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【结 构 式】 
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【分子编号】51731 【品名】(3R,4S,6S,9aS)-6-[(1E,3E)-1,3-decadienyl]-4-methyloctahydro-2H-quinolizin-3-yl methoxymethyl ether; (3R,4S,6S,9aS)-6-[(1E,3E)-1,3-decadienyl]-3-(methoxymethoxy)-4-methyloctahydro-2H-quinolizine 【CA登记号】 |
【 分 子 式 】C22H39NO2 【 分 子 量 】349.5572 【元素组成】C 75.59% H 11.25% N 4.01% O 9.15% |
合成路线1
该中间体在本合成路线中的序号：(IV)The hydrolysis of the chiral isopropylidene ketal (I) with HCl in refluxing methanol, followed by selective monosilylation of the resulting primary OH group with tert-butyldiphenylsilyl chloride, protection of the secondary OH group with MOM-Cl and Hunig base, and desilylation with HF and pyridine gives the perhydroquinolizine-4-methanol derivative (II).The reaction of the OH group of (II) with I2 and PPh3¸, and deiodination of the resulting iodo derivative with Bu3SnH and AIBN yields the 4-methyl derivative (III), which is condensed with trans-2-nonenal and BuLi, and treated with Na/Hg to afford the 6-(1,3-decadienyl) derivative (IV). The deprotection of (IV) with HCl in refluxing methanol provides the secondary alcohol V), which is finally acetylated with acetic anhydride and pyridine to furnish the target (-)-clavepictine A.
| 【1】 Toyooka, N.; Nemoto, H.; Application of chiral building blocks to the synthesis of drugs. Drugs Fut 2002, 27, 2, 143. |
| 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) | 51729 | (4aR,6aS,10S,11aS)-3,3-dimethyl-10-[(phenylsulfonyl)methyl]decahydro[1,3]dioxino[4,5-c]quinolizine; [(4aR,6aS,10S,11aS)-3,3-dimethyldecahydro[1,3]dioxino[4,5-c]quinolizin-10-yl]methyl phenyl sulfone | C20H29NO4S | 详情 | 详情 | |
| (II) | 51730 | [(3R,4S,6S,9aS)-3-(methoxymethoxy)-6-[(phenylsulfonyl)methyl]octahydro-2H-quinolizin-4-yl]methanol | C19H29NO5S | 详情 | 详情 | |
| (III) | 51726 | [(4S,6S,7R,9aS)-7-(methoxymethoxy)-6-methyloctahydro-2H-quinolizin-4-yl]methyl phenyl sulfone; (3R,4S,6S,9aS)-3-(methoxymethoxy)-4-methyl-6-[(phenylsulfonyl)methyl]octahydro-2H-quinolizine | C19H29NO4S | 详情 | 详情 | |
| (IV) | 51731 | (3R,4S,6S,9aS)-6-[(1E,3E)-1,3-decadienyl]-4-methyloctahydro-2H-quinolizin-3-yl methoxymethyl ether; (3R,4S,6S,9aS)-6-[(1E,3E)-1,3-decadienyl]-3-(methoxymethoxy)-4-methyloctahydro-2H-quinolizine | C22H39NO2 | 详情 | 详情 | |
| (V) | 51732 | (3R,4S,6S,9aS)-6-[(1E,3E)-1,3-decadienyl]-4-methyloctahydro-2H-quinolizin-3-ol | C20H35NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The hydrolysis of the chiral isopropylidene ketal (I) with HCl in refluxing methanol, followed by selective monosilylation of the resulting primary OH group with tert-butyldiphenylsilyl chloride, protection of the secondary OH group with MOM-Cl and Hunig base, and desilylation with HF and pyridine gives the perhydroquinolizine-4-methanol derivative (II).The reaction of the OH group of (II) with I2 and PPh3, and deiodination of the resulting iodo derivative with Bu3SnH and AIBN yields the 4-methyl derivative (III), which is condensed with trans-2-nonenal and BuLi, and treated with Na/Hg to afford the 6-(1,3-decadienyl) derivative (IV).Finally the deprotection of (IV) with HCl in refluxing methanol provides the target (+)-clavepictine B.
| 【1】 Toyooka, N.; Nemoto, H.; Application of chiral building blocks to the synthesis of drugs. Drugs Fut 2002, 27, 2, 143. |
| 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) | 51729 | (4aR,6aS,10S,11aS)-3,3-dimethyl-10-[(phenylsulfonyl)methyl]decahydro[1,3]dioxino[4,5-c]quinolizine; [(4aR,6aS,10S,11aS)-3,3-dimethyldecahydro[1,3]dioxino[4,5-c]quinolizin-10-yl]methyl phenyl sulfone | C20H29NO4S | 详情 | 详情 | |
| (II) | 51730 | [(3R,4S,6S,9aS)-3-(methoxymethoxy)-6-[(phenylsulfonyl)methyl]octahydro-2H-quinolizin-4-yl]methanol | C19H29NO5S | 详情 | 详情 | |
| (III) | 51726 | [(4S,6S,7R,9aS)-7-(methoxymethoxy)-6-methyloctahydro-2H-quinolizin-4-yl]methyl phenyl sulfone; (3R,4S,6S,9aS)-3-(methoxymethoxy)-4-methyl-6-[(phenylsulfonyl)methyl]octahydro-2H-quinolizine | C19H29NO4S | 详情 | 详情 | |
| (IV) | 51731 | (3R,4S,6S,9aS)-6-[(1E,3E)-1,3-decadienyl]-4-methyloctahydro-2H-quinolizin-3-yl methoxymethyl ether; (3R,4S,6S,9aS)-6-[(1E,3E)-1,3-decadienyl]-3-(methoxymethoxy)-4-methyloctahydro-2H-quinolizine | C22H39NO2 | 详情 | 详情 |