- METHOD FOR PRODUCING AMIDE CARBOXYLIC ACID COMPOUND, AND METHOD FOR PRODUCING AMIDE ALCOHOL COMPOUND, AND METHOD FOR PRODUCING LACTONE COMPOUND
-
PROBLEM TO BE SOLVED: To provide a production method for efficiently obtaining a high-purity amide carboxylic acid compound, which is useful as a synthetic intermediate of biotin. SOLUTION: In a method for producing an amide carboxylic acid compound, an anhydride of a specific ureido compound is brought into contact with an optically active amine such as N-Me-R-α-methyl benzyl amine to obtain a mixture comprising an amide carboxylic acid compound, and then, the amide carboxylic acid compound is isolated from the obtained mixture. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
- -
-
-
- Practical Synthesis of (+)-Biotin Key Intermediate by Calcium Borohydride Reduction and Temperature-Dependent Purity Upgrade during Crystallization
-
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)
-
- Method for stereoselectively synthesizing chiral lactone, chiral compound and application of chiral compound
-
The invention relates to the field of organic synthesis, and discloses a method for stereoselectively synthesizing chiral lactone, a chiral compound and application of the chiral compound in synthesis of biotin. The method comprises the following steps: (1) carrying out first reaction on cyclic anhydride, cyclic chiral alcohol and organic alkali tertiary amine to obtain dicarboxylic acid mono-ester quaternary ammonium salt; (2) carrying out second reaction on the dicarboxylic acid mono-ester quaternary ammonium salt and a reducing agent after intermediate treatment or no intermediate treatment to obtain alcohol acid; and (3) under an acidic condition, carrying out a third reaction on the alcohol acid to obtain the chiral lactone shown in the formula (I). According to the method disclosed by the invention, the target product can be obtained with high selectivity and high yield.
- -
-
-
- HYDRATE OF AMIDOALCOHOL COMPOUND, PRODUCTION METHOD THEREOF, AND PRODUCTION METHOD OF LACTONE COMPOUND
-
PROBLEM TO BE SOLVED: To provide a hydrate of an amidoalcohol compound, which is an intermediate raw material of biotin synthesis, a production method thereof, and a production method of a lactone using an amidoalcohol compound. SOLUTION: A hydrate of an amidoalcohol compound is represented by a formula (I). (In the formula, R1 and R2 are each a substituted/unsubstituted benzyl group, R3 is a substituted/unsubstituted phenyl group, and n is 0-1.) SELECTED DRAWING: None COPYRIGHT: (C)2022,JPOandINPIT
- -
-
Paragraph 0024; 0029; 0089; 0114-0117
(2021/11/26)
-
- METHOD FOR PRODUCING LACTONE COMPOUND
-
PROBLEM TO BE SOLVED: To provide a production method that produces a lactone compound, an important intermediate in biotin production, with high purity and efficiency. SOLUTION: A method for producing a lactone compound includes bringing an amide alcohol compound represented by the formula (1) (where R1 and R2 may be different from each other to represent a substituted or unsubstituted benzyl group, R3 is a substituted or unsubstituted phenyl group) into contact with hydrogen chloride in a solvent including an aprotic polar solvent. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
- -
-
Paragraph 0072-0073; 0075
(2021/05/28)
-
- Synthetic method of (3S,6R)-1,3-dibenzyltetrahydrofuroimidazole-2,4-dione
-
The invention discloses a synthetic method of (3aS,6aR)-1,3-dibenzyltetrahydrofuroimidazole-2,4-dione. The method uses a cyclic anhydride as a starting raw material, and the cyclic anhydride is subjected to selective alcoholysis, reduction and cyclization to prepare the chiral lactone (3aS,6aR)-1,3-dibenzyltetrahydrofuroimidazole-2,4-dione. The process route is simple, raw materials are cheap andreadily available, the diastereoselectivity of an alcoholysis reaction is high, a chiral alcohol reagent can be recovered and applied through simple extraction, and the production cost is reduced. Themethod has the advantages of simple and convenient operation, mild reaction conditions, high yield, and good stereoselectivity, and has relatively good application values and economic benefits.
