Cocaine, molecular structure

MACCS-II enables direct interface with other database management systems, such as the Relational Database Management System (RDBMS) and Oracle, so that databases which contain text and numeric data for which special interfaces are normally needed can be constructed. For example, an Oracle MACCS-II linked system is currendy being used by the National Institute on Dmg Abuse (113) to develop a database that will allow scientists to determine the molecular structures of cocaine and other controlled substances as well as designer dmgs. 

Distinction should be made at this time between diastereoisomers and enantiomers. The former are characterized by the presence of at least two closely associated asymmetric centers in the molecular structure, either of which can epimerize. Altogether then there are two pairs of enantiomers for a total of four stereochemically unique individuals. Diastereoisomers have different physical properties and as a result discriminations, and even separations, can be done relatively easily. Enantiomers on the other hand differ in only one physical property, i.e. the direction of rotation of polarized light. Reaction of an enantiomeric racemic mixture with a third chiral species will produce a mixture of diastereomers therefore facilitating their identification or their separation. Early examples of this were the separations done by fractional crystallization of salts produced by a derivatization reaction with, for example, the alkaloid (-)-brucine. Fractional crystallization would never seem to be an effective analytical method yet it was used with some success in a forensic sciences context to confirm the presence of (L)-cocaine by a carefully contrived microcrystalline test. The physical properties... 

Morphine, cocaine, and mescaline are all examples of drugs that occur in plants but are commonly available in refined form as white powders, sold both legally and illegally. Some of them, such as mescaline, can easily be synthesized in laboratories, but even when they are, we can still call them natural drugs because the molecules already exist in nature. Others, such as cocaine and morphine, have more complex molecular structures. Chemists can make them in laboratories, but it is not cost efficient to do so. All the cocaine and morphine on the black market and in pharmacies arc extracted from coca leaves and opium poppies. 

FIGURE 14.1 Molecular structure of some of the common illicit drugs (top left to right bottom) cocaine, heroin hydrochloride, amphetamine, benzodiazepine derivative, sodium barbiturate, and psilocin. Note that all these are nitrogen bases. 

A refresher on molecular structure when every second bond is a double bond (e.g. benzene) the molecule is flat and rigid. A saturated ring (no double bonds), as in cocaine, is three-dimensional and fairly rigid. A saturated aliphatic molecule without a double bond (e.g. ethanol) is three-dimensional and flexible. For conformation, see Section 12.3. 

The observation that very significant parts of the cocaine molecule could be deleted from synthetic analogs without loss of biologic activity led to the search for the minimal structural feature consistent with activity. This exercise, sometimes referred to as molecular dissection, not only led to great simpli-fi cation of the structure of local anesthetics but resulted fi-tially in the preparation of active molecules that bear only the remotest structural relation to the prototype, cocaine. 

Walsh SL, Preston KL, SuUivan JT, Fromme R, Bigelow GE (1994) Fluoxetine alters the effects of intravenous cocaine in humans. J Clin Psychopharmacol 14 396-407 Weyand S, Shimamura T, Yajima S, Suzuki S, Mirza O, Krusong K, Carpenter EP, Rutherford NG, Hadden JM, O Reilly J, Ma P, Saidijam M, Patching SG, Hope RJ, Norbertczak HT, Roach PC, Iwata S, Henderson PJ, Cameron AD (2008) Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter. Science 322 709-713... 

Extension of Tropine Alkaloids. Here again, medicinal chemists have gone beyond nature by molecular modification. While cocaine possesses topical anesthetic activity but no local infiltration value as an anesthetic, a number of very useful, local anesthetic agents such as procaine and lidocaine have been derived from our knowledge of the structure of cocaine. Chemists have broadened the scope of usefulness of the cocaine structure. 

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