📝 Acetate - Mevalonate Pathway (Short Notes)

🔷 SLIDE 19 — Overview (पहले ये याद करो)

Mevalonate Pathway
= Isoprenoid Pathway = HMG-CoA Reductase Pathway

📍 कहाँ होता है?
   → Eukaryotes + Archaea + Some Bacteria

🧱 क्या बनाता है?
   → 2 five-carbon units:
      ├── IPP (Isopentenyl Pyrophosphate)
      └── DMAPP (Dimethylallyl Pyrophosphate)

🎯 इनसे क्या बनता है?
   → Isoprenoids (30,000+ biomolecules)
      ├── Cholesterol
      ├── Vitamin K
      ├── Coenzyme Q10
      └── Steroidal Hormones

▶ Start: Acetyl CoA (active acetate)
▶ End: IPP + DMAPP

🔀 IPP + DMAPP → via Squalene →
      ├── Steroids
      └── Triterpenoids

➕ Also produces:
   Monoterpenoids, Sesquiterpenoids, Diterpenoids,
   Carotenoids, Polyphenols, Glycosides, Alkaloids
   (with other pathways)

🔷 SLIDE 20 — Step-by-Step Pathway (Flowchart)

Pyruvic Acid (Glycolysis का end product)
        ↓
   Acetyl CoA (C2)
        ↓ [Claisen condensation — 2 molecules]
   Acetoacetyl CoA (C4)
        ↓ [+ 3rd Acetyl CoA → Aldol addition]
   β-Hydroxy β-Methylglutaryl CoA (HMG-CoA)
        ↓ [Reduction]
   Mevalonic Acid ⭐ (Main precursor for Terpenoids)
        ↓ [ATP mediated phosphorylation]
   Mevalonic Acid Diphosphate
        ↓ [Decarboxylation]
   IPP — Isopentenyl Pyrophosphate (C5) — Unit 1
        ↓ [Isomerase enzyme]
   DMAPP — Dimethylallyl Pyrophosphate (C5) — Unit 2
        ↓ [IPP + DMAPP → Prenyl Transferase (Electrophilic addition)]
   GPP — Geranyl Pyrophosphate (C10)
   → Precursor of MONOTERPENES
        ↓ [+ 1 IPP]
   FPP — Farnesyl Pyrophosphate (C15)
   → Precursor of SESQUITERPENES
        ↓ [+ 1 IPP]
   GGPP — Geranyl Geranyl Pyrophosphate (C20)
   → Produces DITERPENES
        ↓ [+ 1 IPP]
   Geranyl Farnesyl PP (C25)
   → SESTERTERPENES
        ↓
   ┌─────────────────────────────┐
   │ 2 FPP (tail-to-tail)        │
   │ → C30 = TRITERPENE          │
   │ 2 GGPP (tail-to-tail)       │
   │ → C40 = TETRATERPENE        │
   └─────────────────────────────┘

⚡ Quick Trick — Carbon count याद रखो

🧠 Exam ke liye 3 lines recap:

Acetyl CoA → HMG-CoA → Mevalonic Acid → IPP/DMAPP → GPP(C10) → FPP(C15) → GGPP(C20) → Triterpenes/Tetraterpenes

Key enzyme = HMG-CoA Reductase (rate-limiting step)

IPP = active isoprene unit (building block of all terpenoids)

📝 Acetate - Mevalonate Pathway (Short Notes)

🔷 SLIDE 19 — Overview (Start here)

Mevalonate Pathway
= Isoprenoid Pathway = HMG-CoA Reductase Pathway

📍 WHERE does it occur?
   → Eukaryotes + Archaea + Some Bacteria

🧱 WHAT does it produce?
   → 2 five-carbon (C5) units:
      ├── IPP (Isopentenyl Pyrophosphate)
      └── DMAPP (Dimethylallyl Pyrophosphate)

🎯 WHAT is made from these?
   → Isoprenoids (30,000+ biomolecules)
      ├── Cholesterol
      ├── Vitamin K
      ├── Coenzyme Q10
      └── Steroidal Hormones

▶ START: Acetyl CoA (active acetate)
▶ END:   IPP + DMAPP

🔀 IPP + DMAPP → via Squalene →
      ├── Steroids
      └── Triterpenoids

➕ Also produces (with other pathways):
   Monoterpenoids, Sesquiterpenoids, Diterpenoids,
   Carotenoids, Polyphenols, Glycosides, Alkaloids

🔷 SLIDE 20 — Step-by-Step Flowchart

Pyruvic Acid  ← (end product of Glycolysis)
        ↓
   Acetyl CoA  (C2)
        ↓  [Claisen Condensation — 2 molecules combine]
   Acetoacetyl CoA  (C4)
        ↓  [+ 3rd Acetyl CoA → Aldol Addition]
   HMG-CoA  (β-Hydroxy β-Methylglutaryl CoA)
        ↓  [Reduction]
   Mevalonic Acid ⭐  ← MAIN PRECURSOR for Terpenoids
        ↓  [ATP-mediated Phosphorylation]
   Mevalonic Acid Diphosphate
        ↓  [Decarboxylation]
   IPP — Isopentenyl Pyrophosphate  (C5)  [Unit 1]
        ↓  [Isomerase enzyme]
   DMAPP — Dimethylallyl Pyrophosphate  (C5)  [Unit 2]
        ↓
   [IPP + DMAPP → Prenyl Transferase — Electrophilic Addition]
        ↓
   GPP — Geranyl Pyrophosphate  (C10)
        → Precursor of MONOTERPENES
        ↓  [+ 1 IPP]
   FPP — Farnesyl Pyrophosphate  (C15)
        → Precursor of SESQUITERPENES
        ↓  [+ 1 IPP]
   GGPP — Geranyl Geranyl Pyrophosphate  (C20)
        → Produces DITERPENES
        ↓  [+ 1 IPP]
   Geranyl Farnesyl PP  (C25)
        → SESTERTERPENES

   ┌──────────────────────────────────┐
   │  2 × FPP  (tail-to-tail fusion)  │
   │  → C30 unit = TRITERPENE         │
   │                                  │
   │  2 × GGPP (tail-to-tail fusion)  │
   │  → C40 unit = TETRATERPENE       │
   └──────────────────────────────────┘

⚡ Carbon Count Table — Must Remember

🧠 3-Line Exam Recap

Acetyl CoA → HMG-CoA → Mevalonic Acid → IPP/DMAPP → GPP(C10) → FPP(C15) → GGPP(C20) → C25 → Triterpene/Tetraterpene

Key enzyme = HMG-CoA Reductase (rate-limiting step of the pathway)

IPP = active isoprene unit = basic building block of ALL terpenoids

📝 Acetate-Malonate Pathway (Short Notes)

