The application of vinylogous iminium salt derivatives to an efficient synthesis of the pyrrole containing alkaloids Rigidin and Rigidin E

Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity

“…The synthetic methods used to prepare the highly functionalized pyrroles and related derivatives depicted in Scheme I can be found in previously reported work [19][20][21][22][23].…”

Exploring Natural Product Chemistry and Biology with Multicomponent Reactions. 5. Discovery of a Novel Tubulin-Targeting Scaffold Derived from the Rigidin Family of Marine Alkaloids

“…This sequence constitutes the first synthesis of rigidins B, C and D, while rigidin A is accessed via a significantly improved method compared with the previously described routes. 13–16 In addition, our reaction sequence leads to an expedient preparation of what we call the first-generation library of rigidin analogues based on the 7-deazaxanthine skeleton and possessing variable substituents in the aromatic moieties. Finally, in addition to these synthetic 7-deazaxanthines 22a–j , we prepared a dithia variant 22k , which is obtained by treating pyrrole 21 with carbon disulfide in pyridine (Figure 3).…”

“…10 Further work in this area was hampered by the miniscule isolation yields of these natural products (0.0015 % for A, 0.00031 % for B, 0.00008 % for C, 0.00004 % for D, and 0.018 % for E based on dry weight). Up to 2011, the synthetic accomplishments in the rigidin area included three total syntheses of rigidin A 13–16 and one of rigidin E. 16 These approaches involved lengthy synthetic sequences and/or low overall yields and did not offer a solution to the natural product supply problem. More importantly, however, the lack of synthetic flexibility impeded their use for the preparation of analogues for structure-activity relationship (SAR) a studies.…”

The application of vinylogous iminium salt derivatives to efficient formal syntheses of the marine alkaloids lamellarin G trimethyl ether and ningalin B

“…One of the synthetic strategies that we have employed15–19 in the past utilizes a 2,4-disubstituted pyrrole, which can be prepared from an appropriate vinamidinium salt, as a basic building block for the construction of many of the natural products depicted in Figure 2. Such pyrroles have been formylated at C-5 by a microwave accelerated version18 of the Vilsmeier-Haack-Arnold procedure and further elaborated to yield storniamide type alkaloids.…”

“…We have previously reported formal syntheses of related pyrrole containing natural products (Figure 2) such as polycitone A15 (14) , ningalin B16 (16) , lukianol A17 (17) and permethyl storniamide18 (18) . We have also completed a total synthesis of the pyrrolopyrimidine alkaloids rigidin19 (9) and rigidin E (13) . In this paper we now describe the evolution of our strategy as it relates to the modular and the convergent syntheses of lamellarin G trimethyl ether (8).…”