1. A General Synthetic Route to Isomeric Pyrrolo[1,2- x][1,4]diazepinones
Elena Y Zelina, Tatyana A Nevolina, Ludmila N Sorotskaja, Dmitry A Skvortsov, Igor V Trushkov, Maxim G Uchuskin J Org Chem. 2018 Oct 5;83(19):11747-11757. doi: 10.1021/acs.joc.8b01669. Epub 2018 Sep 5.
A simple one-pot method for the synthesis of isomeric pyrrolo[1,2- x][1,4]diazepinones in reasonable yields was developed. The method is based on the condensation of readily available N-Boc amino acids with biomass-derived furans containing aminoalkyl groups followed by deprotection, furan ring opening, and Paal-Knorr cyclization. Using this approach, we synthesized pyrrolo[1,2- a][1,4]diazepin-3(2 H)-ones from furfurylamines and β-amino acids and pyrrolo[1,2- d][1,4]diazepin-4(5 H)-ones from 2-(2-furyl)ethylamines and α-amino acids. The cytotoxicity of the synthesized pyrrolodiazepinones was studied.
2. Constrained Dipeptide Surrogates: 5- and 7-Hydroxy Indolizidin-2-one Amino Acid Synthesis from Iodolactonization of Dehydro-2,8-diamino Azelates
Ramakotaiah Mulamreddy, William D Lubell Molecules. 2021 Dec 23;27(1):67. doi: 10.3390/molecules27010067.
The constrained dipeptide surrogates 5- and 7-hydroxy indolizidin-2-one N-(Boc)amino acids have been synthesized from L-serine as a chiral educt. A linear precursor ∆4-unsaturated (2S,8S)-2,8-bis[N-(Boc)amino]azelic acid was prepared in five steps from L-serine. Although epoxidation and dihydroxylation pathways gave mixtures of hydroxy indolizidin-2-one diastereomers, iodolactonization of the ∆4-azelate stereoselectively delivered a lactone iodide from which separable (5S)- and (7S)-hydroxy indolizidin-2-one N-(Boc)amino esters were synthesized by sequences featuring intramolecular iodide displacement and lactam formation. X-ray analysis of the (7S)-hydroxy indolizidin-2-one N-(Boc)amino ester indicated that the backbone dihedral angles embedded in the bicyclic ring system resembled those of the central residues of an ideal type II' β-turn indicating the potential for peptide mimicry.
3. Synthesis of Four Enantiomers of (1-Amino-3-Hydroxypropane-1,3-Diyl)Diphosphonic Acid as Diphosphonate Analogues of 4-Hydroxyglutamic Acid
Liwia Lebelt, Iwona E Głowacka, Dorota G Piotrowska Molecules. 2022 Apr 22;27(9):2699. doi: 10.3390/molecules27092699.
All the enantiomers of (1-amino-3-hydroxypropane-1,3-diyl)diphosphonic acid, newly design phosphonate analogues of 4-hydroxyglutamic acids, were obtained. The synthetic strategy involved Abramov reactions of diethyl (R)- and (S)-1-(N-Boc-amino)-3-oxopropylphosphonates with diethyl phosphite, separation of diastereoisomeric [1-(N-Boc-amino)-3-hydroxypropane-1,3-diyl]diphosphonates as O-protected esters, followed by their hydrolysis to the enantiomeric phosphonic acids. The absolute configuration of the enantiomeric phosphonates was established by comparing the 31P NMR chemical shifts of respective (S)-O-methylmandelic acid esters obtained from respective pairs of syn- and anti-[1-(N-Boc-amino)-3-hydroxypropane-1,3-diyl]diphosphonates according to the Spilling rule.
