Synthesis of an iminosugar based peptidomimetic analogue

Synthesis of Somatostatin Mimetics Based on 1‐Deoxynojirimycin

“…(15). Sodium cyanoborohydride (26.7 mg, 0.42 mmol) was added to a solution of aldehyde 13 [10] (40 mg, 0.133 mmol) and the amine 12 (46 mg, 0.85 mmol) in MeOH (4 mL). Then acetic acid (0.6 mL) was added and the mixture was stirred at room temperature for 15 h under N 2 .…”

“…The piperidine 12 was then converted into 15 by a reductive amination reaction using sodium cyanoborohydride and aldehyde 13 (50 %). [10] Efforts to obtain 15 by the N-alkylation of 12 with the triflate 14 in the presence of NaH were not successful, despite this approach being successful during the The reaction of 16 using 10 % Pd-C in MeOH in the presence of H 2 for 1 h led to reduction of the azide group giving 6; the use of the same conditions for 15 h in the presence of HCl led to reduction of the azide and the removal of the benzyl protecting groups and gave 5 (Scheme 3). The catalytic removal of the benzyl protecting groups in the presence of the DNJ nitrogen atom was only possible under these acidic conditions.…”

“…This is presumably because they are not as readily available as pyranosides and their preparation is not trivial. [8,9] Potential advantages of investigating 1-deoxymannojirimycin (DMJ) [10] or 1-deoxynojirimycin (DNJ, 3, Figure 1) or other iminosugars compared with pyranosides as scaffolds include the possibility that the protonated ring nitrogen atom could contribute a charged hydrogen bonding group to enhance interactions of a particular ligand with a receptor. Also pharmacophoric groups can be grafted to the ring nitrogen.…”

Carbohydrate-Based Scaffolds in Drug Discovery

“…From a selection of several mannose and glucose derivatives, compound 42 proved to be the most active with an IC 50 of 3.81 M. Introduction of sidechains as in compound 43, which were intended to participate favourably in additional hydrogen bonding at the binding site, did not improve binding [44]. The use of 1-deoxymannojirimycin as a scaffold to introduce a positive charge similar to the proposed binding conformation of 44 led to the synthesis of compound 45 [44,45]. However, 45 still showed only moderate binding to HIV-1 protease.…”

Carbohydrate‐Based Molecular Scaffolding

“…An iminosugar has been also used by Chery et al [61] as scaffold in the synthesis of a peptidomimetic analog of a known HIV-1 protease inhibitor. A b-Dglucopyranoside-based scaffold (115, Fig.…”