|
【结 构 式】 
|
【分子编号】22433 【品名】5-hydroxy-6-[(2S,3R)-3-hydroxy-2-methylbutanoyl]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one 【CA登记号】 |
【 分 子 式 】C22H26O6 【 分 子 量 】386.44484 【元素组成】C 68.38% H 6.78% O 24.84% |
合成路线1
该中间体在本合成路线中的序号：(XXXII)4) The aldol condensation of the previously described benzodipyran (VII) with acetaldehyde catalyzed by TiCl4/lithium diisopropylamide (LDA) in heptane/THF/ethylbenzene gives a racemic mixture of the enantiomers (XXXI) and (XXXII), which is enzymatically resolved with lipase PS-30 or lipase-AK and vinyl acetate in tert-butyl methyl ether to yield a mixture of unchanged 3(S)-hydroxy-2(R)-methylbutyryl-enantiomer (XXXI) and acetylated enantiomer (XXXIII), which are easily separated by column chromatography. The cyclization of (XXXI) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF gives the (10R,11R)-precursor (XXXIV), which is finally reduced with NaBH4/triphenylphosphine oxide /CeCl3 in ethanol and purified by chiral HPLC.
| 【1】 Castañer, J.; Leeson, P.; Sorbera, L.A.; Calanolide A. Drugs Fut 1999, 24, 3, 235. |
| 【2】 Khilevich, A.; Mar, A.; Flavin, M.T.; et al.; Synthesis of (+)-calanolide A, an anti-HIV agent, via enzyme-catalyzed resolution of the aldol products. Tetrahedron Asymmetry 1996, 7, 11, 3315. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 22409 | 5-hydroxy-2,2-dimethyl-6-propionyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C20H22O5 | 详情 | 详情 | |
| (XXXI) | 22432 | 5-hydroxy-6-[(2R,3S)-3-hydroxy-2-methylbutanoyl]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C22H26O6 | 详情 | 详情 | |
| (XXXII) | 22433 | 5-hydroxy-6-[(2S,3R)-3-hydroxy-2-methylbutanoyl]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C22H26O6 | 详情 | 详情 | |
| (XXXIII) | 22434 | (1R,2S)-3-(5-hydroxy-2,2-dimethyl-8-oxo-10-propyl-2H,8H-pyrano[2,3-f]chromen-6-yl)-1,2-dimethyl-3-oxopropyl acetate | C24H28O7 | 详情 | 详情 | |
| (XXXIV) | 22410 | (10R,11R)-6,6,10,11-tetramethyl-4-propyl-10,11-dihydro-2H,6H,12H-dipyrano[2,3-f:2,3-h]chromene-2,12-dione | C22H24O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXV)5) Synthesis of [14C]-labeled calanolide A: The aldol condensation of benzodipyran (VII) with [1,2-14C]-labeled acetaldehyde catalyzed by TiCl4/lithium diisopropylamide (LDA) in heptane/THF/ethylbenzene gives a racemic mixture of enantiomers (XXXV) and (XXXVI), which is enzymatically resolved with lipase-AK and vinyl acetate in tert-butyl methyl ether to yield a mixture of unchanged 3(S)-hydroxy-2(R)-methylbutyryl enantiomer (XXXVI) and acetylated enantiomer (XXXVII), which are easily separated by column chromatography. The cyclization of (XXXVI) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF gives the (10R,11R)-precursor (XXXVIII), which is finally reduced with NaBH4/triphenylphosphine oxide /CeCl3 in ethanol and purified by chiral HPLC.
| 【1】 Rizzo, J.D.; Filer, C.; Khilevich, A.; Giltner, J.; Xu, Z.-Q.; Flavin, M.T.; Gaddam, S.; Synthesis of dual C-14-labeled (+)-calanolide A, a. J Label Compd Radiopharm 1997, 39, 11, 901. |
| 【2】 Castañer, J.; Leeson, P.; Sorbera, L.A.; Calanolide A. Drugs Fut 1999, 24, 3, 235. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 22409 | 5-hydroxy-2,2-dimethyl-6-propionyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C20H22O5 | 详情 | 详情 | |
| (XXXV) | 22433 | 5-hydroxy-6-[(2S,3R)-3-hydroxy-2-methylbutanoyl]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C22H26O6 | 详情 | 详情 | |
| (XXXV) | 45297 | 5-hydroxy-6-[(2S,3R)-3-hydroxy-2-methylbutanoyl]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C22H26O6 | 详情 | 详情 | |
| (XXXVI) | 22432 | 5-hydroxy-6-[(2R,3S)-3-hydroxy-2-methylbutanoyl]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C22H26O6 | 详情 | 详情 | |
| (XXXVI) | 45296 | 5-hydroxy-6-[(2R,3S)-3-hydroxy-2-methylbutanoyl]-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one | C22H26O6 | 详情 | 详情 | |
| (XXXVII) | 22434 | (1R,2S)-3-(5-hydroxy-2,2-dimethyl-8-oxo-10-propyl-2H,8H-pyrano[2,3-f]chromen-6-yl)-1,2-dimethyl-3-oxopropyl acetate | C24H28O7 | 详情 | 详情 | |
| (XXXVII) | 45298 | (1R,2S)-3-(5-hydroxy-2,2-dimethyl-8-oxo-10-propyl-2H,8H-pyrano[2,3-f]chromen-6-yl)-1,2-dimethyl-3-oxopropyl acetate | C24H28O7 | 详情 | 详情 | |
| (XXXVIII) | 22410 | (10R,11R)-6,6,10,11-tetramethyl-4-propyl-10,11-dihydro-2H,6H,12H-dipyrano[2,3-f:2,3-h]chromene-2,12-dione | C22H24O5 | 详情 | 详情 | |
| (XXXVIII) | 45299 | (10R,11R)-6,6,10,11-tetramethyl-4-propyl-10,11-dihydro-2H,6H,12H-dipyrano[2,3-f:2,3-h]chromene-2,12-dione | C22H24O5 | 详情 | 详情 |