ARGENTUM Exhibit 1155
` Argentum Pharmaceuticals LLC v. Research Corporation Technologies, Inc.
`IPR2016-00204
`
`Page 00001
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`192
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`CHAPTER 5
`
`Stereochemistry
`
`is no reason for the dextrorotatory product to be favored over a levorotatory one or vice
`versa. The (+) product and the (—) product are favored equally, and they are formed
`in equal amounts: a racemic mixture.
`
`5-1
`
`Enantiomeric Excess
`
`and Optical Purity
`
`Sometimes we deal with mixtures that are neither optically pure (all one enantiomer)
`nor racemic (equal amounts of two enantiomers). In these cases, we specify the optical
`purity (o.p.) of the mixture. The optical purity of a mixture is defined as the ratio of
`its rotation to the rotation of a pure enantiomer. For example, if we have some [mostly
`(+)] butan-2-01 with a specific rotation of +9.72°, we compare this rotation with the
`+ l3.5° rotation of the pure (+) enantiomer.
`observed rotation
`Op = "4 —*‘;—"’
`rotation of pure enantiomer
`
`X
`
`0 _ _9.72"‘
`/0
`13.50
`
`X 100% = 72.0%
`
`The enantiomeric excess (e.e.) is a similar method for expressing the relative
`amounts of enantiomers in a mixture. To compute the enantiomeric excess of a mixture.
`we calculate the excess of the predominant enantiomer as a percentage of the entire
`mixture. For a chemically pure compound, the calculation of enantiomeric excess gen-
`erally gives the same result as the calculation of optical purity, and we often use the two
`terms interchangeably. Algebraically, we use the following formula:
`_ld—l|
`X 1007 _ (excess of one over the other) X 1000/
`_’d+l
`0 _
`(entire mixture)
`0
`
`o.p. = e.e.
`
`The units cancel out in the calculation of either e.e. or o.p., so these formulas can be used
`whether the amounts of the enantiomers are expressed in concentrations, grams, or per-
`centages. For the butan-2-01 mixture just described, the optical purity of 72% (-2-,
`implies that d — l = 72%, and we know that d + l = 100%. Adding the equations
`gives 2d = 172%. We conclude that the mixture contains 86% of the d or (+) enan-
`tiomer and 14% of the l or (—) enantiomer.
`
`
`Calculate the e.e. and the specific rotation of a mixture containing 6.0 g of (+)-butan-2-01
`l
`and 4.0 g of (—)-butan-2-ol.
`5 Sfllflilllil
`’
`In this mixture, there is a 2.0 g excess of the (+) isomer and a total of 10.0 g, for an e.e. of 2041
`i We can envision this mixture as 80% racemic [4.0 g(+) and 4.0 g(- )] and 20% pure (+).
`
`'
`
`0.p. = e.e. =
`
`6.0 — 4.0
`
`2_o
`
`=
`
`= 20%
`
`‘ The specific rotation of enantiomerically pure (+ )-butan—2-ol is +13.5°. The rotation of this
`mixture is
`
`observed rotation = (rotation of pure enantiomer) X (o.p.)
`
`.
`
`= (+13.5°) x (20%) = +2.7°
`
`Application: Drugs .................................... ...
`Several racemic drugs have recently
`i
`become available as pure active enan-
`5
`tiomers. For example, the drug Nexium®
`(for controlling acid reflux) contains iust
`the active enantiomer of the racemic
`mixture in Pri|osec®.
`
`5
`
`"1-.~.i
`
`
`
`
`
`
`
`
`
` ~-...- ‘in-‘_\I «.. V... r—.r.
`When optically pure (R)—2-bromobutane is heated with water, butan-2-01 is the product.
`reaction forms twice as much (S)—butan-2—ol as (R)-butan-2-ol. Calculate the e.e. and the s
`ciflc rotation expected for the product.
`
`
`0 A chemist finds that the addition of (+ )-epinephrine to the catalytic reduction of butan-2-0
`(Figure 5-16) gives a product that is slightly optically active, with a specific rotation of +0.45‘
`‘ Calculate the percentages of (+ )-butan—2-ol and (- )-butan—2-ol formed in this reaction.
`
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`ORGANIC
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`CHEMISTRY
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`EIGHTH EDITION
`
`L.G. WADE, IR.
`
`WHITMAN COLLEGE
`
`PEARSON
`
`San Francisco Upper Saddle River
`Indianapolis New York
`Boston Columbus
`Amsterdam Cape Town Dubai
`London Madrid Milan Munich
`Paris Montreal Toronto
`
`Delhi Mexico City
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`Séo Paulo
`
`Sydney Hong Kong
`
`Seoul
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`Singapore Taipei Tokyo
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