Abstract
An Ugi multicomponent reaction with chiral cyclic amino acids, benzyl isocyanide and cyclic ketones (or acetone) has been exploited as key step for the generation of peptidomimetics. After a straightforward set of elaborations, the peptidomimetics were converted into polycyclic scaffolds displaying two orthogonally protected secondary amines. Libraries of compounds were obtained decorating the molecules through acylation/reductive amination reactions on these functional groups.
Highlights
Drug research is nowadays suffering from the relatively low number of newly approved medicines with a clear health benefit for patients
Among Multicomponent reactions (MCRs), isocyanide (Koopmanschap et al, 2014; Giustiniano et al, 2017)-based ones, and the Ugi reaction (U-4CR) (Dömling and Ugi, 2000; Dömling, 2006), are by far the most versatile and exploited ones, because different variants are available. One of these is the so-called Ugi-5-center-4-component reaction (U-5C-4CR) that, employing α (Demharter et al, 1996; Ugi et al, 1996; Park et al, 1998; Kim et al, 2001; Zimmer et al, 2001; Liu and Dömling, 2009; Mandai et al, 2011; Mimura et al, 2015)- or β (Basso et al, 2004, 2005, 2010)-amino acids as bifunctional reagents, generates α,α′-imino dicarboxylic acid derivatives A according to the general mechanism depicted in Scheme 1
Our studies started by investigating the reactivity of trans4-hydroxy-L-proline with N-Boc-azetidinone and benzyl isocyanide in methanol (Scheme 3)
Summary
Drug research is nowadays suffering from the relatively low number of newly approved medicines with a clear health benefit for patients. Novel scaffolds with new modes of action are highly desirable, and the possibility to assemble them through straightforward, yet complexity generating, procedures is a major challenge. Among MCRs, isocyanide (Koopmanschap et al, 2014; Giustiniano et al, 2017)-based ones, and the Ugi reaction (U-4CR) (Dömling and Ugi, 2000; Dömling, 2006), are by far the most versatile and exploited ones, because different variants are available. One of these is the so-called Ugi-5-center-4-component reaction (U-5C-4CR) that, employing α (Demharter et al, 1996; Ugi et al, 1996; Park et al, 1998; Kim et al, 2001; Zimmer et al, 2001; Liu and Dömling, 2009; Mandai et al, 2011; Mimura et al, 2015)- or β (Basso et al, 2004, 2005, 2010)-amino acids as bifunctional reagents, generates α,α′-imino dicarboxylic acid derivatives A according to the general mechanism depicted in Scheme 1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
