1 Conformational Analysis Towards Structural Biology Chem3D Embed - - PDF document

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Carey Chapter 3 Conformations of Alkanes and Cycloalkanes Figure 3.5 Energy distribution vs. Temp. G = H - T S YSU YSU Conformational Analysis Towards Structural Biology Cytosine (C) (from TGCA alphabet in DNA YSU YSU

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Carey Chapter 3 – Conformations of Alkanes and Cycloalkanes

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Figure 3.5 – Energy distribution vs. Temp.

G = H - TS

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Conformational Analysis – Towards Structural Biology

Cytosine (C) (from TGCA alphabet in DNA

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Conformational Analysis – Towards Structural Biology

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Cytosine (C) (from TGCA alphabet in DNA

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Conformational Analysis – Towards Structural Biology

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Conformational Analysis – Medicinal Chemistry

Thymidine – incorporated into DNA as “T” Zidovudine (AZT) – incorporated into DNA instead

f T – stops chain growth

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Conformational Analysis – Medicinal Chemistry

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3.1 Conformational analysis of Ethane

Since single bonds can rotate around the bond axis, different conformations are possible ‐ conformational analysis

Figure 3.1 – Different representations of ethane ‐ ChemDraw YSU YSU

Different 3‐D depictions of Ethane Rotation around the central C‐C bond will cause the hydrogens to interact ‐ rotamers or conformers “Wedge/dash” “Sawhorse” “Newman”

3.1 Conformational Depictions of Acyclic Molecules

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3.1 Definitions for Using Newman Projections

Gauche torsion angle 60o Eclipsed torsion angle 0o Anti torsion angle 180o

Both gauche and anti conformers are staggered Eclipsed conformers are destabilized by torsional strain

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3.1 – Conformational Analysis of Ethane

Figure 3.4 – Rotation around the C‐C bond of Ethane

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3.2 Conformational Analysis of Butane

Figure 3.4 – Rotation around the C‐C bond of Ethane YSU YSU

3.3 Conformations of higher alkanes

Anti (staggered) eclipsed eclipsed

Applicable for any acyclic molecule

Gauche (staggered)

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3.4 Cycloalkanes – most are not planar

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3.5 Cyclopropane and Cyclobutane

Figure 3.10 – Depictions of Cyclopropane and Cyclobutane

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3.6 Conformations of Cyclopentane

Figure 3.12 – Important conformations of Cyclopentane

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3.7 Conformations of Cyclohexane

Conformationally flexible (without breaking bonds) Chair Boat Chair

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3.7-3.8 Cyclohexane – axial and equatorial positions

Figures 3.13 & 3.14 – Axial and Equatorial positions in cyclohexane chair and boat conformations YSU YSU

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3.7-3.8 Cyclohexane – axial and equatorial positions

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3.9 Conformational inversion – ring flipping

Figure 3.18 – Energetics

f the ring‐flip

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3.10 Equilibrium constants for ring-flips

G = H – TS G = ‐ RTlnK

Reactants Products

Equilibrium Constant (K) = [Products] [Reactants]

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3.10 Equilibrium constants for ring-flips

G = ‐ RTlnK Equilibrium Constant (K) = [Right‐Side] [Left‐Side]

Left-Side Right-Side

K > 1, RHS favoured; K ~ 1, equal; K < 1, LHS favoured

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3.10 Analysis of monosubstituted cyclohexanes

G = ‐0.24 Kcal/mol K = 1.5

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3.10 Analysis of monosubstituted cyclohexanes

G = ‐7.3 Kcal/mol K = 19

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3.10 Analysis of monosubstituted cyclohexanes

G = ‐8.6 Kcal/mol K = 32.3

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3.10 Analysis of monosubstituted cyclohexanes

G = ‐8.6 Kcal/mol K = 32.3

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3.10 Analysis of monosubstituted cyclohexanes

G = ‐22.8 Kcal/mol K = >9999

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3.10 Analysis of monosubstituted cyclohexanes

G = ‐22.8 Kcal/mol K = >9999

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3.10 Analysis of monosubstituted cyclohexanes

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3.11 Disubstituted Cyclopropanes – Stereoisomers

Figure 3.20 YSU YSU

3.12 Disubstituted Cycloalkanes - Stereoisomers

Cis‐1,2‐dimethylcyclopropane is less stable than the trans isomer Cis‐1,2‐dimethylcyclohexane is less stable than the trans isomer Cis‐1,3‐dimethylcyclohexane is more stable than the trans isomer Cis‐1,4‐dimethylcyclohexane is less stable than the trans isomer All based on interactions between substituents and

ther groups on the ring

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3.12 Disubstituted Cyclohexanes – Energy Differences

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3.13 Medium and large rings - Cyclodecane

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3.13 Medium and large rings - Erythromycin

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3.13 Medium and Large Rings – YSU Chemistry

O O O O O Ph N O O O O O Ph N O O O O O N2 N N N Rh2+

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3.14 Polycyclic Ring Systems

adamantane

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3.14 Polycyclic Ring Systems - Cholesterol

cholesterol

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3.14 Polycyclic Ring Systems - Bicyclics

Bicyclobutane Bicyclo[3.2.0]heptane Bicyclo[2.2.2]octane Bicyclo[2.1.0]pentane Bicyclo[4.1.0]heptane Bicyclo[4.2.2]decane

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3.15 Heterocyclic Compounds

tetrahydrofuran pyrrolidine piperidine indole YSU YSU

morphine ritilin librium

3.15 Heterocyclic Compounds

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3.15 Heterocyclic Compounds - Carbohydrates

O OH HO HO OH OH

D‐Glucose (dextrose, blood sugar)