Pharmacognosy I Lec #6 2 PDF

Secondary Metabolites Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  ‫املستقلبات الثانوية‬ ‫ الجزيئات العضوية التي ال تشارك في النمو والتطور الطبيعي للكائن الحي‬-...

Secondary Metabolites Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  ‫املستقلبات الثانوية‬ ‫ الجزيئات العضوية التي ال تشارك في النمو والتطور الطبيعي للكائن الحي‬- ‫ وغالبًا ما تلعب‬،‫ بل إلى إضعاف قدرة الكائن الحي على البقاء على قيد الحياة على املدى الطويل‬،‫ ال يؤدي غياب املستقلبات الثانوية إلى املوت الفوري‬-.‫مهما في دفاع النبات‬ً ‫دورا‬ ً ‫ يتم تصنيعها بواسطة النباتات والفطريات والبكتيريا والطحالب والحيوانات‬- ‫ مثل التربينات واملركبات الفينولية والقلويدات‬،‫ يتم تصنيف معظم املستقلبات الثانوية‬-.‫على أساس أصلها الحيوي‬.‫ حيث توجد معظم املستقلبات األولية في كل أنسجة‬،‫ تشترك غالبية النباتات في نفس املسارات الحيوية األساسية‬-.‫ أدى الحفاظ على هذا النواة األيضية إلى عدد محدود من األطر األيضية‬- Secondary Metabolites ‫ تولد‬،‫خصيصا‬ ً ‫ باإلضافة إلى بعض التغييرات الكيميائية بسبب اإلنزيمات املصممة‬،‫ مثل الجليكوزيالت واملثيلة واألسيلة والفسفرة‬،‫إن التعديالت املتكررة‬ ‫مجموعة متنوعة من التعديالت في‬ ‫الهياكل األساسية‬ - Organic molecules that are not involved in the normal growth and development of an organism - Absence of secondary metabolites does not result in immediate death, but rather in long-term impairment of the organism’s survivability, often playing an important role in plant defense. - Synthesized by plants, fungi, bacteria, algae, and animals - Most of secondary metabolites, such as terpenes, phenolic compounds and alkaloids are classified based on their biosynthetic origin. - The majority of plants share the same fundamental biosynthetic pathways, with most primary metabolites present in every tissue. - Te maintenance of this metabolic core has resulted in a limited number of metabolic frameworks. Frequent modifcations, such as glycosylation, methylation, acylation and phosphorylation, as well as a few chemical changes due to tailored enzymes, generate a variety of modifcations in basic structures Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  Secondary Metabolites - Secondary metabolites are frequently produced at highest levels during a transition from active growth to stationary phase to collectplants waituntil activegrowth - A simple classification of secondary metabolites includes tree main groups: terpenes (such as plant volatiles, cardiac glycosides, carotenoids and sterols), phenolics (such as phenolic acids, coumarins, lignans, stilbenes, flavonoids, tannins and lignin) and nitrogen containing compounds (such as alkaloids and glucosinolates) ‫غالبًا ما يتم إنتاج املستقلبات الثانوية بأعلى مستوياتها أثناء‬ ‫االنتقال من النمو النشط إلى مرحلة الثبات‬ ‫لجمع النباتات حتى النمو النشط‬ Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5 :‫ يتضمن التصنيف البسيط للمستقلبات الثانوية مجموعات رئيسية من األشجار‬- ،‫ والكاروتينات‬،‫ والجليكوسيدات القلبية‬،‫التربينات )مثل املواد املتطايرة النباتية‬ ،‫ والليجنني‬،‫ والكومارين‬،‫ والفينوالت )مثل األحماض الفينولية‬،(‫والستيروالت‬ ،‫والستيلبينات‬ ‫ والليجنني( واملركبات املحتوية على النيتروجني )مثل‬،‫ والعفص‬،‫والفالفونويدات‬ (‫القلويدات والجلوكوزينوالت‬  talked about these in thissemester The three main types of Secondary Metabolites. Source: Zhao, Yiu, et al. 2023 Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  have Physies stationary gate phase x Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  ‫تتكون الجليكوسيدات من جزأين مستقلني كيميائيًا ووظيفيًا؛‬.(‫جزء الجاليكون )الجينني( وجزء الجاليكون )السكاريد‬ ‫( بواسطة رابطة غليكوزيدية‬A) ‫( بجزء الجاليكون‬X) ‫ يرتبط جزء السكاريد‬- Glycosides ‫لـ‬ ‫ الرابطة الجليكوسيدية غير مستقرة في الغالب وعرضة للتحلل املائي )بواسطة األحماض‬-.(‫ بيتا جلوكوزيداز‬،‫ على سبيل املثال‬،‫املخففة أو اإلنزيمات‬ - Glycosides are comprised of two chemically and functionally independent parts; the aglycone (genin) and the glycone (saccharide) parts. 