A Synthetic Approach to Ervatamine-Silicine Alkaloids. Enantioselective Total Synthesis of (−)-16-Episilicine

Abstract

Starting from an appropriate unsaturated phenylglycinol-derived oxazolopiperidone lactam, the synthesis of (-)-16-episilicine is reported, the key steps being a stereoselective conjugate addition, a stereoselective alkylation, and a ring-closing metathesis reaction. This represents the first enantioselective total synthesis of an alkaloid of the silicine group.

Stereoselective Conjugate Addition Reactions to Phenylglycinol‐Derived, Unsaturated Oxazolopiperidone Lactams

“…[13] The enantioselective synthesis of the indole alkaloid (À)-16-episilicine [14] further illustrates the potential and versatility of phenylglycinol-derived unsaturated oxazolopiperidone lactams as starting building blocks for the enantioselective assembly of complex piperidine-containing natural products. www.chemeurj.org 16-Episilicine can be envisaged as a 3,4,5-trisubstituted piperidine in which the ethyl substituent and the substituent at the piperidine 4-position are in cis positions.…”

Molecular Iodine‐Mediated Cascade Reaction of 2‐Alkynylbenzaldehyde and Indole: An Easy Access to Tetracyclic Indoloazulene Derivatives

“…Interestingly, indole fused azulene derivatives exhibit anticancer and antineoplastic properties. [2] In fact, the syntheses of some indole fused tetracyclic azulene derivatives have reported in the literature using various metal catalysts. [4] However, to the best of our knowledge, there is no efficient, non-metallic protocol available for the construction of indole fused azulene tetracyclic derivatives.…”

“…9-Iodo-5-methoxy-14-methyl-2-(7-methyl-1H-indol-3-yl)- 10-phenyl-12-azatetracyclo[9.7.0.0 3,8 .0 13,18 ]octadeca-1(11),3(8), 4,6,9,13,15,17-octaene (3m) 9, 145.8, 144.6, 138.5, 13.5, 13.2, 135.9, 131.9, 130.4, 129.6, 127.6, 127.5, 126.1, 123.1, 122.6, 122.1, 121.1, 120.8, 119.9, 119.3, 118.1, 116.5, 115.5, 113.8, 111.9, 111.2, 105.6, 55.3,39.09, 17.0, 16.3 + : 606.1168. 9-Iodo-14-methyl-2-(7-methyl-1H-indol-3-yl) -5-nitro-10-phenyl-12-azatetracyclo[9.7.0.0 3,8 .0 13,18 ]octadeca-1(11),3(8), 4,6,9,13,15,17-octaene (3n) 2, 145.6, 145.4, 143.8, 141.7, 136.6, 136.2, 136.0, 130.2, 129.5, 128.0, 127.8, 125.9, 125.4, 123.7, 122.9, 122.4, 121.8, 121.2, 120.9, 120.1, 119.9, 119.6, 118.2, 116.5, 116.1, 112.5, 101.7, 38.4, 17.0, 16.6 9, 144.7, 138.6, 136.6, 135.4, 135.1, 132.0, 130.3, 129.6, 128.0, 127.6, 127.5, 127.0, 126.6, 126.4, 125.8, 122.5, 122.3, 121.1, 119.5, 119.3, 118.2, 116.6, 115.5, 113.8, 111.9, 111.2, 105.7, 55.3, 39.1, 23.5, 23.1, 14.4 8 .0 13,18 ]octadeca-1 (11),3(8), 4,6,9,13,15,17-octaene (3p) 2,145.6,145.5,143.8,141.7,136.2,135.8,135.1,130.0,129.6,127.9,127.7,127.3,126.6,126.1,125.5,122.8,122.5,121.7,121.6,119.9,119.7,119.3,118.3,116.5,116.1,112.4,…”

“…[1] Particularly, the seven-membered ring (azulene) annulated tetracyclic indole moiety occurs in numerous biologically active natural products and pharmaceutical intermediates, which display potent antihistaminic, antimicrobial and anticancer activities. [1,2] In general, the construction of medium sized rings is unambiguously considered to be a cumbersome task due to a combination of the transannular interactions and unfavourable entropic and enthalpic factors.…”

Palladium‐Catalyzed Annulation of Diarylamines with Olefins through CH Activation: Direct Access to N‐Arylindoles

“…[16] These scaffolds were previously synthesized from heteroannulation of internal alkynes or dienes through intramolecular approaches. [17] Under the present reaction conditions both cyclic olefins as well as cyclic dienes afforded the desired N-phenyl tricyclic indole compounds (Table 4).…”