[CH:1]1[CH:2]=[CH:3][C:4]2[C:17](=[O:18])[C:16]3[C:8]4[C:9]([CH:13]=[CH:14][N:15]=3)=[CH:10][CH:11]=N[C:7]=4[C:5]=2[CH:6]=1.C[O:20]C1C=NC2C3C=CC=CC=3C(C3C=2C=1C=CN=3)=O.CC1C2=C3C(=NC=C2)C(=O)C2C(=CC=CC=2)C3=NC=1.BrC1C(=O)C2C(C(=O)C=1)=CC=CC=2.CN(C)N=C/C=C/COC.CN(C)N=C/C=C/CC>>[CH3:11][CH2:10][C:9]1[CH:13]=[CH:14][N:15]=[C:16]2[C:17]([C:4]3[C:5]([C:7](=[O:20])[C:8]=12)=[CH:6][CH:1]=[CH:2][CH:3]=3)=[O:18]It was unexpectedly discovered that a modification of the foregoing method for preparing sampangine enabled the preparation of 3-methoxysampangine (19) and 3-methylsampangine (14) heretofore never achieved. The Hetero Diels-Alder reaction of 2-bromo-1,4-naphthoquinone (1) with (E)-4-methoxy-2-butenal N,N-dimethylhydrazone (17) or (E)-2-pentenal N,N-dimethylhydrazone (12) gave 4'-methoxycleistopholine (18) or homocleistopholine (13), respectively, in modest yield. Generation of the sampanglue nucleus (i.e., 3-methoxysampangine (19)and 3-methylsampangine (14)) was accomplished through condensation of the corresponding cleistopholine with dimethylformamide dimethylacetal. For the 3-methylsampangine reaction, at least two additional compounds, 4'-oxohomocleistopholine (15) and dimer 16, were produced in significant quantities. The exact yields for 15 and 16 remain undetermined due to difficulty in isolation. Chromatography of the reaction product gave fractions consisting of recovered homocleistopholine (11%), 3-methylsampangine (6%), and a fraction consisting of compounds 14-16. Recrystallization of the latter fraction from ethyl acetate followed by manual separation of the crystal types gave pure 15 and 16; 3-methylsampangine crystallized as long yellow needles, 4'-oxohomocleistophiline (6%, 15) as nearly perfect golden octahedra, and dimer 16 (6%) as rectangular yellow plates. ##STR3##
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