🔷 SLIDE 27 — Overview

ACETATE-MALONATE PATHWAY
        |
        ▼
Works with → ACP (Acyl Carrier Protein)
        |
        ▼
Produces → Fatty Acyl Thioesters of ACP
        |
        ▼
These are important intermediates in Fatty Acid Synthesis
        |
        ▼
C2 Acetyl CoA units added at later stage
        |
        ▼
Produces EVEN number of Fatty Acids:
   ├── Smallest → n-Tetranoic acid (Butyric acid) C4
   └── Largest  → n-Ecosanoic acid (Arachidic acid) C20

        |
        ▼
Unsaturated Fatty Acids
→ made by direct DEHYDROGENATION of Saturated FA

        |
        ▼
ENZYMES control position of double bonds in fatty acids

🔷 SLIDE 28 — Key Enzyme & Steps

COMMITMENT STEP ⭐
        |
        ▼
Formation of MALONYL-CoA
(No other metabolic role — only precursor to fatty acids)
        |
        ▼
FATTY ACID SYNTHASE (FAS)
→ carries out CHAIN ELONGATION steps

        |
    ┌───┴────────────────────────┐
    ▼                            ▼
IN MAMMALS                  IN BACTERIA & PLANTS
FAS = Large                 Individual proteins
Multienzyme Complex         associate into large complex
2 subunits                  Each protein catalyzes
Each subunit has            one individual step
multiple enzyme activities

⚡ Key Points Box (write these in notes)

🧠 3-Line Exam Recap

Acetate + ACP → Fatty Acyl Thioesters → Even-chain Fatty Acids (C4 to C20)

Malonyl-CoA formation = Commitment step (only job = fatty acid precursor)

FAS = Chain elongation enzyme - multienzyme complex in mammals, individual proteins in bacteria/plants

📝 Amino Acid Pathway (Short Notes)

🔷 WHAT IS AN AMINO ACID?

AMINO ACID
     |
     ├── Amine group    → -NH2
     ├── Carboxyl group → -COOH
     └── Side chain     → R group (unique to each AA)

🔷 CLASSIFICATION OF AMINO ACIDS

20 Protein Amino Acids
         |
    ┌────┴──────────────────┐
    ▼                        ▼
NONPOLAR / HYDROPHOBIC    POLAR / HYDROPHILIC
(9 AAs)                   (9 AAs)
Glycine                   Serine
Alanine                   Cysteine
Valine                    Tyrosine
Leucine                   Glutamic acid
Methionine                Aspartic acid
Phenylalanine             Lysine
Proline                   Arginine
Isoleucine                Threonine
Tryptophan                Histidine

         |
         ▼
    SULPHUR-CONTAINING (special group)
         ├── Cystine
         └── Methionine

🔷 WHERE DO AMINO ACIDS COME FROM?

All 20 Protein AAs are derived from intermediates of:

   ┌─────────────────────────────────┐
   │  Glycolysis                     │
   │       OR                        │
   │  Citric Acid Cycle (Krebs)      │
   │       OR                        │
   │  Pentose Phosphate Pathway      │
   └─────────────────────────────────┘
              |
              ▼
   Nitrogen enters via:
   → Glutamate  +  Glutamine

🔷 WHO CAN SYNTHESIZE AMINO ACIDS?

Bacteria & Plants → Can synthesize ALL 20 AAs ✅

Mammals → Can synthesize only ~10 AAs
          (those with SIMPLE pathways) ⚠️

Remaining ~10 = ESSENTIAL AAs
               (must be taken from diet)

⚡ Quick Summary Table

🧠 3-Line Exam Recap

AA = -NH2 + -COOH + R group. Total 20 protein AAs.

All 20 AAs derived from Glycolysis / Citric Acid Cycle / Pentose Phosphate Pathway. Nitrogen enters via Glutamate & Glutamine.

Bacteria & Plants = synthesize all 20. Mammals = only ~10 (simple pathway ones).

📝 TRACER TECHNIQUE — 5 Mark Notes

🔷 INTRODUCTION (Slide 34)

5 Techniques to investigate biosynthetic pathways:
1. Tracer Technique      ⭐ (uses radioactive isotopes)
2. Isolated organ/tissue
3. Grafting method
4. Mutant strains
5. Enzymatic studies

🔷 WHAT IS TRACER TECHNIQUE? (Slide 35)

Radioactive isotope-labelled compound
        ↓
Given to plant → enters Metabolic Pool
        ↓
Traces different intermediates & steps
in biosynthetic pathway at given rate & time

ISOTOPES:
├── Stable isotopes → don't emit radiation
│   e.g. 2H, 13C, 15N, 18O
└── Radioactive isotopes → unstable, emit radiation ⚡
    e.g. 14C, 3H, 32P, 131I
    → Radioactivity = phenomenon of emitting radiation

🔷 SIGNIFICANCE (Slide 36)

✅ Works in living systems
✅ Wide range of isotopes available
✅ High sensitivity
✅ More effective
✅ Simple administration & isolation
✅ Accurate results (with enough metabolic time)

🔷 TRACER ELEMENTS USED (Slides 37 & 38)

Study               → Tracer used
─────────────────────────────────
Protein/Alkaloid/AA → N atom (more specific than C)
Glycosidic linkage  → O, N, S, C atom
Terpenoids          → O atom
Glucose             → 14C marked glucose

🔷 STEPS IN TRACER TECHNIQUE (Slide 38)

STEP 1 → Preparation of labelled compound
        ↓
STEP 2 → Incorporation of labelled compound
        ↓
STEP 3 → Separation & Isolation of labelled compound
        ↓
STEP 4 → Determination of nature of metabolites
         in various biochemical fractions

🔷 STEP 1 — Preparation (Slide 39)

Use radioactive isotopes (14C, 3H, 32P, 131I)
        OR
Stable isotopes (2H, 15N, 13C, 18O)
→ Radioactive C & H mostly used
→ Long half-life isotopes preferred

🔷 STEP 2 — Incorporation Methods (Slides 41 & 42)

i)   Root feeding    → roots = biosynthetic site
                       e.g. Tobacco (hydroponic culture)
ii)  Stem feeding    → cut end of stem dipped in solution
                       (not for latex plants)
iii) Direct injection → hollow stem plants
                        e.g. Umbelliferae, Opium poppy
                        (micro syringe used)
iv)  Infiltration    → thread through stem → dipped in solution
v)   Floating method → leaf disc floated on compound solution
                       (when small amount of material available)
vi)  Spraying        → sprayed on leaves
                       e.g. Steroids

🔷 STEP 3 — Separation Methods (Slide 43)

Tissue Type            → Method
──────────────────────────────────
Soft tissue (fresh)    → Infusion, Maceration
Hard tissue            → Decoction, Hot percolation
Unorganized drug       → Maceration with solvent
Fat & oil              → Non-polar solvent
Alkaloids/Glycosides   → Slightly polar solvent
Plant phenol           → Polar solvent

🔷 CRITERIA for selecting tracer (Slide 40)

✔ Sufficient starting concentration
✔ Physical & chemical nature must be known
✔ Long half-life
✔ Should NOT damage tissue
✔ Low radiation energy

DETECTION instruments:
→ Scintillation chamber, GM counter,
  Autoradiography, NMR, MS-ionization technique

🧠 Exam One-liner

Tracer Technique = radioactive/stable isotope labelled compound → given to plant → traces biosynthetic pathway through 4 steps: Preparation → Incorporation → Separation → Determination

📝 TRACER TECHNIQUE — STEP 4 + Detection Instruments + Methods (Part 2)

🔷 STEP 4 — Detection Instruments (Slides 44-48)

DETECTION OF RADIOACTIVITY
         |
    ┌────┴──────────────────────────────┐
    ▼                                    ▼
RADIOACTIVE isotopes              STABLE isotopes
(3H, 14C)                         (2H, 13C, 15N)
         |                               |
Liquid Scintillation Counter      ┌──────┼──────┐
(soft & easily absorbed           ▼      ▼      ▼
 radiation)                       MS    NMR   Autoradiography
         |
    GM Counter
(measures alpha, beta,
 gamma by ionization in gas)
         |
    Ionization Chamber
(simplest gas-filled detector
 for x-rays, gamma, beta)

