Enantiomers compounds

It is often possible to convert an achiral compound to a chiral compound by (1) addition of a chiral group (2) running an asymmetric synthesis, and (3) cleavage of the original chiral group. An example is conversion of the achiral 2-pentanone to the chiral 4-methyl-3-heptanone (50). In this case, >99% of the product was the (5) enantiomer. Compound 49 is called a chiral auxiliary because it is used to induce asymmetry and then is removed. 

Know the primary methods for obtaining single enantiomer compounds... 

From January 2004 to June 2006, approximately 66% of all drugs approved by the U.S. Food and Drug Administration (FDA) were single enantiomer compounds (Figure 13.10).11 Only 7% of the approved drugs were mixtures of stereoisomers. 

Therefore, techniques for preparing single enantiomer compounds are of vital importance for both medicinal and process chemists. 

Approaches to single enantiomer compounds can be divided into two categories. One, the product may be formed as a racemic mixture with the desired enantiomer being separated afterward. This is a resolution approach. Two, a synthetic route may be designed to prepare mostly, if not exclusively, a single enantiomer. This technique is called asymmetric synthesis. 

Compounds with n different stereogenic centers may exist in a maximum of 2" forms. Of these, there will be 272 pairs of enantiomers. Compounds from different enantiomeric pairs are diastereomers. If two (or more) of the stereogenic centers are identical, certain isomers will be achiral. A meso form is an optically inactive, achiral form of a compound with stereogenic centers. Tartaric acid, which has two identical stereogenic centers, exists in three forms the R,R and S,S forms (a pair of enantiomers) and the achiral meso form. 

Issues related to prior art enablement, prima facie obviousness and secondary considerations of nonobviousness often intertwine in obvious determinations during patent prosecution and litigation since their definitional boundaries are often not well demarcated. In the case Sterling Drug Inc. v. Watson,69 the USPTO rejected claims to various single enantiomer compounds,70 and this decision was appealed to the U.S. District Court for the District of Colombia. The claims in question—10,12, and 14—are presented in Figure 8.18 together with the claimed structures (L-arterenol is the neurotransmitter norepinephrine).71... 

Chromatograms of the optical resolution of (I) and (II) Eire shown in Figure. 1. Compound (II) is completely resolved into its enantiomers chromatographically. The g-factor remains at its constant optimum value throughout the elution band of each enantiomer. Compound (I) in contrast is incompletely resolved, giving a single absorbance elution band, but a double bisignate difference absorbance band. The fractions of (I) eluted in the volume between the vertical dashed lines are incompletely resolved. Values for the g-max factors have been determined from the CD and absorption spectra of (I) and (II). 

In a field closely related to biphenyl, hindered rotation around the pyridyl-amide bond allowed the resolution of the nicotinamide analogue 142 into enantiomers. Compound 142 was optically stable at 25°C in water at higher temperatures racemization occurs (e.g., t1/2 = 3.1 hr at 100°C) (82RTC191 ... 

Strictly speaking, the availability of single-enantiomer compounds is not a future trend since some of them have already made an entry into clinical medicine. However, this technique s full potential is still unrealized, and it may lead to increased availability of many better and safer medications. The field of stereochemistry, which deals with the three-dimensional structure of molecules, teaches us that chemical compounds, medications included, can occur as a mixture of molecules whose structures are mirror images of each other. This means that two molecules that are otherwise identical may be spatially oriented in opposite directions, say, one to the right, the other to the left. Molecules so characterized are called enantiomers. 

ENANTIOMERS Compounds with the same molecular formula as the API, which differ in the spatial arrangement of atoms within the molecule and are on superimposabie mirror images. 

Enantiomer compounds have identical chemical reactivities except for their reactions with other chiral substances and how they affect plane polarized light. Enantiomers cause polarized light to rotate. If the light is rotated to the right, it gets the (+) symbol if it is rotated to the left, it gets the (-) symbol. 

Propose structures for compounds E-H. Compound E has the molecular formula CsHs and is optically active. On catalytic hydrogenation E yields F. Compound F has the molecular formula C5H10. is optically inactive, and cannot be resolved into separate enantiomers. Compound G has the molecular formula CgHio and is optically active. Compound G contains no triple bonds. On catalytic hydrogenation G yields H. Compound H has the molecular formula CeH, is optically inactive, and cannot be resolved into separate enantiomers. 

Schemes Gelators that gel as a single enantiomer. Compounds 13-21 are described in references [23-31], respectively...

Of the two thousand or so drug substances currently marketed worldwide, over 70% are synthetic. The remainder are derived either directly, or by semi-synthesis, from natural sources. Those in the latter category, perhaps not surprisingly, are overwhelmingly single enantiomer compounds. Examples include naturally occurring substances such as quini-dine/quinine and the semi-synthetic beta lactam antibiotic ampicillin. 

Compound A has molecular formula CsHio- Hydroboration-oxidation of compound A produces a pair of enantiomers, compounds B and C. When treated with HBr, compound A is converted into compound D, which is a tertiary alkyl bromide. When treated with O3 followed by DMS, compound A is converted into compounds E and F. Compound E has three carbon atoms, while compound F has only two carbon atoms. Identify the structures of compounds A, B, C, D, E, and F. 

Although in the past many of these compounds have been used in racemic form, the current trend in the pharmaceutical industry is toward enantiomerically pure drugs. The enantioselective synthesis or the chiral separation of racemic mixtures is often difficult, and synthetic chemistry is increasingly looking toward the use of enzymes for the preparation of single enantiomer compounds to be used for the generation of p-substituted pharmaceutical intermediates [9, 10], an area that our group has also focused on [11, 12]. 

Optical isomers Enantiomers compounds with chiral atoms that rotate plane polarized light in opposite directions (+/— or d/1). 

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