Paul M. Dewick

Medicinal natural products

Medicinal natural products , Medicinal natural products , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی

The biosynthesis of C5–C25 terpenoid compounds

Covering: 1998–2000. Previous review: Nat. Prod. Rep., 1999, 16, 97This review covers recently-published experimental information on the biosynthesis of terpenoids in the range C5–C25. In addition to sections on the mevalonate and mevalonate-independent (deoxyxylulose phosphate) pathways, the review considers in turn hemiterpenoids, polyprenyl diphosphate synthases, monoterpenoids, sesquiterpenoids, diterpenoids, and sesterterpenoids. The literature from January 1998 to December 2000 is reviewed, with 248 references cited.

LIGNANS OF FORSYTHIA INTERMEDIA

Abstract Leaf and stem material of Forsythia intermedia contains four main lignans and their O -glucosides. These were identified as the dibenzylbutyrolactone derivatives (−)-arctigenin, arctiin [(−)-arctigenin 4′- O -glucoside], matairesinol and (−)-matairesinol 4′- O -glucoside, together with the furofuran lignans (+)-phillygenin, phillyrin [(+)-phillygenin 4- O -glucoside], (+)-epipinoresinol and (+)-epipinoresinol 4′- O -glucoside. The lignan contents varied according to tissue type and season. Full spectral data for the lignans are presented. The 1 H NOE difference spectra recorded for phillygenin and epipinoresinol necessitate the reversal of earlier chemical shift assignments for axial and equatorial protons on C-9 of furofuran lignans having one axial and one equatorial aryl group (the epi series).

Aryltetralin lignans from Podophyllum hexandrum and Podophyllum peltatum

Abstract Roots of Podophyllum hexandrum and P. peltatum contain the same range of ten aryltetralin lignans: podophyllotoxin, 4′-demethylpodophyllotoxin, α-peltatin, β-peltatin, desoxypodophyllotoxin, podophyllotoxone, isopicropodophyllone, 4′-demethyldesoxypodophyllotoxin, 4′-demethylpodophyllotoxone and 4′-demethylisopicropodophyllone, although the relative proportions are markedly different. The latter two compounds are previously unreported natural products, but 4′-demethylisopicropodophyllone may well be an artefact resulting from epimerization of 4′-demethylpodophyllotoxone. The peltatins have not previously been isolated from P. hexandrum .

Biosynthesis of pterocarpan phytoalexins in Trifolium pratense

Abstract Feeding experiments have demonstrated that 7,2′-dihydroxy-4′-methoxy-isoflavone-[ 14 C-Me] and -isoflavanone-[ 14 C-Me] are extremely efficient precursors of the phytoalexin demethylhomopterocarpin in Cu 2+ -treated red clover seedlings. Neither of these compounds, nor demethylhomopterocarpin-[ 14 C-Me], was incorporated into a second pterocarpan phytoalexin, maackiain. 3-Hydroxy-9-methoxypterocarp-6a-ene-[ 14 C-Me] was a poor precursor of both pterocarpans. A biosynthetic pathway to demethylhomopterocarpin via 2′-hydroxylation of formononetin (7-hydroxy-4′-methoxyisoflavone) and subsequent reduction to the isoflavanone is proposed. The conversion of this isoflavanone into the pterocarpan may involve the corresponding isoflavanol and a carbonium ion intermediate. The branch-point to maackiain is probably at the formononetin stage. The presence of two coumestans, 9- O -methylcoumestrol and medicagol, previously unreported in red clover, is demonstrated. Biosynthetic implications are discussed.

The biosynthesis of C 5 –C 25 terpenoid compounds

This review covers recently-published experimental information on the biosynthesis of terpenoids in the range C5–C25. In addition to sections on the mevalonate and mevalonate-independent (deoxyxylulose phosphate) pathways, the review considers in turn hemiterpenoids, polyprenyl diphosphate synthases, monoterpenoids, sesquiterpenoids, diterpenoids, and sesterterpenoids. The literature from January 1998 to December 2000 is reviewed, with 248 references cited.

