33607-60-2

Usage

Uses

Used in Pharmaceutical Industry:
cis-(-)-1,3-Dibenzylhexahydro-2-oxo-1H-thieno[3,4-d]imidazole-4-valeric Acid is used as a protected intermediate for the synthesis of biotin (B389040) derivatives. This application is significant because biotin derivatives have various biological activities and are used in the development of drugs for different therapeutic areas.
As a protected intermediate, cis-(-)-1,3-Dibenzylhexahydro-2-oxo-1H-thieno[3,4-d]imidazole-4-valeric Acid is essential in the chemical synthesis process, allowing for the creation of biotin derivatives with specific properties and functions. These derivatives can then be utilized in the development of medications targeting various health conditions and diseases.

Upstream product

• 52608-08-9 (+/-)-[3-(1,3-dibenzyl-2-oxo-(3ar,6ac)-hexahydro-thieno[3,4-d]imidazol-4t-yl)-propyl]-malonic acid 
• 2067-33-6 5-bromopentanoic acid 
• 56198-37-9 5-iodovaleric acid tert-butyl ester 
• 75-44-5 phosgene 
• 95954-55-5 5-((2S)-3c,4c-bis-benzylideneamino-tetrahydro-thiophen-2r-yl)-pentanoic acid methyl ester 
• 863203-60-5 5-((3aS,6aR)-1,3-dibenzyl-4-hydroxy-2-oxohexyl-1H-furo[3,4-d]imidazol-4-yl)pentenoic acid 
• 153991-84-5 (E)-5-[(3aR,6aS)-1,3-Dibenzyl-2-oxo-hexahydro-thieno[3,4-d]imidazol-(6E)-ylidene]-pent-3-enoic acid 
• 452100-87-7 (3aS,4Z,6aR)-5-{hexahydro-1,3-dibenzyl-2-oxo-4H-thieno[3,4-d]imidazol-4-ylidene}pentanoic acid 
• 100-46-9 benzylamine 
• 51591-75-4 cis-1,3-dibenzyl-2-oxoimidazolidine-4,5-dicarboxylic acid 
• 292151-18-9 ethyl (3aS,4Z,6aR)-5-[1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-5-ylidene]-pentanoate 
• 28092-52-6 (3aS,6aR)-1,3-dibenzyltetrahydro-1H-thieno[3,4-d]imidazole-2,4-dione 
• 41302-32-3 ethyl 5-iodopentanoate 
• 777940-99-5 2-[(4R)-3-benzyl-2-oxathiazolidin-4-yl]-2-benzylaminoacetonitrile 

Downstream Products

• 76335-62-1 (+/-)-5-[1( oder !3)-benzyl-2-oxo-(3ar,6ac)-hexahydro-thieno[3,4-d]imidazol-4t-yl]-valeric acid 
• 608-16-2 (+/-)-biotin methyl ester 
• 58-85-5 biotin 
• 22342-46-7 (2S,3S,4R)-cis-5-(3,4-diaminotetrahydro-2-thienyl)valeric acid 

Relevant academic research and scientific papers

N, N ' - di-substituted biotin compound (by machine translation)

[Problem] N, N ' - di-substituted biotin compound of high purity can be efficiently produced. (2) Formula [a]Biotin reaction of a halide, (4) wherein(Where R is an alkyl group or the like) to give an ester compound, followed by hydrolysis. [Drawing] no (by machine translation)

Synthesis method of d-biotin

The invention discloses a synthesis method of d-biotin. The synthesis method comprises the following steps: taking cysteine hydrochloride, benzaldehyde and benzyl isocyanate as starting materials, andsubjecting the starting materials to condensation, cyclization, reduction, condensation, oxidation, reduction, cyclization, elimination, catalytic hydrogenation and debenzylation sequentially to obtain the d-biotin. The method has the advantages that the raw materials are cheap and easy to obtain, the safety is good, the reaction conditions are mild and easy to control, the production cost is lowered, green and environmental protection is achieved, the reaction yield is high, separation is easy, and the purity of the obtained d-biotin is high.

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.

PROCESS FOR THE MANUFACTURE OF (+)-BIOTIN

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).

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.

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.

Total synthesis of D-(+)-biotin

The total synthesis of D-(+)-biotin has been described starting from D-(+)-glucosamine using acyliminium chemisty. A total synthesis of D-(+)-biotin is described starting from D-(+)-glucosamine using acyliminium chemistry.

A practical synthesis of (+)-biotin from L-cysteine

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.

INTERMEDIATE FOR BIOTIN AND PROCESS FOR PRODUCING THE SAME

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.

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.