TY - JOUR

T1 - Scaffold diversity through intramolecular cascade reactions of solid-supported cyclic N-acyliminium intermediates

AU - Le Quement, Sebastian T.

AU - Nielsen, Thomas E.

AU - Meldal, Morten

PY - 2007/11

Y1 - 2007/11

N2 - The solid-phase synthesis of pharmacologically interesting heterocycles is presented. The formation of a series of (5,5)-, (5,6)-, (6,5)-, and (6,6)-fused bicyclic ring systems was systematically studied by implementation of a common strategy involving N-acyliminium intermediates. These are highly reactive and transformed further in intramolecular cascade reactions with strong as well as weak C, N, S, and 0-nucleophiles. The methodology was successfully applied to the conversion of peptidomimetics into constrained small molecule core structures, such as the hexahydropyrrolo[2,1-b][1,3]oxazines, generally with full control of diastereoselectivity (>20:1) and in purities above 90%.

AB - The solid-phase synthesis of pharmacologically interesting heterocycles is presented. The formation of a series of (5,5)-, (5,6)-, (6,5)-, and (6,6)-fused bicyclic ring systems was systematically studied by implementation of a common strategy involving N-acyliminium intermediates. These are highly reactive and transformed further in intramolecular cascade reactions with strong as well as weak C, N, S, and 0-nucleophiles. The methodology was successfully applied to the conversion of peptidomimetics into constrained small molecule core structures, such as the hexahydropyrrolo[2,1-b][1,3]oxazines, generally with full control of diastereoselectivity (>20:1) and in purities above 90%.

UR - http://www.scopus.com/inward/record.url?scp=36749090670&partnerID=8YFLogxK

U2 - 10.1021/cc700097k

DO - 10.1021/cc700097k

M3 - Journal article

C2 - 17994787

AN - SCOPUS:36749090670

VL - 9

SP - 1060

EP - 1072

JO - ACS Combinatorial Science

JF - ACS Combinatorial Science

SN - 2156-8952

IS - 6

ER -