Diterpenes

 C 20 compounds  GGPP(head to tail of IPP + FPP) Many important diterpenes in nature:  In plants e.g. phytol (part of chlorophyll)  Vitamin E & K  Vitamin A is C20 (diff. biosynthesis & cleavage of tetraterpenes)  Gibberellins (plant growth hormones)  Taxol (anticancer), Stevioside (non-calorie sweetening agent, ginkgolides,…  Toxic diterpenes (tumor promoters)  Some alkaloids have a diterpene moiety in their structures

Important Diterpene Phytol Simplest and most important is Phytol From GGP, Lipophilic side- chain of chlorophylls Haem molecules, porphyrin component of haemoglobin Phytylo substituent in vit K 1 (Phylloquinone) Phytyl diphosphate gp in vit E gp (tocopherols)

Phytol Simplest & most important diterpene Reduced form of geranylgeraniol Lipophilic side-chain of chlorphylls Phytol is the side chain component of chlorophyll

Gibberellins Acids First isolated from fungus Gibberella fujikuroi (Wollenweber found to stimulate growth in seedlings) Higher plant, rich source Auxins & gibberellins regulate plant growth 2 groups: C20 (gibberellin A 13 ) & C 19 (gibberellic acid)

Taxus baccata أو شجر الطقسوس زرنب English yew (one of oldest tree in the world) Taxus brevifolia رجل الجراد Pacific Yew

Taxus brevifolia (Taxaceae) Bark of pacific yew tree provided 1971 diterpene ester Paclitaxel (Taxol ® ) USA & NW Canada 100 yrs old tree x3 provides 1g taxol (Rx course 2g/pt) All parts rich in diterpene derivatives of taxane (taxadiene) nucleus high yield Least amount Paclitaxel in bark Cytotoxic (anti-tumour) Low H 2 O solubility

T. baccata leaves T. baccata (English yew) source of starting material for semi- synthesis of taxol 8-10yrs old Taxol R of ovarian & breast cancer, lung cancer, head and neck cancer Very low water sol. 10-deacetylbaccatin III > active than taxol & > water sol. Microtubule binding preventing tubulin formation & depolymerization (mitotic spindle poison)

Stevioside Leaves of the plant Stevia rebaudiana (Asteraceae) Intensely sweet X > sweet than sucrose Commercial non-calorific sweetening agent

Forskolin (Colforsin) Roots of Coleus forskohlii (Lamiaceae) Ayurvedic medicine Hypotensive + inotropic action on cardiac muscle Potent stimulator of adenylate cyclase activity Rx glaucoma, CHF, Hypertension, bronchial asthma

Ginkgo biloba leaves (Ginkgoaceae) The only survivor of this family native to China. جنكو، شجرة المعبد، معبلة Mixture of flavonoids and terpenes

Ginkgo Terpenes Diterpenes lactones (Ginkgolides A,B, C, J,M) Ginkgolide A 30% Bilobalide C15 terpene (degradation product of ginkgolides???)

Chemical composition of G. biloba Standardized extracts: 1.(24% flavonoids: 6 % terpenes) 2.< 5ppm alkyl phenols (mutagenic & dermatitis) Alkyl phenols derivatives of ginkgolic acid Flavonoids inc. biflavonoids (antioxidant) Gingkolides (most pharmac- ological activity)

Medical Value of Ginkgo Marketed against cerebral vascular disease and senile dementia Biologically active as the whole extract not isolated comp Improves peripheral and cerbrovascular circulation (improving brain blood circulation) Enhances cognitive function and delays Alzheimer's symptoms Assist with symptoms of vertigo, tinnitus & hearing loss Potent & selective antagonist of PAF (Ginkgolides) Antagonistic effect on glycine receptors & GABA receptors Bilobalide lacks PAF effects, shows neruprotective effect Gingolides and ginkgo extract possess anti-inflammatory effect Gingolic acids & its alkyl derivatives ?? allergic dermatitis, GI irritation upon contact with or ingestion of fruits & leaves

12 symptoms of the elderly (result of impaired cerebral circulation) Difficulties in concentration Difficulties in short term memory Absent mindedness Confusion Lack of energy, apathy Tiredness Decreased physical performance Depressive mood Anxiety Dizziness Tinnitus Frequent headache

Medical Value of Ginkgo biloba cont CI:  Anticoagulant Rx  Hypo and hypertensive drugs  Epileptic pts  Asthmatic pts Seasonal variation of the active compounds occurs with the highest concentrations occurring in Autumn when the leaves begin to change colour. Regardless of the time of year, the concentration of the active compounds in the leaves is very low, which is the reason for the extraction process. The use of crude leaf powder or tea from the leaves is probably ineffective.

Toxic Diterpenes Members of the family Euphorbiaceae (Euphorbia spp. sap) & Thymelaeaceae (ornamental plants) Tumor promoters, severe skin dermatitis, induces cell proliferation and platelets aggregation, irritant to the GI & eye; Leaches into soil (careful edible plants cultivation) Ericaceae: Andromedotoxins, irritation to mucous membranes, GI, vomiting, diarrhea, dizziness, headache, (honey!)