Synthesis and modification of dibenzylglycine derivatives via the Suzuki-Miyaura cross-coupling reaction.
The objective of this paper is to describe in details of various available methods to prepare C(alpha,alpha)-dibenzylglycine (Dbzg) and then include our work involving the synthesis of side chain Dbzg derivatives. alpha,alpha-Disubstituted amino acids (alpha,alphaAAs) are important members in the family of modified amino acids. Replacement of the alpha-hydrogens of glycine 1 by alkyl groups leads to alpha,alphaAAs. The steric hindrance of the quaternary centre of Aib 2 combined with the helix-forming capacity has attracted the attention of structural biologists and protein crystallographers. Dbzg 3 is a special structural variant of Aib. The presence of two benzyl groups at C(alpha)-position not only impart rigidity to the peptide backbone in which it is incorporated, but also acts as a useful vehicle for studying pi-pi interactions. Although several C(alpha,alpha)-disubstituted glycines such as C(alpha,alpha)-diethyl glycine (Deg), C(alpha,alpha)-dipropyl glycine (Dpg) etc. have been studied in detail, not much has been known about Dbzg because of limited availability of synthetic procedures. Various Dbzg derivatives 19a-f have been prepared using ethyl isocyanoacetate 14 as a glycine equivalent (eq.). A useful and simple methodology has been developed using the Suzuki-Miyaura cross-coupling reaction for the modification of Dbzg derivatives 17d, 19d, 22. Using this 'Building Block Approach' (Accounts of Chemical Research 36, 2003, 342) one can generate a variety of Dbzg derivatives 20a-f and 23a-e, which may find useful applications in combinatorial synthesis and QSAR studies.
Kotha
S
S
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai 400076, India. srk@chem.iitb.ac.in
Behera
M
M
D000085:Acetates / Q000737:chemistry; D001965:Bromides / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
D000085:Acetates; D001965:Bromides; D003432:Cross-Linking Reagents; C007170:cyanoacetic acid; D005998:Glycine