Contrary to earlier reports, the base-induced rearrangement of the 7-hydroxy-7H-indolenines derived from ajmalicine (l), yohimbine (5), corynanthine (6), methyl reserpate (16), and methyl isoreserpate (17) in each case furnished not just one, but two epimeric spiro-pseudoindoxyl derivatives which have opposite configuration at the spiro centre C(2). In all cases, the major component was shown by NOE experiments to be the A-type isomer (carbonyl group located below the plane defined by rings C and D). The thermodynamically less stable B-type pseudoindoxyl epimers 4,10, 12, and 22 were isolated and characterized for the first time.
1. Introduction.
-Within the Aristotelia alkaloid family, the formation of pseudoindoxyls ( = 1,2-dihydro-3H-indo1-3-ones) and oxindoles ( = 1,3-dihydro-2H-ind01-2ones) from the corresponding 3H-indol-3-01 precursors was shown recently to proceed under strict kinetic control [l]. This is not the case within alkaloid families that contain a tetrahydro$ -carboline ring system, such as the yohimbane and heteroyohimbane alkaloids, because subsequent equilibration at the spiro centre and/or C(3) usually takes place. Early claims that certain oxindole alkaloids endowed with this skeleton are equilibrated upon treatment with AcOH or Ac,O [2] were confirmed by a Canadian team who demonstrated that such oxindoles are isomerized under very mild conditions and that they differ in their relative configuration at the spiro centre [3]. These findings were rationalized by Wenkert et al. [4] who postulated a retro-Mannich cleavage of the C(3)-C(7) bond, followed by rotation of the oxindole side chain and a Mannich ring re-closure (for reviews, see [S]).
Curiously, the above type of isomerization seemingly has never been observed in the case of the related pseudoindoxyls: no matter whether compounds endowed with this functional unit were isolated from plant material or prepared by partial synthesis from their indole precursors, in each case, only a single spiro epimer was isolated'). However, inspection of Dreiding models or even just a glance at the perspective drawings of ') In a preliminary communication, Finch et al. [6] mentioned that, on treatment with hot AcOH, yohimbine pseudoindoxyl was transformed to the extent of ca. 10% into an isomeric pseudoindoxyl which was 'instantly reconverted to the starting material in the presence of base'. However, this compound was not characterized and was not mentioned anymore in the full paper of these authors [7].
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The standard nomenclature for the description of the relative configuration of yohimbane-type alkaloids was followed [3]; normal: rings D and E trans-fused (i.e. 2qB) and H-C(3) on a-face;pseudo : D/E trans (Le. 2q(i), H-C(3) ong -face; allo : D/E cis (i.e. 20a), H-C(3), H-C( 15), and H-C(20) all on a -face; epiuNo : D/E cis (i.e. 20a), H-C(3) onp -face. Following a convention introduced by Taylor and coworkers [6] [7], the relative configuration at the spiro centre C(2) is designated as A (carbonyl group below the plane defined by rings C and D) or B (carbonyl group above this plane). The only other possibilities type pseudo-A or -B ) are ruled out by the I3C-NMR chemical-shift values of C(3), C(5), C(15), and C(21) [El (see, e.g., Table 2, 5 vs. 6, 7 vs. 9 and 18 vs. 20).