A Reinvestigation of the Oxidative Rearrangement of Yohimbane‐Type Alkaloids. Part A. Formation of pseudoindoxyl ( = 1,2‐dihydro‐3H‐indol‐3‐one) derivatives

Abstract

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.

Corynanthean, eburnan, secoleuconoxine, and pauciflorine alkaloids from Kopsia pauciflora

“…This assignment also received additional support from examination of the chemical shifts of the indolic NH in other corynanthean-type pseudoindoxyl alkaloids. The indolic NH resonances in all corynanthean-type pseudoindoxyl alkaloids with 2R configuration (or A configuration) are consistently observed above 5 ppm in the 1 H NMR spectrum, while the indolic NH in the 2S counterparts are observed below 5 ppm (Stahl and Borschberg, 1994). Compound 5 is therefore tetrahydroalstonine pseudoindoxyl (5), with an allo A configuration (allo: H-3, H-15, and H-20 on a-face; A configuration: carbonyl below C/D plane) (Phillipson and Supavita, 1983;Stahl and Borschberg, 1994).…”

“…The indolic NH resonances in all corynanthean-type pseudoindoxyl alkaloids with 2R configuration (or A configuration) are consistently observed above 5 ppm in the 1 H NMR spectrum, while the indolic NH in the 2S counterparts are observed below 5 ppm (Stahl and Borschberg, 1994). Compound 5 is therefore tetrahydroalstonine pseudoindoxyl (5), with an allo A configuration (allo: H-3, H-15, and H-20 on a-face; A configuration: carbonyl below C/D plane) (Phillipson and Supavita, 1983;Stahl and Borschberg, 1994). Although 5 is encountered as a natural product for the first time, an alkaloid corresponding to 5 was previously obtained during oxidative transformation of tetrahydroalstonine as part of a larger study on the oxidative transformation of yohimbinoid alkaloids (Finch et al, 1965).…”

“…The 1 H and 13 C NMR data (Tables 1 and 3) (Stahl and Borschberg, 1994), except for some differences. In the 1 H NMR spectrum of ajmalicine pseudoindoxyl (6) The configuration at C-2 was assigned as R, from the observed reciprocal NOEs between the indolic NH and H-6b.…”

New Strategies for the Synthesis of Monoterpene Indole Alkaloids

“…The major, more polar isomer was identical with Taylor's compound [31] and was shown unambiguously to represent the A-type pseudoindoxyl 149 [83]. The major, more polar isomer was identical with Taylor's compound [31] and was shown unambiguously to represent the A-type pseudoindoxyl 149 [83].…”

“…We decided to take a closer look at this puzzling situation and started our investigation with the commercially available ajmalicine (140, Scheme 24), a member of the heteroyohimbane alkaloid class [83]. However, inspection of Dreiding models gave no indication of a big difference in strain or steric hindrance between the two epimers, and force-field calculations (PM3) disclosed only a small difference in their heats of formation, favouring the A-type pseudoindoxyl by 1.5-2 kcal/mol.…”