【结 构 式】 |
【分子编号】32709 【品名】Cytarabine; Cytosine Beta-D-Arabinofuranoside; 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone 【CA登记号】147-94-4 |
【 分 子 式 】C9H13N3O5 【 分 子 量 】243.21944 【元素组成】C 44.45% H 5.39% N 17.28% O 32.89% |
合成路线1
该中间体在本合成路线中的序号:(I)This compound can be obtained in two different ways: 1) By condensation of 1-beta-D-arabinofuranosylcytosine (I) with palmitic anhydride (II) in hot dioxane. 2) By acylation of cytidine (III) with palmitic anhydride (II) in hot dioxane to yield N4-palmitoylcytidine (IV), which is then isomerized by treatment with POCl3 in ethyl acetate.
【1】 Ishida, T.; et al.; JP 7626884 . |
【2】 Ishida, T.; et al.; JP 7707974 . |
【3】 Ishida, T.; et al.; JP 7632573 . |
【4】 Akiyama, M.; et al.; The synthesis of new derivatives of 1-beta-D-arabinofuranosylcytosine. Chem Pharm Bull 1978, 26, 3, 981-984. |
【5】 Ishida, T.; et al.; JP 7648679 . |
【6】 Ishida, T.; et al. (Asahi Chemical Industry Co., Ltd.); N4-Acylarabinonucleosides. DE 2461862 . |
【7】 Ishida, T.; et al. (Asahi Chemical Industry Co., Ltd.); N4-Acylarabinonucleosides and the preparation thereof. DE 2426304 . |
【8】 Cabanillas, F.; Castaner, J.; Palmitoyl/Stearoyl Ara-C. Drugs Fut 1980, 5, 12, 617. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 32709 | Cytarabine; Cytosine Beta-D-Arabinofuranoside; 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone | 147-94-4 | C9H13N3O5 | 详情 | 详情 |
(II) | 39214 | acetic hexadecanoic anhydride | C18H34O3 | 详情 | 详情 | |
(III) | 27920 | Cytidine; 4-amino-1-((2S,3S,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one;4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone | 65-46-3 | C9H13N3O5 | 详情 | 详情 |
(IV) | 27921 | N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl]hexadecanamide | C25H43N3O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(I)This compound can be obtained in two different ways: 1) By condensation of 1-beta-D-arabinofuranosylcytosine (I) with docosanoyl anhydride (II) in hot dioxane. 2) By acylation of cytidine (III) with docosanoyl anhydride (II) as before to give N4-docosanoylcytidine (IV), which is then isomerized by treatment with POCl3 in ethyl acetate.
【1】 Akiyama, M.; et al.; The synthesis of new derivatives of 1-beta-D-arabinofuranosylcytosine. Chem Pharm Bull 1978, 26, 3, 981-984. |
【2】 Ishida, T.; et al.; JP 7626884 . |
【3】 Ishida, T.; et al.; JP 7648679 . |
【4】 Ishida, T.; et al.; JP 7632573 . |
【5】 Ishida, T.; et al.; N4-Acylarabinonucleosides apparatus for handling articles. DE 2461862; FR 2342070; JP 51019777 . |
【6】 Ishida, T.; et al.; N4-Acylarabinonucleosides and the preparation thereof. DE 426304; FR 2231388; GB 1449708; JP 50018482 . |
【7】 Serradell, M.N.; Cabanillas, F.; Castaner, J.; Blancafort, P.; Behenoyl Ara-C. Drugs Fut 1980, 5, 12, 603. |
【8】 Ishida, T.; et al. (Asahi Chemical Industry Co., Ltd.); Process for preparing N4-acylcytarabines. JP 52007974 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 32709 | Cytarabine; Cytosine Beta-D-Arabinofuranoside; 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone | 147-94-4 | C9H13N3O5 | 详情 | 详情 |
(II) | 32710 | docosanoic anhydride | 55726-23-3 | C44H86O3 | 详情 | 详情 |
(III) | 27920 | Cytidine; 4-amino-1-((2S,3S,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one;4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone | 65-46-3 | C9H13N3O5 | 详情 | 详情 |
(IV) | 31711 | 1-(2-diazo-1-phenylethyl)benzene | C14H12N2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(I)The title cytarabine 5'-ester was synthesized by condensation of cytarabine - HCl (I) with elaidoyl chloride (II) in DMA.
【1】 Borretzen, B.; Myhren, F.; Dalen, A.; Stokke, K.T. (Norsk Hydro AS); Improved therapeutic agents. WO 9705154 . |
合成路线4
该中间体在本合成路线中的序号:(XIV)The Boc-protected amino alcohol (VIII) is condensed with ethyl bromoacetate (IX) in the presence of potassium tert-butoxide to afford ether (X). After alkaline hydrolysis of the ethyl ester group of (X), the resultant carboxylic acid (XI) is activated as the thioimide (XIII) upon treatment with thiazolidine-2-thione (XII) and EDC. Coupling of the acyl thiazolidinone (XIII) with cytosine arabinoside (XIV) leads to the N-acyl cytosine derivative (XV). The Boc protecting group of (XV) is then removed under acidic conditions to furnish amine (XVI).
【1】 Choe, Y.H.; et al.; Anticancer drug delivery systems: multi-loaded N-4-acyl poly(ethylene glycol) prodrugs of ara-C. II. Efficacy in ascites and solid tumors. J Control Release 2002, 79, 1-3, 55. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VIII) | 57574 | tert-butyl 2-(2-hydroxyethoxy)ethylcarbamate | C9H19NO4 | 详情 | 详情 | |
(IX) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
(X) | 57575 | ethyl 2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azatridecan-13-oate | C13H25NO6 | 详情 | 详情 | |
(XI) | 57576 | 2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azatridecan-13-oic acid | C11H21NO6 | 详情 | 详情 | |
(XII) | 54751 | Thiazolidine-2-thione | C3H5NS2 | 详情 | 详情 | |
(XIII) | 57577 | tert-butyl 2-{2-[2-oxo-2-(2-thioxo-1,3-thiazolidin-3-yl)ethoxy]ethoxy}ethylcarbamate | C14H24N2O5S2 | 详情 | 详情 | |
(XIV) | 32709 | Cytarabine; Cytosine Beta-D-Arabinofuranoside; 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone | 147-94-4 | C9H13N3O5 | 详情 | 详情 |
(XV) | 57578 | tert-butyl 2-{2-[2-({1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl}amino)-2-oxoethoxy]ethoxy}ethylcarbamate | C20H32N4O10 | 详情 | 详情 | |
(XVI) | 57579 | 2-[2-(2-aminoethoxy)ethoxy]-N-{1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl}acetamide | C15H24N4O8 | 详情 | 详情 |