Enantioselective total synthesis of (1R,3S,4R,5R)-1-amino-4,5-dihydroxycyclopentane-1,3-dicarboxylic acid. A full-aldol access to carbaketose derivatives.
The enantioselective synthesis of cyclopentanedicarboxylic amino acid 1, a novel rigid and functionalized L-glutamic acid analogue, has been achieved in 15 linear steps from silyloxypyrrole 3, utilizing L-glyceraldehyde 4 as the source of chirality. The key steps in the synthesis are three sequential aldol-based carbon-carbon bond-forming reactions: two crossed vinylogous aldol additions (2 + 3 --> 8 and 4 + 5 --> 10 + 11) and one intramolecular silylative aldolization (6 --> 7). En passant, the short syntheses of (2S)-2-hydroxymethylglutamic acid (16) and its (2R)-enantiomer ent-16, a potent metabotropic glutamate receptor agonist, have been achieved.
Battistini
Lucia
L
Dipartimento Farmaceutico, Università di Parma, Parco Area delle Scienze 27A, I-43100 Parma, Italy.
Curti
Claudio
C
Zanardi
Franca
F
Rassu
Gloria
G
Auzzas
Luciana
L
Casiraghi
Giovanni
G
D002384:Catalysis; D003998:Dicarboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D018698:Glutamic Acid / Q000737:chemistry; D007202:Indicators and Reagents; D015394:Molecular Structure; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013237:Stereoisomerism
C486180:(1R,3S,4R,5R)-1-amino-4,5-dihydroxycyclopentane-1,3-dicarboxylic acid; D003998:Dicarboxylic Acids; D007202:Indicators and Reagents; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid