Thirteen alkaloids were isolated from the nonphenolic basic fraction of the tubers of Corydalis remota cultivated in Dalian, Liaoning province. The most interesting of these is corymotine, a new tetrahydroprotoberberine alkaloid that bears an unusual 13,13-dimethylated substitution pattern. The tubers of Corydalis remota Fisch. (Fumariaceae) have been used as an analgesic in northeastern China in place of "yanhusuo," a well-known traditional Chinese herbal medicine from the tubers of Corydalis yanhusuo W.T. Wang. No systematic chemical studies on this plant have been previously reported in the literature, although past experimental work on Corydalis is noted (1-3). Chemical investigations of the tubers of C. remota cultivated in Dalian, Liaoning province, were carried out in our laboratory with a view towards finding correlations, if any, between the two plant species. From the nonphenolic basic fraction of the methanolic extracts of the tubers of C. remota, 13 alkaloids were separated by routine flash chromatography and preparative tlc. Among these alkaloids, 12 were found to be known compounds that widely occur in the genus Corydalis. A minor nonphenolic base, corymotine [1], was unusual and deserved special attention. The new protoberberine alkaloid, corymotine, is the first tetrahydroprotoberberine dimethylated at C-13. Its uv spectrum was indicated with a maximum at 281 nm. The mass spectrum displayed major peaks at m/z [M]+ 383, 368, 352, 192, and 177, indicating a fragmentation pattern of a tetrahydroprotoberberine (4). A retro-Diels-Alder decomposition is in Figure 1. The base peak m/z 192 corresponding to ions a and b indicated that both rings A and B plus rings C and D might each possess two methoxyl groups. In the ¹H-nmr spectrum of corymotine, two singlet signals at δ 0.99 and δ 1.50 revealed the possibility of a gem-methyl group. H-14 appeared as a singlet and certified the gem-methyl group at C-13 rather than at C-8. Some previous studies (5,6) supported the conclusion that the chemical shifts at δ 1.0 and δ 1.5 were indicative of the 13-Meₐ and 13-Meᵦ, while signals are at δ 1.4 and δ 1.5 for 8-Meₐ and 8-Meᵦ, respectively. The signal at δ 6.62 was assigned to H-4 in ring A based upon the fact that upon irradiation at δ 2.28 of the aliphatic proton H-5, only the signal at δ 6.62 was sharpened and increased by 21% of the peak area. Upon irradiation at δ 3.86 (-OMe), the nOe enhancement of 20% and 21% of peak areas at δ 6.62 and δ 6.79, respectively, was observed. Thus, δ 6.79 was assigned for H-1. The chemical shifts of the two low-field protons of H-8 at δ 3.76 and δ 4.17 were deshielded by the aromatic ring D, the lone pair on the adjacent nitrogen, and the oxygen at C-9 (5). The chemical shift of the other two aromatic protons at δ 7.07 and δ 6.82 appeared as double duplet peaks could only be ortho-coupled (J=9 Hz). It indicated that the two methoxyl groups in ring D may be assigned to 9,10 substitution. In alkaloids with 10,11 substitution, the H-8 would appear as a broad singlet centered at δ 4.05 (6). The H-11, H-12 substituted dimethoxyl compound had not yet been found to occur naturally. Therefore, the rational structure of corymotine [1] must be a 2,3,9,10-tetramethoxyl substitution pattern. From the previous studies (7) of the stereochemistry of tetrahydroprotoberberine, it could be inferred that corymotine existed in solution as a mixture of cis and trans conformers at the B/C ring junction. This observation is supported by the fact that the ¹³C nmr signal for C-6 at 49.4 and the ¹H-nmr chemical shift difference of 0.41 ppm for the protons at H-8 as well as the weak Bohlmann bands at 2745, 2780, and 2830 cm⁻¹ were all in good agreement with those reported (8,9) for tetrahydroprotoberberines with a mixture of cis and trans conformers. The specific rotation of corymotine was [α]²⁵D -188° in CHCl₃, so that, the absolute conformation should be assigned as 14S (10) for corymotine.