Oxindole Alkaloids. I. Oxidative-Rearrangement of Indole Alkaloids to their Oxindole Analogs

The chloroindolenine – imino ether – oxindole sequence. A reexamination

“…It is interesting to note that lower Rf in silica gel chromatography of epimeric chlorindolenines has been associated with greater basicity, and led Dolby and Gribble (9) to an assignment of epimer configuration contrary to ours. These authors isolated "about equal amounts" of epimeric chlorides from the tetracyclic base, Contrary to the claim of Finch and Taylor (2) no quantitation of the isomeric ratio has hitherto been published for the products of chlorination of either yohimbine or yohimbane; these authors reported a "50:50 mixture" for the former and made an unsubstantiated claim that "equal amounts" (of epimers) have been "proved conclusively" in the case of the chloroyohimbanes by Shave1 and Zinnes (8). In this study, the ratios of epimers in the crude reaction products from yohimbine were estimated from peak areas of chromatograms following hplc analysis; the ratios of a / p were observed to be 3: 1 for the chlorides and 1 :3 for the methyl ethers.…”

“…Addition of methanol to the imine bond of 9a-and 9P-chloro-9H-yohimbine may occur from cr and P faces of the plane of the ring network, with strikingly different results. In the case of each of the three substrates which undergo rearrangement, only one of the two possible addition products (as illustrated in Scheme 2) provides the appropriate anti alignment of the C8-C13 and C-Cl boods,14 namely the products of P addition of methanol to 9P-chloro-9H-deserpidine and 9P-chloro-9H-yohimbine (6 and 7, respectively) in which the alignment is almost ideal for a planar four-centred transition state, and the product of a addition of methanol to 9cr-chloro-9H-yohimbine (8) in which only relatively unencumbered rotation about the C8-C9 bond is needed to optimize alignment of the skewed C-Cl bond. However, in the first two cases, the benzene ring attached to C9 must adopt an axial configuration, a factor which would be expected to disfavour their rearrangement relative to the third substrate (2) for which the benzene ring in the addition compound (8) is equatorially oriented.…”

Synthesis of (±)‐Strychnofoline via a Highly Convergent Selective Annulation Reaction

“…[13] Corynantheal (14) is likely to be the last of the Corynanthe-type intermediates. [14] Usambaridine Br (15) has been isolated from the leaves of Strychnos usambarensis, together with strychAbstract: Studies aimed at preparing (AE )-strychnofoline by total synthesis are detailed. The route described makes use of a recently developed MgI 2 -mediated ring-expansion reaction of spiro[cyclopropan-1,3'-oxindole] with a cyclic disubstituted aldimine.…”

“…[1] Usambaridine Br (15) is likely converted to strychnofoline (1) by an oxidative rearrangement, a sequence which is probably responsible for the origin of all oxindole alkaloids of the Strychnos family. [15] Within the context of complex molecule syntheses, the successful preparation of spiro[-perhydroindolizine-oxindoles] has been effected following four general strategies.…”

“…[1] Usambaridine Br (15) is likely converted to strychnofoline (1) by an oxidative rearrangement, a sequence which is probably responsible for the origin of all oxindole alkaloids of the Strychnos family. [15] Within the context of complex molecule syntheses, the successful preparation of spiro[-perhydroindolizine-oxindoles] has been effected following four general strategies. The first was reported for the total synthesis of related antineoplastics, [16] wherein condensation of a 2-oxytryptamine with an aldehyde afforded an intermediate imine that subsequently participated in an intramolecular Mannich reaction.…”