84333-01-7Relevant articles and documents
Synthesis of the Kopsia alkaloids (+/-)-pauciflorine B, (+/-)-lahadinine B, (+/-)-kopsidasine, (+/-)-kopsidasine-N-oxide, (+/-)-kopsijasminilam and (+/-)-11-methoxykopsilongine
Magnus, Philip,Gazzard, Lewis,Hobson, Lindsay,Payne, Andrew H.,Rainey, Trevor J.,Westlund, Neil,Lynch, Vince
, p. 3423 - 3444 (2007/10/03)
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 geenrate 18f, and quenching the reaction with trimethylsilyl cyanide. Treatment of 22 with acryloyl chloride (excess) at 75 deg C gave 23, which was directly treated with N-hydroxy-2-thiopyridone/Et3N to give 24. Irradiation of 24 in the presence of r-BuSH resulted in reductive decarboxylation to give 26 and a small amount o fthe 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 α,β-unsaturated ester followed by α-hydroxylation and gave 28 (11,12-demethoxy lahadinine B). Exposure of 26 to Phl(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 chracterized 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-oxdide 32 which underwent fragmentation to give 33 when exposed to trifluoroacetic anhydrde. when the diene 33 was treated with Mn(dpm), (cat)/PhSiH3/O2 in isopropyl alcohol at 0 deg C, it was converted into kopsijasminilam 4. Peracetic acid in ErOAc (10 percent) was used to quench the AgBH4/THF conversion of 28 into 37, and resulted in 42/42a (4:1, 65 percent) along with small amounts of 38 and 41c. Application of these procedures, with some modifications, to the 11,12-dimethoxy substituted system gave (+/-)-lahadinine B 64. Treatment of 64 with triethylsilane in the presence of trifluoroacetic acid cleanly converted it into 11-methoxykopsilongine 65 (93 percent). Treatment of (+/-)-lahadinine B 64 with AgBF4/THF followed by work-up with EtOAc/MeCO3H (10 percent) gave (+/-)-pauciflorine 6 and the double bond isomer 6a.
