Complete NMR elucidation of a novel trishomocubane hydantoin and its mono- and bis-t-Boc protected derivatives

• Published in: Magnetic resonance in chemistry 2004-07, Vol.42 (7), p.617-623
• Main Authors: Fourie, Louis, Govender, Thavendran, Hariprakasha, Humcha K., Kruger, Hendrik G., Raasch, Terrence
• Format: Article
• Language: English
• Subjects: 13C NMR; 1H NMR; Alkanes - analysis; Alkanes - chemistry; cage hydantoin; Carbon Isotopes; Hydantoins - analysis; Hydantoins - chemistry; Magnetic Resonance Spectroscopy - methods; Models, Molecular; Molecular Conformation; NMR; Peptides - analysis; Peptides - chemistry; Protons; t-Boc protection; trishomocubane
• ISSN: 0749-1581; 1097-458X
• DOI: 10.1002/mrc.1397

The syntheses of a novel trishomocubane hydantoin and its mono‐ and bis‐protected t‐Boc derivatives are described. The less nucleophilic N‐3′ nitrogen of the hydantoin ring is protected first when treated with di‐tert‐butyl dicarbonate (t‐Boc anhydride), possibly owing to steric hindrance by the bulky trishomocubane cage skeleton. More basic conditions were required to form the bis‐protected t‐Boc hydantoin with the same reagent. The structures of these novel compounds were elucidated with 2D NMR techniques. The proton spectrum of the trishomocubane skeleton is complex owing to major overlap of proton signals. A high‐level DFT calculation was used to determine some of the crucial interatomic positions, which assisted with the elucidation of the structures. The assignment of proton and carbon signals of the three structures is described and it differs significantly from each other and also from the trishomocubanol precursor. The bis‐Boc hydantoin is required for a more facile hydrolysis to the corresponding trishomocubane amino acid at room temperature. Copyright © 2004 John Wiley & Sons, Ltd.