1268237-46-2

Basic information

• Product Name: 3'-Epi GeMcitabine 3',5'-Dibenzoate
• Synonyms: 3'-Epi GeMcitabine 3',5'-Dibenzoate;4-AMino-1-(3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-D-threo-pentofuranosyl)-2(1H)-pyriMidinone;ZPUUYUUQQGBHBU-UHFFFAOYSA-N
• CAS NO: 1268237-46-2
• Molecular Formula: C23H19F2N3O6
• Molecular Weight: 471.4102664
• Product Categories: Bases & Related Reagents;Intermediates & Fine Chemicals;Metabolites & Impurities;Nucleotides;Pharmaceuticals;Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals, Nucleotides, Bases & Related Reagents
• Mol File: 1268237-46-2.mol

Chemical Properties

• Appearance: /
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly, Heated), Methanol (Slightly)
• CAS DataBase Reference: 3'-Epi GeMcitabine 3',5'-Dibenzoate(CAS DataBase Reference)
• NIST Chemistry Reference: 3'-Epi GeMcitabine 3',5'-Dibenzoate(1268237-46-2)
• EPA Substance Registry System: 3'-Epi GeMcitabine 3',5'-Dibenzoate(1268237-46-2)

Safety Data

• Hazardous Substances Data: 1268237-46-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3'-Epi GeMcitabine 3',5'-Dibenzoate is used as an intermediate in the preparation of Gemcitabine impurities for the pharmaceutical industry. Its role in the synthesis process is crucial for the development of effective medications, particularly those targeting cancer treatment.
As an intermediate, 3'-Epi GeMcitabine 3',5'-Dibenzoate contributes to the overall production of Gemcitabine, a nucleoside analog used as an antineoplastic agent. Gemcitabine is known for its application in the treatment of various types of cancer, including pancreatic, non-small cell lung, bladder, and breast cancer. The presence of 3'-Epi GeMcitabine 3',5'-Dibenzoate in the synthesis process ensures the quality and efficacy of the final product, ultimately benefiting patients undergoing cancer treatment.

Upstream product

• 71-30-7 Cytosine 
• 134877-42-2 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-diphenylmethyl ester-1-methanesulfonate 
• 134877-42-2 3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-1-O-methanesulfonyl-D-erythro-pentofuranose 
• 18037-10-0 2,4-O,N-bis(trimethylsilyl)cytosine 
• 73416-12-3 4-Amino-1-trimethylsilanyl-1H-pyrimidin-2-one 
• 122111-01-7 2-deoxy-2,2-difluoro-D-erythro-pentonic acid γ-lactone 3,5-dibenzoate 
• 1173824-58-2 (2R,3R)-2-((benzoyloxy)methyl)-4,4-difluoro-5-hydroxyoxolan-3-yl benzoate 

Downstream Products

• 1535166-20-1 C₂₈H₃₂F₂N₄O₅ 
• 1535166-24-5 C₂₃H₂₄F₂N₄O₃ 

Relevant articles and documents

Preparation method of beta-configuration gemcitabine hydrochloride intermediate

The invention provides a preparation method of a beta-configuration gemcitabine hydrochloride intermediate, which comprises the following step: in a solvent, in the presence of an alpha-configurationgemcitabine hydrochloride intermediate II', reacting a gemcitabine hydrochloride intermediate I with silanized cytosine to prepare the beta-configuration gemcitabine hydrochloride intermediate II. Thebeta-configuration gemcitabine hydrochloride intermediate II is prepared in the presence of the alpha-configuration gemcitabine hydrochloride intermediate II', and the production of the alpha-configuration gemcitabine hydrochloride intermediate is effectively inhibited, so that the yield and the purity of a target product, namely the beta-configuration gemcitabine hydrochloride intermediate II, are improved, and post-treatment steps are simplified.

Stereoselective N-glycosylation with N4-acyl cytosines and efficient synthesis of gemcitabine

Through systematical comparison of various N4-protected cytosine derivatives in the glycosylation step of gemcitabine synthesis, highly beta-stereoselective and high yielding TBAI catalyzed N-glycosylation was achieved with N4-Bz cytosine and anomeric mixture of 2,2‘-difluororibose mesylate donor. The subsequent global deprotection gave gemcitabine efficiently. Meanwhile, the anomeric chloride intermediate and fluoride-displaced side products of this N-glycosylation were identified, too. This new glycosylation method reveals the importance of N4-protection in the stereoselective preparation of pyrimidine nucleoside, also provides a potential alternative to current industrial process to gemcitabine.

