drawing] no (by machine translation)
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Paragraph 0075-0078
(2020/09/24)
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- Synthesis method of thiolactone
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The invention discloses a synthesis method of thiolactone. The method includes the following step of conducting the reaction shown in the description on a compound II and a thio agent under the protection of inert gas to obtain a compound I. In the synthesis method, complete reaction can be carried out without adding any organic solvent as the reaction solvent, operation and after-treatment are simple, the product purity is high, the yield is high, the environmental pollution is small, and the method has broad industrial application prospects.
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Paragraph 0039-0052
(2019/07/08)
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- Process development and scale-up for the preparation of roche thiolactone: Key intermediate for (+)-biotin
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The main objective of this paper was to report a short and efficient synthesis of Roche thiolactone starting from cis-1,3-dibenzyltetrahydro-2H-furo-[3,4-d]-imidazole-2,4,6-trione (2) with an overall yield of 74%. The optimized synthetic route consists of three chemical steps and the final process of thiolactonization of (3aS,6aR)-lactone 4 using xanthate ionic liquid in solvent-free conditions to furnish Roche thiolactone 1 not only features the yield improvement of 1 by optimizing reaction variables but also highlights simplifying the subsequent workup procedure.
- Hong, Dan-Feng,Xi, Chang-Cheng,Liu, Wen-Guang,Xiong, Fei,Luo, Cheng-En,Ma, Chao,Zhang, Shu-Ping
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p. 373 - 377
(2020/01/03)
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- Method for Producing Intermediate of Biotin and Method for Producing Biotin
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In the method, a trione compound represented by the following formula (1) is (i) reduced by NaAlH2(OCH2CH2OCH3)2 and subsequently further reduced by a metal borohydride salt, or (ii) reduced by calcium borohydride, thereby producing an amide alcohol compound represented by the following formula (3) (wherein, R1 and R2 may be the same or different and each represents a hydrogen atom or a protecting group of an ureylene group; R4 represents an alkyl group, an aralkyl group, or an aryl group; and each of R5, R6, and R7 represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom).
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-
Paragraph 0324; 0325
(2020/01/08)
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- A biotin intermediate THIONES method for the preparation of
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The invention relates to a preparation method for the biotin intermediate thioketone. The preparation method comprises the following steps: with a mixed solution of potassium thioacetate and thioacetic acid as a thiolizing reagent and mixing the thiolizing reagent with (3aS,6aS)1,3-dibenzyl-tetrahydro-4H-furo[3,4-d]imidazole-2,4(1H)-dione; recovering benzene from a mixed system and carrying out dehydration; and finally carrying out a sulfuration reaction under the protection of nitrogen so as to obtain (3aS,6aS)1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione. According to the invention, the mixed solution of potassium thioacetate and thioacetic acid is used as the thiolizing reagent, (3aS,6aS)1,3-dibenzyl-tetrahydro-4H-furo[3,4-d]imidazole-2,4(1H)-dione is added, benzene low temperature reflux and a water separator are employed for water separation and removal of water in the system, so a high purity product is obtained. The method provided by the invention overcomes the disadvantages of easy deterioration and decomposition of the thiolizing reagent, great influence of water in the system on the sulfuration reaction, etc. and has the advantages of improved sulfuration efficiency, good product quality and high yield.
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Paragraph 0031-0035
(2017/02/23)
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- (3aS, 6aR)-1, 3-dibenzyl-tetrahydro -4H-thieno [3, 4-d] imidazole -2, 4-(1H)-dione simple method for preparing
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The invention relates to a simple preparation method for (3aS,6aR)-1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4-(1H)-dione. The method comprises the following steps: with L-cysteine methyl/ethyl ester hydrochloride as a starting raw material, carrying out N-benzyl protection, ester group reduction and mercapto protection so as to obtain (R)-2-benzylamino-3-acetylmercapto-propanol; then carrying out oxidation with sulfur trioxide-pyridine so as to prepare aldehyde; reacting aldehyde with benzylamine and sodium cyanide so as to prepare (2R,2S),(3R)-dibenzylamino-4-acetylmercapto-n-butyronitrile; carrying out amidation and deprotection cyclization so as to obtain (3aS,6aR),(3aR,6aR)-1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4-(1H)-dione; and carrying out thermal arrangement so as to obtain (3aS,6aR)-1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4-(1H)-dione. The method has the advantages of cheap and easily available raw materials, easily operable reaction conditions, high reaction selectivity, low cost and applicability for industrial production.
