Determination of stereochemistry by using spectroscopic method of natural products

Hon. Balasaheb Jadhav Arts, Commerce & Science College, Ale, Tal- Junnar, Dist- Pune Pin- 412411.

Asst. Prof. Kadam Sushma S.

The essence of knowledge is that you have it and you share it with others

Modern science is based on interaction between disciplines :Organic chemistry began as tentative attempt to understand the chemistry of life. Chemist co-operate with physicist, mathematician, molecular engineering, biologist, material scientist, computer expert, to understand how molecules behave & to understand how molecules determine life process. Organic Chemistry is science of molecules. It is study of molecules of nature and interesting in their own right because of their function important to our life.

The organic chemistry often creates a new molecules has given us new materials such as new dyes, clothes, perfumes new drug to cure diseases.
Their one type of chemistry; it goes on both inside our brain & bodies and also in flask & reactors, born ideas in our minds & the skill in our hand.

Future of organic compound :Light emitting the polymer Polymer that conducted electricity Self producing organic compound Molecules that work Nano even molecules that think may transformed our world way not get imagined.

Some wonderful structures :Beautiful examples of molecular architecture.

Palytoxins :Most toxic naturally occurring compound with potentional anti-cancer activity.

Brevetoxin :(Unique cyclic polyether dinoflagellate toxin)

- Wonderful & deadly molecule 22 stereogenic centers. - causing NSP (neurotoxic shelfish poisoning) - six, seven, eight, membered ring but each one with oxygen & no more than one oxygen.

Red tide (Harmful agal bloom)

Tetra tertiary Butyl Tetrahedrane :-

Tetra-tert-butyltetrahedrane
The tert-butyl substituted compound was first synthesised starting from a cycloaddition of an alkyne with t-Bu substituted maleic anhydride, followed by rearrangement with carbon dioxide expulsion to a and its bromination, followed by addition of the fourth t-Bu group and a with expulsion of carbon monoxide.

 How Coupling varies with the angle between bond?

Connections :-

How ring size affect coupling?

How electronegative atoms reduced coupling?

How pi system increases geminal coupling?

How proton attach to same carbon can be different and can couple to one another?

What homotopic, enatiotopic and diastereotopic?

The Nuclear Over Hauser Effect.

Relative to another function in the molecule

Chirality (Stereogenic Centre)
Non-superimposeable
Mirror images Requires 4 different groups May or may not be stable (Amines) Called enantiomers Configuration R or S
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Many Chiral molecules present in nature as single enantiomers (enantiomerically Pure). Useful in Chemistry of Drug Designed.

- Adrenaline (Epinephrine) :- Human Harmone is produced in moments of stress and increase our Blood Pressure & heart rate ready for fight or flight.

- Enantiomerically Pure - Diastereoisomers - Antiasthma intermediates

* * * *

(-) pseudoephedrine

(+) Ephedrine

Pharmacological activity of Diasteromers:Pseudoephedrine is a diastereomer of ephedrine. Pseudoephedrine is a chiral molecule, meaning it occurs in both "left-handed" and "right Handed configurations which are not superimposable.

Chiral Drugs:- that have different (Enantiomers of drug

therapeutic effect)

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* * *

Darvon (Painkiller)

Novrad (Anticough)

Karplus Equation :It is useful to deduce the relation between dihedral angle & coupling constant.

coupling constant Varies with dihedral angle

148

119

138

117

125

116

 Basic Features of Karplus Equation :-

The Karplus curve for the dependence of the vicinal 3J HH coupling on the dihedral angle, : the heavy line is the theoretical curve; the shaded area is the range of experimental results. Note that the prediction that 3J 3 180 > J0 is confirmed.