- -
-
Paragraph 0051-0068
(2020/02/27)
-
- Method for stereoselective synthesis of chiral lactone
-
The invention relates to the field of organic synthesis, and discloses a method for stereoselective synthesis of chiral lactone. The method includes the following steps: (1) carrying out a first reaction on cyclic anhydride represented by formula (1), chiral alcohol represented by formula (2) and an organic alkali tertiary amine represented by NRRR in the presence of a protective gas anda solvent to obtain a quaternary ammonium salt represented by formula (3); (2) carrying out a second reaction on the quaternary ammonium salt represented by the formula (3) and a reducing agent to obtain a quaternary ammonium salt of alcohol acid, represented by formula (4); (3) carrying out a third reaction on the quaternary ammonium salt of the alkyd, represented by the formula (4), and an alkaline substance to obtain a metal salt of the alkyd; and (4) carrying out a fourth reaction on the metal salt of the alkyd to close the ring. The method for stereoselective synthesis of chiral lactone can achieve recovery of chiral alcohol and the organic tertiary amine at a high recovery rate without using expensive lithium hydroxide, and can obtain the target product at a high yield.
- -
-
-
- Novel asymmetric synthesis method for biotin chiral lactone
-
The invention discloses a novel asymmetric synthesis method for biotin chiral lactone. According to the method, by taking cycloanhydride as an initial raw material, the chiral lactone (3S,6R)-1,3-dibenzyl tetrahydrofuroimidazole-2,4-dione is prepared by selective alcoholysis, reduction and cyclization. The method is simple in process route, the raw material is cheap and easily available, and an alkaline catalyst is nearly insoluble in water and is recycled and reused through simple extraction, so that the production cost is lowered, and the diastereoselectivity of the alcoholysis reaction is improved. The method has the advantages of being simple to operate, mild in reaction condition, high in yield and high in stereoselectivity and has relatively good application value and economical benefits.
- -
-
-
- Process development and scale-up for the preparation of roche thiolactone: Key intermediate for (+)-biotin
-
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
-
p. 373 - 377
(2020/01/03)
-
- Method for Producing Intermediate of Biotin and Method for Producing Biotin
-
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).
- -
-
-
- Synthesis method of biotin intermediate
-
The invention discloses a synthesis method of a biotin intermediate. The existing cyclic anhydride monoester compound is subjected to diastereomeric selective resolution by using a chiral resolving agent. The existing chiral resolving agent has the problems of high cost and low recovery reuse rate. According to the method provided by the invention, naphthenic acid is used as an initial raw material; the naphthenic acid is subjected to cyclization dewatering to prepare annular racemization carboxylic acid anhydride; reduction is performed to obtain racemization d,1-lactone; then, D-amino-compounds are used for resolution, so that a chiral product (4S,5R)-monoamide is separated out in a precipitate form; finally, acidolysis preparation is performed to obtain a biotin intermediate (3aS, 6aR)-lactone. The economic cheap and easy-to-recover and reuse D-amino-compounds are used as the preferred resolving agent; the reaction is simple; the post treatment is convenient; the cost is low; the pollution is little; all waste leftovers can be converted into the initial raw materials of naphthenic acid through oxidization; the goal of green, environment-friendly, economic and regenerated circulation reuse can be really achieved.
- -
-
-
- Chiral squaramide-mediated methanolytic desymmetrization of prochiral cyclic anhydride: A convenient approach for synthesizing roche lactone
-
The main objective of this report was to develop an improved process for the asymmetric synthesis of (3aS, 6aR)-lactone 1, which is the key chiral intermediate of (+)-biotin. This practical and efficient process includes a novel chiral squaramide alkamine derivatives 5 mediated methanolytic desymmetrization of prochiral cyclic anhydride 3 to produce the enantiomerically enriched precursor of Roche lactone.
- Ding, Liang-Qian,Hong, Dan-Feng,Liu, Wen-Guang,Ma, Hui,Tan, Qing-Gang,Wang, Shi-Heng,Wu, Si-Qin,Xiong, Fei
-
p. 429 - 432
(2018/09/25)
-
- A NEW CHIRAL BIPHENYL DIPHOSPHINE LIGAND AND PROCESS FOR PREPARATION THEREOF
-
The present invention is related to a new chiral biphenyl diphosphine ligand of formula (I), wherein R1, R2, and R3 are independently H, alkyl or aryl; R6 and R7 is independently a substituent; and A is independently aryl or heteroaryl, optionally substituted by one or more substituents, or a stereoisomer thereof, or a stereoisomeric mixture thereof.
