A Biomimetic Synthetic Approach to the Frondosins

Abstract

The frondosins are a family of five marine sponge-derived meroterpenoids. We propose that the 6-7 ring system common to each of the frondosins is biosynthesized via ring expansion of a 6-6 ring system. Compelling evidence in favour of this proposal was obtained in the form of a biomimetic synthesis of the frondosin 6-7 ring system, which features a highly stereo-and regio-selective ring expansion cascade reaction as the key step.

Access to 5-Methyl-5H-naphtho[2,3-c]carbazole-8,13-dione Derivatives via Copper-Catalyzed Intramolecular Isomerization

“…Orange solid; mp 237−238 °C; yield 27.7 mg, 78%; R f = 0.35 (3:1 CH 2 Cl 2 /PE); 1 H NMR (400 MHz, CDCl 3 ) δ 9.09 (d, J = 7.9 Hz, 1H), 8.21 (d, J = 24.3 Hz, 2H), 7.72 (s, 2H), 7.31 (s, 1H), 7.18 (dt, J = 14.8, 7.0 Hz, 2H), 4.02 (s, 3H), 2.90 (s, 3H), 2.79 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 186. 4, 185.1, 144.9, 141.8, 139.5, 134.4, 134.3, 133.3, 132.9, 131.9, 131.2, 126.4, 126.3, 125.8, 125.2, 123.1, 120.4, 120.2, 119.9, 116.8, 32.6, 25.3, 20.8 2,5,carbazole -8,13-dione (2f) (new). Orange solid; mp 208−209 °C; yield 25.1 mg, 74%; R f = 0.37 (3:1 CH 2 Cl 2 /PE); 1 H NMR (400 MHz, CDCl 3 ) δ 9.12 (s, 1H), 1H),8.21 (d,J = 5.0 Hz,1H),2H),7.40 (s,1H),7.38 (s,1H),7.28 (s,1H), 3.80 (s, 3H), 2.97 (s, 3H), 2.62 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 186.…”

“…Orange solid; mp 152−153 °C; yield 14.2 mg, 42%; R f = 0.37 (3:1 CH 2 Cl 2 /PE); 1 H NMR (400 MHz, CDCl 3 ) δ 9.28 (d,J = 8.6 Hz,1H),1H),1H),2H),7.53 (t,J = 8.3 Hz, 1H), 7.39 (s, 1H), 7.32 (q, J = 3.5 Hz, 2H), 3.77 (s, 3H), 3.35 (q, J = 7.4 Hz, 2H), 1.37 (d, J = 7.3 Hz, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 186. 2,185.0,145.9,144.4,143.1,134.7,133.9,133.4,132.8,132.1,127.7,127.6,126.5,126.2,125.3,122.3,120.3,120.2,115.2,108.3,30.2,29.0,15.6;HRMS (ESI) 133.3, 133.0, 132.6, 130.2, 127.9, 126.7, 125.7, 123.0, 101.9, 39.2, 24 furan-5(9bH)-one (4u) (new). Yellow solid; mp 223−224 °C; yield 7.6 mg, 17%; R f = 0.10 (3:1 CH 2 Cl 2 / PE); 1 H NMR (400 MHz, CDCl 3 ) δ 8.09 (d,J = 7.8 Hz,1H),7.89 (d,J = 7.6 Hz,1H),7.66 (t,J = 7.5 Hz,1H),7.54 (t,J = 7.7 Hz,1H),7.31 (d,J = 8.3 Hz,1H),7.20 (d,J = 7.8 Hz,3H),7.12 (d,J = 7.8 Hz,…”

“…Red solid; mp 173−174 °C; yield 3.9 mg, 12%; R f = 0.35 (3:1 CH 2 Cl 2 /PE); 1 H NMR (400 MHz, CDCl 3 ) δ 2H),2H),7.41 (d,J = 8.0 Hz,1H),7.35 (d,J = 8.2 Hz,1H),7.31 (s,1H),7.26 (d,J = 15.1 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 5.31 (s, 1H), 5.06 (s, 1H), 3.86 (s, 3H), 1.75 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 185. 2,184.1,146.3,139.2,138.7,136.8,133.6,133.3,132.5,132.3,131.5,127.4,126.5,126.4,122.1,121.2,120.0,119.8,109.5,107.9,33.2,22.6;HRMS (ESI)…”

Bioactive Prenyl- and Terpenyl-Quinones/Hydroquinones of Marine Origin †

“…A different rearrangement of the sesquiterpenoid skeleton led to a 6–7 carbocyclic framework as in frondosins (frondosin A, 250 ) or liphagal ( 251 ) ( Figure 22 ). Although these compounds were described before the period covered by this review, several synthetic studies have been performed during this time to clarify conflicting assignments on some stereocentres [ 107 , 108 , 109 ]. These were well compiled in the Wright’s review [ 108 ].…”

Celebrating RACI and Academy of Science Awards

“…[7] Jonathan George (University of Adelaide) was awarded the Organic Division's Beckwith Lectureship for 2015 and has contributed a research communication with co-workers K. K. W. Kuan, and A. M. C. Hirschvogel entitled 'A Biomimetic Synthetic Approach to the Frondosins'. [8] Chengzhong (Michael) Yu (University of Queensland) won the 2015 Le Fèvre Memorial Prize (issued by the Academy and presented by the RACI). He has contributed a research paper with co-workers C. Lei, L. Zhou, C. Xu, X.…”