1410783-69-5Relevant articles and documents
Novel synthesis of various orthogonally protected Cα- methyllysine analogues and biological evaluation of a Vapreotide analogue containing (S)-α-methyllysine
Banerjee, Souvik,Wiggins, Walker J.,Geoghegan, Jessie L.,Anthony, Catherine T.,Woltering, Eugene A.,Masterson, Douglas S.
supporting information, p. 6307 - 6319 (2013/09/23)
Prochiral malonic diesters containing a quaternary carbon center have been successfully transformed into a diverse set of tBoc-Fmoc- α2,2-methyllysine-OH analogues through chiral malonic half-ester intermediates obtained via enzymatic (Pig Liver Esterase, PLE) hydrolysis. The variety of chiral half-ester intermediates, which vary from 1 to 6 methylene units in the side chain, are achieved in moderate to high optical purity and in good yields. The PLE hydrolysis of malonic diesters with various side chain lengths appears to obey the Jones's PLE model according to the stereochemical configurations of the resulting chiral half-esters. The established synthetic strategy allows the construction of both enantiomers of α2,2-methyllysine analogues, and a (S)-β2,2- methyllysine analogue from a common synthon by straightforward manipulation of protecting groups. Two different straightforward and cost effective synthetic strategies are described for the synthesis of α2,2-methyllysine analogues. The described strategies should find significant usefulness in preparing novel peptide libraries with unnatural lysine analogues. A Vapreotide analogue incorporating (S)-α2,2-methyllysine was prepared. However, the Vapreotide analogue with (S)-α-methyl-α-lysine is found to lose its specific binding to somatostatin receptor subtype 2 (SSTR2).
A stereoselective cyclization strategy for the preparation of γ-lactams and their use in the synthesis of α-Methyl-β-proline
Banerjee, Souvik,Smith, Justin,Smith, Jillian,Faulkner, Caleb,Masterson, Douglas S.
, p. 10925 - 10930 (2013/02/22)
A straightforward stereoselective and enantiodivergent cyclization strategy for the construction of γ-lactams is described. The cyclization strategy makes use of chiral malonic esters prepared from enantiomerically enriched monoesters of disubstituted malonic acid. The cyclization occurs with the selective displacement of a substituted benzyl alcohol as the leaving group. A Hammett study illustrates that the cyclization is under electronic control. The resulting γ-lactam can be readily converted into a novel proline analogue.
