Isolation and Confirmation of the Proposed Cleistanthol Biogentic Link from Croton insularis

Abstract

The proposed cleistanthol biosynthetic intermediate en route to spruceanol, and other related family members, was isolated for the first time from Croton insularis, confirming the Jacobs-Reynolds hypothesis. Anticancer evaluation of the new isolates and their aerial oxidation products is also reported.

Unprecedented 1,14‐seco‐Crotofolanes from Croton insularis: Oxidative Cleavage of Crotofolin C by a Putative Homo‐Baeyer–Villiger Rearrangement

“…The HRMS of EBC-240 and EBC-241 (7 and 8) gave the molecular formula C 20 H 26 O 5 , which suggests eight DBE for both compounds. According to the 1 H NMR spectrum coupling constants (see Tables S4 and S5 in the Supporting Information) and analysis of the COSY spectra correlations for 7 and 8, the following sets of atom connections C-19-C-2-C-3, C-13-C-7-C-8 and C-10-C-11 were found, which were the same as observed for EBC-233 (5).…”

“…A second dioxygenated compound, EBC-300 (6), was also isolated. The HRMS gave an identical molecular formula C 20 H 24 O 4 to that of EBC-233 (5), with very similar 13 C NMR and DEPT multiplicity characteristics, which suggested the same structure as EBC-233 (5). However, a difference in d H and d C values (see Table S3 in the Supporting Information) was apparent for the nuclei at positions 7, 8, 12, 13, and 18, which could be explained by the addition of singlet oxygen from the alternate face of EBC-162 (4).…”

“…Further chromatography afforded a new compound, EBC-233 (5). 13 C and DEPT NMR spectroscopic data (see Table S2 in the Supporting Information) revealed a very similar structure to that of EBC-162 (4).…”

“…[3] In the same report, however, crotofolin B (3), C (4) ( Figure 1), and D were claimed to be isolated from the same source, [3] but citing unpublished results (i.e. no characterization data) and not presenting a structural drawing or characterization data for crotofolin D. Since that time there have only been very seldom reports from Croton species detailing crotofolane-type natural products, [4] with not a single addition to the nonlactone crotofolin C (4) type surfacing.In a continuing program aimed at evaluating the anticancer active constituents of Croton insularis (Baill), found in the northern rainforest of Australia, [5] we isolated EBC-162 (crotofolin C (4)) and a range of oxidized family members. EBC-162 (4), isolated from the stems collected in March 2009, was then stored over a four-year time period to determine whether prolonged exposure to air, solvent, and trace acid, would infer artefacts of isolation.…”

“…In a continuing program aimed at evaluating the anticancer active constituents of Croton insularis (Baill), found in the northern rainforest of Australia, [5] we isolated EBC-162 (crotofolin C (4)) and a range of oxidized family members. EBC-162 (4), isolated from the stems collected in March 2009, was then stored over a four-year time period to determine whether prolonged exposure to air, solvent, and trace acid, would infer artefacts of isolation.…”