1 2 - the saccharide part (X) is linked to the aglycone (A) portion by a glycosidic bond is For - The glycosidic bond is mostly unstable and susceptible to hydrolysis (by t diluted acids or by enzymes, e.g., β-glucosidases). t aglycone by contains a hydroxyl group Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  ‫بنية وتصنيف الجليكوسيدات‬ ‫ أنواع‬4 ‫ )إذا كانت الرابطة الجليكوسيدية عن طريق األكسجني(؛ الشكل األكثر وفرة‬O-‫ جليكوسيدات‬- ‫في‬ ‫النباتات‬ ‫ )ارتباط عبر الكربون(؛ هذا النوع من االرتباط مقاوم للتحلل املائي‬C-‫ جليكوسيدات‬- (SH- ‫ )ارتباط عبر الكبريت؛ يجب أن يحتوي األجاليكون على مجموعة‬S-‫ جليكوسيدات‬- ‫موجودة في‬ Glycosides (‫الجلوكوسينوالت )ثيوجاليكوسيدات‬ mostabundant 4 (NH- ‫ )ارتباط عبر النيتروجني؛ يجب أن يحتوي األجاليكون على مجموعة‬N-‫ جليكوسيدات‬- ‫موجودة‬.‫في النيوكليوسيدات‬ Structure and Classification of Glycosides 4types - O-glycosides (if the glycosidic bond is via oxygen); the most abundant form in 1 plants 2 - C-glycosides (linkage via a carbon); this type of linkage is resistant to hydrolysis mare 3 - S-glycosides (linkage via a sulfur; aglycone must have —SH group) present in glucosinolates (thioglycosides) - N-glycosides (linkage via a nitrogen; aglycone must have —NH group) present 4 in nucleosides. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  Glycosides glycosides - The configuration of the anomeric carbon of the glycone can exist as α or β diastereoisomer with the β- forms being most common and active 1 2 - Extraction of glycosides from plant material (previously dried and properly stored to avoid decomposition of glycosides by plant enzymes) is usually performed with the use of polar solvents (water, hydro-alcoholic solutions, and alcohols). polarity sincewater their solubility - The overall effect of glycosides is dependent on their two components; the aglycone portion primarily influences the therapeutic direction, while the saccharide part (sugar chain/s) increases water solubility, pharmacokinetics, and pharmaco- dynamics properties. - Glycosides are also called “heterosides”. ‫يمكن أن يوجد تكوين الكربون األنوميري للغليكون على شكل متماكب فراغي ألفا أو بيتا مع كون‬ ‫أشكال بيتا هي األكثر شيو ًعا ونشاطًا‬ ‫ يتم عادةً استخراج الجليكوسيدات من املواد النباتية )املجففة مسب ًقا واملخزنة بشكل صحيح لتجنب‬- Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5 ‫تحلل الجليكوسيدات بواسطة إنزيمات النبات( باستخدام‬.(‫املذيبات القطبية )املاء واملحاليل الكحولية املائية والكحوليات‬ ‫قطبيتها منذ ذوبانها في املاء‬ ‫ يعتمد التأثير الكلي للجليكوسيدات على مكونيها؛ يؤثر جزء األجليكون بشكل أساسي على االتجاه‬- ‫سالسل السكر( من‬/‫ بينما يزيد جزء السكاريد )سلسلة‬،‫العالجي‬.‫ وخصائص الديناميكية الدوائية‬،‫ وحركية الدواء‬،‫ذوبانها في املاء‬  ‫سالسل السكاريد املرتبطة باأللجيكون واح ًدا‬/‫يمكن أن يكون عدد وحدات‬ ‫ والتي تُرى‬،(‫ أو ثالثة )ترايديسموسيد‬،(‫ أو اثنني )بيديسموسيد‬،(‫)مونوديسموسيد‬.‫عادةً في جليكوسيدات السابونني‬ ‫أو‬ ‫أيضا تصنيف الجليكوسيدات )بسبب طبيعة السكر املتصل( على أنها‬ ً ‫ يمكن‬- Glycosides ‫ وما إلى‬،‫ وروتينوسيدات‬،‫ وزيلوسيدات‬،‫ ورامنوسيدات‬،‫ وأبيوسيدات‬،‫غاالكتوزيدات‬.‫ذلك‬ ‫ أو وف ًقا ألنشطتها؛ تسمى هيتروسيدات فعالة للقلب‬- Nomenclature - The number of saccharide units/chains attached to the algycone can be one (monodesmoside), two (bidesmoside), or three (tridesmo- or In side), which are commonly seen in saponin glycosides. - Glycosides also may be classified (due to the nature of the attached sugar) as galactosides, apiosides, rhamnosides, xylosides, rutinosides, etc. - or according to their activities; called cardioactive heterosides us Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  means it'dbe in the exam if shehighlights something CARDIOTONIC HETEROSIDES fm - Cardioactive heterosides are present in many genera within the Apocynaceae and Asclepiadaceae families and are also found in select genera of the Tiliaceae, Plantaginaceae, Asparagaceae, Ranunculaceae, Leguminosae, and Moraceae families. - Typically, they occur in small quantities (less than 1%) throughout various parts of the plant. - At therapeutic doses, these compounds enhance the contractility of the heart muscle and help regulate heart rhythm disorders. - However, due to the narrow margin between therapeutic and toxic doses, careful dosing is essential to ensure safety and effectiveness. