SHIKIMATE PATHWAY NAT PROD

Natural Products from Shikimate Pathway (Phenolics) AP DR. KHAIRANA HUSAIN NFNF1813  INTRODUCTION Form a large group of substances At least 1 aromatic ring substituted by at least 1 –OH group (free or as in ester, ether or glycosides) Depends on biogenesis...

Natural Products from Shikimate Pathway (Phenolics) AP DR. KHAIRANA HUSAIN NFNF1813  INTRODUCTION Form a large group of substances At least 1 aromatic ring substituted by at least 1 –OH group (free or as in ester, ether or glycosides) Depends on biogenesis The shikimate pathway → benzoic acids, cinnamic acid derivatives, lignans, lignins, phenylpropenes, coumarins, flavonoids & quinones The acetate pathway → aromatic polyketides (e.g. simple phenols, anthraquinones, etc)  Functions of Phenolics Defence mechanism Waste products Most have medicinal properties Starting materials for drug synthesis  Caffeic Acid Derivatives Java Tea (Misai Kucing) Caffeic esters Traditionally used as diuretic, for kidney & bladder disorders, & as adjunct in weight loss preparation  HO O HO COOH HO O COOH HO O COOH O HO O COOH HO O HO Monocaffeoyltartaric acid Dicaffeoyltartaric acid HO O OH OH O HO HO O OH CO2H OH O CO2H HO O O OH HO Rosmarinic acid Lithospermic acid  Caffeic Acid Derivatives As Inhibitors of HIV-1 Integrase 3,5-Dicaffeoylquinic acid (Baccharis genistelloides ) OH OH HO COOH HO OH O O O OH O Chicoric acid (Echinacea angustifolia, E. pallida, E. purpurea) OH OH HO H H OH HOOC COOH O O O O  Simple Coumarins Coumarin & dicoumarol Anticoagulant  Furocoumarins Bergamot oil Citrus aurantium ssp. bergamia To promote skin pigmentation, sun-tanning & treat psoriasis; (aromatherapy) depression Cause photosensitization towards UV light in human (e.g. sunburn & blistering) R R R’ 5 H H : Psoralen 8 OCH3 H : Bergapten O O O H OCH : Xanthotoxin R'  LIGNIN & LIGNANS ❑ Uses –(Traditionally) purgative, anthelmintic, O R emetic & to treat wart O O –(podophyllotoxin) venereal warts & HO O OH precursor for synthesis of etoposide & (R) O tenoposide O O OH OH R = CH : Etoposide O O O R = Thienyl : Tenoposide O O H3CO OCH3 O O OH O O H3CO OCH3 H3CO OCH3 OH OR Podophyllotoxin R = H : -Peltatin R = CH : -Peltatin Biosynthesis of Various Flavonoids OH O O CAoS OH O OH 3 HO R O R CAoS O R = H : coumaroyl CoA O O malonyl CoA R = OH : caffeoyl CoA OH OH HO O HO OH de R R on hy r ati dr og ig en ylm OH O ati OH O a r on FLAVANONES CHALCONES ISOFLAVONES FLAVONES OH OH HO O HO O R R OH dehydrogenation OH OH O OH O FLAVANONOLS FLAVONOLS OH OH HO O HO O R R OH OH OH OH OH FLAVAN-3,4-DIOLS FLAVAN-3-OLS HO R OH OH OHHO HO OH OH OH O O HO O OH OH HO OH R OH O OH OHHO OH OH O O HO R OH O OH HO R OH HO HO R OH R HO ANTHOCYANIDINS PROANTHOCYANIDINS  Biological Properties for Flavonoids Plant pigments Calchones & flavonols – yellow Anthocyanidins – red, blue & violet Antioxidant & free radical scavengers Protection against CV disease & certain cancers Age-related cell degeneration Oxygenase inhibitor : anti-inflammatory & anti-allergic properties Vitamin P Dietary supplement (rutin & hesperidin) Believed to treat capillary bleeding  Medicinally Valuable Flavonoids Quercetin