Crotofolane-Type Diterpenoids: Crotocascarins R-V, Rearranged Trinorcrotofolane: Crotocascarin δ and a Phorbol Derivative from the Leaves of Croton cascarilloides.

Five new crotofolanes, named crotocascarins R-V (1-5), one rearranged trinorcrotofolane, crotocascarin δ, and one phorbol derivative were isolated from the EtOAc-soluble fraction of the MeOH extract of the leaves of Croton cascarilloides. Crotocascarins R (1), T (3), and U (4) possessed isobutyric acid as an acyl moiety and crotocascarin B (2) an acetyl group, whereas crotocascarin V (5) was elucidated to be a hydroxylated compound of crotocascarin K at the 9-position. Crotocascarin δ (6) was a trinor rearranged crotofolane with a tertiary hemiketal functional group at the 8-position. The absolute configuration of the 8-position was determined by the comparison of the experimental electronic circular dichroism (ECD) spectrum and calculated ECD spectra. Compound 7 was a phorbol ester derivative with a peroxide functional group. The fatty acid attached at the 12-position was found to be a single species-i.e., lauric acid (C-12)-from the evidence of the mass spectral data.

Okinawan Subtropical Plants as a Promising Resource for Novel Chemical Treasury.

The Okinawa Islands are a crescent-shaped archipelago and their natural forests hold a huge variety of unique subtropical plants with relatively high endemism. We have performed phytochemical study on Okinawan subtropical plants for many years. In this review, we describe our recent research progress on the isolation of new compounds and their various bioactivities.

Crotofolanes, rearranged crotofolanes, and a novel diterpene: isocrotofolane from Croton cascarilloides, collected in Okinawa.

To this day, since about 50% of all medicines are derived from natural sources, natural product chemistry, especially the search for biologically active natural components, remains extremely important (Newman and Cragg in J Nat Prod 83:770-803, 2020). In this review, we deal with our continuing research work for promising constituents from plants collected in the Ryukyu Archipelago. The isolation of islands in the archipelago by the sea or by straits gives rise to endemic plant species that are unique to the islands. The structural diversity of the constituents produced by this unique flora is of great scientific interest in various aspects, including chemical structures, biosynthesis, and biological activities. The components from this structural diversity have great potential as new pharmaceutical seeds. In our continuing studies, we have successfully investigated new but extremely unusual diterpenoids: crotofolanes and their rearranged varieties (nor-crotofolane, trinor-crotofolane, neocrotofolane) and a glycoside with a new skeletal diterpenoid (isocrotofolane glucoside) from Croton cascarilloides. This review summarizes our reports on the investigation of crotofolanes as well as those on crotofolanes by other research groups.

[Structural Diversity of Chemical Constituents from Okinawan Plants].

In our continuing search for secondary metabolites from plants, we investigated the chemical constituents of various Okinawan plants. From the stems and leaves of Croton cascarilloides (Euphorbiaceae), a great number of rare diterpenoids: crotofolanes; crotocascarins A-Q, and new diterpenoids; rearranged nor-crotofolanes: crotocascarins α-γ; a rearranged crotofolane: neocrotocascarin; and a new skeletal diterpenoid: isocrotofolane glucoside were isolated. Their structures were mainly elucidated from NMR spectroscopic evidence. In addition, absolute configurations of crotocascarins A, B, K and O, crotocascarin α and neocrotocascarin were determined by X-ray crystallographic analyses, chiral HPLC analyses of 2-methylbutyric acid in their molecules, application of the circular dichroism rule for the α,ß-unsaturated γ-lactone ring, and the modified Mosher's method. The absolute structures of crotofolanes were reported for the first time, and a biosynthetic mechanism for the formation of crotocascarin α and neocrotocascarin from crotocascarin B was proposed. Other interesting compounds, namely diosmarioside H: a dimeric ent-kaurane glycoside from the leaves of Diospyros maritima, and melionosides A-C: megastigmane glucosides with a spiro-ring structure from the leaves of Meliosma lepidota ssp. squamulata were also isolated.