benzyl (1S,2R)-1-(aminocarbonyl)-2,3-dihydroxypropylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】28759

【品名】benzyl (1S,2R)-1-(aminocarbonyl)-2,3-dihydroxypropylcarbamate

【CA登记号】

【分子式】C₁₂H₁₆N₂O₅

【分子量】268.26952

【元素组成】C 53.73% H 6.01% N 10.44% O 29.82%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VIII)

Two related syntheses of a known intermediate of carumonam are presented: 1) The reaction of calcium L-threonate (I) with HBr in acetic acid - acetic anhydride and then with refluxing methanol gives methyl (2S,3S)-2,4-dibromo-3-hydroxybutanoate (II), which by reaction with concentrated NH4OH is converted into (2S, 3R)-3-(bromomethyl)oxiranecarboxamide (III). The reaction of (III) with KI and potassium acetate in hot DMF affords (2R, 3S)-3-(acetoxymethyl)oxiranecarboxamide (IV), which is treated with concentrated NH4OH at 60 C and then with benzyl chloroformate (V) to give (2S, 3R)-2-(benzyloxycarbonylamino)-3,4-dihydroxybutanamide (VIII), an intermediate compound previously obtained in the synthesis described in Drugs Fut 1985, 10: 967. 2) The treatment of dibromide (II) with KI and potassium acetate in hot DMF gives methyl (2S,3S)-4-acetoxy-2,3-epoxybutanoate (VI), which is treated first with NaOH in methanol and then with hot NH4OH to yield (2S, 3R)-2-amino-3,4-dihydroxybutanamide (VII). Finally, this compound is treated with benzyl chloroformate (V) as before to give the intermediate (VIII) previously mentioned.

参考文献中间体

合成目标

【1】 Manchand, P.S.; Luk, K.-C.; Belica, P.S.; Choudhry, S.C.; Wei, C.C.; Soukup, M.; A novel synthesis of the monobactam antibiotic carumonam. J Org Chem 1988, 53, 23, 5507.

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)	21521	calcium di[(2R,3S)-2,3,4-trihydroxybutanoate]		C₈H₁₄CaO₁₀	详情	详情
(II)	21522	methyl (2S,3S)-2,4-dibromo-3-hydroxybutanoate		C₅H₈Br₂O₃	详情	详情
(III)	21523	(2R,3R)-3-(bromomethyl)-2-oxiranecarboxamide		C₄H₆BrNO₂	详情	详情
(IV)	21524	[(2S,3R)-3-(aminocarbonyl)oxiranyl]methyl acetate		C₆H₉NO₄	详情	详情
(V)	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(VI)	21525	methyl (2R,3S)-3-[(acetoxy)methyl]-2-oxiranecarboxylate		C₇H₁₀O₅	详情	详情
(VII)	21526	(2S,3R)-2-amino-3,4-dihydroxybutanamide		C₄H₁₀N₂O₃	详情	详情
(VIII)	28759	benzyl (1S,2R)-1-(aminocarbonyl)-2,3-dihydroxypropylcarbamate		C₁₂H₁₆N₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

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

Extended Information