Neighbouring group participation in the reaction of 7-oxo-ent-kaur-16-ene derivatives with diacetoxyiodobenzene. Synthesis of gibberellin analogues

The reaction of different 7-oxo-ent-kaur-16-ene derivatives with diacetoxyiodobenzene has been evaluated for the preparation of gibberellin analogues. Thus, the reaction of 7-oxo-ent-kaur-16-en-18-oic acid methyl ester (3) with this reagent afforded 4-epi-GA₁₂ dimethyl ester (6). This reaction constitutes a good procedure for the preparation of this type of compounds. In some cases, alternative reactions that led to the introduction in the substrate of a conjugated 5,6-double bond or to the formation of a ketal at the 6-position were also produced. The formation of these compounds, or of gibberellin analogues, depends on the neighbouring group participation of the different C-18 and C-19 substituents at C-4.     

Biotransformation of two stemodane diterpenes by Mucor plumbeus

The microbiological transformation of 13α,17-dihydroxy-stemodane (2) by the fungus Mucor plumbeus afforded 13α,17,19-trihydroxy-stemodane (3), 3β,13α,17-trihydroxy-stemodane (5), 3-oxo-13α,17-dihydroxy-stemodane (7), 7α,13α,17,19-tetrahydroxy-stemodane (8), 3β,11α,13α,17-tetrahydroxy-stemodane (10), 3β,7α,13α,17-tetrahydroxy-stemodane (12), 3β,8β,13α,17-tetrahydroxy-stemodane (14), 2α,13α,17-trihydroxy-stemodane (16), 2α,13α,17,19-tetrahydroxy-stemodane (17), 2α,3β,13α,17-tetrahydroxy-stemodane (20) and 3β,11β,13α,17-tetrahydroxy-stemodane (22), whilst the incubation of 13α,14-dihydroxy-stemodane (25) gave 3β,13α,14-trihydroxy-stemodane (28), 2α,13α,14-trihydroxy-stemodane (29) and 13α,14,19-trihydroxy-stemodane (30). Preference for hydroxylations of ring A at C-2(α), C-3(β) and C-19 were observed in both incubations. An interesting rearrangement of 13α,14α-dihydroxy-stemodanes to 14-oxo derivatives with an unusual carbon framework has been observed under acetylation conditions. We have named this skeleton prestemodane, which, as a hydrocarbon ion, had been postulated as a biogenetic precursor of stemodane.     

Microbial transformation of two 15α-hydroxy-ent-kaur-16-ene diterpenes by Mucor plumbeus

The microbiological transformation of candidiol (15α,18-dihydroxy-ent-kaur-16-ene) by Mucor plumbeus led to 3β,15α,18-trihydroxy-ent-kaur-16-ene, 6α,15α,18-trihydroxy-ent-kaur-16-ene, 3α,15α,18-trihydroxy-ent-kaur-16-ene, 11β,15α,18-trihydroxy-ent-kaur-16-ene and 15α,17,18-trihydroxy-11β,16β-epoxy-ent-kaurane, whilst the incubation of 15α,19-dihydroxy-ent-kaur-16-ene gave 9β,15α,19-trihydroxy-ent-kaur-16-ene, 3α,15α,19-trihydroxy-ent-kaur-16-ene, 11β,15α,19-trihydroxy-ent-kaur-16-ene, 6α,15α,19-trihydroxy-ent-kaur-16-ene, 15α,17,19-trihydroxy-11β,16β-epoxy-ent-kaurane, 19-(β-d-glucopyranosyl)-15α-hydroxy-ent-kaur-16-ene and 19-(β-d-glucopyranosyl)-15-oxo-ent-kaur-16-ene. An interesting rearrangement in dilute acid medium of 9β,15α,19-trihydroxy-ent-kaur-16-ene into 16-oxo-19-hydroxy-ent-abiet-8(9),15-diene, is also described in this work.     

Cytotoxic ent-kauranoid derivatives from Isodon rubescens

An extensive study of the diterpenoids produced by the species of Isodon rubescens, has led to the isolation of 12 new ent-kaurane diterpenoids, hebeirubescensins A-L (1-12), and 19 known analogues. Their structures were determined on the basis of spectroscopic analysis. Selected compounds were assayed for their inhibitory ability against human A549, HT-29, and K562 cells. Among them, hebeirubescensins B and C exhibited significant cytotoxicity with IC₅₀ values of <2.0 μM. The structure-activity relationships were discussed.     

Novel tetranortriterpenoid derivatives from Munronia henryi

Six novel tetranortriterpenoid derivatives were isolated from the methanolic extract of the whole bodies of Munronia henryi, namely, munronins A-F (1-6). In compounds (3-6), the side chains are rare in tetranortriterpenoids. Their structures were established by extensive NMR experiments. Based on the diversity of the side chains, possible biodegradations for the side chains of compounds 1-6 from euphane or tirucallane skeleton are proposed. Munronins A-E exhibited moderate antifeeding activity against Pieris brassicae L, while munronin F showed negative activity.     

