The Aspidospermine Group

Development of a β-C–H Bromination Approach toward the Synthesis of Jerantinine E

“…In addition to their daunting structural complexity, a variety of biological activities and medicinal applications have been reported, including anticancer (e.g., jerantinine E, vinblastine, brucine) and insecticidal (e.g., aspidophytine) activities (Figure A). The Aspidosperma alkaloid subfamily consists of more than 250 different members and biosynthetically originates from the condensation of tryptamine with a rearranged secologanin-derived C 9 or C 10 terpene unit . The secondary metabolites jerantinine A–G (Figure B) were isolated in 2008 from leaf extracts of the Malayan plant Tabernaemontana corymbosa and exhibit cytotoxic effects against vincristine-sensitive and vincristine-resistant epidermoid carcinoma cell lines (IC 50 = 0.68–2.55 μM) .…”

“…The Aspidosperma alkaloid subfamily consists of more than 250 different members and biosynthetically originates from the condensation of tryptamine with a rearranged secologaninderived C 9 or C 10 terpene unit. 4 The secondary metabolites jerantinine A−G (Figure 1B) were isolated in 2008 from leaf extracts of the Malayan plant Tabernaemontana corymbosa and exhibit cytotoxic effects against vincristine-sensitive and vincristine-resistant epidermoid carcinoma cell lines (IC 50 = 0.68−2.55 μM). 2a In 2013, Waser reported the first synthesis of the Aspidosperma alkaloid jerantinine E (1) in 17 steps 5 and disclosed its antiproliferative activity against several humanderived breast and lung cancer cell lines (IC 50 = 1.0−6.0 μM) mediated by inhibition of tubulin polymerization.…”

Five-Step Total Synthesis of (±)-Aspidospermidine by a Lactam Strategy via an Azomethine Ylide

“…The Aspidosperma alkaloids comprise the largest family of monoterpene indole alkaloids and include more than 250 natural alkaloids (Figure ). They show a variety of biological activities and have been used in traditional medicines such as antiinflammatory and anticancer drugs . Pentacyclic aspidospermidine ( 1 ) is the parent compound of this large family. , Its relatively simple structure has been recognized as a gateway to the unified synthesis of Aspidosperma alkaloids, including bisindoles such as vinblastine ( 4 ), which is used in cancer chemotherapy .…”

Axially Chiral Cyclic Phosphoric Acid Enabled Enantioselective Sequential Additions

“…In particular, N -heterocycles have been assigned as privileged structures in drug development . For example, imidazoles are often used as core structures of some enzyme inhibitors and drugs, and indolones are important pharmaceutical intermediates . However, molecules having both imidazole and indolone frameworks, 2,3-dihydro-1 H -imidazo­[1,5- a ]­indol-9­(9a H )-one and 1 H -imidazo­[1,5- a ]­indol-9­(9a H )-one (Figure ), have not been developed thus far.…”