 Actually, the magnitude of vicinal (3J) :coupling constants depends upon four factors:
1. The dihedral angle, , between the C-H (this is the prediction of Karplus) 2. The C-C bond length, Rv 3. The H-C-C-H valence angles, and 4. The electronegativity of the substituents on the H-C-C-H

Some examples of bond length dependence

Natural Product Guaiol with elemental sulfur converts into Guazulene (deep blue oil can distilled)
8.2 (1H,S) 7.6 (1H,d, J 4.0) 7.37 (1H, d, J11.0) 7.2 (1H d J 4.0) 6.96 (1 H d J 11) 3.02 ( 1H m J 6.9) 2.78 ( 3H, S) 2.63 ( 3H, S) 1.35 (6H d J 6.9)

The 6H doublet and 1H septuplet are the isopropyl and the 2H singlet belong to the 2CH3 group. (2.78 & 2.63 ppm) 1H Singlet, coupling pair of proton at 5 membered ring & 7 membered ring. With the coupling constant 4Hz & 11Hz.

Guaiazulene
Guaiazulene, also azulon or 1,4-dimethyl-7-isopropylazulene, is a dark blue crystalline hydrocarbon. A derivative of azulene, guaiazulene is a bicyclic sesquiterpene that is a constituent of some essential oils, mainly oil of guaiac and chamomile oil, which also serve as its commercial sources. Various soft corals also contain guaiazulene as a principal pigment.[1] Its low melting point makes guaiazulene difficult to handle, in contrast to the crystalline nature of the parent azulene. The electronic structure (and colors) of guaiazulene and azulene are very similar.

The blue color of the mushroom Lactarius indigo is due to the guaiazulene derivative (7-isopropenyl-4- methylazulen-1-yl)methyl stearate.

 Vicinal coupling constant in Cyclopropane ring

Chrysanthemic acid which is the part of the pyrethrin group of insecticide found in pyrethrum plant. Both cis & tran isomer are important.
H
H H H J =5Hz

J =8Hz In cis proton is triplet & in trans it is dd with 5 Hz In 3 memebered epoxide ring coupling constant is reduced due to the electronegative atom. J are very small in cis J= 5Hz & in trans J = 2 Hz.

The natural product cerulenin is as antibiotic containing cis epoxide. J = 5.5 Hz. Its a spreading out effect.

Structure activity relationship :Thienamycin isolated from fermentation of cultures of Streptomyces cattleya.
OH H H3C O N Thienamycin OO H S NH3+
OH H H S HC H3C N O Carbapenem COOH O Penicillin R R H H H S N N CH3 CH3 COOH

Coupling constant for 4 membered ring ( lactum) :Penicillin - cis, J = 5Hz Thienamycine Trans, J= 2.5 Hz (Vicinal) J = 12.5 18 Hz (Geminal coupling)

Vicinal coupling in structural analysis :-

Aflatoxine occur in moulds, grow on some foods cause liver cancer Slow acting poisons are among the most toxic compound known. The 4H on saturated 5 membered ring appeared as triplet delta H 2.61 & 3.42 Cis coupling at the junction is J=7Hz, 6.89 ppm 1H d J= 7Hz, tt
Cis coupling of olefinic H J= 2.5 Hz.

J= 5Hz.

Geminal coupling in 6 membered ring :Pederin:1.85 (1H, ddd, J5,10,12) 2.10 (1H, ddd, J3, 4,12) 3.75 (1H, dd, J4, 10) 3.85 (1H, ddd, J3, 5, 8) 4.00 (1H, dd, J3,7)

Diastereotopic pair at C5 geminal coupling J = 12Hz. Axial axial coupling J = 10 Hz. LHS chain must be at axial position and its surprising ! But molecule has no choice to play one of the place two side chains axial.

Pi contribution in geminal coupling :- geminal coupling in 6 membered J= 20Hz - 4 membered ring J= 6 Hz - Smaller J value because of next to electronegative atom. - Large J value because of adjacent pi bond.

Taxol :- Anticancer compound. 11Stereogenic

Centres.

- Stereochemistry and the conformation of molecules were

deduced by series of NOE experiment.
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Eradiation of methyl group on the same carbon atom gave the stereochemistry. The alliance between coupling constant & NOE use us powerful method for structural determination. Analysis of coupling constant & NOE allows determination of configuration in non-crystalline compound. Determination of conformation in solution