🔷 INSTRUMENTS — ONE LINE EACH (must write in notes)

🔷 METHODS OF TRACER TECHNIQUE (Slides 49-51)

METHOD 1 — Precursor Product Sequence
         |
Labelled precursor → fed to plant
         ↓
After time → isolate, purify → measure radioactivity
         ↓
Single compound radioactivity = NOT enough evidence
         ↓
Use Double/Triple labelling for confirmation
(different isotopes OR same isotope at 2+ positions)

Example:
Lysine (14C, 15N) → in Nicotiana glauca
→ determined which N forms piperidine ring of Anabasine
(Leete's experiment)

METHOD 2 — Competitive Feeding
         |
A → B → C  (normal pathway)
A → B'→ C  (subsidiary pathway)
         ↓
Feed INACTIVE B and B' separately to 2 plant groups
+ Feed LABELLED A as control
         ↓
If C is inhibited in group with B
but NOT inhibited in group with B'
         ↓
Conclusion: Pathway goes A → B → C ✅

🔷 APPLICATION — Morphine Example (Slide 52)

Tyrosine
   ├→ 3,4-dihydroxyphenyl ethylamine (via DOPA)
   └→ 3,4-dihydroxyphenyl pyruvic acid (DIRECT — no intermediate)
         ↓
Both → Norlaudanosoline → Reticuline → MORPHINE

Key finding: Tyrosine directly gives pyruvic acid
             (DOPA route NOT needed — proved by competitive feeding)

🔷 APPLICATION — Alkaloid Biosynthesis (Slide 53)

14C labelled Tyrosine → Conium maculatum
→ Used to elucidate biosynthesis of Tropane alkaloids
   & Conium alkaloids

🧠 Exam Recap (write this at end of notes)

Step 4 = Detection using GM Counter / Liquid Scintillation / MS / NMR / Autoradiography

2 Methods: (1) Precursor-Product sequence — feed labelled compound, isolate, measure (2) Competitive feeding — feed inactive intermediates to confirm correct pathway

Application: Leete's experiment (Anabasine), Morphine biosynthesis (Tyrosine → DOPA route), Conium alkaloids

📝 METHOD 3 — Sequential Analysis (Short Notes)

🔷 FLOWCHART

METHOD 3 — SEQUENTIAL ANALYSIS
            |
            ▼
Grow plant in atmosphere of 14CO2
            |
            ▼
Analyze plant at different TIME INTERVALS
            |
            ▼
Observe SEQUENCE in which compounds
become radioactively labelled
            |
            ▼
Degrade isolated radioactive compounds
(some units of molecule label faster than others)
            |
            ▼
Determine correct biosynthetic sequence

🔷 KEY POINTS (write these)

✔ Uses 14CO2 atmosphere (not fed directly)
✔ Plant analyzed at given time intervals
✔ Some molecule units label MORE rapidly → noted
✔ Degradation of compound is important step
✔ Used to find PATH OF CARBON in Photosynthesis ⭐

🔷 APPLICATION (Slide 55)

Mentha piperita (Peppermint plant)
        |
        ▼
Exposed to 14CO2 for as short as 5 min
        |
        ▼
Biosynthetic sequence confirmed:

GPP → Piperitone → (-)-Menthone → (-)-Menthol

⚡ All 3 Methods — Quick Recap Table

🧠 One-liner for Exam

Sequential analysis = plant grown in 14CO2 atmosphere → analyzed at time intervals → sequence of labelling reveals biosynthetic pathway → used in elucidation of carbon path in photosynthesis

📝 ALKALOIDS — Short Notes (5 Marks)

🔷 DEFINITION (Slide 2)

ALKALOIDS
= Complex organic compounds
= Natural OR synthetic origin
= BASIC in nature
= Contain 1 or more N atoms in RING system
= Heterocyclic in nature
= Specific physiological action on human/animal body
  (in small quantities)

Word origin: "Alkali-like" → describes bases of botanical group
Importance: Chemical, Physiological, Taxonomic, Biogenetic studies

🔷 PROPERTIES (Slide 3)

Physical:
✔ Colorless, crystalline solids
✔ Slightly soluble in water
✔ Soluble in organic solvents
✔ Exceptions: Coniine & Nicotine = LIQUIDS
✔ Berberine = Yellow | Sanguinarine = Red

With Acids:
→ Form SALTS
→ Salts = soluble in water, sparingly soluble in organic solvents

In plant:
→ Occur in cell sap as water-soluble salts of:
   Malic, Citric, Oxalic, Succinic, Tartaric, Tannic acid

Biosynthesis: from AMINO ACIDS

🔷 CLASSIFICATION (Slides 4-11)

ALKALOIDS
    |
    ├── 1. PHARMACOLOGICAL
    ├── 2. TAXONOMIC
    ├── 3. BIOSYNTHETIC
    └── 4. CHEMICAL

1. Pharmacological (Slide 4)

Based on pharmacological action:
CNS stimulants/depressants, Sympathomimetics,
Analgesics, Purgatives, etc.

Same drug → different alkaloids → different actions:
Opium  → Morphine (narcotic analgesic) ≠ Codeine (antitussive)
Cinchona → Quinine (antimalarial) ≠ Quinidine (cardiac depressant)

2. Taxonomic (Slide 5)

Based on distribution in plant families
→ Named after genus e.g. Ephedra, Cinchona
→ Solanaceous alkaloids, Papillionceous alkaloids

3. Biosynthetic (Slides 5-6)

Based on PRECURSOR amino acid:

Ornithine/Lysine → Tropane, Pyrrolidine, Pyrrolizidine
Tyrosine         → Benzylisoquinoline
Tryptophan       → Indole, Quinoline
Pyridine         → Pyridine, Quinolizidine, Piperidine

4. Chemical (Slides 7-11)

Based on RING STRUCTURE:

A) TRUE ALKALOIDS (heterocyclic ring)

Ring Type         | Examples
──────────────────────────────────────────
Pyrrole/Pyrrolidine  | Hygrine, Coca
Pyridine/Piperidine  | Arecoline, Nicotine, Lobeline
Tropane (bicyclic)   | Atropine, Cocaine, Hyoscine
Indole/Benzopyrrole  | Ergotamine, Strychnine, Reserpine, Vincristine
Quinoline            | Quinine, Quinidine (Cinchona)
Isoquinoline         | Morphine, Codeine, Berberine, Papaverine
Aporphine            | Boldine
Imidazole            | Pilocarpine (Pilocarpus)
Quinazoline          | Vasicine, Vasicinone
Quinolizidine        | Sparteine, Cytisine, Lupanine
Indolizidine         | Swainsonine
Pyrrolizidine        | Senecionine, Seneciphylline

B) PSEUDO ALKALOIDS (false alkaloids)

Type              | Examples
─────────────────────────────────────────
Terpenoid         | Aconine, Aconitine (C20H32 isoprene units)
Purine derivatives| Caffeine, Theophylline, Theobromine (Tea, Coffee)
Steroidal         | Conessine, Solanidine (Kurchi bark)

🧠 Exam Recap (3 lines)

Alkaloid = basic organic compound, N in heterocyclic ring, physiological action in small dose. Biosynthesized from amino acids.