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-
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- (3aS, 6aR) - 1,3- two phenmethyl four hydrogens -4H-thieno [3,4-d] imidazole -2,4 - (1H)-dione method for the synthesis of
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The invention relates to a synthetic method of (3aS, 6aR)-1, 3-dibenzyl tetrahydro-4H-thieno[3, 4-d]imidazole-2, 4-(1H)-dione. The method comprises the following steps: carrying out reaction on nitromethane and carbon disulfide to generate 2-nitryl dithioacetate (II) and directly carrying out reaction on a product and 2-halogenated acetaldehyde glycol to prepare 2-nitryl thioacetyl sulfydryl acetaldehyde glycol (III); and then, sequentially carrying out Mannich reaction, alpha-position substation and amidation and cyclization to prepare (3aS, 6aR), (3aR, 6aR)-1, 3-dibenzyl-tetrahydro-4H-thieno[3, 4-d]imidazole-2, 4-(1H)-dione (VI) and finally carrying out thermal rearrangement to obtain a target compound (I). According to the synthetic method provided by the invention, the raw materials are cheap and easily available, and the method is simple in reaction and easy to operate. Mannich reaction is catalyzed by a chiral catalyst to construct a beta-position chiral center and an alpha chiral center is constructed by SN2 substitution reaction and thermal rearrangement of the alpha-position, so that the synthetic method is low in cost and suitable for industrial production.
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-
Paragraph 0053-0054
(2017/04/08)
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- Highly enantioselective methanolysis of meso-cyclic anhydride mediated by bifunctional thiourea cinchona alkaloid derivatives: Access to asymmetric total synthesis of (+)-biotin
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An enantioselective asymmetric total synthesis of (+)-biotin (1) via the Hoffmann-Roche lactone-thiolactone strategy has been accomplished from commercially available cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2). Strategic transformations include a cinchona alkaloid-based bifunctional thiourea mediated methanolytic desymmetrization of prochiral cyclic anhydride 3 to produce the enantiomerically enriched precursor of Roche lactone 5 and an improved introduction of the 4-carboxybutyl side chain at C-4 position of Roche thiolactone 6 via Grignard reaction.
- Xiong, Fei,Xiong, Fang-Jun,Chen, Wen-Xue,Jia, Hui-Qing,Chen, Fen-Er
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p. 1078 - 1082
(2013/10/21)
-
- Synthetic studies on (+)-biotin, part 151: A chiral squaramide-mediated enantioselective alcoholysis approach toward the total synthesis of (+)-biotin
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An efficient stereocontrolled total synthesis of (+)-biotin (1) has been achieved via the intermediacy of Roche's lactone 5 starting from cis-1,3-dibenzyl-2-imidazole-4,5-dicarboxylic acid (2). The bifunctional cinchona alkaloid-derived squaramide-promoted enantioselective alcoholysis was utilizing as a tool for the construction of two contiguous stereocenters of C-3a and C-6a in biotin molecular with excellent enantioselectivity. In addition, the 4-carboxybutyl side chain was assembled by first using C4+C1 approach via a novel tricyclic thiophanium salt intermediate.
- Chen, Xu-Xiang,Xiong, Fei,Fu, Han,Liu, Zhi-Qian,Chen, Fen-Er
-
experimental part
p. 488 - 491
(2011/05/14)
-
- An improved asymmetric total synthesis of (+)-biotin via the enantioselective desymmetrization of a meso-cyclic anhydride mediated by cinchona alkaloid-based sulfonamide
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The highly enantioselective total synthesis of (+)-biotin 1 via the Hoffmann-Roche lactone-thiolactone strategy has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid 2 with an overall yield of 35%. Two contiguous stereogenic centers at C-3a and C-6a were established through a rapid cinchona alkaloid-based sulfonamide-mediated enantioselective alcoholysis of meso-cyclic anhydride 3 to afford (4S,5R)-cinnamyl hemiester 4h, the direct precursor to (3aS,6aR)-lactone 5 with high enantioselectivity. A one-pot installation of the 4-carboxybutyl side chain was accomplished by a Fukuyama coupling reaction of (3aS,6aR)-thiolactone 6 with the organozinc reagent prepared from ethyl 5-bromopentanoate.
