Isomers levorotatory

The synthesis of dextromethorphan is an outgrowth of early efforts to synthesize the morphine skeleton. /V-Methy1morphinan(40) was synthesized in 1946 (58,59). The 3-hydroxyl and the 3-methoxy analogues were prepared by the same method. Whereas the natural alkaloids of opium are optically active, ie, only one optical isomer can be isolated, synthetic routes to the morphine skeleton provide racemic mixtures, ie, both optical isomers, which can be separated, tested, and compared pharmacologically. In the case of 3-methoxy-/V-methylmorphinan, the levorotatory isomer levorphanol [77-07-6] (levorphan) was found to possess both analgesic and antitussive activity whereas the dextrorotatory isomer, dextromethorphan (39), possessed only antitussive activity. Dextromethorphan, unlike most narcotics, does not depress ciUary activity, secretion of respiratory tract fluid, or respiration. 

Acylation of ami noketone 8 with the acid chloride from p-toluic acid affords the corresponding ester (10) catalytic hydrogenation leads to the bronchodilator bitolerol (11). An analogous scheme starting from the N-methyl ketone (12) and pivaloyl chloride gives ami noalcohol (14). This compound is then resolved to isolate the levorotatory isomer. There is thus obtained the drug dipivefrin. 

The most serious objection to the ketolysis theory has been the report that D-glucose is without effect on the rate of disappearance of ketones in the animal body. This has, however, been denied by one group of investigators and it is possible that the divergent results might be ascribed to the use of the natural levorotatory isomer of /3-hydroxy-butyrate rather than the racemic salt employed by others. 

Levodopa Levodopa, (-)-3-(3,4-dihydroxyphenyl)-L-alanine (10.1.1), is a levorotatory isomer of dioxyphenylalanine used as a precursor of dopamine. There are a few ways of obtaining levodopa using a semisynthetic approach, which consists of the microbiological hydroxylation of L-tyrosine (10.1.1) [1,2], as well as implementing a purely synthetic approach. 

Levorotatory isomers of these drugs are much more powerful adrenoblockers than dextrorotatory isomers however, all of these drugs are made and used as racemic mixtures. 

The best known of the muscarinic blocking drugs are the belladonna alkaloids, atropine (Atropine) and scopolamine (Scopolamine). They are tertiary amines that contain an ester linkage. Atropine is a racemic mixture of DL-hyoscyamine, of which only the levorotatory isomer is pharmacologically active. Atropine and scopolamine are parent compounds for several semisynthetic derivatives, and some synthetic compounds with little structural similarity to the belladonna alkaloids are also in use. All of the antimuscarinic compounds are amino alcohol esters with a tertiary amine or quaternary ammonium group. 

Liothyronine sodium (Cytomel) is the sodium salt of the naturally occurring levorotatory isomer of T3. Liothyronine is generally not used for maintenance thyroid hormone replacement therapy because of its short plasma half-life and duration of action. The use of T3 alone is recommended only in special situations, such as in the initial therapy of myxedema and myxedema coma and the short-term suppression of TSH in patients undergoing surgery for thyroid cancer. The use of T3 alone may also be useful in patients with the rare condition of 5 -deiodinase deficiency who cannot convert T4 to T3. 

The levorotatory isomer of 3-hydroxy-A-methylmorphinan tartrate dihydrate (Levo-dromoran tartrate ) is a more potent analgesic than morphine with an approximately equal margin of safety, but is longer acting and has a lesser constipating action. Contraindications to its use, including the danger of addiction, are similar to those of morphine. 

The term meso (Greek, middle ) was used to describe an achiral member of a set of diastereomers, some of which are chiral. The optically inactive isomer seemed to be in the middle between the dextrorotatory and levorotatory isomers. The definition just given ( an achiral compound with chirality centers ) is nearly as complete, and more easily applied, especially when you remember that chirality centers are usually asymmetric carbon atoms. 