4 classifications: Pharmacological / Taxonomic / Biosynthetic / Chemical

True alkaloids = heterocyclic ring (Morphine, Quinine, Atropine). Pseudo alkaloids = false alkaloids (Caffeine, Aconitine, Conessine)

📝 PART 1 — Protoalkaloids + Isolation/Extraction + Purification

🔷 3. PROTOALKALOIDS (Slide 12)

= Non-heterocyclic / Biological Amines
= N present OUTSIDE the cyclic structure

Type              | Examples
──────────────────────────────────
Alkaloidal Amines | Ephedrine (Ephedra)
                  | Colchicine (Colchicum)

🔷 ISOLATION & EXTRACTION OF ALKALOIDS (Slide 18)

METHOD 1 (Simple)               METHOD 2 (Soxhlet)
─────────────────               ──────────────────
Powdered drug + water           Powdered drug → Soxhlet
        ↓                       → Extract with light petroleum ether
+ Lime + Ammonia solution       → Filtration (remove fats)
(Lime removes acids/tannins)            ↓
Alkaloids freed as BASES        Fat-free extract + Ethanol
        ↓                               ↓
Extract with CHCl3              Concentrate to syrup
(organic solvent)                       ↓
        ↓                       + 2N H2SO4 (mineral acid)
Concentrate organic extract     → Alkaloids become water-soluble salts
        ↓                               ↓
Pure alkaloids ✅               CHCl3 layer discarded
                                        ↓
                                Basify with 10% Ammonia
                                        ↓
                                Extract with CHCl3
                                        ↓
                                Column chromatography
                                        ↓
                                PURE ALKALOIDS ✅

🔷 PURIFICATION OF CRUDE EXTRACT (Slide 19-20)

4 Methods of Purification:

1. Direct Crystallization → from solvent

2. Steam Distillation → for volatile/liquid alkaloids
                         (low molecular weight)

3. Chromatographic Techniques → TLC, Column, GC, HPLC, HPTLC
                                  separates individual alkaloids
                                  from complex mixtures

4. Gradient pH Technique →
   Crude mixture dissolved in 2% tartaric acid
           ↓
   Extract with benzene
           ↓
   pH gradually increased by 0.5 → up to pH 9
           ↓
   Extraction with organic solvent at each pH level
           ↓
   Alkaloids with different basicity extracted separately
   Strongly basic alkaloids extracted LAST

📝 PART 2 — VINCA (Indole Alkaloid) (Slides 23, 25, 26, 27, 28)

VINCA
─────────────────────────────────────────
Synonym        | Catharanthus, Periwinkle
Biological     | Dried whole plant of
Source         | Catharanthus roseus
               | Family: Apocynaceae
               | Also known as Vinca rosea
Geographical   | Indigenous to Madagascar
Source         | Cultivated in India, USA,
               | S. Africa, Europe, Australia
─────────────────────────────────────────
Macroscopic Characters:
• Leaves: green, simple, ovate/oblong, glossy
• Flowers: violet pink/white/carmine-red
• Roots: pale grey, branched tap-root
• Odour: characteristic | Taste: Bitter

CHEMICAL CONSTITUENTS:
20 dimeric indoledihydroindole alkaloids

Most important:
Vincristine ⭐  &  Vinblastine ⭐

Vinblastine = Catharanthine (indole part)
            + Vindoline (dihydroindole part)

Others: Ajmalicine, Lochnerine, Serpentine

Note: 500 kg crude drug → only 1g Vincristine (0.0002%)

USES / PHARMACOLOGICAL ACTION:
Vincristine sulphate:
→ Antineoplastic (arrests mitosis at metaphase)
→ Acute leukemia in CHILDREN (IV)
→ Dose: 10-30 mcg/kg IV (max 2 mg)

Vinblastine sulphate:
→ Antineoplastic (arrests mitosis / interferes AA metabolism)
→ Hodgkin's disease, Non-Hodgkin's lymphoma
→ Breast, uterine, cervical, bronchial cancer
→ Hypotensive + Antidiabetic action
→ Dose: 100 mcg/kg IV

📝 PART 3 — RAUWOLFIA (Indole Alkaloid) (Slide 29)

RAUWOLFIA
─────────────────────────────────────────
Synonym        | Rauwolfia root, Serpentina root,
               | Chhota Chand, Sarpgandha
Biological     | Dried roots of
Source         | Rauwolfia serpentina Benth.
               | Family: Apocynaceae
               | Contains ≥ 0.15% Reserpine + Ajmalcine
Geographical   | Tropical Asia, America, Africa
Source         | India: UP, Bihar, Orissa, Tamil Nadu,
               | WB, Karnataka, Maharashtra, Gujarat
─────────────────────────────────────────
Macroscopic:
• Colour: Root bark = greyish yellow to brown
          Wood = pale yellow
• Odour: Odourless | Taste: Bitter

🧠 Exam Recap

Protoalkaloids = N outside ring (Ephedrine, Colchicine)

Isolation: Method 1 = Lime + CHCl3 | Method 2 = Soxhlet + acid-base extraction + column chromatography

Vinca = Catharanthus roseus, Apocynaceae. Key alkaloids = Vincristine (childhood leukemia) + Vinblastine (Hodgkin's, cancer)

Rauwolfia = R. serpentina, Apocynaceae. Key alkaloids = Reserpine + Ajmalcine

📝 RAUWOLFIA — Complete Short Notes (5 Marks)

🔷 T.S. OF RAUWOLFIA ROOT (Slide 32) — just list these layers!

Outer → Inner:
Stratified Cork → Phelloderm → Starch grains
→ Calcium Oxalate Prisms → Secondary Phloem
→ Vessels → Wood Fibres → Wood Parenchyma → Medullary Ray

🔷 CHEMICAL CONSTITUENTS (Slide 33)

Total alkaloids: 0.7 - 3% (present in bark of roots)
Total: 30 Indole alkaloids

Types: Indole / Indoline / Indolenine / Oxindole / Pseudo-indoxyl

IMPORTANT ALKALOIDS:
⭐ Reserpine (most important)
• Ajmaline          • Ajmalicine
• Rauwolfinine      • Rescinnamine
• Yohimbine         • Serpentine
• Serpentinine

Other constituents: Oleo-resin, Phytosterol,
                    Fatty acids, Alcohol, Sugars

Test: Reserpine = calorimetrically determined
      by reaction with acidic solution + Sodium Nitrite

🔷 CHEMICAL TEST (Slide 35)

Test 1: Freshly fractured surface + Conc. HNO3
        → RED coloration along medullary rays

Test 2: Reserpine + Vanillin in acetic acid
        → VIOLET RED colour

Test 3 (Indole alkaloid test):
        Powdered Rauwolfia + H2SO4
        + p-di-methyl amino benzaldehyde
        → VIOLET to RED colour

🔷 PHARMACOLOGICAL ACTION & USES (Slides 35-36)

ALKALOID          ACTION / USE
──────────────────────────────────────────────────
Reserpine ⭐      • ANTIHYPERTENSIVE ← main use
                  • Lowers BP by depleting catecholamines
                    at nerve endings
                  • Prevents re-uptake of norepinephrine
                  • Used in mild anxiety & neuropsychiatric
                    disorders (tranquilizing effect)

Rescinnamine      • Antihypertensive
                  • Causes mental depression in high doses

Deserpidine       • Antihypertensive + Tranquillizer
                  • Very less side effects

Ajmalicine        • Circulatory diseases
                  • Relieves obstruction of cerebral blood flow

Syrosingopine     • Mild/moderate hypertension
                  • Less sedative than Reserpine

🔷 DOSE (Slide 37)

Rauwolfia:    100-150 mg (oral, twice daily)
Reserpine:    Initial = 250 mcg once/day (oral)
              Maintenance = 100-250 mcg once/day
Rescinnamine: Initial = 500 mcg twice/day (oral)
              Maintenance = 250 mcg daily

🔷 ALLIED DRUGS / SUBSTITUTES (Slides 37-38)

86 different species total.

