| Abstract
| - Of the three theoretically possible, Bsmoc-related, naphthothiophene sulfone-based amino-protectinggroups, the two most readily available derivatives, the α- and β-Nsmoc analogues, have been examinedas substitutes for the Bsmoc residue in cases where the latter lead to oily protected amino acids or aminoacid fluorides. All of the naphtho systems gave easily handled solid amino acid derivatives. Theintermediate sulfone alcohol 11 used as the key reagent for introduction of the α-Nsmoc protecting groupwas readily made from α-tetralone (Scheme 1). The corresponding β-analogue 17 was made similarlyon a small scale, but due to the high cost of β-tetralone, an alternate route involving reaction of rhodaninewith α-naphthaldehyde was used for large-scale work (Scheme 2). All proteinogenic amino acids wereconverted to their α- and β-Nsmoc derivatives. Deblocking studies showed that the reactivity towarddeblocking by piperidine followed the order α-Nsmoc > Bsmoc > β-Nsmoc. 1H NMR experimentsshowed that deblocking of the two new systems was mechanistically similar to that previously establishedfor the Bsmoc derivative in that the reaction is initiated by Michael addition to the β-carbon atom of theα,β-unsaturated sulfone system. Application of α- and β-Nsmoc amino acids to the solid-phase synthesisof two model peptides was examined. An advantage of the α-Nsmoc system over the long-known Bsmocsystem proved to be the milder conditions needed for the deblocking step relative to the Bsmoc case,which is itself more readily deblocked than the classic Fmoc analogue.
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