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【结 构 式】 
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【分子编号】44663 【品名】benzaldehyde 【CA登记号】 |
【 分 子 式 】C7H6O 【 分 子 量 】106.12404 【元素组成】C 79.23% H 5.7% O 15.08% |
合成路线1
该中间体在本合成路线中的序号：(III)A new synthesis of [14C]-labeled paclitaxel has been published: The protection of L-threonine methyl ester (I) with tert-butoxydiphenylchlorosilane (BPS-Cl) gives the compound (II), which is condensed with [14C]-labeled benzaldehyde (III), yielding the imine (IV). The cyclization of (IV) with acetoxyacetyl chloride (V) by means of triethylamine affords the azetidinone (VI), which is deprotected with tetrabutylammonium fluoride to the hydroxy ester (VII). The dehydration of (VII) with p-toluenesulfonyl chloride and triethylamine affords the unsaturated ester (VIII), which by ozonolysis is converted to the oxalimide (IX). Elimination of the oxalyl group with hydrazine gives the labeled azetidinone (X), which is deacetylated to the hydroxyazetidinone (XI) and protected with triethylchlorosilane (TES-Cl) to (XII). The benzoylation of (XII) with benzoyl chloride (XIII) and dimethylaminopyridine (DMAP) yields the corresponding benzoylated compound (XIV), which is then condensed with triethylsilyl-baccatin III (XV) by means of butyllithium to afford silylated labeled paclitaxel (XVI). Finally, this compound is deprotected with HCl. The intermediate silylated baccatin III (XV) is obtained from paclitaxel (XVII) by hydrogenolysis with NaBH4 to baccatin III (XVIII) and silylation with triethylsilyl chloride to (XV).
| 【1】 Walker, D.G.; Swigor, J.E.; Standridge, R.T.; Synthesis of paclitaxel-C3'-C-14. J Label Compd Radiopharm 1995, 36, 5, 479. |
| 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) | 10674 | (2S,3R)-3-Hydroxy-1-methoxy-1-oxo-2-butanaminium chloride | C5H12ClNO3 | 详情 | 详情 | |
| (II) | 10675 | methyl (2S,3R)-2-amino-3-methoxybutanoate | C21H29NO4Si | 详情 | 详情 | |
| (III) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (III) | 44663 | benzaldehyde | C7H6O | 详情 | 详情 | |
| (IV) | 10677 | methyl (2S,3R)-3-methoxy-2-[[(E)-benzylidene]amino]butanoate | C28H33NO4Si | 详情 | 详情 | |
| (IV) | 44664 | methyl (2S,3R)-3-methoxy-2-[[(E)-benzylidene]amino]butanoate | C13H17NO3 | 详情 | 详情 | |
| (V) | 10456 | Acetoxiacetil chloride; 2-chloro-2-oxoethyl acetate | 13831-31-7 | C4H5ClO3 | 详情 | 详情 |
| (VI) | 10679 | methyl (2S,3R)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-3-methoxybutanoate | C32H37NO7Si | 详情 | 详情 | |
| (VI) | 44665 | methyl (2S,3R)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-3-methoxybutanoate | C17H21NO6 | 详情 | 详情 | |
| (VII) | 10680 | methyl (2S,3R)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-3-hydroxybutanoate | C16H19NO6 | 详情 | 详情 | |
| (VII) | 44666 | methyl (2S,3R)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-3-hydroxybutanoate | C16H19NO6 | 详情 | 详情 | |
| (VIII) | 10681 | methyl (Z)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-butenoate | C16H17NO5 | 详情 | 详情 | |
| (VIII) | 44667 | methyl (Z)-2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-butenoate | C16H17NO5 | 详情 | 详情 | |
| (IX) | 10682 | methyl 2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-oxoacetate | C14H13NO6 | 详情 | 详情 | |
| (IX) | 44668 | methyl 2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-oxoacetate | C14H13NO6 | 详情 | 详情 | |
| (X) | 10683 | methyl 2-[(3R,4S)-3-(acetoxy)-2-oxo-4-phenylazetidinyl]-2-oxoacetate | C14H13NO6 | 详情 | 详情 | |
| (X) | 44669 | (3R,4S)-2-oxo-4-phenylazetidinyl acetate | C11H11NO3 | 详情 | 详情 | |
| (XI) | 10459 | (3R,4S)-3-Hydroxy-4-phenyl-2-azetanone | C9H9NO2 | 详情 | 详情 | |
| (XI) | 44670 | (3R,4S)-3-hydroxy-4-phenyl-2-azetidinone | C9H9NO2 | 详情 | 详情 | |
| (XII) | 10685 | (3R,4S)-4-Phenyl-3-[(triethylsilyl)oxy]-2-azetidinone | C15H23NO2Si | 详情 | 详情 | |