R. vomitoria  → African Rauwolfia ⭐
               Commercial source of Reserpine
               Root has 5 discontinued bands of sclerenchyma
               + very large vessels

Others with Reserpine: R. caffra, R. cumminsfi,
R. mombasiana, R. oreogiton, R. obscura,
R. rosea, R. volkensii, R. tetraphylla, R. nitida

R. densiflora  → contains sclerenchyma
R. tetraphylla → uniform cork + sclerides + fibres
                 (devoid of Rescinnamine)

🧠 Exam Recap (3 lines)

Rauwolfia = R. serpentina, Apocynaceae. Dried roots. 0.7-3% alkaloids. Key = Reserpine (antihypertensive)

Reserpine lowers BP by depleting catecholamines at nerve endings. Also used as tranquillizer.

Test: Fractured surface + HNO3 = red colour. Reserpine + Vanillin = violet red.

📝 PART 1 — BELLADONNA (Tropane Alkaloid)

BELLADONNA
──────────────────────────────────────────────
Synonym       | Belladonna leaf, Deadly Night Shade leaf,
              | European Belladonna
Biological    | Dried leaves + aerial parts of
Source        | Atropa belladonna (European)
              | OR Atropa acuminata (Indian)
              | Family: Solanaceae
              | Contains ≥ 0.3% alkaloids (as Hyoscyamine)
Geographical  | England + Europe
Source        | India: Western Himalayas (Shimla to Kashmir)
              | Himachal Pradesh, Jammu, Sindhu & Chanab valley
──────────────────────────────────────────────
Macroscopic:  Odour: Characteristic | Taste: Bitter

CHEMICAL CONSTITUENTS:
Total alkaloids: 0.4 - 1%
• Root = 0.6% | Leaves = 0.4% | Seeds = 0.33%
• Berries (unripe/ripe) = 0.19-0.21%

Main alkaloids:
⭐ Hyoscyamine (main)
⭐ Atropine (racemic form of Hyoscyamine)
• Hyoscine (Scopolamine) | Belladonine
• Scopoletin | Pyridine | N-methyl pyrroline (volatile bases)
• Homatropine = synthetic compound
  (preferred as Atropine synthesis is costly)

CHEMICAL TEST — Vitali-Morin Test ⭐
Sample + H2SO4 OR HNO3 → evaporate to dryness
        ↓
Add methanolic KOH solution
        ↓
VIOLET / BRIGHT PURPLE colour = Tropane alkaloids ✅

PHARMACOLOGICAL ACTION & USES:
→ Parasympatholytic drug with ANTICHOLINERGIC properties
→ Reduces secretions: sweat, saliva, gastric juice
→ Reduces intestinal spasm/gripping
→ Antidote in opium & choral hydrate poisoning

DOSE: 0.6 to 1 ml (Belladonna tincture) — 4 times/day

📝 PART 2 — OPIUM (Quinoline & Isoquinoline Alkaloids)

OPIUM
──────────────────────────────────────────────
Synonym       | Raw Opium
Biological    | Air-dried milky exudate (dried latex)
Source        | From unripe capsules of
              | Papaver somniferum Linn.
              | Family: Papaveraceae
              | Contains ≥ 10% Morphine
              |           ≥ 2% Codeine
Geographical  | India (Rajasthan, MP, UP)
Source        | Pakistan, Afghanistan, Turkey,
              | Russia, China, Iran
──────────────────────────────────────────────
Macroscopic:
• Annual plant, erect stem, 1-1.5 m height
• Opium = rounded, flattened masses, 8-15 cm diameter
• Weight: 300g - 2 kg each
• External: pale olive-brown/olive-gray + poppy leaf fragments
• Internal: coarsely granular, reddish brown, lustrous
• Odour: Strong characteristic | Taste: Bitter

CHEMICAL CONSTITUENTS:
Derived from: Phenylalanine + Tyrosine (amino acids)

2 CHEMICAL TYPES:
┌──────────────────────────────────────────┐
│ Benzylisoquinoline type                  │
│ → Narcotine (Noscapine), Narceine,       │
│   Papaverine                             │
│                                          │
│ Phenanthrene type                        │
│ → Morphine, Codeine, Thebaine            │
└──────────────────────────────────────────┘

OTHER ALKALOIDS:
• Protopine, Hydrocotarnine (minor)
• Salts present as MECONIC ACID salts

OTHER CONSTITUENTS:
• Sugar, Wax, Mucilage
• Salts of Ca, K, Mg
• Poppy seeds = 30-35% fixed oil (colourless, tasteless)
  Used in oil paint industry
• DOES NOT contain: Tannins, Starch, Calcium oxalate

MORPHINE specific:
• Monoacidic + Levorotatory phenolic alkaloid
• -OH group at C-6 position
• Soluble in alkali hydroxides (not NH4OH)
• Diacetyl morphine = HEROIN (more narcotic)
• Loses H2O → Apomorphine (emetic, used in poisoning)

CODEINE: Methyl morphine, monoacidic, levorotatory,
         soluble in water + organic solvents

PAPAVERINE: Weak monoacidic, inactive optically,
            slightly soluble in organic solvents

NARCOTINE: Weak monoacidic, levorotatory

PHARMACOLOGICAL ACTION:
Alkaloid     | Action / Use
─────────────────────────────────────────
Morphine ⭐  | Potent analgesic (narcotic)
             | CNS depression → causes ADDICTION
             | Respiratory depression + Constipation
             | Nausea/vomiting (side effect)
             | Given only in SEVERE pain
Codeine      | Antitussive (cough medicines)
             | Mild analgesic
Papaverine   | Smooth muscle relaxant
             | (intestinal + bronchial + blood vessels)
Narcotine    | Depresses cough reflex
(Noscapine)  | Cough linctuses preparation

DOSE:
Morphine sulphate:        10 mg, 6×/day (parentally)
Codeine sulphate/phosphate: 10-20 mg, 4-6 hrly (oral)
Narcotine (Noscapine):    15 mg, 4×/day (oral)
Papaverine HCl:           150 mg oral / 30 mg parentally

🧠 Exam Recap

Belladonna = Atropa belladonna, Solanaceae. Key alkaloid = Hyoscyamine/Atropine. Uses = anticholinergic, antispasmodic, antidote. Vitali-Morin test = violet/purple.

Opium = Papaver somniferum, Papaveraceae. Dried latex. ≥10% Morphine. Two types: Benzylisoquinoline (Narcotine, Papaverine) + Phenanthrene (Morphine, Codeine).

Morphine = potent analgesic, addictive, respiratory depressant. Codeine = antitussive. Papaverine = smooth muscle relaxant.

