Biomimetic Total Syntheses of Ergot Alkaloids via Decarboxylative Giese Coupling

Abstract

Biomimetic total syntheses of Festuclavine and Pyroclavine were achieved by a sequential radical coupling. The key steps include intramolecular decarboxylative Giese reaction to form the central C ring and 4-nitrobenzenesulfonyl (Ns)-directed indole C4–H olefination to introduce the indole C4 component. In addition, D-ring formation was completed by decarboxylative alkenylation and intramolecular SN2 reaction.

Catalyst-free thiophosphorylation of in situ formed ortho-quinone methides

“…It was, however, revealed that the final products 6h–6j were unstable and rapidly decomposed after isolation. It is noteworthy to mention that attempts to deprotect the tosyl group on the amine moiety 6a under both basic conditions (4-OMePhSH/DIPEA) 20 and acidic conditions (TFA) 21 were unsuccessful, leaving the decomposition of the substrates.…”

“…It was, however, revealed that the final products 6h-6j were unstable and rapidly decomposed after isolation. It is noteworthy to mention that attempts to deprotect the tosyl group on the amine moiety 6a under both basic conditions (4-OMePhSH/ DIPEA) 20 and acidic conditions (TFA) 21 were unsuccessful, leaving the decomposition of the substrates. To rationalize the proposed mechanism of this thiophosphorylation reaction, control experiments were performed to gain a mechanistic perspective on this synthetic transformation (Scheme 6).…”

Total Synthesis of (+)-Isolysergol

“…All the chemicals like (R)-phenyloxirane and all other reagents were purchased commercially from Energy Chemical and used without further purification. NMR spectra were recorded on Bruker ADVANCE 400 ( 1 H 400 MHz, 13 C 100 MHz). Chemical shifts are reported in δ (ppm) relative to TMS in CDCl 3 as internal standard ( 1 H NMR) or the residual CHCl 3 signal ( 13 C NMR).…”

“…After simple filtration and extraction, the collected organic phase was dried with MgSO 3.74 (m, 1H), 3.64 (ddd, J = 14.9, 6.6, 0.8 Hz, 1H), 3.54 (dd, J = 12.0, 10.4 Hz, 1H), 3.44 (dd, J = 11.4, 4.6 Hz, 1H), 3.25 (dd, J = 14.9, 11.8 Hz, 1H), 2.93 (dd, J = 12.0, 8.8 Hz, 1H), 2.65 (ddd, J = 16.9, 4.3, 3.1 Hz, 1H), 2.47 (s, 4H), 2.06 (d, J = 2.9 Hz, 1H), 2.05 (s, 6H). 13…”

“…Although the total syntheses of several members of this class of natural products have been reported, − isolysergol (3) still remains a challenging synthetic target . In 2010, the first asymmetric synthesis of (+)-isolysergol was disclosed by Martin and Deck, which employed a late-stage ring-closing metathesis for the tetracyclic ergoline skeleton construction (Scheme a).…”