New enantioselective entry to cycloheptane amino acid polyols.
[reaction: see text] A diversity-oriented protocol has been developed for the assembly of densely hydroxylated cycloheptane amino acids via succession of a vinylogous Mukaiyama aldol reaction (VMAR), a Morita-Baylis-Hillman reaction (MBHR), and an intramolecular pinacol coupling reaction (IPCR). The plan utilizes D- or L-configured glyceraldehyde derivatives as "chiral" surrogates of glyoxal and N-[(tert-butoxycarbonyl)-2-(tert-butyldimethylsilyl)oxy]pyrrole as the synthetic equivalent of the alpha,gamma-dianion of gamma-aminobutanoic acid. The parallel, asymmetric syntheses of four cycloheptane representatives proceed with high diastereocontrol and virtually complete enantioselectivity in ten steps and overall yields of 15-37%.
Curti
Claudio
C
Dipartimento Farmaceutico, Università di Parma, Parco Area delle Scienze 27A, I-43100 Parma, Italy.
Zanardi
Franca
F
Battistini
Lucia
L
Sartori
Andrea
A
Rassu
Gloria
G
Auzzas
Luciana
L
Roggio
Annamaria
A
Pinna
Luigi
L
Casiraghi
Giovanni
G
D000447:Aldehydes / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D003508:Cycloheptanes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D000596:Amino Acids; D003508:Cycloheptanes; D011108:Polymers; C024617:polyol