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC HETEROSIDES Structure and Components Glycone Part: The glycone portion of cardiac glycosides is responsible for the compound's solubility and stability. Common sugars include glucose, rhamnose, and digitoxose. Aglycone Part is the active part that determines the cardiotonic activity. It is steroidal in nature and consists of a steroid nucleus with a unique lactone ring, which is critical for its biological activity. - Types of Lactone Rings: If the lactone ring attached to the 17th carbon is 5-membered (butenolite), aglycone cardenolite (23 carbons); 6-membered (pentadienolite) is called bufadienolite (24-carbon). 6number 4number Activity: The activity of the compound is due to the lactone ring structure in the aglycone part, which is key for its biological effects. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC HETEROSIDES - Cardiotonic heterosides exert their effect primarily by inhibiting the Na⁺/K⁺-ATPase enzyme on the cardiac cell membrane. - In cardioactive heterosides, the pharmacological activity is primarily determined by the structure of the aglycone. For biological activity, the A/B and C/D ring junctions must adopt a cis configuration. - The cyclopentanoperhydrophenanthrene ring system in the aglycone may not always be fully saturated; if unsaturation is present, it typically occurs between carbons 4 and 5 or carbons 5 and 6. automatically Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC HETEROSIDES up - I For optimal activity, the A, B, C, and D rings must adopt a cis- cis configuration. In cases where they are arranged in a trans-cis configuration, as seen in uzarigenol (which exhibits antidiarrheal effects), the activity is significantly reduced. when it'stransconfiguration - Cardioactive heterosides contain two essential hydroxyl groups: a β-secondary alcohol at carbon 3 (C-3) and a β-tertiary alcohol at carbon 14 (C-14). The absence of the hydroxyl group at C-3 decreases activity but does not eliminate it entirely. The hydroxyl group at C-14 is also crucial and must be in the β-configuration. - For the compound to be active, the lactone ring attached to carbon 17 must be unsaturated and positioned in the β- orientation. - Additionally, unsaturation may sometimes occur between noquestion carbons 11 and 12 (Δ11,12) in the C ring. Fiactivity Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC HETEROSIDES Cardiotonic heterosides can contain either a single sugar unit (monosaccharide) or multiple sugar units, typically ranging from 2 to 4, forming an oligoglycoside structure. When these sugar units are present, they form a glycosidic chain attached to the hydroxyl group at the 3rd carbon of the aglycone. OH The most common sugars in these glycosidic chains include: -L-rhamnose (6-deoxy-L-mannose) -D-fucose (6-deoxy-D-galactose) -L-tevetose (6-deoxy-3-methyl-L-glucose) -D-digitalose (6-deoxy-3-methyl-D-galactose) -D-digitoxose (2,6-dideoxy-D-allose) -D-cymarose (2,6-dideoxy-3-methyl-D-allose) -L-oleandrose (2,6-dideoxy-3-methyl-L-mannose) -D-diginose (2,6-dideoxy-3-methyl-D-galactose) -D-glucose If glucose is present within the glycosidic chain, it is typically positioned at the terminal end of the chain. Additionally, one hydroxyl group on the sugar molecules may be acetylated, as in acetyl digitoxose. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC HETEROSIDES Increased Intracellular Sodium (Na⁺): When Na⁺ levels rise inside the cell, the activity of the Na⁺/Ca²⁺ exchanger is reduced. Increased Intracellular Calcium (Ca²⁺): This change leads to an accumulation of calcium ions inside the cell, which enhances the force of myocardial contraction, known as positive inotropy. Cardiotonic glycosides also have secondary effects such as reducing heart rate (negative chronotropy) and decreasing conduction velocity, which can be beneficial in treating certain arrhythmias. