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Synthesis of Sulfonimidamide‐Based Amino Acid Building Blocks with Orthogonal Protecting Groups
Author(s) -
Chinthakindi Praveen K.,
Benediktsdottir Andrea,
Ibrahim Ayah,
Wared Atta,
Aurell CarlJohan,
Pettersen Anna,
Zamaratski Edouard,
Arvidsson Per I.,
Chen Yantao,
Sandström Anja
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201801541
Subject(s) - chemistry , diastereomer , peptidomimetic , amino acid , chemical space , chirality (physics) , protecting group , combinatorial chemistry , peptide , stereochemistry , organic chemistry , drug discovery , biochemistry , nambu–jona lasinio model , chiral symmetry breaking , alkyl , physics , quantum mechanics , quark
Herein, we report the synthesis of novel sulfonimidamides (SIAs) based on amino acid building blocks using a one‐pot method from tert ‐butyldiphenylsilyl‐protected (TBDPS) sulfonamides, as well as exploration of orthogonal deprotection strategies. Among the several protecting groups investigated, TBDPS showed higher conversion, allowed UV detection and simple diastereomeric separation; in particular in combination with amino acid tert‐ butyl esters. Moreover, we applied the present method to synthesize cyclic five‐membered acyl sulfonimidamides in two steps. The described synthesis of SIA‐based amino acid building blocks in combination with the orthogonal protection groups provide access to unnatural amino acid building blocks useful for further incorporation into larger molecules, such as peptide‐based transition‐state analogues and peptidomimetics. The chirality of the SIA group, as well as its additional point of diversity provided by the extra NH group, creates opportunities for the development of unique compound libraries that explore new chemical space, which is of considerable importance for the pharmaceutical and agrochemical industry.