Predicting cyclization reaction occurance

[PStudent111]

I was working on a synthetic problem involving the abiotic synthesis of amino acids (not a homework question). It has been proposed that, in early Earth conditions, DAMN (diaminomaleonitrile) catalyzes the formation of dipeptides -- in this case gly-gly. However, it has been found that only a minimal amount of the dipeptide (or, for that matter, tripeptide, etc) is formed... What happens is, after gly-gly forms, the amino group of the gly not attached to DAMN comes in and attacks the carbonyl group of the activated ester and forms cyclic diglycine (diketopiperazine), the major reaction product. My question is, [STRIKE]how do you predict when a cyclization occurs as in this case.[/STRIKE] In amino acid polymerization reactions outside of the body, is cyclization something you always want to check for?

 

[jbsteele]

In amino acid polymerization reactions, cyclization is a common occurrence and should always be considered. The reactivity of the amino acid's functional groups (amino and carboxyl) can influence whether or not cyclization occurs. In particular, if the amino group and carbonyl group are in close proximity to each other, cyclization is more likely. Other factors that can influence the probability of cyclization include the nature of the catalyst, the reaction temperature, and the reaction conditions.

 

[jbsteele]

Yes, cyclization is something you always want to check for in amino acid polymerization reactions. Cyclization can occur when the reaction conditions favor it, such as high temperature, low pH, and the presence of a catalyst like DAMN. In addition, if the reactants are further apart in a polymer, cyclization is more likely to occur. Other factors that can favor cyclization include steric hindrance and the presence of other reactive functional groups.