Stereochemistry: Chiral Drugs

Stereochemistry Chiral Drugs: An object is said to be chiral if it and its mirror image are non-superimposable (like our left and right hand) Plane polarized light is light whose electric and magnetic fields oscillate in just one direction Chiral molecules are optically active (meaning that when a beam of plane-polarized light passes through a chiral molecule, it interacts with the molecule in such a way that the angle of the plane of oscillation rotates) Enantiomers, which have the same physical properties, will always rotate plane polarized light by the same degree, but in opposite directions If it rotates light clockwise then it is (+) → dextrorotatory If it rotates light counterclockwise then it is (-) → levorotatory Also, there is no correlation between (+)/(-) to R/S, R can be either and so can S In order to assign R/S, make sure that the lowest priority atom (typically H) is going away from you Enantiomers interact differently with enzymes in our own body (yes they can tell!) Enantiomeric Excess (ee) is a measurement of the degree of purity of any chiral sample (0% means both enantiomers are present in a 1:1 ratio, while 100% means it is purely made up of one enantiomer) If a sample contains 70% of R isomer and 30% of S isomer, then it will have an enantiomeric excess of 40%. This can be rationalized as a mixture of 40% pure R with 60% (30% R and 30% S) of a racemic mixture Structural (Constitutional) Isomers: A structural isomer of a compound is another compound whose molecule has the same number of atoms of each element, but with logically distinct bonds between them Stereoisomers, Enantiomers, & Chirality Centers: Stereoisomers are isomers of a compound that differ in their three dimensional arrangement (can still be connected to the same atoms) Chiral/Chirality Center is a tetrahedral carbon (sp3 hybridized) that has four different groups coming off of it 2n will tell you the maximum amount of stereoisomers there is (n = # of chiral centers) Identifying Chirality Centers: Basically, find a carbon atom attached to four different groups R,S System: If there are ties, write down what the second atom is bonded to and the first point of difference is what you will use in order to determine priorities If double bonded, then it is bonded to it twice If you need to rotate the molecule a lot, pretend it is a Newman Projection and stare down that bond so that the lowest priority is going backward Optical Activity: Enantiomers have the same boiling point, melting point, density, etc. The only difference occurs when you place it into a chiral environment (opposite signs of specific rotations but same magnitude) The more molecules the plane polarized light hits, the more that it will rotate ɑ is known as the observed rotation (+ if clockwise and - if counterclockwise) and depends on the # of molecules hit by the plane polarized light (therefore must be standardized with respect to its concentration) If concentration is doubled, the observed rotation is ALSO doubled If you double the pathlength, then you ALSO double the observed rotation [ɑ] is known as the specific rotation which is the same for all molecules of that specific chirality (CONSTANT whereas observed rotation could change if the variables are different) ɑ [ɑ] = ["]ℓ - The specific rotation can differ at different temperatures and wavelengths Enantiomers & Diastereomers: Enantiomers are stereoisomers that are non superimposable, mirror images that have opposite configuration at all chiral centers (inseparable but can be separated using a chiral stationary phase) Diastereomers are stereoisomers that are non superimposable, non-mirror images that have opposite configuration at some chiral centers (need at least 2 chiral centers and differs at individual chiral centers) → can have different physical properties and similar chemical properties (therefore are separable through physical means) Cis-trans Isomerism: Cis and trans works for groups that are identical to one another on either side of the double bond You can use hydrogen as a group if other groups aren’t identical If two identical groups are bonded to the same carbon on the double bond, you can’t use cis/trans terminology For IUPAC Naming, just place cis- or trans- at the front of the name E-Z System: Cases where cis/trans is not usable because there aren’t identical groups E is big groups are on the opposite side and Z is big groups on the same side (on “za zame zide”) “Big groups” are assigned priority in the exact same way that priority is assigned in R/S configuration For IUPAC Naming, just place (E)- or (Z)- at the front of the name Stereogenic center has to do with double bond stuff?? Conformations of Ethane: Conformations are different arrangements of atoms that result from bond rotation Newman Projection is looking straight down the bond Eclipse conformation is when the groups in the front are directly in front of the groups in the back Staggered conformation is when the groups in the front are in between the groups in the back Staggered anti is when the big group is separated by 180° (pretty stable) Staggered gauche is when the big group is separated by 60° (less stable) Dihedral angle or torsional angle is the angle between the different groups in a Newman projection (stacking on top of one another can lead to torsional strain) Steric hindrance has to do with the idea of bulky things getting in the way of certain reactions and other things occurring Staggered conformation has less potential energy than the eclipsed conformation because of how close the groups get to one another Extra Notes: For Ethylene glycol the OH groups present a unique situation where the dipoles on each stabilize the gauche conformation of one another Meso Compounds are achiral compounds that have chiral centers (can be superimposed and are optically inactive) and must have at least two stereocenters (diastereomeric to the other stereoisomers)