- Xiong, Fei,Chen, Xu-Xiang,Chen, Fen-Er
-
experimental part
p. 665 - 669
(2010/07/17)
-
- Synthesis of dendrimer-type chiral stationary phases based on the selector of (1S,2R)-(+)-2-amino-1,2-diphenylethanol derivate and their enantioseparation evaluation by HPLC
-
In our recent work, a series of dendritic chiral stationary phases (CSPs) were synthesized, in which the chiral selector was L-2-(p-toluenesulfonamido)-3- phenylpropionyl chloride (selector I), and the CSP derived from three-generation dendrimer showed the best separation ability. To further investigate the influence of the structures of dendrimer and chiral selector on enantioseparation ability, in this work, another series CSPs (CSPs 1-4) were prepared by immobilizing (1S,2R)-1,2-diphenyl-2-(3-phenylureido)ethyl 4-isocyanatophenylcarbamate (selector II) on one- to four-generation dendrimers that were prepared in previous work. CSPs 1 and 4 demonstrated the equivalent enantioseparation ability. CSPs 2 and 3 showed the best and poorest enantioseparation ability respectively. Basically, these two series of CSPs exhibited the equivalent enantioseparation ability although the chiral selectors were different. Considering the enantioseparation ability of the CSP derived from aminated silica gel and selector II is much better than that of the one derived from aminated silica gel and selector I, it is believed that the dendrimer conformation essentially impacts enantioseparation.
- He, Bao-Jiang,Yin, Chuan-Qi,Li, Shi-Rong,Bai, Zheng-Wu
-
experimental part
p. 69 - 76
(2010/09/09)
-
- PROCESS FOR THE MANUFACTURE OF (+)-BIOTIN
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Disclosed are processes for preparing synthetic biotin intermediates and a process for preparing biotin using said intermediates. In particular, disclosed is a process for the stereoselective total synthesis of the natural product (+)-biotin of formula (I).
- -
-
Page/Page column 26-27
(2009/05/28)
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- Synthetic studies on (+)-biotin, Part 11:[1] Application of Cinchona alkaloid-mediated asymmetric alcoholysis of meso-cyclic anhydride in the total synthesis of (+)-biotin
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A practical and asymmetric process for the totalsyn thesis of (+)-biotin (1) has been accomplished starting from cis-1,3-dibenzyl-2-oxoimidazolidine-4,5- dicarboxylic acid (2). This approach features a highly enantioselective alcoholysis of mesocyclic anhydride 3 into (4S,5R)-cinnamylhemiest er 4 mediated by Cinchona alkaloids. Another attractive feature of this synthesis involves the use of recyclable palladium nanoparticles-catalyzed assembly of the 4-carboxybutyl chain at C-4 in (3aS,6aR)-thiolactone 7 employing an improved Fukuyamatype cross-coupling reaction.
- Dai, Hui-Fang,Chen, Wen-Xue,Zhao, Lei,Xiong, Fei,Sheng, Hao,Chen, Fen-Er
-
experimental part
p. 1635 - 1641
(2009/07/18)
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- Total synthesis of (+)-biotin via a quinine-mediated asymmetric alcoholysis of meso-cyclic anhydride strategy
-
A concise asymmetric total synthesis of (+)-biotin 1 has been accomplished in which the absolute stereochemistry of C3a, C6a of 1 was established by utilizing an efficient and practical quinine-mediated asymmetric alcoholysis of meso-cyclic anhydride 2 in a single step, the C4 stereochemistry was installed by a direct stereoselective ionic hydrogenation of the thiolactol 7.
- Huang, Jian,Xiong, Fei,Chen, Fen-Er
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p. 1435 - 1442
(2008/12/20)
-
- Synthetic studies on d-biotin, part 9.1) An improved asymmetric synthetic route to d-biotin via Hoffmann-Roche lactone-thiolactone approach
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An efficient and highly stereoselective total synthesis of d-biotin has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2) with an overall yield of 33%. Polymer-supported oxazaborolidine- catalyzed asymmetric reduction of meso-cyclic imide 4 constitutes the key synthetic step in introducing stereogenic centers into the d-biotin molecule.
