Synthesis of the Kopsia alkaloids (±)-pauciflorine B, (±)-lahadinine B, (±)-kopsidasine, (±)-kopsidasine-N-oxide, (±)-kopsijasminilam and (±)-11-methoxykopsilongine
Synthesis of the Kopsia alkaloids (±)-pauciflorine B, (±)-lahadinine B, (±)-kopsidasine, (±)-kopsidasine-N-oxide, (±)-kopsijasminilam and (±)-11-methoxykopsilongine
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DOI：
10.1016/s0040-4020(02)00243-0
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发表时间：
2002-04-22
期刊：
影响因子：
2.1
通讯作者：
Lynch, V
中科院分区：
文献类型：
--
作者：
Magnus, P;Gazzard, L;Lynch, V
13与色胺的Pictet-Spengler缩合得到14，其转化为17。用氯甲酸苯酯处理17得到18，其进行跨环化得到19。更稳定的氰基类似物22通过用Tf2O/DMAP处理18以生成18f，并用三甲基甲硅烷基氰化物淬灭反应来制备。在75 ℃下用丙烯酰氯（过量）处理22得到23，将其直接用N-羟基-2-硫代吡啶酮/Et3N处理得到24。在t-BuSH存在下照射24导致还原脱羧，得到26和少量的2-硫代吡啶基醚25。26中苯胺氮的保护需要使用三光气/吡啶，然后使用甲醇。将27转化为28的最后步骤需要α，β-不饱和酯的共轭还原，然后进行α-羟基化，得到28（11，12-去甲氧基拉哈定宁B）。将26暴露于PhI（0Ac）（2）/MeOH干净地得到26 a，将其用Zn/AcOH直接还原为29。如前所述进行29向30的转化，并且当30用AgBF 4/THF处理，然后用NaHCO 3水溶液处理时，其转化为（+/-）-kopterasine 2，完全表征为其衍生的N-氧化物2a。用AgBF 4/THF处理26，然后用NaHCO3水溶液处理，得到31。用间氯过氧苯甲酸氧化31得到N-氧化物32，当暴露于三氟乙酸酐时，N-氧化物32经历断裂得到33。当二烯33在异丙醇中用Mn（dpm）（3）（cat）/PhSiH3/O-2在0 ℃下处理时，其转化为kopsijasminilam 4。用在EtOAc（10%）中的过乙酸淬灭28向37的AgBF 4/THF转化，得到42/42 a（4：1，65%）沿着少量38和41 c。将这些方法，经过一些修改，应用于11，12-二甲氧基取代的体系，得到（+/-）-拉哈丁B 64。在三氟乙酸存在下用三乙基硅烷处理64将其干净地转化为11-甲氧基kopsilongine 65（93%）。用AgBF 4/THF处理（+/-）-拉哈迪宁B 64，然后用EtOAc/MeCO 3 H（10%）处理，得到（+/-）-少花灵6和双键异构体6a。(C)2002爱思唯尔科技有限公司。保留所有权利。
Pictet-Spengler condensation of 13 with tryptamine gave 14, which was converted into 17. Treatment of 17 with phenyl chloroformate resulted in 18, which underwent transannular cyclization to give 19. The more stable cyano-analog 22 was made by treating 18 with Tf2O/DMAP to generate 18f, and quenching the reaction with trimethylsilyl cyanide. Treatment of 22 with acryloyl chloride (excess) at 75degreesC gave 23, which was directly treated with N-hydroxy-2-thiopyridone/Et3N to give 24. Irradiation of 24 in the presence of t-BuSH resulted in reductive decarboxylation to give 26 and a small amount of the 2-thiopyridyl ether 25. Protection of the aniline nitrogen in 26 required the use of triphosgene/pyridine followed by methanol. The final step for the conversion of 27 into 28 required conjugate reduction of the alpha,beta-unsaturated ester followed by alpha-hydroxylation and gave 28 (11,12-demethoxy lahadinine B). Exposure of 26 to PhI(OAc)(2)/MeOH cleanly gave 26a, which was directly reduced with Zn/AcOH to 29. Conversion of 29 into 30 proceeded as before, and when 30 was treated with AgBF4/THF followed by aqueous NaHCO3 it was converted into (+/-)-kopsidasine 2, completely characterized as its derived N-oxide 2a. Treatment of 26 with AgBF4/THF followed by aqueous NaHCO3 gave 31. Oxidation of 31 with m-chloroperoxybenzoic acid resulted in the N-oxide 32 which underwent fragmentation to give 33 when exposed to trifluoroacetic anhydride. When the diene 33 was treated with Mn(dpm)(3) (cat)/PhSiH3/O-2 in isopropyl alcohol at 0degreesC, it was converted into kopsijasminilam 4. Peracetic acid in EtOAc (10%) was used to quench the AgBF4/THF conversion of 28 into 37, and resulted in 42/42a (4:1, 65%) along with small amounts of 38 and 41c, Application of these procedures, with some modifications, to the 11,12-dimethoxy substituted systems gave (+/-)-lahadinine B 64. Treatment of 64 with triethylsilane in the presence of trifluoroacetic acid cleanly converted it into 11-methoxykopsilongine 65 (93%). Treatment of (+/-)-lahadinine B 64 with AgBF4/THF followed by work-up with EtOAc/MeCO3H (10%) gave (+/-)-pauciflorine 6 and the double bond isomer 6a. (C) 2002 Elsevier Science Ltd. All rights reserved.