Trans Isomerizations in Clavine Alkaloid Biosynthesis

The location of the label from C(2) of mevalonate in the methyl group of chanoclavine I (Fehr et al, 1966) suggested a second cis-trans isomerization during the synthesis of chanoclavine I. In the conversion of isopentenyl pyrophosphate to dimethylallyl pyrophosphate, C(2) of mevalonate becomes the trans-mQihy group of dimethylallyl pyrophosphate (Popjak and Corn-forth, 1966). Because the label is located in the cw-methyl group of chanoclavine I, a cis-trans isomerization apparently occurs in the formation of chanoclavine I from dimethylallyl pyrophosphate. 

Loss of the pro-S hydrogen from C(4) of mevalonate occurs in the normal isomerization of isopentenyl pyrophosphate to dimethylallyl pyrophosphate, whereas the pro R hydrogen is lost in the synthesis of rubber or dolichol, which results in the formation of cis double bonds. The proAS hydrogen of mevalonate was lost (Floss et al, 1968) in forming elymoclavine, supporting the normal pathway for formation of dimethylallyl pyrophosphate and a cis-trans isomerization on the pathway to chanoclavine I. 

Arigoni s group (Pachlatko et al, 1975a,b) synthesized [Z- CH3]-(7), fed it to Claviceps cultures, and showed that the label was located at C(7) ( 98%) of agroclavine and elymoclavine, i.e., in the carbon occupying the cis position. As a cis-trans isomerization occurs between chanoclavine I and agroclavine, another cis-trans isomerization is unequivocally indicated between 7 and chanoclavine I. These isomerizations are shown in Fig. 3. 

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