147698-06-4Relevant academic research and scientific papers
An olefination entry for the synthesis of enantiopure α,ω-diaminodicarboxylates and azabicyclo[X.Y.0]alkane amino acids
Gosselin, Francis,Lubell, William D.
, p. 7463 - 7471 (2007/10/03)
A new approach for synthesizing α,ω-diaminodicarboxylates of various chain lengths has opened the way for making a series of azabicyclo[X.Y.0]alkane amino acids of different ring sizes. β-Keto phosphonates 21-23 were synthesized in 71-90% yield by the addition of the lithium anion of dimethyl methyl phosphonate to the ω-methyl ester of α.-tert-butyl N-(PhF)aspartate 3, glutamate 9, and aminoadipate 12 (PhF = 9-phenylfluoren-9-yl). α,ω-Diaminodicarboxylates 24-26 of nine to eleven carbon chain lengths were prepared in 78-87% yield from the Horner-WadsworthEmmons olefination of α-tert-butyl .ZV-(PhF)aspartatc β-aldehyde (5) with aminodicarboxylate-derived β-keto phosphonates 21-23. The power of this approach for making azabicyclo[X.Y.0]alkane amino acid was then illustrated by the first synthesis of enantiopure indolizidin-9-one amino acid 2 in nine steps and >25% overall yield from inexpensive aspartic acid as chiral educt. Hydrogenation of (2S,8S)-di-tcrt-butyl 4-oxo-2,8-bis[N-(PhF)amino]non-4-enedioate (24) in 9:1 EtOH:AcOH furnished a 9:1 diastereomeric mixture of 6-alkylpipecolate 28 that was subsequently transformed into azabicyclo[4.3.0]alkane amino acid 2 via lactam cyclization and protecting group manipulations. Because α,ω-diaminodicarboxylates 25 and 26 may be similarly converted to heterocycles of larger ring sizes and because alkylation of similar ketones can be used to attach side-chains at different points on the heterocycle, this olefination strategy greatly expands our methodology for synthesizing azabicyclo[X.Y.0]alkane amino acids for the exploration of conformation-activity relationships of various biologically active peptides.
Chirospecific Synthesis of (1S,3R)-1-Amino-3-(hydroxymethyl)cyclopentane, Precursor for Carbocyclic Nucleoside Synthesis. Dieckmann Cyclization with an α-Amino Acid
Bergmeier, Stephen C.,Cobas, Agustin A.,Rapoport, Henry
, p. 2369 - 2376 (2007/10/02)
Carbocyclic nucleosides are important isosters of nucleosides possessing a variety of antiviral and antineoplastic activities.We report here a new method for the chirospecific synthesis of (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.This compound is a key precursor for the synthesis of some carbocyclic nucleosides.The method involves (1) an improved synthesis of (S)-2-aminoadipic acid; (2) Dieckmann cyclization of this α-amino acid to an aminocyclopentanone; and (3) elaboration of the latter to the target (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.The starting (S)-2-aminoadipic acid δ-methyl ester was prepared enantiomerically pure from (S)-aspartic acid in 51percent overall yield.Dieckmann condensation converted this amino acid to a (methoxycarbonyl)-cyclopentanone, and reduction of the ketone followed by elimination yielded (S)-3--1-(methoxycarbonyl)cyclopentene.Reduction of the double bond gave a mixture of the cis and trans diastereomers.This mixture was converted to a single diastereomer by epimerization and trapping of the cis isomer as (1S,4R)-2-(9-phenylfluoren-9-yl)-2-azabicycloheptan-3-one.Hydrolytic cleavage of the lactam followed by reduction gave (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.