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC HETEROSIDES Congestive Heart Failure (CHF): Cardiotonic glycosides are used to increase cardiac output and reduce symptoms of CHF by enhancing myocardial contractility. Atrial Fibrillation and Flutter: Their ability to slow the heart rate and control atrial rhythm makes them useful in managing these arrhythmias. Inotropic Support in Severe Heart Failure: They are sometimes used for their positive inotropic effects in severe or acute heart failure cases. Narrow Therapeutic Index: Cardiac glycosides have a narrow safety margin, meaning therapeutic and toxic doses are close. Monitoring blood levels is essential. Signs of Toxicity: Symptoms include nausea, vomiting, visual disturbances (yellow-green halos), confusion, and potentially fatal arrhythmias. Management of Toxicity: Discontinuation of the drug, correction of electrolyte imbalances (particularly potassium), and in severe cases, administration of digoxin-specific antibody fragments (Digibind). Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC HETEROSIDES don'tusewhen Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5 beam  CARDIOTONIC GLYCOSIDES DROGS Plant name: Digitalis purpurea (red-flowered foxglove) Drog name: Digitalis folium Family: Plantaginaceae - Digitalis folium is derived from the leaves of Digitalis lanata (woolly foxglove) and Digitalis purpurea (red-flowered foxglove), both members of the Plantaginaceae family. - These plants are biennial or perennial, producing only basal rosette leaves during the first year. Medicinally, both the rosette leaves from the first year and the basal and stem leaves from the second year are utilized. - Once harvested, the leaves are quickly dried at an appropriate temperature to prevent hydrolysis of the heterosides. The dried product must be stored in a dry, light-free environment, with a moisture content not exceeding 5% to maintain stability. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Digitoxin, initially isolated in the 19th century, was later succeeded by digoxin due to its improved pharmacokinetic properties. from theirleaves The leaves of Digitalis purpurea contain 0.1–0.4% cardenolide-type heterosides. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Plant name: Digitalis lanata (woolly foxglove) Drog name: Digitalis lanatae folium Family: Plantaginaceae - The concentration of cardenolides in the leaves can exceed 1%. - The primary heterosides in the fresh plant are Lanatosides A, B, C, D, and E. These compounds are structurally similar to the primary heterosides found in Digitalis purpurea, with the exception that the digitoxose unit adjacent to glucose is acetylated at the 3rd position (forming acetyl digitoxose). - Lanatosides A, B, and E readily hydrolyze in an alkaline medium to yield purpureaglycosides A, B, and E (desacetyl-lanatosides A, B, and E). - Alkaline hydrolysis poses a risk of lactone ring opening. When hydrolyzed by α-glucosidase, these compounds yield secondary heterosides. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES - The most commonly used cardioactive heterosides in cardiotonic preparations include digitoxin (digitalin), digoxin, acetyldigoxin, and desacetyl-lanatoside C (deslanoside). - The plant material (referred to as “drog”) is currently utilized to extract digoxin and digitoxin. - Digoxin exerts its effects by increasing the contractile force of the myocardium (positive inotropic effect) and by slowing impulse conduction through the atrioventricular node (negative dromotropic effect). - Digoxin is indicated for the treatment of supraventricular tachycardia and heart failure. The typical daily dose of digoxin ranges from 62.5 to 250 micrograms. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Isaf Plant name: Strophanthus sp. Drog name: Strophanthi semen Family: Apocynaceae importanthere - The dried seeds of Strophanthus species (family Apocynaceae) are the source of these compounds. - The seeds of Strophanthus gratus contain 3–8% cardenolide-type heterosides. - Ouabain (also known as g-strophanthoside), with g-strophanthogenin as its aglycone and rhamnose as its sugar component, is highly polar. Due to its polarity, it is not absorbed orally and is therefore administered intravenously in emergency situations. Its effects are rapid in onset but short in duration. