Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

Abstract

SummaryThis is a review of our efforts toward the synthesis of a group of natural products that display noteworthy biological activity: Fredericamycin A, nothapodytine B, and topopyrones B and D. In each case, directed aromatic functionalization methodology greatly facilitated the assembly of the key molecular subunits.

Selective Synthesis of Trisubstituted Imidazoles by Iodine‐Catalyzed [3+2] Cycloadditions

“…Yield:86%; yellow solid; mp 99-101°C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.51 (d, J = 8.1 Hz, 2H), 7.98 (s, 1H), 7.77 (d, J = 8.2 Hz, 2H), 7.48-7.42 (m, 5H), 7.37-7.30 (m, 2H), 7.27 (dd, J = 5.3, 4.3 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 186.…”

“…Yield:76%; yellow solid; mp 160-162°C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.99 (d, J = 7.7 Hz, 1H), 7.90 (s, 1H), 7.87 (dd, J = 2.4, 1.5 Hz, 1H), 7.46 (t, J = 4.2 Hz, 4H), 7.44-7.39 (m, 2H), 7.31 (dd, J = 7.4, 6.0 Hz, 2H), 7.28-7.25 (m, 3H), 7.13 (dd, J = 8.2, 2.2 Hz, 1H), 3.89 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 187.…”

“…Yield:93%;yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 8.38 (t, J = 1.7 Hz, 1H), 8.35-8.29 (m, 1H), 7.95 (s, 1H), 7.54 (ddd, J = 8.0, 2.1, 1.1 Hz, 1H), 7.45 (dt, J = 5.3, 1.6 Hz, 6H), 7.36-7.29 (m, 2H), 7.27 (ddd, J = 4.0, 3.3, 1.7 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 186.…”

“…Yield:85%; yellow solid; mp 184-186°C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.39-8.31 (m, 2H), 7.88 (s, 1H), 7.61-7.56 (m, 1H), 7.50 (dd, J = 10.3, 4.6 Hz, 2H), 7.45 (dt, J = 8.3, 2.1 Hz, 2H), 7.35-7.28 (m, 3H), 7.27-7.24 (m, 2H), 7.17-7.11 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ) δ 187.74, 162.42 (d, J = 250.0 Hz), 147.51, 141.…”

“…Yield:85%; yellow solid; mp 138-140°C. 1 H NMR (400 MHz, CDCl 3 ) δ 8.35 (dd, J = 5.2, 3.3 Hz, 2H), 7.90 (s, 1H), 7.61-7.55 (m, 1H), 7.54-7.49 (m, 2H), 7.48-7.44 (m, 2H), 7.43-7.39 (m, 1H), 7.35 (dt, J = 3.1, 2.6 Hz, 1H), 7. 34-7.29 (m, 2H), 7.20-7.13 (m, 1H), 7.07 (dd, J = 8.0, 1.2 Hz, 1H), 7.01 (dt, J = 8.9, 2.2 Hz, 1H).…”