(5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2(5H)-furanone -Drug Synthesis Database

【结构式】

【分子编号】29820

【品名】(5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2(5H)-furanone

【CA登记号】50-81-7

【分子式】C₆H₈O₆

【分子量】176.12592

【元素组成】C 40.92% H 4.58% O 54.5%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IX)

L-threonic acid (XI), which is readily available from L-ascorbic acid (IX), is converted to L-N-benzyloxycarbonyl-4-hydroxyallothreoninamide (VIII). This in turn is transformed to (3S,4S)-cis-3-amino-4-carbamoyloxymethyl-2-azetidinone-1-sulfonic acid (XVIII). Condensation of the azetidinone (XVIII) with the activated aminothiazole portion (XIX) followed by a necessary deprotection step affords the monocyclic beta-lactam. Dissolution of the beta-lactam in aqueous sodium acetate yields the disodium salt, carumonam. Other routes of synthesis have been discussed.

参考文献中间体

合成目标

【1】 Weigele, M.; Wei, C.; Tengi, J.; Ro-172301 (AMA-1080), a new monocyclic beta-lactam antibiotic: Stereorational synthesis. Intersci Conf Antimicrob Agents Chemother 1983, Abst 324.
【2】 Hachiguchi, S.; Ochiai, M.; Kishimoto, S.; Matsuo, T.; Kondo, M.; Sendai, M.; Tomimoto, M.; Chemical modification of sulfazecin: Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives. J Antibiot 1985, 38, 3, 346-371.
【3】 Christenson, J.; Squires, E.; Carumonam Sodium. Drugs Fut 1985, 10, 12, 967.

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)	28759	benzyl (1S,2R)-1-(aminocarbonyl)-2,3-dihydroxypropylcarbamate		C₁₂H₁₆N₂O₅	详情	详情
(IX)	29820	(5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2(5H)-furanone	50-81-7	C₆H₈O₆	详情	详情
(X)	10722	1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane	77-76-9	C₅H₁₂O₂	详情	详情
(XI)	29821	calcium di[(2R)-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethanoate]		C₁₄H₂₂CaO₁₀	详情	详情
(XII)	29822	(2R)-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethanamide		C₇H₁₃NO₄	详情	详情
(XIII)	29823	(2S)-2-azido-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanamide		C₇H₁₂N₄O₃	详情	详情
(XIV)	29824	benzyl (1S)-2-amino-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-oxoethylcarbamate		C₁₅H₂₀N₂O₅	详情	详情
(XV)	29825	(2R,3S)-4-amino-3-[[(benzyloxy)carbonyl]amino]-2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-4-oxobutyl 2-chloroacetate		C₁₇H₂₃ClN₂O₆S	详情	详情
(XVI)	29826	N,N,N-tributyl-1-butanaminium (2S,3S)-3-[[(benzyloxy)carbonyl]amino]-2-(hydroxymethyl)-4-oxo-1-azetidinesulfonate		C₂₈H₄₉N₃O₇S	详情	详情
(XVII)	13713	2-Chloroacetyl isocyanate	4461-30-7	C₃H₂ClNO₂	详情	详情
(XVIII)	29827	(2S,3S)-2-[[(aminocarbonyl)oxy]methyl]-3-ammonio-4-oxo-1-azetidinesulfonate		C₅H₉N₃O₆S	详情	详情
(XIX)	29828	tert-butyl 2-([[(Z)-1-(2-amino-1,3-thiazol-4-yl)-2-(1,3-benzothiazol-2-ylsulfanyl)-2-oxoethylidene]amino]oxy)acetate		C₁₈H₁₈N₄O₄S₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Reaction of campestanol (I) with phosphorus oxychloride and pyridine gives the dichlorophosphoryl compound (II). Ascorbic acid (III) is protected as the 5,6-isopropylidene ketal (IV) upon treatment with acetone and fuming sulfuric acid. Condensation of (IV) with acid chloride (II) provides the phosphoryl monochloride (V), which is hydrolyzed under acidic conditions to yield the phosphate diester (VI). Finally, compound (VI) is converted to the target disodium salt by using an ethanolic solution of NaOMe. (1,2)

参考文献中间体

合成目标

【1】 Novak, E.; Milanova, R.K.; Kutney, J.P.; Pritchard, H.P.; Lukic, T. (Forbes Medi-Tech Inc.); Novel structures comprising phytosterol and/or phytostanol and ascorbic acid and use thereof as weight regulating agents. WO 0234241 .
【2】 Chen, H.; Milanova, R.K.; Kutney, J.P.; Hou, D.; Ding, Y. (Forbes Medi-Tech Inc.); Conjugates of phytosterol or phytostanol with ascorbic acid and use thereof in treating or preventing cardiovascular disease. JP 2003522124; WO 0100653 .

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)	64792	Campestanol; (3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(1R,4R)-1,4,5-trimethylhexyl]hexadecahydro-1H-cyclopenta[a]phenanthren-3-ol		C₂₈H₅₀O	详情	详情
(II)	64793			C₂₈H₄₉Cl₂O₂P	详情	详情
(III)	29820	(5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2(5H)-furanone	50-81-7	C₆H₈O₆	详情	详情
(IV)	64794	(5R)-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-3,4-dihydroxy-2(5H)-furanone		C₉H₁₂O₆	详情	详情
(V)	64795			C₃₇H₆₀ClO₈P	详情	详情
(VI)	64796	(5R)-5-[(1S)-1,2-dihydroxyethyl]-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl (3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(1R,4R)-1,4,5-trimethylhexyl]hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl hydrogen phosphate		C₃₄H₅₇O₉P	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Reaction of sitostanol (I) with phosphorus oxychloride and pyridine affords the dichlorophosphoryl compound (II). Ascorbic acid (III) is protected as the 5,6-isopropylidene ketal (IV) upon treatment with acetone and fuming sulfuric acid. Condensation of (IV) with acid chloride (II) provides the phosphoryl monochloride (V), which is hydrolyzed under acidic conditions to yield the phosphate diester (VI). Finally, compound (VI) is converted to the target disodium salt by using an ethanolic solution of NaOMe. (1,2)

参考文献中间体

合成目标

【1】 Chen, H.; Milanova, R.K.; Kutney, J.P.; Hou, D.; Ding, Y. (Forbes Medi-Tech Inc.); Conjugates of phytosterol or phytostanol with ascorbic acid and use thereof in treating or preventing cardiovascular disease. JP 2003522124; WO 0100653 .
【2】 Novak, E.; Milanova, R.K.; Kutney, J.P.; Pritchard, H.P.; Lukic, T. (Forbes Medi-Tech Inc.); Novel structures comprising phytosterol and/or phytostanol and ascorbic acid and use thereof as weight regulating agents. WO 0234241 .

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)	64797	(3S,5S,8R,9S,10S,13R,14S,17R)-17-[(1R,4R)-4-ethyl-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-ol		C₂₉H₅₂O	详情	详情
(II)	64798			C₂₉H₅₁Cl₂O₂P	详情	详情
(III)	29820	(5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2(5H)-furanone	50-81-7	C₆H₈O₆	详情	详情
(IV)	64794	(5R)-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-3,4-dihydroxy-2(5H)-furanone		C₉H₁₂O₆	详情	详情
(V)	64799			C₃₈H₆₂ClO₈P	详情	详情
(VI)	64800	(5R)-5-[(1S)-1,2-dihydroxyethyl]-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl (3S,5S,8R,9S,10S,13R,14S,17R)-17-[(1R,4R)-4-ethyl-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl hydrogen phosphate		C₃₅H₅₉O₉P	详情	详情

Extended Information