📝 GLYCOSIDES — Short Notes (5 Marks)

🔷 ISOLATION OF GLYCOSIDES (Slide 2)

Dried plant material → Coarse powder
        ↓
Extract in SOXHLET APPARATUS with Aqueous Ethanol
        ↓
Non-glycosidal impurities removed by
LEAD ACETATE SOLUTION (precipitates them)
        ↓
Excess lead acetate removed by
H2S gas → Lead precipitates as Lead Sulphide → filter
        ↓
Filtrate contains GLYCOSIDES
        ↓
Remove solvent under reduced pressure
        ↓
Further purification by COLUMN CHROMATOGRAPHY
        ↓
PURE GLYCOSIDES ✅

🔷 TYPES OF GLYCOSIDES (Slides 3, 5, 7, 8)

1. ANTHRAQUINONE GLYCOSIDES (Slide 3)

Aglycone = Polyhydroxy Anthraquinone derivative
Action = CATHARTIC (purgative)
Colour = Orange-red (seen in medullary rays)
Test = BONTRAGER'S TEST ⭐
Most active = in combination with sugar

Common derivatives:
• Chrysophanic acid  • Aloe emodin
• Frangula emodin    • Rhein

Examples of drugs:
Cascara sagrada, Frangula, Aloe, Rhubarb, Senna

2. CYANOPHORE (Cyanogenetic) GLYCOSIDES (Slides 5-6)

Also called = Cyanogenetic glycosides
On hydrolysis → yield HCN (Hydrocyanic acid)

Found mainly in family: ROSACEAE

Most common: AMYGDALIN ⭐
• Found in: Bitter almonds, apricots,
            cherries, peaches, plums kernels

Amygdalin hydrolysis:
Amygdalin → 2 Glucose + Benzaldehyde (C6H5CHO) + HCN

Other: PRUNASIN (wild cherry bark)

USE: Syrup form → cough preparations
     (sedative expectorant, pleasant taste)

CHEMICAL TEST:
Drug + water + dilute H2SO4
→ Filter paper soaked in SODIUM PICRATE solution
  suspended above → gently heat
→ BRICK-RED colour on paper = Cyanophore glycosides ✅

3. ISOTHIOCYANATE GLYCOSIDES (Slide 7)

= Glucosinolate compounds
Aglycone contains: ISOTHIOCYANATE (-NCS) group

Principal example: SINIGRIN ⭐ (Black mustard)
Sinigrin hydrolysis →
  Allyl isothiocyanate + Potassium acid sulphate + Glucose

Others:
• Sinalbin → White mustard
• Gluconapin → Rapeseeds

🔷 THERAPEUTIC USES (Slide 8)

Glycoside Type      | Aglycone       | Use
────────────────────────────────────────────────
Cardiac glycosides  | Steroidal      | Cardiotonic
(Digitalis)         | aglycone       | (heart conditions)
────────────────────────────────────────────────
Anthraquinone       | Anthraquinone  | LAXATIVE
(Senna, Rhubarb,    | system         | (purgative)
Aloe)               |                |
────────────────────────────────────────────────
Saponin glycoside   | Glycyrrhetinic | Peptic ULCER
(Liquorice =        | acid (aglycone)| treatment
Glycyrrhizin)       |                |

🧠 Exam Recap (3 lines)

Glycosides isolated by: Soxhlet extraction → Lead acetate removes impurities → H2S removes lead → Column chromatography for purification

3 types: Anthraquinone (cathartic, Bontrager's test) | Cyanophore (HCN on hydrolysis, Amygdalin, sodium picrate = brick red) | Isothiocyanate (Sinigrin, black mustard)

Uses: Cardiac glycosides = cardiotonic | Anthraquinone = laxative | Glycyrrhizin aglycone = peptic ulcer

📝 SENNA — Short Notes (5 Marks)

🔷 DIFFERENCE TABLE — Alexandrian vs Indian Senna ⭐

🔷 CULTIVATION (Slides 10-11)

Plant type: Shrub, ~1 meter height

CULTIVATION STEPS:
Land ploughed 2-3 times → Harrowing → Planking
        ↓
Sow seeds (Broadcasting method)
Seeds abraded (scarped) with sand in mortar pestle
15-25 kg seeds per hectare
        ↓
Soil: Red + Loamy, pH 4.5-7.5
Climate: DRY environment
Sowing season: FEBRUARY TO MARCH
        ↓
Irrigation: 3-4 times (light irrigation only)
No water-logging / very low temp
        ↓
Apply Nitrogenous fertilizers
(leguminous plant but lacks root nodules)

🔷 COLLECTION (Slides 11-14)

Senna = MULTI HARVEST CROP

After 2-3 months of sowing → Harvest begins
Harvesting done in 3 STAGES:

Stage 1: When leaflets are thick, full-grown, greenish
Stage 2: After 1 month (2nd plucking)
Stage 3: After 4-6 weeks (last plucking)

Collect: Bluish-green leaves + Golden-yellow immature pods
         (maximum sennosides present at this stage)

Yield:
• Irrigated land  → 1200 kg leaves + pods per hectare
• Rain-fed land   → 700 kg drug per hectare
• India total     → 25,000 hectares under cultivation
                  → 22,500 tonnes leaves/year
                  → 7,500 tonnes fruit/year

Storage: Protect from light. Potency retained up to 5 years.

🔷 CHEMICAL CONSTITUENTS (Slides 21-23)

MAIN ACTIVE CONSTITUENTS:
⭐ Sennoside A & B (≥ 2.5%) — MOST IMPORTANT
   → Stereoisomers of each other
   → Dimeric glycosides with RHEIN DIANTHRONES as aglycone
   → Purgative property: 40-60%

Sennoside A → Dextrorotatory (trans form)
Sennoside B → Meso form

Sugar part function:
→ Transports aglycone to LARGE INTESTINE
→ Protects aglycone from oxidation

Other constituents:
Sennoside C & D | Rhein | Emodin | Aloe-emodin
Rhein-8-glucoside | Anthrone di-glucoside
Kaempferol | Isohamnetin | Phytosterol
Mucilage | Resin | Myricyl alcohol
Salicylic acid | Chrysophanic acid | Calcium oxalate

Also: 2 Naphthalene glycosides:
→ Tirunelveli glycoside
→ 6-hydroxy musizin glycoside

🔷 SENNOSIDE TYPES — Quick Recap

🔷 PHARMACOLOGICAL ACTION & USES (Slide 28)

Main use: PURGATIVE (laxative) in constipation

MECHANISM:
Anthraquinone glycosides absorbed in intestinal tract
        ↓
Aglycone separated → excreted in COLON
        ↓
Irritates + stimulates colon → increased peristalsis
        ↓
↓ water absorption → soft & bulky faeces

GRIPPING EFFECT: Due to resin / emodin content
→ Counteract by giving with CARMINATIVES

Parenteral route: Drug secreted in colon → therapeutic action

🧠 Exam Recap (3 lines)

Senna = Cassia acutifolia (Alexandrian) / Cassia angustifolia (Indian), family Leguminosae. Anthraquinone glycosides.

Main constituents = Sennoside A & B (stereoisomers, ≥2.5%). Aglycone = Rhein dianthrones. Sugar transports to large intestine.

Use = Purgative. Mechanism = irritates colon → increased peristalsis → soft faeces. Gripping effect due to resin/emodin.

