1609644-41-8Relevant academic research and scientific papers
MACROLIDES AND METHODS OF THEIR PREPARATION AND USE
-
Paragraph 00738, (2014/10/18)
Provided herein are methods of preparing macrolides by the coupling of an eastern and western half, followed by macrocyclization, to provide macrolides, including both known and novel macrolides. Intermediates in the synthesis of macrolides including the eastern and western halves are also provided. Pharmaceutical compositions and methods of treating infectious diseases and inflammatory conditions using the inventive macrolides are also provided. A general diastereoselective aldol methodology used in the synthesis of the western half is further provided.
Stereocontrolled synthesis of syn-β-hydroxy-α-amino acids by direct aldolization of pseudoephenamine glycinamide
Seiple, Ian B.,Mercer, Jaron A. M.,Sussman, Robin J.,Zhang, Ziyang,Myers, Andrew G.
, p. 4642 - 4647 (2014/05/20)
β-Hydroxy-α-amino acids figure prominently as chiral building blocks in chemical synthesis and serve as precursors to numerous important medicines. Reported herein is a method for the synthesis of β-hydroxy- α-amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one-flask protocol. Enolization of (R,R)- or (S,S)-pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of LiCl followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L- or D-threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55-98 %, and are readily transformed into β-hydroxy-α-amino acids by mild hydrolysis or into 2-amino-1,3-diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes. On aldol: Enolization of (R,R)- or (S,S)-pseudoephenamine glycinamide with lithium hexamethyldisilazide (LiHMDS) in the presence of LiCl followed by addition of either an aldehyde or ketone substrate affords aldol addition products which are stereochemically homologous with L- or D-threonine, respectively. These products can be obtained in stereoisomerically pure form in yields of 55-98 %, and are readily transformed into β-hydroxy-α-amino acids by mild hydrolysis or into 2-amino-1,3-diols by reduction.
