2-nitrophenyl isocyanide as a versatile convertible isocyanide: rapid access to a fused gamma-lactam beta-lactone bicycle.
2-Nitrophenyl isocyanide is introduced as a convertible isocyanide with demonstration of its feasibility and applicability in an efficient synthesis of the fused gamma-lactam beta-lactone bicycle of proteasome inhibitor omuralide. Starting from a linear keto acid precursor, the fused gamma-lactam beta-lactone bicycle was prepared in four steps by a sequential biscyclization strategy; a stereocontrolled Ugi reaction and the concomitant direct beta-lactonization following the formation of an N-acylbenzotriazole intermediate. The N-acylbenzotriazole is amenable to intra- or intermolecular attack from a variety of nucleophiles with a catalytic amount of base to form the pyroglutamic acid derivatives.
Gilley
Cynthia B
CB
Department of Chemistry and Biochemistry, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0343, USA.
Kobayashi
Yoshihisa
Y