+)-Thalictrifoline (3) has been synthesized from an optically resolved (+)-8oxo-13-carboxytetrahydroprotoberberine (13) whose absolute configuration was established by correlation with (+)-18. This determines the absolute configurations of (+)-thalictrifoline (3) as 13R, 14R aiid (+)-corydalic acid methyl ester (2) as 3R, 4R. Both G-and w-13-methyltetrahydroprotoberberine alkaloids have been isolated from various species of Corydalis, as exemplified by (+)-cavidine (1, also known as Base isomer /I (mp 259-26l"C, Anal Found: C, 63.47; N, 3.24). The (+)-trans acid 13 afforded a crystalline salt [mp 230-233Β°C dec, [a]D -100' (c = 0.14, CHCl3)] when treated with (-)strychnine in ethyl acetate followed by recrystallization from chloroform-ethyl acetate. This salt gave the free (-)-trans acid !I' [mp 235-240Β°C dec, [a]D -228" (c = 0.116, CHC13-MeOH 3:1)] on decomposition. The (+)-trans isomer 13 [mp 233-235Β°C dec, [a]D + 231" (c = 0.13, CHCl3-MeOH 3:1)] was obtained by decomposition followed by recrystallization of the mother liquors. The (-)-and (+)-trans acids 13' and 13 gave the (-)-trans ester 15' [mp 182-183"C, [a]D -273" (c = 0.096, CHCl3)] and (+)-trans ester 15 [mp 182-183'C, [cx]D t 258" (c = 0.102, CHCl3)], respectively, by treatment with diazomethane. Lithium aluminum hydride reduction of the (+)-trans ester 15 provided the (+)-amino alcohol 16 [mp 147-148"C, [cx]D + 4.8" (c = 0.146, CHC13)]. This radical alteration of the optical rotation relative to (+)-15 and (+)-3 results from a change in conformation of the amino alcohol due to hydrogen bonding.6 Reduction of the mesylate of the (+)-trans amino alcohol 16 with lithium aluminum hydride gave (+)-thalictrifoline [3, mp 149-15l"C, [a]D t 199" (c = 0.136, CHCl3), lit7 mp 155"C].
The IR spectra of the synthetic compound and an authentic sample are identical. This is the first total synthesis of (+)-thalictrifoline.