The order (corynanthe→strychnos→aspidosperma→iboga) in the biosynthesis of indole alkaloids with a close relationship to iridoid glucosides as the precursors has been recently established. In connection with this biosynthetic pathway, an attempt to synthesize these alkaloids from the common intermediate has been extensively made in our laboratory. As a recent successful example, the entitled compound and the relatives have been synthsized in line with this principle. It was previously reported by us that the condensation of 2-hydroxytryptamine hydrochloride (7) with formylacetone ethyleneketal (8) provided the spiro-oxindoles (9a, b), both of which were converted to (10) as a single product. Thus, the iminoethers (17a, b, c) were prepared from (9a, b) via (15a, b), and isolated as three stereoisomers, two (17a, b) of which were cyclized with NaH in DMSO to the pentacyclic derivatives in two isomerides [19a, m.p. 247-249°, δ4.32 (d. J=8.2Hz, C_<19>-H) and 19b, m.p. 230-232°, δ4.02 (d. J=11Hz, C_<19>-H)]. The former (19a) was converted by a chain of reactions of LiAlH_4 reduction, acetylation, and then hydrogenation into Na-acetyldesethylaspidospermidine (21a, IR 2800 and 2740cm^<-1>; NMR (CDCl_3) δ2.24 (s, CH_3CO), 4.40 (q, C_2-H) as a resin (picrate, m.p. 147-150°), which was identified with the product obtained on the Fischer indolization of heating the phenylhydrazone (26, A/B trans) with acetic acid for many hours, followed by reduction and acetylation. The stereochemistry of this compound might be presumed to be identical with that of the natural alkaloids based on the above NMR spectral data, because the C_2-H signals of these alkaloids appear atδ4.5-5.0 (quartet) and are well known as 'aspidosperma finger print', which are remarkably different from the corresponding signal (δ4.92 as a triplet) of "dl-pseudo-(C/D trans)-aspidospermine" synthesized by us. On the other hand, the ketone (10) was reduced with NaBH_4 in i-PrOH to (28) as two isomers, (28a, m.p. 215°) and (28b, m.p. 199-201°). The former (30a) was transformed into the amide [31, m.p. 153-154°; IR υ^<nujol>_<max> 1728, 1640, 1358 and 1169 cm^<-1>; Mass (m/e) 472, 474(M^+)] through tosylation, deacetylation and acylation with β-chloropropionyl chloride. The acrylamide (32) which was obtained by treatment of (31) with K_2CO_3 in ethanol, was cyclized with the Meerwein's reagent in dichloroethane to the lactam [12, m.p. 203-204°, IR υ^<nujol>_<max> 1718, 1638, 1357 and 1168 cm^<-1>; λ^<EtOH>_<max> 257mμ; Mass (m/e) 436 (M^+), which was identified with the product obtained from (19a) by NaBH_4 reduction, tosylation and oxidation with Jones' reagent. Quite similarly, (30a) was converted into the lactam as two stereoisomers [34a, m.p. 191-193°; IR, υ^<EtOH>_<max> 1728, 1645, 1365 and 1172 cm^<-1>; UV, λ^<EtOH>_<max> 257mμ m: Mass (m/e) 464 (M^+), and 34b, m.p. 228-229°; Mass (m/e) 464 (M^+)], a mixture of which on account of scantiness of the quantity, was led to the ethylenethioketal (m.p. 225.5-227°, colorless prisms, Mass (m/e) 540 (M^+). The thioketal was transformed into 7-ethyl-5-des-ethylaspidospermidine (35) in the sequential processes of desulfurization with Raney Nickel, LiAlH_4 reduction and acetylation, the infrared spectrum of (35) is almost identical with that of the corresponding material derived from the natural alkaloid by Kutney. Thus, a series of oxindole derivatives have been transformed into aspidosperma skeltons in two different ways. The relationship between oxindoles and indole alkaloids in biosynthesis is being investigated in connection with the present work.