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Plant name: Strophanthus sp. Drog name: Strophanthi semen Family: Apocynaceae - The dried seeds of Strophanthus species (family Apocynaceae) are the source of these compounds. - The seeds of Strophanthus gratus contain 3–8% cardenolide-type heterosides. - Ouabain (also known as g-strophanthoside), with g-strophanthogenin as its aglycone and rhamnose as its sugar component, is highly polar. Due to its polarity, it is not absorbed orally and is therefore administered intravenously in emergency situations. Its effects are rapid in onset but short in duration. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Plant name: Drimia maritima Drog name: Bulbus Scillae Family: Asparagaceae - The drug Drimia maritima (synonym: Urginea maritima), from the Asparagaceae family, is dried either in sunlight or in an oven at 40–50°C. - It contains approximately 4% bufadienolides. The main active compound, scillaren A, undergoes enzymatic hydrolysis to yield prosillaridin A and one molecule of glucose. When one glucose molecule is attached to scillaren A, it forms the primary glycoside, glucoscillaren A. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Plant name: Drimia maritima Drog name: Bulbus Scillae Family: Asparagaceae - Prosillaridin is effective when administered orally, and its rapid elimination contributes to its safe use. - It exhibits positive inotropic effects, a mildly negative dromotropic effect, a negative chronotropic effect, and a diuretic effect. - Red sage contains a cardiotonic glycoside known as sylliroside, which is used as a rodenticide. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Plant name: Convallaria majalis (lilyflower) Drog name: Convallariae herba Family: Liliaceae - The drug consists of the flowering branch tips of Convallaria majalis (commonly known as lily of the valley) from the family Liliaceae. - When measured on a dry weight basis, it contains 0.1–0.5% cardenolide- type heterosides, primarily concentrated in the flowers and seeds. - The main heteroside, convallatoxin, is poorly absorbed from the intestines. Upon hydrolysis, convallatoxin yields convallatoxygenin and L- rhamnose. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Plant name: Nerium oleander Drog name: Nerii folium Family: Apocynaceae - Oleandrin: The primary glycoside with potent cardiotonic properties.Neriin and digitoxigenin derivatives: Other glycosides contributing to its effects. - Nerium oleander is highly toxic due to its cardiac glycosides. Ingesting any part of the plant, especially leaves or flowers, can lead to severe poisoning. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  CARDIOTONIC GLYCOSIDES DROGS Plant name: Helleborus niger Drog name: Rhizoma Hellebori nigri Family: Ranunculaceae The heteroside known as hellebroside, found in the rhizomes of the plant, contains hellebrigenin as its aglycone in a bufadienolide structure, with rhamnose and glucose as its sugar (ose) components. Plant name: Adonis vernalis Drog name: Adonidis herba Family: Ranunculaceae The aerial parts of the plant contain flavone heterosides as well as 0.2– 0.5% cardenolide-type heterosides. When the heteroside cymarin undergoes hydrolysis, it yields k-strophanthidin and cymarose. Additionally, adonitoxoside produces adonitoxygenin and rhamnose upon hydrolysis. