Amines corrins

Alkylations by oxonium salts have added several new weapons to the synthetic chemist s armamentarium. For example, the O-alkylated products from amides [R1C(OR)=NR2R3]+ (R == CH3 or C2H5) may be hydrolyzed under mild conditions to amines and esters,14-34 reduced to the amines RjCH-jNRaRa by sodium borohydride,13 converted to amide acetals RiC(OR)2NR2R3 by alkoxides,4-16 and (for R3 = H) deproton-ated to the imino esters R1C(OR)=NR2.16-18 Amide acetals and imino esters are themselves in turn useful synthetic intermediates. Indeed, oxonium salts transform the rather intractable amide group into a highly reactive and versatile functionality, a fact elegantly exploited in recent work on the synthesis of corrins.34... 

The types of model systems in which 5-coordinate species have been invoked range from the relatively electron-deficient cobaloximes to the relatively electron-rich Schiff base complexes, where the corrin ring in cobal-amins is replaced by two dioximato ligands or by a quadridentate N202 dinegative Schiff base ligand, respectively. These two classes of models, in fact, appear to bracket many characteristics of cobalamins since the cobaloximes are too electron-deficient and the Schiff base complexes are too electron-rich [136], As such, an understanding of the differences in properties between these two types... 

Mechanism (1), first suggested almost three decades ago [150], continues to be the most invoked explanation of the role of the enzyme in promoting homolysis. Cleavage of the C—Co bond of sterically hindered alkylcobalamins (e.g., neopentylcobalamin) was markedly increased by diol dehydrase [72], Such cobal-amins do not function as coenzymes but convert to enzyme-bound hydroxocobal-amin in stoichiometric first-order reactions. The strong competitive inhibition by AdoB 12 indicates that labilization occurs at the active site of the enzyme and is suggested to be caused by a steric distortion of the corrin ring. 

One aspect of archaeal corrinoid biosynthesis that remains to be verified is the formation of the l-amino-2-propanol linker in the lower ligand loop of the corrinoid. Possible sources include the reductive amination of lactaldehyde, the reductive amination of pyruvate, or the decarboxylation of threonine. Several bacteria have been shown to directly incorporate N-labeled threonine into aminopropanol and coenzyme Bi2- A threonine decarboxylase (CobD) has been detected in Streptomyces griseus and Salmonella typhimuriumP Studies with CobD from S. typhimurium LT2 were able to clearly demonstrate the decarboxylation of threonine-phosphate however, the timing of the decarboxylation could not be demonstrated and may occur prior to or after addition of the threonine-P to the corrin ring. " ... 

In solution the intramolecular coordination of the nucleotide function to the lower a-axial coordination site of the corrin-bound cobalt center of complete corrins occurs with Httle build-up of strain [149]. This allows the (coordinating) nucleotide to steer the reactivity, as well as the face-selectivity, of certain organometalUc reactions involving the corrin-boimd cobalt center [75]. Experiments by Eschenmoser demonstrated that cobal-amins can self-constitute in solution from the Bi2-nucleotide portion and incomplete cobyrinic acid derivatives to show a remarkable kinetic and thermodynamic preference for the specific formation of the B 12-structure, and to a pre-enzymatic origin of the basic structural elements of the complete corrins [149]. 

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