Biotransformation of sinapic acid by the green algae Stichococcus bacillaris 155LTAP and Ankistrodesmus braunii C202.7a

Sinapic acid was bioconverted by the green alga Stichococcus bacillaris into 4-hydroxy-3,5-dimethoxybenzoic acid, 4-hydroxy-3,5-dimethoxybenzaldehyde and 4-hydroxy-3,5-dimethoxybenzylic alcohol. Incubation of sinapic acid in a culture of the alga Ankistrodesmus braunii gave 3,6-dihydroxy-2,4-dimethoxy-7H-benzocyclohepten-7-one, a new compound formed by bioconversion of thomasidioic acid, the primary oxidative product of sinapic acid.     

New iodotyramine derivatives from Didemnum rubeum

The study of an aqueous extract from the ascidian Didemnum rubeum permitted the isolation of a previously reported derivative diiodo-tyramine derivative together with six new iodo-tyramine derivatives. Their structures were elucidated by NMR and MS analysis.     

Coelodiol and coeloic acid, ent-isocopalane diterpenes from the Indonesian sponge Coelocarteria cfr. singaporensis

Two novel ent-isocopalane diterpenes, coelodiol (1) and coeloic acid (2), the latter characterized by an unique oxidative degradation of ring A, have been isolated from the Indonesian sponge Coelocarteria cfr. singaporensis. The stereostructure of these metabolites has been established through interpretation of NMR data and application of the exciton chirality CD method. Coelodiol (1) and coeloic acids (2) were found to inhibit the growth of MKN-45 cell line (human gastric adenocarcinoma).     

Biotransformation of triptolide by Cunninghamella blakesleana

Biotransformation of triptolide 1 by Cunninghamella blakesleana (AS 3.970) was carried out. Seven biotransformation products were obtained and four of them were characterized as new compounds. On the basis of their NMR and mass spectral data, their structures were characterized as 5α-hydroxytriptolide 2, 1β-hydroxytriptolide 3, triptodiolide 4, 16-hydroxytriptolide 5, triptolidenol 6, 19α-hydroxytriptolide 7 and 19β-hydroxytriptolide 8. All the new transformed products (2, 3, 7 and 8) were found to exhibit potent in vitro cytotoxicity against some human tumor cell lines.     

3-Oxyanthranilic acid derivatives from Actinomadura sp. BCC27169

Eight new compounds including 9′-[2-amino-3-(4″-O-methyl-α-rhamnopyranosyloxy) phenyl]nonanoic acid (1), 9′-[2-amino-3-(4″-O-methyl-α-ribopyranosyloxy)phenyl] nonanoic acid (2), 11′-[2-amino-3-(4″-O-methyl-α-rhamnopyranosyloxy)phenyl]undecanoic acid (3), 11′-[2-amino-3-(4″-O-methyl-α-ribopyranosyloxy)phenyl]undecanoic acid (4), 8-(4′-O-methyl-α-rhamnopyranosyloxy)-3,4-dihydroquinolin-2(1H)-one (5), 8-(4′-O-methyl-α-ribopyranosyloxy)-3,4-dihydroquinolin-2(1H)-one (6), 8-(4′-O-methyl-α-rhamnopyranosyloxy)-2-methyquinoline (7), and 8-(4′-O-methyl-α-ribopyranosyloxy)-2-methylquinoline (8) were isolated from Actinomadura sp. BCC27169. The chemical structures of these compounds were determined based on NMR and high-resolution mass spectroscopy. The absolute configurations of these monosaccharides were revealed by the hydrolysis of compounds 7 and 8. Compounds 3 and 8 exhibited antitubercular activity at MIC 50 μg/mL. Only compound 3 showed cytotoxicity against KB cell at IC₅₀ 18.63 μg/mL, while other isolated compounds were inactive at tested maximum concentration (50 μg/mL).     

Two novel tricyclic diterpenoids from Isodon rubescens var. taihangensis

Two novel tricyclic diterpenoids rubescensins U (1) and V (2) were isolated from the leaves of Isodon rubescens var. taihangensis. They were elucidated as a 8,15-seco-ent-kauranoid and an ent-abietanoid, respectively, by 1D and 2D NMR spectra, and single crystal X-ray analysis. Compound 1 is the first example of an 8,15-seco-ent-kaurane from the plants genus Isodon. A discussion of their biogenesis is described.     

Terpenoid metabolites of the nudibranch Hexabranchus sanguineus from the South China Sea

Chemical analysis of the secondary metabolite pattern of the nudibranch Hexabranchus sanguineus collected from the South China Sea revealed the presence of both sesquiterpenoids and diterpenoids, exhibiting very different structural features. Two new molecules, compounds 1 and 4, were isolated together with known compounds 2 and 3, and chemically characterized. This is the first report of terpenoids from H. sanguineus. The remarkable diversity of metabolites possessed by H. sanguineus supports some recent phylogenetic studies that place the mollusc near the steam of the dorid nudibranch tree.     