- Chen, Fen-Er,Jia, Hui-Qing,Chen, Xu-Xiang,Dai, Hui-Fang,Xie, Bin,Kuang, Yun-Yan,Zhao, Jian-Feng
-
p. 743 - 746
(2007/10/03)
-
- Synthetic studies on d-biotin, part 8: An efficient chemoenzymatic approach to the asymmetric total synthesis of d-biotin via a polymer-supported PLE-mediated desymmetrization of meso-symmetic dicarboxylic esters
-
A practical chemoenzymatic method for the asymmetric total synthesis of d-biotin (1) starting from the commercially available cis-1,3-dibenzyl-2- imidazolidone-4,5-dicarboxylic acid (2) has been developed. The key step of the synthesis is the highly enantioselective hydrolysis of meso-dicarboxylic esters by a polymer-supported pig liver esterase and introduction of a formyl group at the C-4 position in 4 via a Grignard reaction. The polymer-supported PLE can be recovered quantitatively from the reaction mixture by simple filtration and reused without significant loss of activity.
- Chen, Fen-Er,Chen, Xu-Xiang,Dai, Hui-Fang,Kuang, Yun-Yan,Xie, Bin,Zhao, Jian-Feng
-
p. 549 - 554
(2007/10/03)
-
- A practical synthesis of (+)-biotin from L-cysteine
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α-Amino aldehyde 4, which is readily derived from L-cysteine through cyclization and elaboration of the carboxy group, was subjected to the Strecker reaction, which, via sodium bisulfite adduct 16, afforded α-amino nitrile 5 with high diastereose-lectivity (syn/anti = 11:1) and in high yield. Amide 6, derived from 5, was converted to thiolactone 8, a key intermediate in the synthesis of (+)-biotin (1), by a novel S,N-carbonyl migration and cyclization reaction. The Fukuyama coupling reaction of 8 with the zinc reagent 21, which has an ester group, in the presence of a heterogeneous Pd/ C catalyst allowed the efficient installation of the 4-carboxybutyl chain to provide 9. Compound 9 was hydrogenated and the protecting groups removed to furnish 1 in 10 steps and in 34 % overall yield from L-cysteine.
- Seki, Masahiko,Hatsuda, Masanori,Mori, Yoshikazu,Yoshida, Shin-Ichi,Yamada, Shin-Ichi,Shimizu, Toshiaki
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p. 6102 - 6110
(2007/10/03)
-
- An efficient and practical procedure for Strecker reaction: A highly diastereoselective synthesis of a key intermediate for (+)-biotin
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Treatment of α-amino aldehyde 2, which was prepared through Moffatt oxidation of the corresponding β-amino alcohol 5, with aqueous sodium bisulfite allowed clean conversion to a water-soluble bisulfite adduct 6 [>99% conversion, 89% yield (two steps)]. The aqueous solution of 6 was treated with benzylamine followed by easy-handling NaCN to effect the Strecker reaction to afford α-amino nitrile 3 with high diastereoselectivity and in high yield (syn/anti = 11:1, 95% assay yield). Both the compounds syn-3 and anti-3 were converted to a key intermediate 4 for (+)-biotin through S,N-carbonyl migration in high yields.
- Seki, Masahiko,Hatsuda, Masanori,Yoshida, Shin-Ichi
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p. 6579 - 6581
(2007/10/03)
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- INTERMEDIATE FOR BIOTIN AND PROCESS FOR PRODUCING THE SAME
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The present invention is to provide a process for preparing a synthetic intermediate of biotin which is industrially advantageous, and discloses a process for preparing a compound represented by the formula (I) : ???wherein R1 and R2 may be the same or different from each other, and each represents hydrogen atom, a benzyl group which may have a substituent(s) on the benzene ring, a benzhydryl group which may have a substituent(s) on the benzen ring, or a trityl group which may have a substituent(s) on the benzene ring, R3 represents cyano group, carboxyl group, an alkoxycarbonyl group, an alkylthiocarbonyl group, or a carbamoyl group which may have a substituent, or a salt thereof which comprises subjecting a compound represented by the formula (II-a) : ???wherein the symbols have the same meanings as defined above, or a salt thereof to ring transformation.
