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

Abstract

Recently 1 we described an amino-protecting group, the Bsmoc residue 1, which is deblocked under conditions of Michael addition by means of a primary or secondary amine, most often piperidine. This process of addition to an α, β-unsaturated system contrasts with the standard β-elimination process involved in the deblocking of the Fmoc 2 and related base-sensitive amino protecting groups. Because of its unique deblocking chemistry the Bsmoc group provides a number of advantages over Fmoc chemistry in terms of speed and completeness of deblocking 3 , selectivity, etc. In addition a remarkable reactivity difference has emerged between Bsmoc and Fmoc amino acids with the Bsmoc derivatives being more reactive in acylation reactions than their Fmoc counterparts to an extent which becomes greater and greater as the steric requirements between the coupling components increase. 4 These various advantages of Bsmoc chemistry justify its continued evaluation and the amelioration of some limited but exact deficiencies of the Bsmoc system itself.

Enabling the Development of N-Heterocyclic Carbene (NHC) Catalyzed Reactions: Practical Methods for the Preparation of 1-Acyl-2-Alkylcycloalkenes from Cycloalkanones

“…The aqueous phase was extracted with CH 2 Cl 2 (3 Â 50 mL) and the combined organic layers washed with NaHCO 3 (2 Â 20 mL of a saturated aqueous solution), dried (MgSO 4 ) and the volatiles evaporated. The resulting residue was purified by flash column chromatography to afford, after concentration of the appropriate fractions, compounds 10a, [14] 10o [15] and 10p, [16] which matched previously reported data.…”

Facile synthesis of 5-arylidene rhodanine derivatives using Na2SO3 as an eco-friendly catalyst. Access to 2-mercapto-3-aryl-acrylic acids and a benzoxaborole derivative

“…49 They have been also employed as precursors of amino acids, 50 benzo[b]thiophenes 51 and naptho[1,2-b]thiophenes. 52 Selected previously synthesized 5-arylidene rhodanine derivatives are subjected to basic hydrolysis to afford new 2-mercapto-3-arylacrylic acids in good to excellent yields, the boronic acid function being compatible with these experimental conditions (Table 3).…”

Greening the synthesis of peptide therapeutics: an industrial perspective

“…42 The 1,1-dioxobenzo[b]thiophene-2-ylmethyloxy carbonyl (Bsmoc) protecting group was originally developed by Carpino et al for continuous solution-phase synthesis 86,87 and was later adopted by the CEM corporation as a suitable protecting group for water-based SPPS. 88 The Bsmoc protecting group and related 2-(tert-butylsulfonyl)-2-propenyloxycarbonyl (Bspoc) 87,89 and 1,1-dioxonaphtho[1,2-b]thiophene-2-methyloxycarbonyl (a-Nsmoc) 90 groups offer some advantages over Fmoc-chemistry, undergoing a different mechanism for deprotection that allows efficient removal of the protection group and scavenging even at low amine concentrations. 86,87,89,91 The Bsmoc strategy has been applied for the synthesis of several peptide targets 88,92,93 but the approach has not found widespread use, most likely due to a signicant difference in price and availability between Bsmoc and Fmoc-protected amino acids.…”