📝 ALOE — Short Notes (5 Marks)

🔷 BASIC INFO

Synonyms: Aloe, Musabbar, Kumari, Kuvarpathu
Biological Source: Dried juice from transversally
                   cut leaves of Aloe species
Family: Liliaceae

4 VARIETIES:
Species              | Common Name      | Source
──────────────────────────────────────────────────
Aloe barbadense      | Curacao/Barbados | North Africa
Aloe ferox Miller    | Cape aloe        | South Africa
Aloe perryi Baker    | Socotrine aloe   | Socotraa, E. Africa
Aloe perryi Baker    | Zanzibar aloe    | Zanzibar
                     | (variety of Socotrine)

🔷 VARIETIES DIFFERENCE TABLE ⭐ (Slide 42)

KEY POINT:
• Crystalline aloe = CURACAO → insoluble in cresol
  → shows SHINING BRIGHT colour under polarized light
• Amorphous aloe = CAPE → dissolves in cresol
  → remains INVISIBLE under polarized light

🔷 CULTIVATION & COLLECTION (Slides 37-38)

~200 species of Aloe genus

CULTIVATION:
Propagation: ROOT SUCKERS (NOT seeds)
Rows: 50 cm apart
Soil: POOR GRADE
Climate: DRY environment
Manure: N + K + P mixture
No water-logging (roots shallow)

COLLECTION:
• First harvest: 2nd year of cultivation
• Drug obtained for 12 YEARS continuously
• After 12 years → plants uprooted → land replanted

HOW JUICE IS COLLECTED:
Cut leaves near base
        ↓
Juice from parenchymatous cells of pericycle
exudes out (pressure by mucilage cells)
        ↓
Single incision = sufficient to draw out
all juice from pericyclic cells

🔷 CHEMICAL CONSTITUENTS (Slides 46-48)

Major source: ANTHRAQUINONE glycosides

⭐ ALOIN = Principal active constituent
   = Mixture of glycosides
   Main component = BARBALOIN
   (= Aloe-emodin anthrone C-10 glucoside)

Barbaloin properties:
→ C-glycoside
→ NOT hydrolysed by dilute acid or alkali
→ FeCl3 decomposes it by oxidative hydrolysis
  → Aloe-emodin-anthrone + Aloe-emodin + Glucose

Barbaloin content:
• Curacao = 22% (highest)
• Indian Aloe vera = 3.5-4% (very less)
• Curacao has 2.5× more aloe-emodin than Cape

Resin = contains ALOESIN
(C-glucosyl chromone)
→ also responsible for PURGATIVE action

Other constituents:
Isobarbaloin | B-barbaloin | Aloe-emodin | Resins
Aloetic acid | Homonataloin | Aloesone
Chrysophenic acid | Chryssamminic acid
Galacturonic acid | Choline | Saponins
Mucopolysaccharides | Glucosamines
Hexuronic acid | Coniferyl alcohol

🔷 USES (Slide 52)

1. PURGATIVE ⭐
   → Effect mainly on COLON
   → Strongest purgative among anthracene glycoside drugs
   → Given with CARMINATIVES to counter gripping action

2. ALOIN preferred nowadays over crude aloe
   (both are official)

3. Ingredient of compound tincture of BENZOIN
   (Friar's Balsam)

🧠 Exam Recap (3 lines)

Aloe = dried juice of Aloe species, family Liliaceae. 4 types: Curacao, Cape, Socotrine, Zanzibar.

Main constituent = Aloin (Barbaloin). Curacao = 22% Barbaloin, crystalline. Cape = amorphous. Aloesin (resin) also purgative.

Use = Purgative (acts on colon). Given with carminatives. Also used in Friar's Balsam.

📝 BITTER ALMOND — Short Notes (5 Marks)

🔷 BASIC INFO

BITTER ALMOND (Cyanophore Glycoside)
─────────────────────────────────────────────
Synonym        | Amygdala Amara
Biological     | Dried RIPE SEEDS of
Source         | Prunus amygdalus Batsch
               | var. Amara (D.C.) Focke
               | Family: ROSACEAE
Geographical   | Native: Iran & Asia Minor
Source         | Cultivated: Sicily, Italy, Spain,
               | Portugal, S. France, Morocco

Note: Botanically difficult to distinguish
      from Sweet Almond (Prunus communis)

🔷 MACROSCOPIC CHARACTERS

Colour  : Brown
Odour   : Odourless
Taste   : BITTER
Size    : 20 mm length × 125 mm width × 10 mm thick
Shape   : Flattened, oblong, ovoid
          with markings on testa

🔷 CHEMICAL CONSTITUENTS (Slide 58-59)

Fixed oil (bland)    : 40-50%
Proteins             : 20%
Volatile oil         : 0.5%
Enzyme               : EMULSIN
Bitter glycoside     : AMYGDALIN (1-3%) ⭐

HYDROLYSIS OF AMYGDALIN:
(by enzyme emulsin in presence of water)

AMYGDALIN
        ↓
2 Glucose + Benzaldehyde (C6H5CHO) + HCN

Key points:
• HCN = very POISONOUS → drug unsuitable
  for internal consumption
• Bitter almond oil contains:
  80% Benzaldehyde + 2-6% HCN

🔷 USES

1. SEDATIVE → due to HCN content
2. Oil → demulcent SKIN LOTION
3. Used in preparation of:
   • Amygdalin
   • Bitter almond water
   • Perfumery
   • Liquors
4. NOT used for flavouring of foods
   (due to HCN toxicity)

🔷 CHEMICAL TEST (from previous slide knowledge)

Drug + water + dil. H2SO4
→ Filter paper soaked in SODIUM PICRATE
  suspended above → gently heat
→ BRICK-RED colour = Cyanophore glycoside ✅

🧠 Exam Recap (2 lines)

Bitter Almond = Prunus amygdalus var. Amara, Rosaceae. Dried ripe seeds. Key glycoside = Amygdalin (1-3%).

Amygdalin + Emulsin + water → 2 Glucose + Benzaldehyde + HCN. HCN = poisonous. Uses = sedative, skin lotion, perfumery.

📝 PART 1 — TERPENOIDS (Introduction)

TERPENOIDS
= Large class of naturally occurring organic compounds
= Derived from 5-carbon unit → ISOPRENE (C5H8)
= Also called ISOPRENOIDS
= Follow ISOPRENE RULE

BASIC UNIT: Isoprene (C5H8)
            2-methyl-1,3-butadiene

CLASSIFICATION (by number of isoprene units):

Isoprene units | Carbon atoms | Class
──────────────────────────────────────
2 units        | C10          | Monoterpenes
3 units        | C15          | Sesquiterpenes
4 units        | C20          | Diterpenes
6 units        | C30          | Triterpenes
8 units        | C40          | Tetraterpenes
n units        | (C5)n        | Polyterpenes

BIOSYNTHESIS: Via Mevalonate Pathway
Acetyl CoA → HMG-CoA → Mevalonic acid → IPP
→ DMAPP → GPP(C10) → FPP(C15) → GGPP(C20)
→ All Terpenoids

EXAMPLES:
• Monoterpenes  → Menthol, Camphor, Limonene
• Sesquiterpenes → Artimisinin, Farnesol
• Diterpenes    → Taxol, Phytol, Retinol (Vit A)
• Triterpenes   → Sterols, Saponins, Glycyrrhizin
• Tetraterpenes → Carotenoids (β-carotene)

📝 PART 2 — GENTIAN (Iridoid Glycoside / Bitter Tonic)