Industrial preparation process for key intermediate sulfonated saccharide of Gemcitabine

The invention relates to a preparation method for a compound represented by a formula (I) shown in the description, i.e., a key intermediate sulfonated saccharide of Gemcitabine. The final product is prepared through subjecting a compound represented by a formula (II) shown in the description to sodium borohydride reduction, hydroxyl protection and resolution. The method is simple in process, high in yield and high in product purity and has no need of harsh reaction conditions, thereby being very suitable for industrial production.

A miazines new compounds

The invention relates to a new pyrimidine compound. The experiment proves that the new compound disclosed in the specification can inhibit growth of tumor cells, and has favorable effectiveness and safety when being used for preparing antineoplastic drugs. The vessel irritation experiment proves that the new compound does not have hemolysis or irritation and can be prepared into an injection for clinical use.

Preparation method of difluoro nucleoside anticancer drugs capable of destroying cell replication

The invention relates to a preparation method of difluoro nucleoside anticancer drugs capable of destroying cell replication. The preparation method comprises steps as follows: cytosine is taken as a raw material and subjected to a reaction with hexamethyl disilazane, a silyl ether protecting group is generated and docked with 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate-1-methanesulfonate, and a final product is obtained after post-processing with hydrochloric acid. According to the method, the technology is simple, the operating condition is more convenient, the generation proportion of required isomers is high, the solvent is environment-friendly, harsh reaction conditions are not needed, and the method is suitable for industrial production.

Inactivation of lactobacillus leichmannii ribonucleotide reductase by 2',2'-difluoro2'-deoxycytidine s'-triphosphate: Covalent modification

Ribonucleotide reductase (RNR) from Lactobacillus leichmannii, a 76 kDa monomer using adenosylcobalamin (AdoCbl) as a cofactor, catalyzes the conversion of nucleoside triphosphates to deoxynucleotides and is rapidly ( 3H]- and [5-3H]F2CTP were synthesized and used independently to inactivate RNR. Sephadex G-50 chromatography of the inactivation mixture revealed that 0.47 equiv of a sugar was covalently bound to RNR and that 0.71 equiv of cytosine was released. Alternatively, analysis of the inactivated RNR by SDS-PAGE without boiling resulted in 33% of RNR migrating as a 110 kDa protein. Inactivation of RNR with a mixture of [1'-3H]F2CTP and [1'-2H]F 2CTP followed by reduction with NaBH4, alkylation with iodoacetamide, trypsin digestion, and HPLC separation of the resulting peptides allowed isolation and identification by MALDI-TOF mass spectrometry (MS) of a 3H/2H-labeled peptide containing C731 and C736 from the C-terminus of RNR accounting for 10% of the labeled protein. The MS analysis also revealed that the two cysteines were cross-linked to a furanone species derived from the sugar of F2CTP. Incubation of [1-3H]F2CTP with C119S-RNR resulted in 0.3 equiv of sugar being covalently bound to the protein, and incubation with NaBH4 subsequent to inactivation resulted in trapping of 2'-fluoro-2'-deoxycytidine. These studies and the ones in the preceding paper (DOI: 10.1021/bi9021318) allow proposal of a mechanism of inactivation of RNR by F2CTP involving multiple reaction pathways. The proposed mechanisms share many common features with F2CDP inactivation of the class I RNRs.

Stereospecific synthesis of 2-deoxy-2,2-difluororibonolactone and its use in the preparation of 2'-deoxy-2',2'-difluoro-β-D-ribofuranosyl pyrimidine nucleosides: The key role of selective crystallization

A stereospecific synthesis of 2'-deoxy-2',2'-difluorocytidine (gemcitabine), a potential anticancer agent, is described. The stereoselectivity was accomplished via two diastereoselective crystallizations, i.e. the crystallization of the key intermediate, difluororibonolactone 2a, and the crystallization of the hydrochloride salt of gemcitabine 16b from the anomeric mixture. Because of the availability of 2a in large quantities, other 2'-deoxy-2',2'-difluoropyrimidine nucleosides such as 2'-deoxy-2',2'-difluorouridine (19) were synthesized for structure-activity relationship studies.