Search

Three procedures have been investigated for the isolation of tyrosol (1) and hydroxytyrosol (2) from a phenolic extract obtained from the solid residue of olive milling. These three methods, which facilitated the recovery of these phenols, were chemical or enzymatic acetylation, benzylation, and carbomethoxylation, and subsequent carbonylation or acetonation reactions. Several new lipophilic alkyl-carbonate derivatives of hydroxytyrosol have been synthesized, coupling the primary hydroxy group of this phenol, through a carbonate linker, using alcohols with different chain lengths. The antioxidant properties of these lipophilic derivatives have been evaluated by different methods and compared with free hydroxytyrosol (2) and also with the well-known antioxidants BHT and α-tocopherol. Three methods were used for the determination of this antioxidant activity: FRAP and ABTS assays, to test the antioxidant power in hydrophilic media, and the Rancimat test, to evaluate the antioxidant capacity in a lipophilic matrix. These new alkyl-carbonate derivatives of hydroxytyrosol enhanced the antioxidant activity of this natural phenol, with their antioxidant properties also being higher than those of the commercial antioxidants BHT and α-tocopherol. There was no clear influence of the side-chain length on the antioxidant properties of the alkyl-carbonate derivatives of 2, although the best results were achieved mainly by the compounds with a longer chain on the primary hydroxy group of this natural phenolic substance.

Microbial transformation of triterpenoids has provided new derivatives that are potentially useful for pharmacological studies. In these biotransformation processes, several reactions that are difficult to achieve by chemical means have been accomplished, such as: introduction of hydroxyl groups into remote positions of the molecules; selective cleavage of the side chains of tetra-cyclic terpenoids to produce C19 steroids; regioselective glycosidic transfer reactions; selective ring cleavage through a Baeyer-Villiger-type oxidation to render seco-triterpenoids; and carbon skeleton rearrangements involving a methyl group migration. These biotransformations have also been used as in vitro models to mimic and predict the mammalian metabolism of biologically active triterpenoids.

Biotransformations of sesquiterpenoids by Rhizopus species have been used to provide new derivatives with potential biological activities. In these fungal transformation processes, the main action of the Rhizopus genus has been the introduction of hydroxyl groups into remote positions of the molecules, which is difficult to achieve by chemical means. Other reactions carried out with stereo-selectivity by these microorganisms have been: epoxidations of double bonds, hydrogenations of the exocyclic C-C double bond of the lactone rings, and reductions of carbonyl groups giving Salcohols. Several reactions have also been performed by these fungi with regio-selectivity, such as oxidations of hydroxyl groups and deacetylations. In some biotransformation processes, a carbon skeleton rearrangement of the substrate has taken place.

Microbial transformations of manoyl oxides by filamentous fungi have been used to introduce hydroxyl groups, regio- and stereoselectively, into substrates at positions difficult to achieve by chemical means. The principal objective of most papers published in this field has been to produce new, highly oxygenated, bioactive manoyl-oxide compounds that present a large diversity of biological properties. The manoyl oxides most frequently studied at present are forskolin and its derivatives, the pharmacological activity of which is related to their ability to activate AC (adenylate cyclase), thus generating an increase in intracellular cAMP (cyclic adenosine monophosphate). The microbial hydroxylation of forskolin and 1,9-dideoxyforskolin has been extensively studied, using the fungi Scopuloriopsis sp., Syncephalastrum sp., Neurospora crassa, Mortierella isabellina and several Aspergillus sp.. Other biotransformation studies of natural manoyl oxides and hemi-synthetic enantio derivatives, carried out via the biomimetic cyclization of ent-8α-hydroxylabda-13(16),14- dienes, have used filamentous fungi Curvularia lunata, Cunninghamella elegans, Fusarium moniliforme, Gibberella fujikuroi, Gliocladium roseum, Mucor plumbeus, Rhizopus nigricans and Neurospora crassa. In some cases, the new hydroxylations were introduced at the same positions as in natural forskolin, yielding some noteworthy products that show biological activities.

Biotransformations of 4α- and 4β-hydroxyeudesmane derivatives by the filamentous fungus Gliocladium roseum were achieved. Hydroxylation at C-11 was the main action of this microorganism, producing new cryptomeridiol (12 and 14) and 4-epi-cryptomeridiol derivatives (6 and 7), respectively, in good yields. The biotransformation activity of G. roseum toward 4β-hydroxyeudesmane was focused on the isopropyl moiety, but more scattered on the 4α-hydroxylated derivative, acting in both the “A” and “B” rings and the isopropyl group of the molecule. Semisyntheses of 11-hydroxyeudesmanolides from the isolated 11,12-dihydroxylated metabolites were also accomplished and used in assigning the stereochemistry of hydroxylation.

