Synthesis and derivatisation of a novel spiro[1-benzofuran-2,4′-piperidin]-3-one scaffold

Abstract

The synthesis of a novel spiro[1-benzofuran-2,4'-piperidin]-3-one scaffold has been achieved in five steps with an overall yield of 47%. The versatility of the spiropiperidine scaffold in the context of library synthesis is exemplified by selective and sequential derivatisation of the amino and aryl bromide functional groups, including the development of multi-step telescope reaction matrices.

Discovery, Synthesis, and Pharmacological Evaluation of Spiropiperidine Hydroxamic Acid Based Derivatives as Structurally Novel Histone Deacetylase (HDAC) Inhibitors

“…(E)-N-Hydroxy-3-{3-oxospiro[benzofuran-2(3 H),4 0 -piperidin]-5-yl}acrylamide (35) was synthesized as described in Scheme 4. The spirobenzofuran 32 39 was coupled with methyl acrylate following the procedures outlined in Scheme 2 for the acrylic esters 18 and 19. Basic hydrolysis of the methyl ester afforded the acrylic acid 34, which was then subsequently converted into the desired hydroxamic acid according to Scheme 1.…”

Synthesis of novel 1-thia-5,9-diaza-spiro[5.5]undec-2-ene and its recyclization to 1,5,9-triaza-spiro[5.5]undec-2-ene and/or spiro(piperidine-4,2’-thieno[2,3-d]pyrimidine)

“…These compounds, display pronounced antimicrobial, 1 analgesic, 2 anti-inflammatory, 2 antimycobacterial, 3 antifungal, 4 antitumor 5,6 and antiviral 5,6 activities. Among these heterocycles, spiropiperidines have been identified as privileged structures in medicinal chemistry 7 and have attracted increasing interest in the past five years. The most recent reports are representative of their wide range of biological activities as components of new SCD-1 inhibitors, 8 nociceptin receptor ligands, 9 CCR5 antagonists, 10 NPYY 11 receptor antagonists, 11 CGRP receptor antagonists, 12 tryptase inhibitors, 13 PGD2 receptor antagonists 14 and ChK1 kinase inhibitors.…”