Morphine, mirror image

The biological consequences of molecular shape can be dramatic. Look at the structures of dextromethorphan and levomethorphan, for instance. (The Latin prefixes dextro- and levo- mean "right" and "left," respectively.) Dextromethorphan is a common cough suppressant found in many over-the-counter cold medicines, but its mirror-image, levomethorphan, is a powerful narcotic pain-reliever similar in its effects to morphine. The two substances are chemically identical except for their shapes, yet their biological properties are completely different. 

Sinomenine is the main alkaloid of the roots and stems of Sinomenium acutum Rehder and Wilson and Sinomenium diversifolius Diels, climbing plants indigenous to the woods of southern Japan (89). Sinomenine contains a hydrophenanthrene nucleus and an ethanamine bridge and is structurally very similar to morphine and codeine. The configuration at the asymmetric centers, C-5, C-9, C-12, and C-14 is the mirror image of those in morphine it affords a route to interesting enantiomorphs of morphins and morphinone derivatives. 

Other examples of alkaloids possessing the morphinan skeleton include sinomenine [6—8] isolated from the roots of Sinomenium acutum (Menisper-maceae), and metaphanine [9—14] isolated from the stems of Stephania japonica (Menispermaceae). Sinomenine possesses the mirror image skeleton to that of morphine, and is derived from (S)-reticuline. On the other hand, metaphanine possesses the hasubanan skeleton. Total syntheses of metaphanine have been reported [15,16]. 

Early confirmation of the existence of drug receptors was provided by substances that form pairs of optically-active stereoisomers. Numerous drugs, including morphine, atropine, and adrenaline, can be obtained in two forms, namely as dextro- and laevo-rotatory isomers (see Section 13.1), which differ strikingly in biological potency. Because the two members of such pairs have identical chemical and physical properties, and differ only in that their molecules are built as mirror images of one another, it is evident that the shape of a drug molecule is crucial for its action and that a part of the molecule may have to fit a structure complementary to it (Cushny, 1926). 

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