Several ent-labda-13(16),14-dienes, ent-13-epi-manoyl oxides and the new natural products ent-6α,8α-dihydroxylabda-13(16),14-diene, ent-18-hydroxy-15(16)peroxylabd-13-ene,ent-16,18-dihydroxymanoyl oxide, ent-13-epi-16,18-dihydroxymanoyl oxide and ent-6α16,18-trihydroxymanoyl oxide have been isolated from Sideritis arborescenssubsp. paulii. The structures of these compounds have been established by spectroscopic means and chemical correlations.

Rearrangements of ent-18-acetoxy-14α-(benzoyloxy)-15α,16α-epoxybeyerane and ent-18-acetoxy-14β-(benzoyloxy)-15α,16α-epoxybeyerane, catalyzed by ruthenium acetylacetonate, were carried out. With the 14-endo-(benzoyloxy) compound, ent-18-acetoxy-14α-(benzoyloxy)beyera-9,15-diene, ent-18-acetoxy-15α-(benzoyloxy)-14α-hydroxykaur-16-ene, ent-18-acetoxy-15α-(benzoyloxy)-14α-hydroxy-(16S)-kaur-11-ene, and ent-18-acetoxy-14α-hydroxy-(16R)-kauran-15-one were isolated. However, rearrangement of the 14-exo-(benzoyloxy) compound gave ent-18-acetoxy-15β-(benzoyloxy)-14α-hydroxykaur-16-ene, ent-18-acetoxy-15β-(benzoyloxy)-14α-hydroxyatis-16-ene, ent-18-acetoxy-14β-(benzoyloxy)-16β-chloro-15α-hydroxybeyerane, ent-18-acetoxy-15β-benzoyloxy)-14α-hydroxy-(16S)-kaur-11-ene, ent-18-acetoxy-15β-(benzoyloxy)-12α-chloro-14α-hydroxy-(16S)-kaurane, and ent-18-acetoxy-14β-(benzoyloxy)-12α-chloro-15α-hydroxybeyerane. The influence of the C-14 benzoyloxy substituent and its arrangement are discussed by comparison with other rearrangement processes reported previously.

Microbial transformations of ent-atisene and ent-beyerene compounds were carried out using cultures of R. nigricans and F. moniliforme. Rhizopus nigricans metabolized all of the substrates, at higher yields than F. moniliforme, to give an ent-3β hydroxylation (60−65% for ent-atisenes and 80−85% for ent-beyerenes). Moreover, the double bond of the ent-beyerene skeleton was epoxidized by both fungi at lower yields (3−6%). Fusarium moniliforme produced a number of additional minor products by hydroxylation at other positions.

Several ent-manoyl oxides obtained from natural products through chemical and microbiological procedures were tested in vitro as inhibitors of the growth of the promastigote and amastigote forms of Leishmania donovani. Compounds 3, 6, 7, and 15 showed significant antileishmanial activity. (3S)-ent-3β-Acetoxy-12-oxo-8α,13-epoxylabda-9,14-diene (15), whose semisynthesis is described, totally inhibited the promastigote forms of L. donovani at a concentration of 100 mg/mL after 24 h of incubation. Functionalization of this series of compounds plays an important role in the antileishmanial activity observed.

From the aerial parts of Sideritis varoisubs. oriensisthe previously known 1 β-hydroxy-6β-acetoxyeudesm-4(15)-ene, 1β-hydroxy-6β-acetoxyeudesm-3-ene,1β-hydroxy-6β-acetoxyeudesm-4-ene, 1β,4β-dihydroxy-6β- acetoxyeudesmane and the new 1 β,4α-dihydroxy-6β-acetoxyeudesmane, as well as the ent-8α-hydroxylabda-13(16), 14-dienes 6-deoxyandalusoic acid, 6-deoxyandalusal, 6-deoxyandalusol, 18-deoxyandalusol, andalusol, the ent-13-epi- manoyl oxide varodiol and the ent-kaur- 15-ene sideridiol were isolated. The stereochemistry at C-4 of the isolated eudesmanes, which has been under discussion for other similar compounds, was elucidated by chemical and spectroscopic means.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Incubation of the manoyl oxide (Ia) or the normanoyl oxide (Ib) with Rhizopus nigricans cultures leads mainly to the products (II) resulting from hydroxylation at C‐20. Additionally, a variety of other hydroxylation and deacetylation products are isolated, among them (III) and (IV).

The biotransformation of ent‐3β‐hydroxy‐13‐epi‐manoyl oxide (ribenol) (II), related to forskolin (I), gives the monohydroxy‐ (IIIa) and dihydroxy‐ (IIIb) derivatives.

Microbial transformation of the title compound (I) yields the hydroxylated metabolites (II)‐(V).