Synthesis of New Allocolchicinoids with Seven‐ and Eight‐Membered B‐Rings by Enyne Ring‐Closing Metathesis

Abstract

Total syntheses of allocolchicines 4 and 5, with the ester functionality in the C-ring at the C10 or C11 positions, is reported. An asymmetric synthesis of (7S)-allocolchicine 5 is also described. The main features included the elaboration of a common intermediate, the AB bicyclic ring system, in which the construction of the seven-membered ring was achieved by an enyne ring-closing metathesis (RCM) reaction. A subse-

Synthesis of indole-derived allocolchicine congeners exhibiting pronounced anti-proliferative and apoptosis-inducing properties

“…[31][32][33][34][35][36][37][38][39][40][41][42][43] For the construction of the carbocyclic skeleton of 5 [31][32][33][34][35][36][37][38][39][40][41][42][43] For the construction of the carbocyclic skeleton of 5…”

“…Multiple strategies to access the tricyclic fused ring system of allocolchicine (2) and its analogues have been developed to date. [31][32][33][34][35][36][37][38][39][40][41][42][43] For the construction of the carbocyclic skeleton of 5, we followed the strategy depicted in Scheme 1, which relies on intramolecular Friedel-Crafts acylation and Pd-catalysed cross-coupling as the C-C bond forming steps.…”

Recent Synthetic Strategies to Access Seven-Membered Carbocycles in Natural Product Synthesis

“…In 2008 the ene-yne ring-closing metathesis was also used by Hanna and Boyer in their synthesis of (7S)-allocolchicine (Scheme 50), a substance with antitumor activity similar to that of colchicine, but possibly displaying better tolerability. 88 The enyne 230 was prepared in eight steps with high yield from the acid 229. A metathesis reaction catalyzed by Grubbs' second-generation catalyst then gave the bicyclic 231 in excellent yield, from which the natural product was obtained in seven further highyielding steps.…”

Total Synthesis of (±)-Allocolchicine and Its Analogues Using Co-Catalyzed Alkyne [2 + 2 + 2]-Cyclotrimerization

“…7 On the other hand, Fagnou’s group documented the Pd-catalyzed intramolecular direct arylation to install the B ring of allocolchicine. 8 Coming to the other allocolchicinoids that are currently in clinical trials, Maudet’s 9 report on the synthesis of N -acetylcolchicinol using modified Ziegler Ullmann coupling, Hanna’s 10 enyne ring-closing metathesis (RCM) and Diels–Alder aromatization for B and C ring construction, synthesis of NSC 51046 by Green’s 11 group employing an intramolecular Nicholas reaction for B ring construction, as well as synthesis of NSC 51046 by DeShong’s 12 group employing the siloxane coupling-ring expansion protocol are the remarkable examples in this regard. Moreover, Norman’s group developed an approach for the synthesis of 6-oxa-allocolchicinoids by [2 + 2 + 2]-cycloaddition as well as synthesized various allocolchicine analogues with pyridine C ring through intermolecular Vollhardt diyne-nitrile cyclotrimerization in another report.…”