(2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate -Drug Synthesis Database

【结构式】

【分子编号】29143

【品名】(2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate

【CA登记号】

【分子式】C₂₇H₂₁NO₇

【分子量】471.46628

【元素组成】C 68.78% H 4.49% N 2.97% O 23.75%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(II)

A new synthesis of thiazofurin has been described: The reaction of 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (I) with trimethylsilyl cyanide and SnCl4 in dichloromethane gives 2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl cyanide (II), which is treated with H2S gas and dimethylaminopyridine (DMAP) in ethanol yielding the corresponding thioamide (III). The carefully controlled cyclization of (III) with 3-bromopyruvic acid ethyl ester (IV) by means of NaHCO3 in dimethoxyethane, followed by treatment with trifluoroacetic anhydride and 2,6-lutidine in the same solvent affords 2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)thiazole-4-carboxylic acid ethyl ester (V). Elimination of the benzoyl protecting groups of (V) with NaOEt in ethanol gives 2-(beta-D-ribofuranosyl)thiazole-4-carboxylic acid ethyl ester (VI). Which is finally treated with dry ammonia in methanol to afford the target amide.

参考文献中间体

合成目标

【1】 Garcia-Munoz, G.; Stud, M.; Fuertes, M.; Synthesis of C-glycocyl thiazoles. J Org Chem 1976, 41, 4074.
【2】 Ramasamy, K.S.; Averett, D.; A modified synthesis of tiazofurin. Nucleosides Nucleotides 1999, 18, 11-12, 2425.
【3】 Eastland, G.; Tiazofurine. Drugs Fut 1985, 10, 4, 304.

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)	26984	(2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate		C₂₈H₂₄O₉	详情	详情
(II)	29143	(2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate		C₂₇H₂₁NO₇	详情	详情
(III)	29144	(2R,3S,4R,5R)-2-(aminocarbothioyl)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate		C₂₇H₂₃NO₇S	详情	详情
(IV)	25183	ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate	70-23-5	C₅H₇BrO₃	详情	详情
(V)	29145	ethyl 2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,3-thiazole-4-carboxylate		C₁₁H₁₅NO₆S	详情	详情
(VI)	34062	ethyl 2-[(2R,3S,4R,5R)-3,4-bis(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-2-furanyl]-1,3-thiazole-4-carboxylate		C₃₂H₂₇NO₉S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The reaction of 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (I) with Tms-CN and SnCl4 in dichloromethane gives the carbonitrile (II), which is cyclized with L-cysteine methyl ester (III) by means of TEA in dichloromethane to yield the thiazoline carboxylate (IV). The dehydrogenation of (IV) by means of BrCCl3 and DBU in the same solvent affords the thiazole carboxylate (V), which is finally treated with ammonia in methanol to hydrolyze the benzoate groups and form the carboxamide residue of the target tiazofurin.

参考文献中间体

合成目标

【1】 Brown, R.S.; et al.; A concise route to tiazofurin. Tetrahedron Lett 2002, 43, 37, 6561.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	61497	(2S,3R,4R,5R)-2-(acetyloxy)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate	C₂₈H₂₄O₉	详情	详情
(II)	29143	(2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate	C₂₇H₂₁NO₇	详情	详情
(III)	27413	methyl (2R)-2-amino-3-sulfanylpropanoate	C₄H₉NO₂S	详情	详情
(IV)	61498	methyl 2-{(2R,3S,4R,5R)-3,4-bis(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-2-furanyl}-4,5-dihydro-1,3-thiazole-4-carboxylate	C₃₁H₂₇NO₉S	详情	详情
(V)	61499	methyl 2-{(2R,3S,4R,5R)-3,4-bis(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-2-furanyl}-1,3-thiazole-4-carboxylate	C₃₁H₂₅NO₉S	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 synthesis of selenazole is as follows: 2,3,5-Tri-O-benzoyl-beta-D-ribofuranosyl-1-carbonitrile (I) is treated with liquid hydrogen selenide, using 4-(dimethylamino)pyridine as a catalyst, under nitrogen at room temperature to give 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonselenenoamide (II). (II) is treated, in acetonitrile, with ethyl bromopyruvate. After an hour the solvent is removed in vacuo and the residue triturated with sodium bicarbonate and extracted with ethyl ether. After workup to remove the ether, chromatographic separation of the alpha- and beta-anomers on silica gel gives ethyl 2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)selenazole-4-carboxylate (III). Compound (III) is dissolved in methanol and treated with ammonia at 0 C. After 48 h the solvent is removed, the residue extracted with chloroform, the chloroform layer discarded and the residue chromatographed on silica gel. Recrystallization of the major product from 2-propanol yields crystalline 2-beta-D-ribofuranosylselenazole-4-carboxamide. The preparation of the 5'-phosphate derivative is also described.

