931114-72-6Relevant articles and documents
1,1-Dioxonaphtho[1,2-b]thiophene-2-methyloxycarbonyl (α-Nsmoc) and 3,3-dioxonaphtho[2,1-b]thiophene-2-methyloxycarbonyl (β-Nsmoc) amino-protecting groups
Carpino, Louis A.,Abdel-Maksoud, Adel Ali,Ionescu, Dumitru,Mansour,Zewail, Mohamed A.
, p. 1729 - 1736 (2007/10/03)
Of the three theoretically possible, Bsmoc-related, naphthothiophene sulfone-based amino-protecting groups, the two most readily available derivatives, the α- and β-Nsmoc analogues, have been examined as substitutes for the Bsmoc residue in cases where the latter lead to oily protected amino acids or amino acid fluorides. All of the naphtho systems gave easily handled solid amino acid derivatives. The intermediate sulfone alcohol 11 used as the key reagent for introduction of the α-Nsmoc protecting group was readily made from α-tetralone (Scheme 1). The corresponding β-analogue 17 was made similarly on a small scale, but due to the high cost of β-tetralone, an alternate route involving reaction of rhodanine with a-naphthaldehyde was used for large-scale work (Scheme 2). All proteinogenic amino acids were converted to their α- and β-Nsmoc derivatives. Deblocking studies showed that the reactivity toward deblocking by piperidine followed the order α-Nsmoc > Bsmoc > β-Nsmoc. 1H NMR experiments showed that deblocking of the two new systems was mechanistically similar to that previously established for the Bsmoc derivative in that the reaction is initiated by Michael addition to the β-carbon atom of the α,β-unsaturated sulfone system. Application of α- and β-Nsmoc amino acids to the solid-phase synthesis of two model peptides was examined. An advantage of the α-Nsmoc system over the long-known Bsmoc system 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.