- -
-
Page/Page column 19
(2018/11/22)
-
- Method for synthesizing optical pure biotin intermediate lactone
-
The invention relates to a method for preparing optical pure biotin intermediate lactone II through catalytic desymmetrisation reduction of anhydride I. According to the method, the biotin intermediate anhydride I is used as a reaction substrate; under the catalysis effect of transmission metal, the optical pure biotin intermediate lactone II is prepared. Compared with a conventional method, the method provided by the invention has the characteristics that the catalyst consumption is low; the conversion rate is high; the ee value is high; the cost is low; the operation is simple; the green and environment-friendly effects are achieved. The method is suitable for large-scale industrial production.
- -
-
Paragraph 0027-0030; 0033
(2017/08/14)
-
- A key intermediate D-biotin (3aS, 6aR)-the method for preparing lactone
-
The invention relates to a preparation method of a D-biotin key intermediate (3aS, 6aR)-lactone. The method comprises the following steps: with (S)-beta-hydroxyl-gamma-butyrolactone as an initial raw material, firstly, carrying out sulfonylation to protect hydroxyl, and then carrying out alpha-bromo-substitution and amination reaction, so as to prepare (2R, 3R)-2,3-dibenzyl amino-gamma-butyrolactone and (2R,3R)-2,3-dibenzyl amino-gamma-butyrolactone mixtures; and carrying out amidation on triphosgene to form a ring, so as to prepare (3aR,6aR)-1,3-dibenzyl tetrahydro-4H-furo [3,4-d] iminazole-2,4-(1H)-diketone and (3aR,6aR)-1,3-dibenzyl tetrahydro -4H-furo [3,4-d] iminazole-2,4-(1H)-diketone mixtures; and heating and rearranging, so as to obtain a target compound (I). The method is short in reaction route, high in reaction selectivity, and suitable for industrialized production; and the reaction condition is easy to operate.
- -
-
Paragraph 7-9
(2019/02/04)
-
- Highly enantioselective methanolysis of meso-cyclic anhydride mediated by bifunctional thiourea cinchona alkaloid derivatives: Access to asymmetric total synthesis of (+)-biotin
-
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
-
p. 1078 - 1082
(2013/10/21)
-
- Chemoenzymatic synthesis of d-biotin intermediate lactone via lipase-catalyzed desymmetrization of meso diols
-
A chemoenzymatic methodology for the asymmetric synthesis of d-biotin intermediate lactone ((3aS, 6aR)-tetrahydro-1,3-dibenzylhexahydro-1H-Furo[3,4-d] imidazole-2,4-dione) 1 has been demonstrated. The key step of the synthetic routes is Lipozyme RM IM catalyzed desymmetrization of meso-diols 3. The highest enantiomeric excess (e.e. > 98%) and yield (>90%) of the product was achieved with Lipozyme RM IM in Dioxane/Toluene (1:3, v/v) at 35 C. Furthermore, Lipozyme RM IM showed an excellent operational stability, retaining above 80% of the initial activity after 10 cycles of reaction. d-Biotin intermediate lactone 1 was obtained subsequently by Jones oxidation, basic hydrolysis and lactonization.
- Zheng, Jian-Yong,Wang, Sheng-Fan,Zhang, Yin-Jun,Ying, Xiang-Xian,Wang, Yu-Guang,Wang, Zhao
-
-
- Desymmetric hydrogenation of a meso-cyclic acid anhydride toward biotin synthesis
-
Catalytic reactivity in the hydrogenation of a cyclic anhydride to a biotin synthetic intermediate has been investigated on the basis of Lyons' original method using Wilkinson Ru complex, revealing the high performance of DPPF and XANTPHOS diphosphines possessing wide bite angles. The results have shown a new trail for design of the corresponding asymmetric catalysts, and the potential utility of (S,S)-Et-FerroTANE and (S,S)-(R,R)-Ph-TRAP has been demonstrated.
- Yoshimura, Masahiro,Tsuda, Kazuomi,Nakatsuka, Hiroshi,Yamamura, Tomoya,Kitamura, Masato
-
experimental part
p. 10006 - 10010
(2012/02/15)
-
- Synthetic studies on (+)-biotin, part 151: A chiral squaramide-mediated enantioselective alcoholysis approach toward the total synthesis of (+)-biotin
-
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
-
p. 488 - 491
(2011/05/14)
-
- 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)
-
- An improved asymmetric total synthesis of (+)-biotin via the enantioselective desymmetrization of a meso-cyclic anhydride mediated by cinchona alkaloid-based sulfonamide
-
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)
-
- A novel cost-effective thiourea bifunctional organocatalyst for highly enantioselective alcoholysis of meso-cyclic anhydrides: Enhanced enantioselectivity by configuration inversion
-
A novel inexpensive thiourea bifunctional organocatalyst which can promote the highly enantioselective (up to 95% ee) alcoholysis of mesocyclic anhydrides has been developed. Computational studies on the catalytic process as well as a synthetic application of this new catalyst are also presented.