参考文献中间体

合成目标

【1】 Srivastava, P.; Robins, R.K.; Synthesis and antitumor activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide and related derivatives. J Med Chem 1983, 26, 3, 445-448.
【2】 Eastland, G.W.; Selenazole. Drugs Fut 1985, 10, 5, 409.

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)	29143	(2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate		C₂₇H₂₁NO₇	详情	详情
(II)	29370	(2R,3R,4S,5R)-5-(aminocarboselenoyl)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate		C₂₇H₂₃NO₇Se	详情	详情
(III)	25183	ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate	70-23-5	C₅H₇BrO₃	详情	详情
(IV)	29731	N-(5-amino-6-chloro-4-pyrimidinyl)-N-[6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]amine; N(4)-[6-(benzyloxy)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-6-chloro-4,5-pyrimidinediamine		C₁₉H₂₁ClN₄O₃	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

Reaction of 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (I) with trimethylsilyl cyanide in the presence of boron trifluoride gave nitrile (II), which was treated with liquid hydrogen sulfide and DMAP to yield thioamide (III). Condensation of this thioamide with bromoketone (IV) in acetonitrile afforded the thiazole derivative (V). Hydrolysis of the benzoate esters of (V) using sodium methoxide in methanol, followed by protection of the resulting 2,3-diol with acetone and triethyl orthoformate produced the corresponding isopropylidene ketal (VI). Treatment of the primary alcohol group of (VI) with sulfamoyl chloride gave rise to the sulfamate ester (VII). Further condensation of (VII) with N-Boc-L-leucine furnished (IX). The Boc and isopropylidene groups of (IX) were finally eliminated with trifluoroacetic acid to provide the title compound.

参考文献中间体

合成目标

【1】 Wang, W.; Gallant, P.; Hill, J.M.; Yu, G.; Wendler, P.; Kluge, A.F.; Yu, X.Y.; Synthesis and structure-activity relationships of a series of novel thiazoles as inhibitors of aminoacyl-tRNA synthetases. Bioorg Med Chem Lett 1999, 9, 3, 375.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	20984	methyl (Z)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E)-3-oxo-3-(4-propylcyclohexyl)-1-propenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate	C₃₃H₅₂O₇	详情	详情
(II)	29143	(2S,3S,4R,5R)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]-2-cyanotetrahydro-3-furanyl benzoate	C₂₇H₂₁NO₇	详情	详情
(III)	29144	(2R,3S,4R,5R)-2-(aminocarbothioyl)-4-(benzoyloxy)-5-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate	C₂₇H₂₃NO₇S	详情	详情
(IV)	29211	1-bromo-4-phenyl-2-butanone	C₁₀H₁₁BrO	详情	详情
(V)	29212	[(2R,3R,4S,5R)-3,4-bis(benzoyloxy)-5-(4-phenethyl-1,3-thiazol-2-yl)tetrahydro-2-furanyl]methyl benzoate	C₃₇H₃₁NO₇S	详情	详情
(VI)	29213	[(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol	C₁₉H₂₃NO₄S	详情	详情
(VII)	29214	[(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methylsulfamate	C₁₉H₂₄N₂O₆S₂	详情	详情
(VIII)	23663	(2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine	C₁₁H₂₁NO₄	详情	详情
(IX)	29215	tert-butyl (1S)-1-[[([[(3aR,4R,6R,6aS)-2,2-dimethyl-6-(4-phenethyl-1,3-thiazol-2-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methoxy]sulfonyl)amino]carbonyl]-3-methylbutylcarbamate	C₃₀H₄₃N₃O₉S₂	详情	详情

Extended Information