An Enantioselective Total Synthesis of (+)-Geissoschizine

Abstract

[formula: see text] A concise asymmetric synthesis of the indole alkaloid (+)-geissoschizine (1) has been completed. The synthesis features the highly diastereoselective vinylogous Mannich reaction of 3 with 4 to give 5, which is elaborated into the key tetracyclic intermediate 7 in two steps. Following the stereoselective introduction of the ethylidene moiety to give 9, reduction of the lactam and radical decarboxylation via an acyl selenide gave 12, which was converted into (+)-geissoschizine by formylation. The synthesis requires only 11 chemical operations and proceeds in an overall yield of 17%.

Indolo[2,3-a]quinolizidines and Derivatives: Bioactivity and Asymmetric Synthesis

“…A concise synthesis of (+)-geissoschizine (76) by the reduction of the lactam carbonyl group, as described by Martin and co-workers, [53] satisfactorily afforded ()-deplanchine (90).…”

The Chiral Pool in the Pictet–Spengler Reaction for the Synthesis of β-Carbolines

“…The synthesis involved the preparation of a dihydrocarboline iminium salt followed by a highly selective attack at C-3 of a vinyl ketene acetal from the face opposite to the carboxyl group at C-5 (Scheme 5) [36,37].…”

Biomimetic Synthesis of Alkaloids Derived from Tryptophan: Indolemonoterpene Alkaloids

“…The first achievements, taking place in the early 1970s, implied the condensation of tryptamine (5) with secologanin (6), to give strictosidine (7) and/or its C3 epimer vincoside (27), followed by the hydrolysis of the sugar moiety with β-glucosidase and subsequent rearrangement and/or reduction to give monoterpenoid indole alkaloids ( Figure 3.5). However, this initial approach suffered several drawbacks, such as the facile reaction of N4 of 7 and 27 with the carbomethoxy group at C16 to give the corresponding lactams.…”

“…However, this initial approach suffered several drawbacks, such as the facile reaction of N4 of 7 and 27 with the carbomethoxy group at C16 to give the corresponding lactams. (27) and N b -benzyltrptamine (28) A benzyl protecting group at N4, introduced by using N b -benzyltryptamine (28) as starting material, circumvented this problem and afforded the first biomimetic syntheses of several heteroyohimbine alkaloids, exemplified by 3-iso-19-epiajmalicine (29), 19-epiajmalicine (30) [20], and 1-methyltetrahydroalstonine (31) (Figure 3.6) [21].…”