Aryltetralin lignans from Linum flavum and Linum capitatum.

Abstract Phytochemical analysis of ethanol extracts from Linum flavum, L. flavum compactum and L. capitatum has demonstrated their capability of producing and storing relatively large amounts of cytotoxic aryltetralin lignans structurally related to podophyllotoxin. 5-Methoxypodophyllotoxin, its glucoside and acetate are the main constituents of both roots and stem/leaves of L. flavum and L. flavum compactum, the roots containing up to 3.5% dry weight of these compounds. Althogh 5-methoxypodophyllotoxin and its glucoside were also found in L. capitatum roots, stem/leaves were shown to produce α- and β-peltatins and their 5-O-glucosides. Coniferyl alcohol and coniferin were present in all three plants.

Matairesinol as precursor of Podophyllum lignans

Abstract The dibenzylbutyrolactone lignan (−)-[14C]matairesinol was efficiently incorporated into the aryltetralin lactone lignans podophyllotoxin, 4′-demethylpodophyllotoxin, β-peltatin, α-peltatin and 4′-demethyldesoxypodophyllotoxin in one or more of the plant systems Podophyllum hexandrum root, P. peltatum leaf or Diphylleia cymosa leaf. This demonstrates matairesinol to be a common precursor of the 3′,4′,5′-trimethoxy and 4′-hydroxy-3′,5′-dimethoxy groups of Podophyllum lignans, and it may represent the branch-point compound to the two series of compounds. No incorporation of matairesinol into the arylnaphthalene lactone lignan diphyllin in D. cymosa was detected.

Tumour-inhibitory aryltetralin lignans in Podophyllum versipelle, Diphylleia cymosa and Diphylleia grayi

Abstract Roots/rhizome of Podophyllum versipelle contain eight aryltetralin lignans: podophyllotoxin, desoxypodophyllotoxin, β-peltatin, podophyllotoxone, and the four corresponding 4′-demethyl derivatives, together with O-glucosides of podophyllotoxin, 4′-demethylpodophyllotoxin, β-peltatin and α-peltatin. β-Peltatin is the major constituent (1.4%), and while the podophyllotoxin content (0.32%) is higher than that of P. peltatum (0.25%), it is considerably inferior to that of P. hexandrum (4.3%). Roots and leaves of Diphylleia cymosa and D. grayi also contain Podophyllum lignans and their O-glucosides, together with the arylnaphthalene lignan diphyllin. Lignan patterns in Diphylleia roots are markedly different from those in the leaves. The podophyllotoxin content of D. grayi root is high (1.3%), whilst only small amounts are found in D. cymosa roots which accumulate β-peltatin instead. The leaves of D. cymosa contain relatively high levels of podophyllotoxin (0.54%), 4′-demethylpodophyllotoxin (0.10%), 4′-demethyldesoxypodophyllotoxin (0.11%) and diphyllin (0.13%), and are potentially a good alternative source of lignans for drug use.

Biosynthetic relationship of aryltetralin lactone lignans to dibenzylbutyrolactone lignans

Abstract Feeding experiments in Podophyllum hexandrum plants have shown that the dibenzylbutyrolactone lignan yatein is a satisfactory precursor of the aryltetralin lignan podophyllotoxin. The corresponding cis isomer of yatein was also incorporated, but to a lesser extent, and probably via yatein. Podorhizol, epipodorhizol and anhydropodorhizol were not incorporated into podophyllotoxin, despite the demonstrated presence of both podorhizol and anhydropodorhizol in P. hexandrum plants. A biosynthetic sequence from yatein to podophyllotoxin via a key quinonemethide intermediate is proposed. This intermediate is probably also the precursor of both podorhizol and anhydropodorhizol. Matairesinol is proposed as the branchpoint compound to the trimethoxy and hydroxydimethoxy series of aryltetralin lignans in Podophyllum . Labelling patterns in podophyllotoxin and 4′-demethylpodophyllotoxin derived from [ S -methyl- 14 C]methionine support this suggestion.