Synthesis of 4-hydroxy-β3-homoprolines and their insertion in α/β/α-tripeptides.
The stereoselective syntheses of 2-cyclopropyl- and (2S)-2-hydroxymethyl-(3R,4S)-4-hydroxy-β(3)-homoproline are described. The reported amino acids were constructed through 1,3-dipolar cycloaddition of strained alkylidenecyclopropanes with enantiopure pyrroline N-oxides derived from malic acid followed by thermal rearrangement of the adducts in the presence of trifluoroacetic acid. The two-step sequence afforded the homoprolines suitably protected to be directly used as building blocks in peptidomimetic synthesis as proved by the synthesis of the two model mixed α/β/α tripeptides Phe-β(3)-HPro-Val.
Dipartimento di Chimica Ugo Schiff, Università degli Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino, FI, Italy. franca.cordero@unifi.it
Franca M
FM
Cordero
Carolina
C
Vurchio
Marco
M
Lumini
Alberto
A
Brandi
D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D013237:Stereoisomerism
D009842:Oligopeptides; D011758:Pyrroles; C013231:pyrroline; D011392:Proline; C010983:homoproline