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-
-
- Synthetic Studies on d-Biotin, Part 6:1 An Expeditious and Enantiocontrolled Approach to the Total Synthesis of d-Biotin via a Polymer-Supported Chiral Oxazaborolidine-Catalyzed Reduction of meso-Cyclic Imide Strategy
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An efficient and highly enantioselective synthesis of d-biotin from the known cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (5) was accomplished in 48% overall yield. The key reactions in the sequence involve the catalytic enantioselective reduction of meso-cyclic imide 6 using polymer-supported chiral oxazoborolidine, derived from (S)-α,α -diphenylprolinol and polymer-bound sulfonyl chloride, and the installation of the C5 side chain at C4 in the thiolactone 9 via a Ni/C-catalyzed Fukuyama coupling reaction.
- Chen, Fen-Er,Yuan, Jian-Li,Dai, Hui-Fang,Kuang, Yun-Yan,Chu, Yong
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p. 2155 - 2160
(2007/10/03)
-
- Synthetic studies on d-biotin. Part 7: A practical asymmetric total synthesis of d-biotin via enantioselective reduction of meso-cyclic imide catalyzed by oxazborolidine
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A novel and convenient method for the stereoselective synthesis of d-biotin 1 starting from the commercially available cis-1,3-dibenzyl-2- imidazolidone-4,5-dicarboxylic acid 2 has been developed. The key features of this synthesis include the enantioselective reduction of a meso-cyclic imide, mediated by a chiral oxazborolidine catalyst, derived from (1S,2S)-(+)-threo-1- (4-nitrophenyl)-2-amino-1,3-propanediol and the direct introduction of a C 5 side chain to the (3aS,6aR)-thiolactone through a modified di-Grignard reaction. Enantioselectivities of 98% in the oxazborolidine- catalyzed asymmetric reduction process have been achieved.
- Chen, Fen-Er,Dai, Hui-Fang,Kuang, Yun-Yan,Jia, Hui-Qing
-
p. 3667 - 3672
(2007/10/03)
-
- 2-Thiazolidinone: A novel thiol protective surrogate of complete atom efficiency, a practical synthesis of (+)-biotin
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2-Thiazolidinone derivatives were shown to be novel protective surrogates of a thiol group in L-cysteine derivatives. After elaboration at the C-4 substituent, the thiol group was completely liberated by simple heating in DMF whose atom efficiency is 100%. A practical synthesis of (+)-biotin was accomplished by the use of the strategy employing 4-functionalized 2-thiazolidinone derivatives as the intermediates, allowing a synthesis of (+)-biotin in 10 steps and in 31% overall yield. Short steps, high yield, and ease of operation of the present approach would permit the hitherto most efficient access to (+)-biotin.
- Seki, Masahiko,Kimura, Mayumi,Hatsuda, Masanori,Yoshida, Shin-Ichi,Shimizu, Toshiaki
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p. 8905 - 8907
(2007/10/03)
-
- A Facile Synthesis of a Key Intermediate for (+)-Biotin via Strecker Reaction
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The Strecker reaction of (2R,4R)-2-phenyl-3-phenoxycarbonylthiazolidine-4- carbaldehyde (4b), which was readily prepared from L-cysteine, with benzylamine and trimethylsilyl cyanide provided α-amino nitrile 5b stereoselectively (syn-anti, 2:1), Amidation of 5b and subsequent cyclization gave bicyclic compound 6, which, upon reduction with zinc dust, hydrolysis and subsequent cyclization, furnished thiolactone 2, a key intermediate for (+)-biotin (1).
- Mori, Yoshikazu,Kimura, Mayumi,Seki, Masahiko
-
p. 2311 - 2316
(2007/10/03)
-
- A novel synthesis of a key intermediate for (+)-biotin from L-aspartic acid
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The aldol reaction of an N-Cbz-3-amino-4-butanolide 4, derived from L-aspartic acid, with formaldehyde gave the trans-disubstituted 3-amino-4-butanolide 5 stereoselectively. Following protection of the hydroxyl group of 5, amidation and oxidation provided the β-substituted L-asparagine derivative 6. The Hofmann rearrangement of 6 with sodium hypochlorite in the presence of sodium hydroxide and subsequent hydrogenation gave the bicyclic lactone 11, which upon dibenzylation and thionation, gave the thiolactone 2, a key intermediate for the synthesis of (+)-biotin (1).