🔷 BASIC INFO

GENTIAN
─────────────────────────────────────────────
Synonym        | Gentian root, Gentiana,
               | Radix Gentianae
Biological     | Dried partially FERMENTED
Source         | rhizome and root of
               | Gentiana lutea
               | Family: GENTIANACEAE
Geographical   | Perennial herbaceous tree
Source         | Hilly areas of S. & Central Europe
               | Jura, Vosges mountains, Yugoslavia

🔷 COLLECTION & PREPARATION (Slide 16)

Large fleshy roots + erect rhizomes
from 2-5 year old plants → DUG UP
        ↓
Collection in AUTUMN
        ↓
Cut longitudinally into SLICES
(At this stage = white, odourless)
        ↓
SLOW DRYING or FERMENTATION
(slow heating, kept in heaps)
        ↓
Become DARK/YELLOW + develop
CHARACTERISTIC ODOUR ✅

🔷 MACROSCOPIC CHARACTERS (Slide 17)

Rhizome: Yellowish-brown, transverse annulations,
         conical buds at top
Root:    Narrower, continuous with rhizome,
         longitudinally wrinkled, circular scars of rootlets
Odour:   Peculiar (special)
Taste:   Sweet → then INTENSELY BITTER
Fracture: Short & smooth (dried drug)
          Tough & flexible (moist drug)

🔷 CHEMICAL CONSTITUENTS (Slides 20-21)

MAIN ACTIVE CONSTITUENTS:

1. GENTIOPICRIN ⭐ (= Gentiopicroside)
   → Bitter glycoside
   → Water soluble, crystalline
   → Bitter value = 12,000
   → On fermentation/drying:
      Gentiopicrin → Gentiogenin + Glucose
   → Contains MONOTERPENE IRIDOIDS

2. AMAROGENTIN ⭐ (MOST BITTER substance in nature!)
   → Bitter even at 5.8 LAKH times dilution!
   → Mainly responsible for bitter taste

3. GENTIANIN / GENETICIN
   → Flavonoid alkaloid
   → Geneticin gives YELLOW colour to drug

OTHER CONSTITUENTS:
• Gentisic acid
• Gentianose (trisaccharide: 2 Glucose + 1 Fructose)
• Gentiobiose (disaccharide)
• Sucrose

Note: Drug should yield ≥ 33% water soluble extractive
      (decreases with excessive fermentation)

🔷 CHEMICAL TEST + USES + PREPARATIONS (Slides 21-22)

CHEMICAL TEST:
Gentian extract under UV radiation
→ LIGHT BLUE FLUORESCENCE ✅

USE:
→ BITTER TONIC
→ Stimulates gastric secretion
→ Improves APPETITE (digestive stimulant)

PREPARATIONS:
1. Concentrated Compound Gentian Infusion:
   Gentian + Bitter orange peel + Lemon peel
   + Alcohol 25%

2. Compound Gentian Tincture:
   Gentian + Bitter orange peel + Cardamom seed
   + Alcohol 46%

🧠 Exam Recap (3 lines)

Terpenoids = isoprene-based compounds (C5 unit). Classified as Mono(C10), Sesqui(C15), Di(C20), Tri(C30), Tetra(C40). Biosynthesized via Mevalonate pathway.

Gentian = Gentiana lutea, Gentianaceae. Dried fermented rhizome/root. Key = Gentiopicrin (bitter value 12,000) + Amarogentin (most bitter substance in nature).

Use = Bitter tonic, improves appetite. UV test = light blue fluorescence. Preparations = Compound infusion & Compound tincture.

📝 ARTIMISIA — Short Notes (5 Marks)

🔷 BASIC INFO

ARTIMISIA (Sesquiterpene — Terpenoid)
─────────────────────────────────────────────
Synonym        | Qninghao, Sweet-annie,
               | Worm weed, Santonica
Biological     | Chinese traditional herb
Source         | Artemisia annua Linn.
               | Family: ASTERACEAE
               | Contains ≥ 0.8% ARTEMISININ
               | (on dried basis)

Other species: A. cina, A. brevifolia, A. maritima
               (source of Santonin from flower heads)

Geographical   | Endemic to CHINA
Source         | Wild in Europe & America
               | Cultivated: Vietnam, China, Iran,
               | Turkey, Australia
               | India (experimental): Gujarat, J&K,
               | UP, Himachal Pradesh, Karnataka

🔷 MACROSCOPIC CHARACTERS (Slide 25)

• Annual herb, 0.7-1.75 m height
• Branches: deeply grooved
• Leaves: bipinnate compound, dark green
• Odour: STRONGLY AROMATIC
• Taste: BITTER
• Leaves: 0.25-0.5 cm wide, 5-7 cm long,
  lanceolate oblong, deeply cut segments
• Flowers: tiny green-yellow, in clusters
• Stems: cylindrical, 2-5 mm diameter,
  30-80 cm length

🔷 CHEMICAL CONSTITUENTS (Slides 27-29)

MAIN ACTIVE CONSTITUENT:
⭐ ARTEMISININ (= Qinghaosu)
   → Sesquiterpene LACTONE
   → Has INTERNAL PEROXIDE LINKAGE ← key feature
   → Only A. annua contains Artemisinin + Deoxy-artemisinin (1%)
   → Sparingly soluble in water
   → Decomposes in many solvents

UNIQUE FEATURE:
Unlike other antimalarials — DOES NOT contain
heterocyclic ring with nitrogen
→ New type of structure in antimalarials ⭐

Other constituents:
• Artemisinic acid (Qinghao acid)
• Arteannuin A and B
• Amyrin | Luteolin
• β-sitosterol | Stigmasterol

Volatile oil: 0.3-0.4%
→ Artemisia alcohol, Artemisia ketone,
  Camphor, Caryophyllene, Myrcene

FLOWER HEAD CONSTITUENTS:
• Volatile oil: 2-3% (80% Cineole + Pinene + Resin)
• SANTONIN (3%) = bicyclic sesquiterpene lactone
  (anhydride of santoninic acid)
• Active: L-α Santonin (2.3-3.6%)
  D-α Santonin = INACTIVE
• ARTIMISIN (8-hydroxy santonin) =
  bitter substance, responsible for bitter taste

🔷 USES (Slides 30-31)

ARTEMISININ:
→ ANTIMALARIAL ⭐ (main use)
  Mechanism: Rapid blood schizonticidal activity
  → Arrests trophozoite development
  → Acts against BOTH:
    Chloroquine-sensitive &
    Chloroquine-resistant Plasmodium falciparum
    & Plasmodium vivax
→ MOST POTENT drug for CEREBRAL MALARIA ⭐
→ Anti-HIV activity

DERIVATIVES:
• ARTESUNATE → effective antimalarial
• ARTEMETHER → developed by C.D.R.I. Lucknow
• ARTEMISIC ACID → antibacterial +
  cytotoxic + anti-inflammatory

SANTONIN (from Santonica flower head):
→ Strong ANTHELMINTIC ⭐
  (especially for round worms)
→ In TOXIC doses: yellow & violet vision
  → PROHIBITED in U.S.A.

🧠 Exam Recap (3 lines)

Artimisia = Artemisia annua, Asteraceae. Contains ≥0.8% Artemisinin. Type = Sesquiterpene lactone with internal peroxide linkage. No N-heterocyclic ring — unique among antimalarials.

Uses: Artemisinin = antimalarial (cerebral malaria, chloroquine-resistant), anti-HIV. Artesunate & Artemether = derivatives.

Flower head (Santonica) = Santonin (3%) → anthelmintic for round worms. Toxic dose = colour vision changes. Prohibited in USA.