Doering and coworkers 3 > have avoided this difficulty using an optically active and deuterium, labeled diester to obtain stereochemical results fully consonant with our model. The levorotatory isomer was converted to a mixture of products from which the levorotatory antipode was obtained by resolution and found by nmr spectroscopy to have the deuterium atoms at the position shown. 

Pyrethroid insecticides can exist as enantiomers because they have two chiral centers, i.e., asymmetric carbons at C-l and C-3. An enantiomer exhibits optical activity and R/S configuration. Thus, a pyrethroid can show as either dextrorotatory (+) or levorotatory (-) isomer. A pyrethoid also can exist as either R or S form. However, only C-l is important to the biological activity of these compounds, and, for activity, it must be in the R position. As shown next, to be the 1R form, the -COOR group must be below the page. The IS form, which has -COOR group above the page, is nontoxic. Therefore, the active isomer of deltamethrin is expressed as (+)-ris-(lR) deltamethrin. The active isomer of permethrin is (lR)-ds-permethrin. 

Levamisole is the levorotatory isomer of tetramisole. Originally used only as an antihelminthic drug, it acts by paralysing the musculature of susceptible nematodes so that they are expelled by peristalsis. It is rapidly metabolized and excreted, with a half-hfe of about 4 hours. 

Levobupivacaine is the levorotatory isomer, 5(—)-bupiva-caine, of bupivacaine, an amide local anesthetic. 

The cardiovascular system is more resistant to the toxic effects of local anesthetics than the nervous system. Mild circulatory depression can precede nervous system toxicity, but seizures are more likely to occur before circulatory collapse. The intravenous dose of lidocaine required to produce cardiovascular coUapse is seven times that which causes seizures. The safety margin for racemic bupivacaine is much lower. The stereospecific levorotatory isomers levobupivacaine and ropivacaine are less cardiotoxic, and have a higher safety margin than bupivacaine, but not lidocaine in the case of ropivacaine this may be at the expense of reduced anesthetic potency (14,15). Toxicity from anesthetic combinations is additive. 

Praziquantel is effective in human cysticercosis in doses of 10-100 mg/kg for 3-21 days (1). Initially, longer courses of praziquantel were advocated, but even shorter treatment regimens are equally effective a complete course can be administered in a single day with comparable efficacy as conventional therapy of 15 days. Praziquantel was originally introduced as a racemic mixture there is evidence that the levorotatory isomer is relatively more effective, but has the same incidence of adverse reactions (2). 

Sulpiride and its levorotatory isomer levosulpiride are dopamine receptor antagonists. The pharmacology, efficacy, and tolerability of levosulpiride for dyspepsia and emesis have been reviewed (1). 

GRAS listed. Both the racemic mixture and the levorotatory isomer are accepted as food additives in Europe. The dl- and L-forms are included in the FDA Inactive Ingredients Guide (oral preparations). Included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients. 

Dimethindene Maleate. Dimcthindcne maleutc, ( )2-ll- 2- 2-dimethylamino)cthyl inden-3-yl ethyl pyri-dinc bimaleate (I I) (Forhistal Maleutc). occurs as a white to off-white crystalline powder that has a characteristic odor and is. sparingly soluble in water. This potent untihistaminic agent may be considered a derivative of the un.saturated pro-pylumines. The principal side effect is some sedation or drow.sinc.ss. The untihistaminic activity resides mainly in the levorotatory isomer. ... 

The optical activity of tylophorine arises from the chiral center at C-13a, Fig. (3). The levorotatory isomer has a 13a-R-configuration (13aa), while the dextrarotatory enantiomer has a 13a-S-orientation (13ap) [43, 46]. 

Thebaine (59), which is present in large amounts from the species of poppy Papaver bracteatum (292), serves as the precursor for the 6,14-erecfoetheno opiates. Although the natural levorotatory isomer of thebaine is inactive as an analgesic, it was recently reported that the (- -) isomer exhibits significant antinociceptive activity (369) both isomers exhibit some affinity for opioid receptors [the (- -) isomer for receptors and the (-) isomer for 8 receptors], but the affinities were very low (fiM). 

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