- Seki, Masahiko,Shimizu, Toshiaki,Inubushi, Koichi
-
p. 361 - 364
(2007/10/03)
-
- An efficient and enantioselective synthesis of d-biotin
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An efficient and enantioselective synthesis of d-biotin 1 starting from cis-1,3-dibenzyl-2-imidazo-lidone-4,5-dicarboxylic acid (6) is described. The key steps are the enantioselective reduction of meso-1,2-dicarboxylic thioanhydride 8 to prepare the (3as, 6ar)- thiolactone 9 and the introduction of the C6 side chain at C-2 in 9 via a modified Grignard reaction. This novel synthesis proceeded in six steps to afford 1 with 21% overall yield.
- Chen,Huang,Fu,Cheng,Zhang,Li,Peng
-
p. 2004 - 2008
(2007/10/03)
-
- Synthesis of d-Biotin Chiral Intermediates via a Biochemical Method
-
The enzyme-catalyzed kinetic resolution of (+/-)-(3aα,4α,6aα)-4-acetoxy-1,3-dibenzyl-3a,4,6,6a-tetrahydro-1H-thienoimidazol-2(3H)-one was examined.Lipase B from Pseudomonas fragi and rabbit liver esterase gave (-)--1,3-dibenzyl-3a,4,6,6a-tetrahydro-4-hydroxy-1H-thienoimidazol-2(3H)-one , while Streptomyces rochei var. volubilis gave the alcohol (S)-(2), which is a key intermediate in the synthesis of d-biotin, with high enantioselectivity.
- Yamano, Toru,Tokuyama, Shinji,Aoki, Isao,Nishiguchi, Yumiko,Nakahama, Kazuo,Takanohashi, Kunio
-
p. 1456 - 1460
(2007/10/02)
-
- Optical Resolution of a d-Biotin Chiral Intermediate by Use of Lipoprotein Lipase
-
An efficient optical resolution of (+/-)-3aα,4α,6aα)-1,3-dibenzyl-3a,4,6,6a-tetrahydro-4-hydroxy-1H-thienoimidazol-2(3H)-one was accomplished by acylation with lipoprotein lipase from Pseudomonas aeruginosa TE3285 in toluene. The lipase acylated (R)-1 enantioselectively, and unreacted (S)-1, which is a chiral d-biotin intermediate, was isolated in excellent chemical and optical yields (>99percent e.e.). Effects of acylating agents, water content and molecular sieves were also investigated.
- Tokuyama, Shinji,Yamano, Toru,Aoki, Isao,Takanohashi, Kunio,Nakahama, Kazuo
-
p. 741 - 744
(2007/10/02)
-
- Synthesis of (+)-biotin: Efficient resolution of key intermediates
-
Enantiomerically pure 4-chlorothieno[3,4-d]imidazol-2-one (+)-2 and thieno[3,4-d]imidazol-2,4-dione (+)-5, key intermediates in independent routes to (+)-biotin (6), have been prepared by resolution via the corresponding diastereomeric ethers (3d-g and 3'd-g). Efficient procedures to recycle the undesired diastereomers and recover the chiral auxiliary have been developed.
- Bihovsky,Bodepudi
-
p. 7667 - 7676
(2007/10/02)
-
- Nucleophilic Displacements on an α-Chloro Thioether by Organocuprates: A Novel Synthesis of Desoxybiotin
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Reactions of organometallic reagents with α-chloro thioether 2, which is readily prepared from thienoimidazolone 1, have been investigated as an approach to the synthesis of biotin (10).Methyllithium and methylmagnesium bromide attack exclusively from the less hindered exo face, affording 4, while lithium dimethylcuprate attacks from the endo face with inversion of configuration, affording 5.Lithium dipentylcuprate affords predominantly exo isomer 6, while halide-free lithium methylpentylcuprate affords predominantly endo isomer 7.Debenzylation of 7 yields desoxybiotin (9) which can be microbially oxidized to biotin (10).Alternatively, 2 was hydrolyzed and oxidized to thiolactone 13, a known precursor of biotin.
- Bates, Hans Aaron,Rosenblum, Stuart B.
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p. 3447 - 3451
(2007/10/02)
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