| (XII) | 44673 | (3R,4S)-3-hydroxy-4-phenyl-2-azetidinone | C9H9NO2 | 详情 | 详情 | |
| (XIII) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (XIV) | 10687 | (3R,4S)-1-Benzoyl-3-hydroxy-4-phenyl-2-azetidinone | C16H13NO3 | 详情 | 详情 | |
| (XIV) | 44671 | (3R,4S)-1-benzoyl-3-hydroxy-4-phenyl-2-azetidinone | C16H13NO3 | 详情 | 详情 | |
| (XV) | 10473 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C37H52O11Si | 详情 | 详情 | |
| (XVI) | 10689 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | n/a | AB | 详情 | 详情 |
| (XVI) | 44672 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C47H51NO14 | 详情 | 详情 | |
| (XVII) | 10595 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | 33069-62-4 | C47H51NO14 | 详情 | 详情 |
| (XVIII) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C31H38O11 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The synthesis of ring labeled [14C]-atorvastatin has been described: The Grignard reaction of phenylmagnesium chloride (I) with [14C]-labeled CO2 (II) in THF/ethyl ether gives the benzoic acid (III), which is reduced with LiAlH4 in ethyl ether to the benzyl alcohol (IV). The oxidation of (IV) with pyridinium dichromate affords the benzaldehyde (V), which is condensed with the isobutyrylacetamide (VI) by means of beta-alanine in acetic acid yielding a mixture of the cis- and trans-benzylidene derivatives (VII). The condensation of (VII) with 4-fluorobenzaldehyde (VIII) by means of triethylamine and a thiazolium bromide catalyst affords the 1,4-dione (IX), which is cyclized with the chiral amino ester (X) in hot heptane/toluene/THF providing the protected pyrroloheptanoic ester (XI). The deprotection of (XI) in acidic medium, followed by the hydrolysis of the ester group with NaOH affords the sodium salt (XII), which is finally treated with calcium acetate in THF/water.
| 【1】 Woo, P.W.K.; et al.; Atorvastatin, an HMG-CoA reductase inhibitor and efficient lipid-regulating agent. Part I. Synthesis of ring-labeled [C-14] atorvastatin. J Label Compd Radiopharm 1999, 42, 2, 121. |
| 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) | 27910 | chloro(phenyl)magnesium | 100-59-4 | C6H5ClMg | 详情 | 详情 |
| (III) | 10202 | Benzoic acid | 65-85-0 | C7H6O2 | 详情 | 详情 |
| (III) | 45234 | benzoic acid | C7H6O2 | 详情 | 详情 | |
| (IV) | 18710 | Benzyl alcohol; Phenylmethanol | 100-51-6 | C7H8O | 详情 | 详情 |
| (IV) | 45235 | phenylmethanol | C7H8O | 详情 | 详情 | |
| (V) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (V) | 44663 | benzaldehyde | C7H6O | 详情 | 详情 | |
| (VI) | 15448 | 4-Methyl-3-oxo-N-phenylpentanamide; 4-Methyl-3-oxopentanoic acid anilide | 124401-38-3 | C12H15NO2 | 详情 | 详情 |
| (VII) | 15450 | (Z)-2-isobutyryl-N,3-diphenyl-2-propenamide | 125971-57-5 | C19H19NO2 | 详情 | 详情 |
| (VII) | 45236 | (Z)-2-isobutyryl-N,3-diphenyl-2-propenamide | C19H19NO2 | 详情 | 详情 | |
| (VIII) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (IX) | 15426 | 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-N-phenylpentanamide | 125971-96-2 | C26H24FNO3 | 详情 | 详情 |
| (IX) | 45237 | 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-N-phenylpentanamide | C26H24FNO3 | 详情 | 详情 | |
| (X) | 15444 | (4R,6R)-tert-Butyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate; (4R-Cis)-1,1-Dimethylethyl-6-aminoethyl-2,2-dimethyl-1,3-dioxoane-4-acetate | 125995-13-3 | C14H27NO4 | 详情 | 详情 |
| (XI) | 15452 | tert-butyl 2-((4R,6R)-6-[2-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl)acetate | C40H47FN2O5 | 详情 | 详情 | |
| (XI) | 45238 | tert-butyl 2-((4R,6R)-6-[2-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl)acetate | C40H47FN2O5 | 详情 | 详情 | |
| (XII) | 27911 | sodium (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate | C33H34FN2NaO5 | 详情 | 详情 | |
| (XII) | 45239 | sodium (3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate | C33H34FN2NaO5 | 详情 | 详情 |