Divergent synthesis of withasomnines via synthesis of 4-hydroxy-1H-pyrazoles and Claisen rearrangement of their 4-O-allylethers

5-(Methylthio)tetrazoles as versatile synthons in the stereoselective synthesis of polycyclic pyrazolines via photoinduced intramolecular nitrile imine–alkene 1,3-dipolar cycloaddition

“…19 Several syntheses of the achiral pyrazole congener withasomnine have been reported, most of which start from a pyrazole or pyrrolidine scaffold with cyclization of a sidechain to install the second ring. 20,21 In contrast, the first synthesis of the pyrazoline congener (–)-newbouldine was reported only recently by Trauner, using reductive cyclization of a nitroalkyl-substituted pyrrolidine and confirming the racemic nature of this natural product. 22 …”

An efficient one pot regioselective synthesis of a 3,3′-spiro-phosphonylpyrazole-oxindole framework via base mediated [1,3]-dipolar cycloaddition reaction of the Bestmann–Ohira reagent with methyleneindolinones

“…1) Hence, considerable efforts have been devoted to develop new and efficient synthetic strategies to access these important structural motifs. 15 Few pyrazoles such as Withasomnine, 16,17 celecoxib and Viagra exhibits important therapeutic potential (Withasomnine: analgesic and CNS depressant; Celecoxib: nonsteroidal antiarthritic drug and Viagra: phosphodiesterase inhibitor). Very recently, the synthesis of natural and non-natural phosphonate analogues incorporating nucleotides, azaheterocycles and their biological activities have been reviewed.…”

Divergent Synthesis and Evaluation of Inhibitory Activities against Cyclooxygenases-1 and -2 of Natural Withasomnines and Analogues

“…[27][28][29][30][31][32][33][34][35][36] In the course of our synthetic studies of small natural products and their analogues, [37][38][39][40][41][42] we recently reported the divergent synthesis of withasomnines 1a-c and their analogues via 4-hydroxypyrazole intermediates in a preliminary communication. 43) We herein describe the details of the divergent synthesis of natural 1a-c as well as nine withasomnine analogues 1d-l, which were easily prepared by the Suzuki-Miyaura coupling of key intermediate 16. In this work, we focused on the use of 4-hydroxypyrazole intermediates followed by the Claisen rearrangement of their 4-O-allyl ethers.…”