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【结 构 式】 
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【分子编号】22417 【品名】5-hydroxy-2,2-dimethyl-8-oxo-10-propyl-2H,8H-pyrano[2,3-f]chromene-6-carbaldehyde 【CA登记号】 |
【 分 子 式 】C18H18O5 【 分 子 量 】314.33792 【元素组成】C 68.78% H 5.77% O 25.45% |
合成路线1
该中间体在本合成路线中的序号：(XV)2) The condensation of 5,7-dihydroxy-4-propyl-2H-1-benzopyran-2-one (III) with N-methylformanilide (XII) by means of POCl3 in hot dichloromethane gives the carbaldehyde (XIII), which is cyclized with 3-chloro-3-methyl-1-butyne (XIV) by means of ZnCl2 /K2CO3 in hot 2-butanone/DMF, yielding the benzodipyran-carbaldehyde (XV). The enantioselective reaction of (XV) with 2(E)-butene and the chiral borane (+)-(E)-crotyldiisopinocamphenylborane (XVI) affords the single (R, R)-enatiomer (XVII). The selective silylation of (XVII) with TBDMS-Cl as usual gives the monosilyl ether (XVIII), which is cyclized by means of mercuric acetate and NaBH4 in THF, yielding the silylated (10R,11R,12R)-benzotripyran (XIX). The desilylation of (XIX) with tetrabutylammonium fluoride in THF gives the (10R,11S,12R)-benzotripyran (XX) (calanolide B), which is converted into calanolide A by inversion of the C-12 OH-group carried out with a modified Mitsunobu reaction with dimethyl azodicarboxylate (DEAD)/trimethylphosphine/chloroacetic acid in toluene/THF, followed by treatment with NH4OH in methanol.
| 【1】 Tagliaferri, F.; Deshpande, P.P.; Yan, S.; Victory, S.F.; Baker, D.C.; Synthesis of optically active calanoides A and B. J Org Chem 1995, 60, 10, 2964. |
| 【2】 Castañer, J.; Leeson, P.; Sorbera, L.A.; Calanolide A. Drugs Fut 1999, 24, 3, 235. |
| 【3】 Tagliaferri, F.; Yan, S.; Deshpande, P.P.; Baker, D.C.; Victory, S.F. (University of Tennessee, Knoxville); Synthesis of optically active calanolides A and B . US 5608085; WO 9626934 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17343 | 2-Butene-cis; (Z)-2-butene | 590-18-1 | C4H8 | 详情 | 详情 | |
| (III) | 22405 | 5,7-dihydroxy-4-propyl-2H-chromen-2-one | C12H12O4 | 详情 | 详情 | |
| (XII) | 20360 | methyl(phenyl)formamide;N-Methylformanilide;N-Formyl-N-methylaniline;Methylphenylformamide;N-methyl-N-phenylformamide;N-Methyl-N-formylaniline;N-Formyl-N-methylaniline | 93-61-8 | C8H9NO | 详情 | 详情 |
| (XIII) | 22415 | 5,7-dihydroxy-2-oxo-4-propyl-2H-chromene-8-carbaldehyde | C13H12O5 | 详情 | 详情 | |
| (XIV) | 22416 | 3-chloro-3-methyl-1-butyne | 1111-97-3 | C5H7Cl | 详情 | 详情 |
| (XV) | 22417 | 5-hydroxy-2,2-dimethyl-8-oxo-10-propyl-2H,8H-pyrano[2,3-f]chromene-6-carbaldehyde | C18H18O5 | 详情 | 详情 | |
| (XVI) | 22418 | (E)-2-butenyl[bis(2,6,6-trimethylbicyclo[3.1.1]hept-3-yl)]borane | C24H41B | 详情 | 详情 | |
| (XVII) | 22419 | 5-hydroxy-6-[(1R,2R)-1-hydroxy-2-methyl-3-butenyl]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C22H26O5 | 详情 | 详情 | |
| (XVIII) | 22420 | 6-((1R,2R)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-3-butenyl)-5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C28H40O5Si | 详情 | 详情 | |
| (XIX) | 22421 | (10R,11R,12R)-12-[[tert-butyl(dimethyl)silyl]oxy]-6,6,10,11-tetramethyl-4-propyl-11,12-dihydro-2H,6H,10H-dipyrano[2,3-f:2,3-h]chromen-2-one | C28H40O5Si | 详情 | 详情 | |
| (XX) | 22413 | (10R,11S,12R)-12-hydroxy-6,6,10,11-tetramethyl-4-propyl-11,12-dihydro-2H,6H,10H-dipyrano[2,3-f:2,3-h]chromen-2-one | C22H26O5 | 详情 | 详情 |