Malformins, a class of bicyclic pentapeptides derived from the fungus Aspergillus niger, have been shown to cause stem curvature, thickening, and malformations, as well as to inhibit stem elongation when applied to internodes of bean plants. Research has also indicated malformin A1 to be a mammalian toxin.  The C-C disulfide-mimetic derivative (cyclo-D-allylgly-D-allylgly-L-val-D-leu-L-ile) of malformin A1 has been synthesized using a solid phase synthesis/ring closing metathesis (RCM) approach.  Ruthenium-based ring closure of the allylglycine pendant olefins presents a particular challenge due to their unfavorable orientation across the intervening s-trans amide bond. Temporary protection of the amide nitrogen with a bulky 2,4-dimethoxybenzyl group has been shown by others to promote adoption of the favorable s-cis conformation for efficient RCM.  Application of this substitution and the challenges of coupling hindered secondary amines will be discussed in the context of this molecule.  Furthermore, a comparative structural study of the derivative and parent compound will be presented.

Synthesis and structural analysis of the C-C disulfide-mimetic derivative of malformin A1

245th National Meeting (2013)

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