Almost always present in plant tissues Powerful antioxidant, chelating metals, scavenging free radicals & prevent oxidation of low density lipoprotein  Rutin (= rutoside) Its derivatives are also used for venous insufficiency, varicoses & haemorrhoids Fagopyrum esculentum Rutin, from Eucalyptus macroryncha in MeOH (30x) Polarized Light  Citroflavonoids Fruits & peels of Citrus spp. Main phytochemicals – Flavonone glycosides (e.g. hesperidin, neohesperidin, naringin) – Flavone glycosides (e.g. diosmetin & rutin) Used for venous insufficiency & haemorrhoids Naringin Hesperidin  ANTHOCYANINS R1 OH Fruit of blueberry (Vaccinium myrtillus) HO O R2 Fruit of blackcurrant (Ribes nigrum) OH Leaves of grapevine OH (Vitis vinifera var. tinctoria) Leaves of hibiscus R1 = R2 = H : pelargonidin (Hibiscus rosa-sinensis) R1 = OH ; R2 = H : cyanidin Uses : vitamin P & non- R1 = OCH3 ; R2 = H : peonidin toxic colouring agents R1 = R2 = OH : delphinidin R1 = OCH3 ; R2 = OH : petunidin R1 = R2 = OCH3 : malvidin  TANNINS Common sources Witch hazel (Hamamelis virginiana) bark & leaves treat venous insufficiency & haemorrhoids Pale catechu (Uncaria gambir) leaves astringent & antidiarrheal Witch Hazel Hawthorn (Crataegus spp.) berries cardiac, diuretic, astringent, tonic Green tea (Camelia sinensis) leaves (epigallocatechine gallate) anticancer Hawthorn  OH HO O OH OH 4 OH OH OH HO HO O HO O 8 OH OH 4 OH OH OH OH OH HO HO O HO O 8 OH OH 4 O OH OH OH OH OH HO OH HO OH 6 8 O OH OH O 4 O HO O HO OH HO HO OH OH HO HO HO OH Example of procyanidin made of Example of procyanidin with an six flavan-3-ols units linked additional interflavanic ether linkage 4→8 or 4→6  Hydrolysable tannins HO OH OH Esters of glucose & phenolic acid HO molecules OH O O O O HO O OH Pentagalloylglucose – Gallic acid → gallotannins (e.g. O O O O HO O O OH pentagalloylglucose) – Hexahydroxydiphenic acid → HO OH HO OH OH ellagitannins OH HO Complex tannins OH HO HO Ellagitannins + a flavonoid (e.g. O HO O flavonol, proanthocyanidin, HO O O O O O OR Ellagitannins flavone) HO O O HO OH OH HO OH  STILBENES Resveratrol Source : grapes, red wine & other food products Antioxidant, anti-inflammatory, anti-platelet & cancer preventative properties OH HO OH QUINONES Henna Lawsone Uses Colouring & cosmetic Fungicide (Traditionally) treat superficial wound (Root decoction) abortifacient  ANTHRAQUINONES Senna Local senna – Gelenggang kecil (C. obtusifolia) – Gelenggang besar (C. alata) – Kacang kota/ketepeng hutan (C. occidentalis) Leaves -D-Glc-O Sennidins A, B, C & D O OH Laxative 10 R H H COOH 10' R = COOH ; 10-R, 10’-R : sennidin A R = COOH ; 10-R, 10’-S : sennidin B -D-Glc-O O OH R = CH2OH ; 10-R, 10’-R : sennidin C R = CH2OH ; 10-R, 10’-S : sennidin D DIARYLHEPTANOIDS Tumeric Curcuma longa ( C. domestica) Curcumin Uses – (Curcumin) anti-inflammatory – (Extract) hepatoprotective – (Traditional) Choleretic & cholagogue – (Food) spice & non-toxic colouring agent ARYLALKANONES Ginger Zingiber offficinale Gingerols & gingerones Uses (Gingerols) cholagogue & hepatoprotective (Extract) antiulcer & purgative (Powder) antinausea Gingerone (Traditional) stomachic & postpartum treatment