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Cua, Pilar, Renon

HC Plants and animals Friedrich Kekul HC of turpentine


C10H16

Camphor -> Terpenoids


C10H16O

Otto Wallach
5n carbon atoms Isoprene units = 2methylbuta-1,3diene

Leopold Ruzicka
Rule of Ruzicka classification by number of C

Robert Robinson
Head to tail

Number of carbon atoms

Value of n

Class

10 15 20 25 30 40 >40

2 3 4 5 6 8 >8

Monoterpenes(C10H16) Sesquiterpenes(C15H24) Diterpenes(C20H32) Sesterpenes(C25H40) Triterpenes(C30H48) Tetraterpenes(C40H64) Polyterpenes(C5H8)n

Acyclic Monocyclic Bicylcic Tricyclic Tetracyclic

Extracts /steam distillates of terpenes


Natural flavor additive Fragrance Pharmacological Agent of pollination Plant adaptation and protection Growth hormone and pheromones

Citral Camphor

Limonene

Menthol

Terpineol

-pinene

Santonin Abscisic acid

Artemisinin

Hormones Tetracyclic triterpenes Cyclopentaperhydrophanthrene backbone Me at C10 and C13- angular methyl groups
Above plane

Subs at same side = and solid wedge Non-polar


Cross cell membrane

Source
Phtyosterol Zoosterol Ergosterol Ecdysteroid

Most common and abundant Precursor of other steroids Cell membrane component Squalene 8 asym C and 256 stereoisomer

Cholic and chenodeoxycholic acid Vitamin D

Glucocorticoids Mineralcorticoids O at C11

Cortisone

Aldosterone

Male sex hormone Testes Male secondary sex characteristics

Testosterone

5-dihydrotestosterone

Female sex hormones Ovaries Female secondary characteristics Regulate menstrual cycle
Estradiol Estrone

Prepare lining of uterus for implantation of an ovum Maintenance of pregnancy Prevent ovulation during pregnancy Progesterone

Synthetic steroid

Deliberate damage of plant to collect the resin. Use of incision into the tree where the resin runs through. Used in collecting latex for rubber and gum turpentine.

Oil extraction where physical pressure is applied The sample is pressed until the oil comes out of it. Used for citrus oil due to abundance of raw materials.

Three forms of distillation:


Dry or empyrumatic Steam distillation Hydrodiffusion

Involves high temperature The vessel containing the plant sample is directly heated Used for oils derived from wood to vaporize chemical components

Water is added to the plant sample Limits the temperature to 100C Lessens degradation of hydrocarbons

Essentially is steam distillation. Difference is the introduction of steam at the top of the vessel while water and oils are collected at the bottom. Plan materials carried down by the condensate. Saves energy because it is not necessary to vaporize the oil.

Use of suitable solvent to dissolve desired sample Comes in different type of solvents Inlcudes:
Ethanolic Extraction Enfleurage Simple Solvent Extraction

Use of ethanol to extract desired sample Not useful for extraction from plant sample because of high proportion of water to oil More useful with products like ambergris.
Ambergris comes from sperm whales; used in perfumes.

Ancient method of extraction Plant material is covered in purified fat Purified fat absorbs oil Oil can be extracted from fat using ethanolic extraction Similar to maceration; difference is the presence of heat in maceration

Use of petroleum ether, acetone, hexane and ethyl acetate and combinations to extract desired oil. Previously benzene was used but due to health concerns was stopped. Use of liquid carbon dioxide as solvent very effective but expensive. Products are called concrete or resinoids

Same as simple solvent extraction Polarity of sample is taken into consideration May include more purification steps to separate steroids from lipoproteins to increase yield. Glasswares must be properly silanise using dimethyldichlorosilane to prevent steroids from binding

Based on two systems:


One using diatomaceous inactivated earth The other one using microparticulate silica.

Analyte is eluted by passing through the solid matrix with organic solvent. Water is absorbed by the matrix.

Uses an antibody bound to a matrix Analyte is percolated through the antibody Eluted by changing the concentration of salt May use highly selective antibodies or low specific antibodies.

Molecularly Imprinted Polymers


May be regarded as synthetic antibodies Highly selective to specific sample

Restricted Access Material


Restricts molecules which are compatible with the RAM Binds with specific molecules and elutes other

Large number of sample in one run If steroid is UV absorbing the use of UV light and fluorescent adsorptive material could be used. Usually uses silica gel plates Solvent: combination of chloroform, benzene, ethyl acetate, hexane, etc.

Partition system where the steroid solute is in the vapor phase. Due relatively high molecular weight of steroids and their derivatives, GLC has to be carried out at high temperatures, usually in excess of 200C. The sample is carried through the system by a gas, usually helium, because it is less dense than nitrogen. Originally carried out using packed columns but today capillary columns of glass or fused silica are more popular.

