David Din Belle

Total syntheses of tacamine-type indole alkaloids of Tabernaemontana eglandulosa☆

Abstract Total syntheses are described for seven tacamine-type indole alkaloids (1–7) found in Tabernaemontana eglandulosa. (±)-Tacamine (1), (±)-16-epitacamine (2), and (±)-apotacamine (3) were prepared from pentacyclic intermediates 18. Apotacamine (3) was also obtained from aldehyde 12 via epimerization of 20-epiapotacamine (19) by the Polonovski-Potier reaction. Homologation of ester 13 led to 20-epitacamonine (23), which was similarly converted to (±)-tacamonine (4). Reduction of 4 gave (±)-descarbomethoxytacamines 5 and 6. Aldehyde 11 was reacted with trimethylsilyl cyanide (TMSCN) to yield the two (±)-17-hydroxytacamonines (7), of which the isomer with an axial hydroxy group (17β-OH) was found to be identical with the natural compound. Finally, an attempt to prepare (±)-19S-hydroxytacamine (8) is described. As an intermediated for this, a new synthesis of the pyridine alkaloid methyl 5-(1′-hydroxyethyl)nicotinate (34) was achieved.

TOTAL SYNTHESIS OF THE INDOLE ALKALOID ()-TACAMONINE

Abstract A simple and efficient method is described for the preparation of tacamonine (1) from the easily accessible ester 3. The method is based on the stereoselective synthesis of 20-epitacamonine (7), which is transformed to 1 using the Polonovski-Potier reaction.

Controlled Epimerization of Indolo[2,3-a]quinolizidine Derivatives: An Efficient Total Synthesis of (+-)-Tacamonine

Abstract Base-catalysed epimerization of the easily accessible trans ester 3 at C-1 gives rise in good yield to the seemingly less stable cis ester 2, which can be converted into the indole alkaloid tacamonine (1) in three steps.

Total Synthesis of the Indole Alkaloid ()-Tacamine

Abstract The mixture of pentacyclic intermediates ( 4 ) was successfully converted into the pharmacologically interesting indole alkaloid (±)-tacamine ( 1 ). In a similar manner, the two unnatural isomers of 1 , (±)-14-epitacamine ( 9 ) and (±)-14-epi-16-epitacamine ( 10 ), were obtained from intermediate 7 . The key reaction, an acid-catalyzed displacement of the dimethylamino group with the hydroxyl group, is believed to take place via an iminium intermediate.

Stereoselective synthesis of methyl 3α-ethyl-1,2,3,4,6,7,12,12bβ-octahydroindolo[2,3-a]quinolizine-1α-carboxylate: A key intermediate for the preparation of tacamine-type indole alkaloids

Abstract Methyl 3α-1,2,3,4,6,7,12,12bβ-cotahydroindolo[2,3- a ]quinolizine-1α-carboxylate ( 6 ), a key intermediate for the synthesis of tacamine-type indole alkaloids, was prepared in six simple steps from methyl 5-(1′-hydroxyethyl)nicotinate ( 7 ). The last step was the catalytic hydrogenation of the two ethylidene isomers 14 and 15 , both of which gave the target ester stereoselectively.

Syntheses of (±)-17α- and (±)-17β-hydroxytacamonine; determination of configuration at C-17

Abstract Both (±)-17α-hydroxytacamonine ( 3 ) and its 17β-isomer ( 4 ) were synthesized in two steps (one-pot) from aldehyde mixture 5/6 via the cyanohydrin reaction. NMR spectral characterization of isomer 3 revealed it to be unidentical with natural 17-hydroxytacamonine, whereas spectral data of isomer 4 were in agreement with those published for the natural isomer. The configuration at C-17 was confirmed by NOE difference spectroscopy.

Easy access to the voaketone ring system

Abstract Intramolecular aldol condensation of ketoaldehyde 8 affords three new compounds: enone 9 , hydroxyketone 10 , and enone 11 . Enone 9 possesses the ring system of (−)-voaketone ( 1 ), which is a skeletal rearrangement product of the indole alkaloid (−)-voacangine.

First total synthesis of 19S-hydroxytacamine, an indole alkaloid from Tabernaemontana eglandulosa, and of its C-19 stereoisomer, 19R-hydroxytacamine

Abstract 19S-Hydroxytacamine (3) and 19R-hydroxytacamine (4) were prepared from cis hydroxyesters 7 and 8 via corresponding O-TMS esters 9 and 22. Comparison of the spectral data of isomers 3 and 4 with those of 19-hydroxytacamine from Tabernaemontana eglandulosa confirms that isomer 3 represents the naturally occurring 19-hydroxytacamine.