Amine protection amide

An isomiinchnone-based strategy has also been deployed to gain access to a new class of 5-functionalized adenosines [158]. Elaboration of the 5 -aminoadenosine 201 employing amine protection, amide formation with methyl malonyl chloride and the usual diazotransfer reaction led to the a-di-azoimide 202. The Rli2(pfbm)4-catalyzed reaction of the diazoimide 202 in the presence of ethyl vinyl ether yielded the endo-selective cycloadducts 203a... 

It should be noted that when a BOC-protected amide is subjected to MeONa treatment the amide bond is cleaved in preference to the BOC group (85-96% yield) because of the difference in steric factors. The BOC group can be removed by the methods used to remove it from simple amines. 

A number of people must be thanked for their contributions and help in completing this project. I am grateful to Gordon Bundy, who loaned me this card file, which provided many references that the computer failed to find, and to Bob Williams, Spencer Knapp, and Tohm Fukuyama for many references on amine and amide protection. I thank Theo Greene who checked and rechecked the manuscript for spelling and consistency and for the herculean task of checking all the references to make sure my 3s and 8s and 7s and 9s were not interchanged, all w iihout... 

Formation of an amide bond (peptide bond) will take place if an amine and not an alcohol attacks the acyl enzyme. If an amino acid (acid protected) is used, reactions can be continued to form oligo peptides. If an ester is used the process will be a kinetically controlled aminolysis. If an amino acid (amino protected) is used it will be reversed hydrolysis and if it is a protected amide or peptide it will be transpeptidation. Both of the latter methods are thermodynamically controlled. However, synthesis of peptides using biocatalytic methods (esterase, lipase or protease) is only of limited importance for two reasons. Synthesis by either of the above mentioned biocatalytic methods will take place in low water media and low solubility of peptides with more than 2-3 amino acids limits their value. Secondly, there are well developed non-biocatalytic methods for peptide synthesis. For small quantities the automated Merrifield method works well. 

For amine protection, sulfonamides such as 9 offer several advantages over urethanes 5 or amides 7. In particular, secondary amines protected as the urethane or the amide exist as mixtures of rotational isomers, confusing NMR characterization and making crystallization more difficult. The limitation has been that sulfonamides have been difficult to remove. Masanobu Uchiyama of the University of Tokyo reports (J. Am. Chem. Soc. 2004,126, 8755) the development of transition metal ate complexes that catalyze electron-transfer reduction. While the sulfonamide 10 is inert to Mg in THF, inclusion of a catalytic amount of the ate complex 11 led to 12 in quantitative yield. 

Regarding amine protecting groups, both amides and uretanes49 resist... 

Only the azide anion amongst the multitude of possible nitrogen nucleophiles had reported utility in alkynyliodonium salt addition chemistry at the inception of this project. Therefore, extension of this chemistry to amines and amide derivatives occupied our attention at the outset. The requirement for a soft, polarizable nucleophile limited our options, and screening a primary amine as well as some common amide derivatives in the prototype transformation 35 + 36 - 38 led to the first sense that this goal was achievable (Scheme 6).5a c In fact, the common amine protecting group tosyl proved to be the most effective modulator of amine nucleophilicity in this assay. Interestingly, amide pKa does not... 

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