-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】2-[[3-[N'-[4-Chloro-3-(trifluoromethyl)phenyl]ureido]-3-deoxy-2-O-[2-deoxy-2-[3-(trifluoromethyl)benzamido]-beta-D-glucopyranosyl]-4-O-methyl-alpha-D-glucopyranos-1-yloxyuronamide](hydroxy)phosphoryloxy]hexadecanoic acid

【CA登记号】244292-42-0

【分子式】C₄₅H₆₂ClF₆N₄O₁₆P

【分子量】1095.43029

【开发单位】Incara (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY

合成路线1 合成路线2

合成路线1

The compound was obtained by solid-phase synthesis on an aminoethyl-photolinker AM resin. Deprotection of hydroxyl and amino groups from disaccharide-resin (I) by means of hydrazine provided (II). Reaction of the resulting free C-2' amino group of (II) with 3-(trifluoromethyl)benzoic acid (III) in the presence of HATU afforded the corresponding amide (IV). Reacetylation of (IV) with acetic anhydride and dimethylaminopyridine gave triacetate (V). Subsequent reduction of the azido group of (V) by means of trimethyl phosphine provided the C-3 amine (VI), which was condensed with 4-chloro-3-(trifluoromethyl)phenyl isocyanate (VII) yielding urea (VIII).

参考文献中间体

【1】 Allanson, N.; Sofia, M.J.; Hatzenbuhler, N.T.; et al.; Discovery of novel disaccharide antibacterial agents using a combinatorial library approach. J Med Chem 1999, 42, 17, 3193.

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)	37863	(2R,3R,4R,5R,6S)-3-(acetoxy)-2-[(acetoxy)methyl]-6-[[(2S,3R,4S,5S,6S)-6-(aminocarbonyl)-4-azido-5-methoxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl]oxy]-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)tetrahydro-2H-pyran-4-yl acetate		C₃₃H₃₅N₅O₁₃S	详情	详情
(II)	37864	(2S,3S,4S,5R,6S)-5-[[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]-4-azido-3-methoxy-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-carboxamide		C₁₉H₂₇N₅O₈S	详情	详情
(III)	17890	3-(trifluoromethyl)benzoic acid; m-Trifluoromethylbenzoic acid	454-92-2	C₈H₅F₃O₂	详情	详情
(IV)	37865	(2S,3S,4S,5R,6S)-4-azido-5-[((2S,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[[3-(trifluoromethyl)benzoyl]amino]tetrahydro-2H-pyran-2-yl)oxy]-3-methoxy-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-carboxamide		C₂₇H₃₀F₃N₅O₉S	详情	详情
(V)	37866	(2R,3R,4R,5R,6S)-3-(acetoxy)-2-[(acetoxy)methyl]-6-[[(2S,3R,4S,5S,6S)-6-(aminocarbonyl)-4-azido-5-methoxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl]oxy]-5-[[3-(trifluoromethyl)benzoyl]amino]tetrahydro-2H-pyran-4-yl acetate		C₃₃H₃₆F₃N₅O₁₂S	详情	详情
(VI)	37867	(2R,3R,4R,5R,6S)-3-(acetoxy)-2-[(acetoxy)methyl]-6-[[(2S,3R,4S,5S,6S)-4-amino-6-(aminocarbonyl)-5-methoxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl]oxy]-5-[[3-(trifluoromethyl)benzoyl]amino]tetrahydro-2H-pyran-4-yl acetate		C₃₃H₃₈F₃N₃O₁₂S	详情	详情
(VII)	37868	1-chloro-4-isocyanato-2-(trifluoromethyl)benzene; 4-chloro-3-(trifluoromethyl)phenyl isocyanate	327-78-6	C₈H₃ClF₃NO	详情	详情
(VIII)	37869			C₄₁H₄₁ClF₆N₄O₁₃S	详情	详情

合成路线2

Cleavage of the anomeric thiophenyl group of (VIII) by means of mercuric trifluoroacetate produced the desired lactol (IX). Attachment of the phospholipid unit to lactol (IX) was carried out by reaction with phosphoramidite (X). The resulting phosphite ester (XI) was then oxidized to phosphate (XII) using meta-chloroperbenzoic acid. Subsequent basic hydrolysis of (XII) removed the protecting groups to give (XIII). Finally, photolytic cleavage of the resin (XIII) furnished the title disaccharide derivative.

参考文献中间体

【1】 Allanson, N.; Sofia, M.J.; Hatzenbuhler, N.T.; et al.; Discovery of novel disaccharide antibacterial agents using a combinatorial library approach. J Med Chem 1999, 42, 17, 3193.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIII)	37869		C₄₁H₄₁ClF₆N₄O₁₃S	详情	详情
(IX)	37870		C₃₅H₃₇ClF₆N₄O₁₄	详情	详情
(X)	37871	methyl 2-[[(2-cyanoethyl)(diisopropylamino)phosphino]oxy]hexadecanoate	C₂₆H₅₁N₂O₃P	详情	详情
(XI)	37872		C₅₅H₇₃ClF₆N₅O₁₈P	详情	详情
(XII)	37873		C₅₅H₇₃ClF₆N₅O₁₉P	详情	详情
(XIII)	37874		C₄₅H₆₂ClF₆N₄O₁₆P	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)