- Wang, Su-Xi,Chen, Fen-Er
-
scheme or table
p. 547 - 552
(2009/10/25)
-
- 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
-
p. 1435 - 1442
(2008/12/20)
-
- Synthetic studies on (+)-biotin, Part 11:[1] Application of Cinchona alkaloid-mediated asymmetric alcoholysis of meso-cyclic anhydride in the total synthesis of (+)-biotin
-
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)
-
- A practical formal synthesis of D-(+)-biotin from 4-formylazetidin-2-one
-
A practical synthesis of (3S,6R)-1,3-dibenzyltetrahydro-1H-furo[3,4-d] imidazole-2,4-dione, an important intermediate in the synthesis of biotin, from 4-formyl-3-mesyloxyazetidin-2-one has been achieved. Acid-catalyzed azetidin-2-one ring opening followed by a one-pot conversion of diamine hydrochloride to a cyclic urea and hydroxymethylene to chloromethylene by triphosgene to obtain (4S,5R)-methyl-1,3-dibenzyl-5-chloromethyl-2- oxoimidazolidine-4-carboxylate is the key step in this synthesis. Georg Thieme Verlag Stuttgart.
- Kale, Ajaykumar S.,Puranik, Vedavati G.,Deshmukh, Abdul Rakeeb A. S.
-
p. 1159 - 1164
(2008/02/02)
-
- Synthetic studies on d-biotin, part 9.1) An improved asymmetric synthetic route to d-biotin via Hoffmann-Roche lactone-thiolactone approach
-
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)
-
- Method for selectively dissociating cyclic carboxylic acid anhydrides
-
The invention relates to a method for selectively dissociating cyclic carboxylic acid anhydrides. According to the inventive method, a chiral amino alcohol with a tertiary amino group that may have a partially or completely bridged structure is used as the chiral auxiliary reagent.
- -
-
Page/Page column 11-12; 14-15
(2008/06/13)
-
- 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 PROCESS FOR THE STEREOSELECTIVE SYNTHESIS OF LACTONES
-
A process is described for the stereoselective synthesis of a chiral lactone which can be used as an intermediate in the synthesis of biotin. The process includes a reaction sequence in which a cyclic meso-carboxylic acid anhydride is converted with the aid of a chiral alcohol with ring opening into a dicarboxylic acid monoester. With respect to the dicarboxylic acid monoester obtained from the cyclic meso-carboxylic acid anhydride and the chiral alcohol, the reaction proceeds diastereoselectively. The reaction is performed in the presence of a specific catalyst improving the diastereomeric purity of the dicarboxylic acid monoester.
- -
-
-
- 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
-
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)
-
- 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
-
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
-
p. 2155 - 2160
(2007/10/03)
-
- A novel synthesis of a key intermediate for (+)-biotin from L-aspartic acid
-
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)
-
- A formal catalytic asymmetric synthesis of (+)-biotin with modified cinchona alkaloids
-
A formal catalytic asymmetric synthesis of (+)-biotin was realized. The key steps involve a catalytic, highly enantioselective and quantitative desymmetrization of a meso cyclic anhydride followed by a one-pot chemoselective reduction to form the optically active lactone intermediate in the Goldberg - Sternbach (+)-biotin synthesis.
- Choi,Tian,Deng
-
p. 1737 - 1741
(2007/10/03)
-
- Enantioselective reduction of meso-cyclic-1,2-dicarboxylic anhydrides and 1,2-dicarboximides: Asymmetric synthesis of bicyclic lactones and hydroxylactams
-
Chiral bicyclic lactones (3,8,9) and bicyclic hydroxylactams (10-13) were synthesized by highly enantioselective reduction of meso-cyclic-1,2- dicarboxylic anhydrides (1, 4) and meso-cyclic-1,2-dicarboximides (2) with lithium aluminum hydride (LiAlH4)-alcohol(ROH)-(R)- or (S)-1,1'-bi-2- naphthol complex [(R)- or (S)-BINAL-H(ROH)]. Treatment of the hydroxylactams (10-13) with triethylsilane (Et3SiH) and trifluoroacetic acid (CF3CO2H) gave chiral bicyclic lactams (14, 15) in quantitative yields. Removal of the N-4-methoxyphenyl group of the lactams (14, 15) with cerium(IV) ammonium nitrate (CAN) proceeded smoothly to give the corresponding N-unsubstituted lactams (16, 17) in high optical purity.
