Amino acid-catalyzed synthesis of amino acid derivatives : Application and semi-synthesis of Paclitaxel, Docetaxel and their derivatives

University dissertation from Stockholm : Department of Organic Chemistry, Stockholm University

Abstract: This thesis deals with different applications of organocatalysis, where amino acid derivatives and small peptides are applied as catalysts. First, the development of environmentally friendly aldol reactions, carried out in aqueous media is illustrated. The corresponding ?-hydroxy ketones are formed with ee´s up to 99%. Chapter 3 describes the ability of ?3-amino acids to selectively catalyze Mannich-type reactions and govern the formation of products with high anti-selectivity (up to >19:1) and ee´s up to 99%. In the following chapter, an amino acid-catalyzed one-pot three component Mannich reaction between dihydroxyacetone and PMP-protected imines, is presented. The corresponding a,a’-dihydroxy-b-aminoketones are obtained in high yields and with 82-95% ee. Next, an aza-Morita-Baylis-Hillman reaction was investigated where L-proline is the catalyst. The reaction proceeds with excellent chemo- and enantioselectivity to give the corresponding compounds in good yields and with 97-99% ee. Finally, the last part describes development of a proline-catalyzed Mannich reation between N-acyl imines and protected ?-hydroxyaldehyes, providing access to different ?-hydroxy-?-amino acids in good yields and high enantioselctivity (92-99% ee). The obtained amino acids were further applied in the semisynthesis of paclitaxel and docetaxel derivatives.

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