High temperatures are not required. Material can be recovered from the column eluates for further analytical procedures. The resolution achieved by HPLC is superior to TLC and paper chromatography, Methods of linking HPLC to mass spectrometers have greatly improved, allowing the routine use of LC-MS and LCMS-MS Typically, columns are 100300 mm in length and around 45 mm internal diameter.

Bromine adds to unsaturated double and triple bonds to form dibromoalkanes and tetrabromoalkanes Gets decolorized until reaction is complete

Uses acetic anhydride and sulfuric acid Color changes from pink to green Happens because of the hydroxyl group of cholesterol increases conjugation in the ring

Sample + FeCl36H20 + glacial acetic acid + concentrated sulfuric acid = bluish green color Alternatively :
Sample + perbenzoic acid + glacial acetic acid Heat + sulfuric acid = bluish green color

Is also known as dodeca molybdophosphoric acid or PMA It is a yellow-green compound, freely soluble in water and polar organic solvents such as ethanol. Conjugated, unsaturated compounds reduce PMA to molybdenum blue. Increase in intensity means increase in double bonds stained

Oxidize the carbon-carbon double bond to give alkanediols or the carbon-carbon triple bond to give carboxylic acids. A brown precipitate of MnO2 is produced. Disappearance of the characteristic color of permanganate ion is a positive test for unsaturation. Compounds containing certain other types of functional groups may also decolorize permanganate ion.

A chloroform solution of sterol with 90% tricholoracetic acid which gives a blue or pink color.

Cholesterol + excess phosphoric acid + ferric ions (FeCl3) = reddish purple color Alternative:
sulfuric acid + cholesterol in chloroform = twophase system red upper layer and green lower layer

Cholesterol + glacial acetic acid + ferric chloride + concentrated sulfuric acid = purple color

Elucidation is done by spectral comparison Chromophores and structural environment detected for unknown samples

OH single bonds vibrate with 3600 cm-1, carbonyl double bonds with 1700 cm-1, and carbon-oxygen single bonds with 1200 cm-1

NMR spectra of steroids measured in CDCl3. 1D proton NMR spectra have overlapping signals of CH2 and CH groups that appear as a characteristic hump in the region 0.52.5 ppm. 13C NMR eliminates this problem

Detects the molecular mass of a compound with a precision of 10-4 mass units. Due to the isotope mass defect of elements the molecular formula of a terpene can be determined by high-resolution mass spectrometry of the molecular ion. For example, the molecular formula C17H22O4 of acanthifolin from Senecio acanthifolius (Asteraceae) is calculated from the molecular mass of 290.1525 determined by high-resolution mass spectrometry of the molecular ion.

This determines the arrangement of atoms within a crystal and provides information about:
1) 3D picture of the density of electrons within a crystal, 2) mean positions and sizes of the atoms in the crystal, 3) lengths, angles, and types of chemical bonds and 4) chemical functions, interactions, and processes.

Menthol and Cholesterol

Chemical Synthesis

Chemical Synthesis

Biosynthesis

Step 2: Decarboxylation

Step 4: Cleavage

Biosynthesis

Malaria and dengue fever Blood-feeding arthropods Bunyavirus DEET Picardin PMD Beautyberry = Callicarpa

Beautyberry insect repellent property


Callicarpenal Intermedeol Spathulenol

Low isolated amount

Stereoselective synthesis of (-)-callicarpenal

a. ethylene glycol PTSO in benzene

b. Ketal in THF + Li/NH3


Allyl bromide

c. OsO4 NMO acetone/H2O

d. O3, THF PPh3 NaBH4 e. CH2Cl2 TIPSOTf 2,6-lutidine f. TPAP NMO CH2Cl2

g. CH3PPh3Br NaHMDS THF

i. TBAF THF

j. HCl THF

k. H2, Crabtrees catalyst ([Ir(COD)(PCy3)(Py)]PF6 CH2Cl2

l. CH3PPh3Br NaHMDS THF

m. RuCl3.H2O EtOH

n. TPAP NMO CH2Cl2

Drug development vary subs and alter stereochem relationships


Change in the biological activity

C11 change -> change in biological effect 11-amino-12-hydroxy/keto steroids potential HIV-1 protease (Salunke et.al.) Short carbon bridges span characteristic portion of steroid backbone

New ring New function at C11 Cholic acid -> stereoselective synthesis of pentacyclic steroids w/ NH2 at C11

b. Ac2O pyridine DMAP

c. mesyl chloride pyridine

cholate

a. Methanol PTSA

methyl-3,7-diacetoxycholate

d. Chen AcOK HMPT


methyl 3,7-diacetyl-12-mesyl cholate

methyl 3,7-diacetylchol-11-enate

e. m-CPBA in CH2Cl2

different amines in ethanol/toluene (1:1) solution 11,12 -epoxide