An asymmetric ent-kauranoid dimer from Isodon rubescens var. lushanensis

A novel asymmetric ent-kauranoid dimer, lushanrubescensin J (1), was isolated from Isodon rubescens var. lushanensis. Its structure was elucidated by the spectroscopic evidences. The stereochemistry was confirmed by the single crystal X-ray diffraction of its tetraacetate. Compound (1) exhibited potent inhibitory activity against K562 cells with IC₅₀ = 0.93 μg/mL.     

Hupermine A,a novel C16N2-type Lycopodium alkaloid from Huperzia phlegmaria

A novel C₁₆N₂-type Lycopodium alkaloid consisting of a quinolizidine with a 6-dimethylaminohexyl side chain, hupermine A (1), was isolated from the club moss of Huperzia phlegmaria, and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data.     

Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin

A convergent synthesis of (4R,15R,16R,21S)-rollicosin (1) and (4R,15S,16S,21S)-rollicosin (2) was accomplished. Hydroxy lactone 6a and/or 6b were synthesized from 4-pentyn-1-ol, and α,β-unsaturated lactone 7 was synthesized from γ-lactone 8 and 5-hexen-1-ol. Inhibitory activity of these compounds was examined with bovine heart mitochondrial complex I.     

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of common cutworm (Spodoptera litura)

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of Spodoptera litura was carried out. Substrate was converted to three new terpenoids, (+)-(1R,2S)-10-hydroxyfenchol, (+)-(1R,2R,3S)-8-hydroxyfenchol and (−)-(1S,2S,6S)-6-exo-hydroxyfenchol, and one known terpenoid, (−)-(1R,2R,3R)-9-hydroxyfenchol. These structures were established by NMR, IR, specific rotation and mass spectral studies.     

Polyisoprenylated benzophenone derivatives from Clusia obdeltifolia

Two new polyisoprenylated benzophenones along with the known compound 28,29-Epoxyplukenetione A were isolated from the hexane extract of Clusia obdeltifolia after extensive chromatographic procedures. One of the new benzophenone presented a novel 9-oxa-tetracyclic [11.3.1.0^1,10.0^3,8]heptadec-10-ene-12,17-dione moiety arising from complex cyclizations of isopentenyl and lavandulyl substituents. The other presented an adamantyl skeleton.     

Bipinnapterolide B, a bioactive oxapolycyclic diterpene from the Colombian gorgonian coral Pseudopterogorgia bipinnata

A unique oxapolycyclic diterpenoid, named bipinnapterolide B, has been isolated from the Colombian gorgonian octocoral Pseudopterogorgia bipinnata, and its structure was deduced from spectral and X-ray diffraction studies. Bipinnapterolide B (3) inhibits the growth of Mycobacterium tuberculosis.     

Isolation and structure determination of new 4,12-dideoxyphorbol esters from Euphorbia pannonica Host.

Phytochemical study of the aerial parts of Euphorbia pannonica led to the isolation of two new tigliane diterpenes, 4,12-dideoxy(4β)phorbol-20-benzoate-13-isobutyrate (1) and 4,12-dideoxy(4β)phorbol-20-benzoate-13-isovalerianate (2). The structures and relative stereochemistry were elucidated on the basis of extensive spectroscopic analyses, including 1D and 2D NMR experiments (¹H NMR, JMOD, COSY, NOESY, HSQC and HMBC).     

Phomachalasins A-D, 26-oxa[16] and [15]cytochalasans produced by Phoma exigua var. exigua, a potential mycoherbicide for Cirsium arvense biocontrol

Phoma exigua var. exigua, a fungal pathogen isolated from Cirsium arvense and Sonchus arvensis, proposed as a biocontrol agent of this noxious perennial weeds, produces in liquid and solid cultures different phytotoxic metabolites with potential herbicidal activity. The phytotoxic cytochalasins B, F, Z2, and Z3 and deoxaphomin were previously identified together with p-hydroxybenzaldehyde. Using spectroscopic methods, four new cytochalasins, termed phomachalasins A-D, were isolated and characterized as three new closely related 26-oxa[16] and one new [15]cytochalasans. They belong to a new subgroup of cytochalasans bearing a 1,2,3,4,6,7-hexasubstituted bicycle[3.2.0]heptene joined to the macrocyclic ring. None of the four new metabolites showed phytotoxic or antimicrobial activity. The lack of both phytotoxic and antimicrobial activities showed by all phomachalasins A-D was probably due to the strong modification of both functionalities and conformational freedom of the macrocyclic ring caused by its junction with the bulky and quite rigid new bicycle, namely bicycle[3.2.0]heptene.