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  SAPONOSIDES - The name “saponin” is derived from the Latin word “sapo,” (Eng. “soap”), reflecting their surfactant properties: ability to form stable soap-like foams in aqueous solutions. - The chemical structure of sapogenin defines the classification of saponins as steroidal or triterpenoid. - Steroidal saponins consist mainly of a C27 spirostane skeleton, generally comprising of a six-ring structure which occur as (25S)-spirostan derivatives (real saponins, neosaponins) or its (25R)-spirostan derivatives (isosaponins). In some cases the aglycone structure is referred to as a furostane skeleton, which is pentacyclic. - It is seen mainly as (25S)- or (25R)-furostan derivatives; in this case the C-26 OH group is engaged in a glycosidic linkage. - Triterpenoid saponins aglycone consist of a pentacyclic C30 skeleton - it is most commonly oleanane or ursane structures, or in a some cases a tetracyclic dammarane type structure as in ginsenosides (Ginseng saponosides) Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  SAPONOSIDES 5 ring Sring 4ring 27C 30C Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  SAPONOSIDES The majority of steroidal saponosides: - There may be a double bond between carbons C-5 and C-6. If this bond is reduced, the structure may have either a 5-α-hydrogen with rings A and B in the trans configuration (as in digitogenin) or a 5-β-hydrogen with rings A and B in the cis configuration (as in similagenin) - A hydroxyl group is always present at carbon 3 - Additional hydroxyl groups may be found at positions C-1, C-2, C-5, or C-6 (as in members of the Liliaceae family), at positions C-2 or C-15 (as in Scrophulariaceae), or at both C-2 and C-15 - A carbonyl group may also be present at C-12 in species of the Amaryllidaceae family. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  SAPONOSIDES The majority of Triterpenic saponosides : - These compounds are biogenetically derived from squalene through a series of ring-closure reactions. Initially, 4-ring dammarane structures are formed, and further ring closures lead to the formation of 5-ring sapogenins of the lupane, ursane, and oleanane types, which are commonly found in nature. - A double bond is typically present between carbons C-12 and C-13. - The methyl groups at positions C-23 and C-28 (and sometimes at C-30) may be oxidized to hydroxymethyl, aldehyde, or carboxyl groups. - Hydroxyl groups may be located at positions C-2, C-7, C-11, C-15, C-16, C-21, or C-22, with the hydroxyl at C-11 particularly prone to oxidation to a ketone. Due to the high number of functional groups in these molecules, additional rings may form via etherification and lactonization. - The aglycone portion can sometimes be partially esterified with low-molecular-weight aliphatic acids. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  SAPONOSIDES Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5  SAPONOSIDES - In steroidal and triterpenoid saponosides, the sugar (ose) units are attached to the secondary hydroxyl group, typically at the 3rd position, via an ether (glycosidic) bond, forming monodesmosidic heterosides. - Sometimes, an additional sugar molecule is attached by ester linkage at the 28th position in triterpenoid saponosides or to the hydroxyl at the 26th position in steroidal saponosides (furostanol type), resulting in bisdesmosidic heterosides. - Saponosides are generally soluble in water and water-alcohol mixtures and show variable solubility in pure alcohol or methanol depending on their polarity. They are insoluble in lipophilic solvents like petroleum ether, ether, and chloroform. - While saponosides can be extracted with water at boiling, extraction with alcohol or water-alcohol mixtures is preferable, as boiling water may cause hydrolysis of bisdesmosidic saponins. - Due to the extraction of many compounds by polar solvents, liquid-liquid extraction is often performed with n- butanol. Saponins dissolved in n-butanol can then be precipitated with ether. - Sapogenins are soluble in lipophilic solvents, pure alcohol, and methanol. They are insoluble in water and may be slightly soluble or insoluble in aqueous alcohol, depending on their polarity. Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5 Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5 Pharmacognosy I Instructor: Sule Nur KARAVUS Fall 2024-Lecture #5