- Matsuki,Inoue,Ishida,Takeda,Nakagawa,Hino
-
-
- Highly enantioselective reduction of meso-1,2-dicarboxylic anhydrides
-
Optically active lactones (2a-2g) were synthesized by highly enantioselective reduction of readily available meso-1,2-dicarboxylic anhydrides (1a-1g) using lithium aluminum hydride-ethanol-1,1'-bi-2-naphthol complex (BINAL-H).
- Matsuki,Inoue,Takeda
-
p. 1167 - 1170
(2007/10/02)
-
- Monoesters of imidazolidinone dicarboxylic acids
-
A novel process for the manufacture of the optically active lactone of the formula STR1 is described.
- -
-
-
- Intermediates to optically active cis-1,3-dibenzyl-hexahydro-1H-furo[3,4-d]imidazole-2,4-dione
-
A process for preparing an optically active cis-1,3-dibenzylhexahydro-1H-furo[3,4-d]imidazole-2,4-dione of the formula: STR1 wherein an asterisk (*) indicates an asymmetric carbon, Bzl represents a benzyl group and the 3a- and 6a-positions take the cis-configuration, which comprises reducing selectively an optically active cis-imidazolidinedicarboxylic acid monoester of the formula: STR2 wherein R is a C1 -C6 alkyl group and Bzl is as defined above with a reducing agent at either one of the carboxyl group and the alkoxycarbonyl group in the said monoester, followed by cyclization, the said monoester being the one obtainable by hydrolysis of a cis-imidazolidinedicarboxylic acid diester of the formula: STR3 wherein R and Bzl are each as defined above with an enzymatic material having a capability of hydrolyzing the ester group in the said diester.
- -
-
-
- BIFUNCTIONAL CHIRAL SYNTHONS VIA BIOCHEMICAL METHODS. 4. CHIRAL PRECURSORS TO (+)-BIOTIN AND (-)-A-FACTOR.
-
The chirons 3 and 4, derived from enzymic enantioselective hydrolysis of 1 and 2, are converted into the chiral lactones 5 and 6, key precursors to (+)-biotin and (-)-A-factor, respectively.
- Wang, Yi-Fong,Sih, Charles J.
-
p. 4999 - 5002
(2007/10/02)
-
- Process and intermediates for the manufacture of (3aS, 6aR)-1,3-dibenzyldihydro-1H-furo[3,4-d] imidazole-2,4(3H,3aH)-dione
-
A process for the manufacture of the optically active lactone of the formula STR1 wherein R represents the benzyl group, is described. In this process an optically active compound of the formula STR2 wherein R has the above significance and R1 signifies the cholesteryl or the cyclohexyl group, is reduced with a dialkylaluminium hydride or a complex borohydride. The compound of formula I is a known, valuable intermediate for, inter alia, (+)-biotin.
- -
-
-
- Asymmetric Hydrolysis of Prochiral Diesters with Pig Liver Esterase. Preparation of Optically Active Intermediates for the Synthesis of (+)-Biotin and (+)-α-Methyl-3,4-dihydroxyphenylalanine
-
With pig liver esterase, 1,3-dibenzyl-4,5-cis-bis(alkyloxycarbonyl)-2-oxoimidazolidine (1) was asymmetrically hydrolyzed to (4S,5R)-1,3-dibenzyl-5-alkyloxycarbonyl-2-oxoimidazolidine-4-carboxylic acid (2).This acid 2 was reduced with lithium borohydride to (4S,5R)-1,3-dibenzyl-5-hydroxymethyl-2-oxoimidazolidine-4-carboxylic acid lactone (3), which is known to be converted to (+)-biotin (4).With the same esterase, diethyl 3,4-dimethoxyphenylmethyl(methyl)malonate (5) was asymmetrically hydrolyzed to (R)-ethyl hydrogen 3,4-dimethoxyphenylmethyl(methyl)malonate (6), which can be converted to (S)-α-methyl-3,4-dihydroxyphenylalanine (L-α-methyldopa) (9).
- Iriuchijima, Shinobu,Hasegawa, Keiko,Tsuchihashi, Gen-ichi
-
p. 1907 - 1910
(2007/10/02)
-