Labdane-type diterpenoids from Croton laevigatus

Abstract

Sixteen new labdane-type diterpenoids (1-9, 11-17) were isolated from the twigs and leaves of Croton laevigatus, along with 15-hydroxylabda-7,13(E)-diene-17,12-olide (10), which is reported here as a natural product for the first time. Their structures were elucidated on the basis of extensive spectroscopic data interpretation, including UV, IR, NMR, and MS, and comparison with literature data. The structures of compounds 7, 8, 10, 14, 15, 16, and 17 were further confirmed by single-crystal X-ray diffraction analysis.The absolute configurations of 10-17 were determined by the CD exciton chirality method and supported by the single-crystal X-ray diffraction analysis of 10, 14, and 15. Crotonlaevins A (1) and B (2) are the reported first labda-type diterpenoids with a dodecahydronaphtho [1,2-c] furan moiety, and compounds 10-17 are the first reported labda-17,12-olide derivatives isolated from nature.

Chemical Constituents from Croton Species and Their Biological Activities

“…laevigatus led to the isolation of 16 new labdanes ( 233 – 248 ). Among them, crotonlaevins A–B ( 233 , 234 ), represents rare labdanes with a dodecahydronaphtho [1,2-c] furan moiety [ 79 ]. Three new labdane diterpenoids ( 260 – 262 ) were found from C. jacobinensis [ 77 ] and C. decalvatus [ 80 ], respectively.…”

Sublyratins A–O, Labdane-Type Diterpenoids from Croton sublyratus

“…The connections of the four units with the quaternary carbons and the other functionalized groups were assigned mainly by analysis of the HMBC spectrum, in which the correlations (Figure A) from H 3 -20 to C-1, C-5, C-9, and C-10 (δ C 39.8), from H 3 -18 and H 3 -19 to C-3, C-4 (δ C 33.1), and C-5, and from H-7 to C-5, C-8, and C-9 helped construct rings A and B and established the attachments of C-18/19 geminal methyls and the C-20 angular methyl. The IHD requirement and the HMBCs from H-7 to C-8 (δ C 123.3), C-9 (δ C 164.8), and C-17 and from H-12 to C-9, as well as the chemical shifts of C-12 (δ C 82.8) and C-17 (δ C 167.7), then indicated the presence in the ring C of an α,β-unsaturated six-membered lactone system, which was supported by comparing the relevant NMR data of 1 with those of its co-isolated known analogue, crotonlaevin N ( 16 ) . The HMBCs from H 2 -11 to C-13, from H 3 -16 to C-12, C-13, and C-14, and from H 2 -15 to C-13 then revealed the C-13–C-16 side chain that was attached to ring C via a C-12/C-13 bond.…”

“…They possess a common planar structure as inferred by their fully consistent 1 H− 1 H COSY and HMBC correlations (Figure S3A, Supporting Information). Interpretation of the NMR data (Table 4) of 10 showed its structure closely resembled that of co-isolated known compound 17, 18 with the only difference being the presence of a OH group at C-6 in 10, which was supported by the chemical shifts of H-6 (δ H 4.38) and C-6 (δ C 68.8), as well as the HMBC correlations from H-5 and H-7 to C-6 and from H-6 to C-8 (δ C 126.7). The NOESY cross-peaks (Figure S3B, Supporting Information) of H-6/H 3 -19 and H 3 -20 further allowed the assignment of an αorientation for OH-6.…”

“…Table 5. 1 H NMR (500 MHz) and 13 C NMR (125 MHz) Data of Compounds 13−15 in CDCl 3 13 14 15 Four known labdane diterpenoids, crotonlaevin N ( 16), 18 crotonlaevin P (17), 18 crotonlaevin O (18), 18 and labda-7,12(E),14-triene-17-oic acid (19), 21 were isolated and identified by comparing their observed and reported spectroscopic data. Thus, reported herein are mainly a total of four groups of diastereomers.…”

Crassifolins Q−W: Clerodane Diterpenoids From Croton crassifolius With Anti-Inflammatory and Anti-Angiogenesis Activities

“…The genus Croton (Euphorbiaceae) is a rich source of diterpenoids with interesting structural diversity such as clerodane-type (Campos et al, 2010;Khanitha and Damrong, 2011;Sun et al, 2014), kauritan-type (Dao et al, 2011;Suwancharoen et al, 2012), heliurane-type (Martha et al, 2011;Huang et al, 2014a), phorbol ester-type (Zhang et al, 2013;Corlay et al, 2014), and trachylobane-type (Martinsen et al, 2010). These diterpenoids exhibited remarkable biological characteristics including anti-inflammatory (Wang et al, 2015), anti-tumor (Fernandes et al, 2013;Young et al, 2013;Maslovskaya et al, 2015), anti-viral (Nina et al, 2014), anti-bacterial (Liu et al, 2014), and anti-oxidation activities (Mariana et al, 2013), which make them particularly valuable for phytochemical and pharmacological research studies.…”