Synthesis of Protected Amino Alcohols and Amino Aldehydes.

Muscle degeneration and wasting in muscular dystrophy (MD) has been shown to be associated with high levels of proteolytic enzymes called Cathepsins. Antipain and leupeptin, naturally occurring peptide aldehydes, have been shown to be of possible therapeutic value in treatment of MD. The cost of these compounds, however, has made large scale clinical studies impossible. The purpose of this work was to develop a general synthesis of protected amino acid aldehydes, and to apply this methodology to the total synthesis of antipain.An efficient, general method for the synthesis of protected amino acid aldehydes was developed. The key intermediates in the synthesis are the corresponding protected amino alcohols. The amino alcohols were synthesized by borane THF reduction of Boc protected amino acids. These compounds had not been previously reported. Oxidation of the amino alcohols with pyridinium dichromate gave the amino aldehydes in high yields. The amino alcohols and aldehydes were characterized by NMR, IR, TLC, optical rotation, and derivatization.A total synthesis of antipain was designed, based on the synthetic method developed above. Although the total synthesis of antipain was not completed, a tetrapeptide which contains all the requisite functionality of the molecule was synthesized and characterized. It is anticipated that this molecule can be readily converted to antipain by use of the methods described above.

Level thesis:degree_level

Thesis

Year

1981

Author dc:creator

• Stanfield, Charles Freeman

• Muscle degeneration
• Proteolytic enzymes
• Amino acids
• Amino alcohols

Repository record dc:identifier

https://digitalcommons.library.uab.edu/etd-collection/7031

OAI identifier oai:identifier

oai:digitalcommons.library.uab.edu:etd-collection-8023