I. Introduction 893 A. The Drug Discovery Process 895 B. Characteristics of Privileged Substructures 896 C. Scope of the Review 897 II. Phenyl-Substituted Monocycles 898 A. Biphenyls 898 B. Arylpiperidines 899 C. Arylpiperazines 901 D. 1,4-Dihydropyridines 901 E. Dihydropyrimidones 902 III. Fused [7−6] Ring Systems 904 A. 1,4-Benzodiazepin-2-ones 904 B. 1,5-Benzodiazepin-2-ones 905 C. 1,4-Benzodiazepin-2,5-diones and Pyrrolo-[2,1-c][1,4]benzodiazepin-5,11-diones 906 D. 1,4-Benzothiazepin-5-ones 907 E. 5,11-Dihydro-benzo[e]pyrido[3,2-b][1,4]diazepin-6-ones 907 IV. Fused [6−6] Ring Systems 908 A. Benzopyrans, Chromones, Coumarins, and Pyranocoumarins 908 1. Benzopyrans 908 2. Chromones 909 3. Coumarins 911 4. Pyranocoumarins 911 B. Quinoxalines/Quinazolines 913 1. 3,4-Dihydroquinoxalin-2-ones (Benzopiperazinones) 913 2. Quinazolinones 915 3. Quinazolindiones 916 4. Imidazoquinoxalines 917 V. Fused [5−6] Ring Systems 919 A. Indoles 919 B. Benzimidazoles 921 C. Benzofurans 922 D. Benzothiophenes 924 VI. Conclusions 925 VII. Acknowledgments 925 VIII. References 925

For Abstract see ChemInform Abstract in Full Text.

[reaction: see text] Cyclic tetrapeptides are an intriguing class of natural products. To synthesize highly strained cyclic tetrapeptides we developed a macrocyclization strategy that involves the inclusion of 2-hydroxy-6-nitrobenzyl (HnB) group at the N-terminus and in the "middle" of the sequence. The N-terminal auxiliary performs a ring closure/ring contraction role, and the backbone auxiliary promotes cis amide bonds to facilitate the otherwise difficult ring contraction. Following this route, the all-L cyclic tetrapeptide cyclo-[Tyr-Arg-Phe-Ala] was successfully prepared.

Head-to-tail cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. They may therefore be considered to be privileged structures. This review outlines the strategies by which both macrocyclic cyclic peptides and cyclic dipeptides or diketopiperazines have been synthesised in combinatorial libraries. It also briefly outlines some of the biological applications of these molecules, thereby justifying their inclusion as privileged structures.