Synfacts 2007(1): 0104-0104  
DOI: 10.1055/s-2006-955686
Polymer-Supported Synthesis
© Georg Thieme Verlag Stuttgart · New York

Solid-Phase Synthesis of β-Lactam Analogues

Contributor(s): Yasuhiro Uozumi, Takayasu Arakawa
S. A. Testero, E. G. Mata*
Universidad Nacional de Rosario-CONICET, Argentina
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Publikationsverlauf

Publikationsdatum:
15. Dezember 2006 (online)

Significance

The solid-phase synthesis of β-lactam analogues of cholesterol absorption inhibitors was achieved via Staudinger reaction and olefin cross-metathesis. The resin-bound aniline 3 was prepared from N-Fmoc p-aminophenol 1 and Wang resin 2 using TMAD and Bu3P as coupling reagents. After Fmoc deprotection, the resulting resin-bound aniline was condensed with aldehyde 4 to give aldimine 5. Construction of the β-lactam ring was performed by the solid-supported Staudinger reaction using Mukaiyama’s reagent as an acid-activating agent to give 3-vinyl-β-lactam 6 with high trans selectivity. Olefin cross-meta­thesis of the resin-bound 3-vinyl-β-lactam 6 proceeded with complete E-selectivity with allylbenzene in the presence of the second-generation Grubbs precatalyst. The resulting β-lactam 7 was converted into the desired inhibitor 8 via cleavage of the resin supports, hydrogenation and methylation.