Establishment of Benzodioxazine Core Structure for Sarcodonin Class of Natural Products by X-ray Analysis

Abstract

Sarcodonin ε (2), isolated from Sarcodon scabrosus, was treated with trimethylsilyldiazomethane to yield a crystalline methylated derivative 6. The structure of 6 was determined by X-ray analysis, which confirmed the presence of an unprecedented N(1b)-OMe group, the configuration at N(1b) and the 1,3,4-substituted phenyl ring structure of 2. More importantly, the structures of 6 and 2 have answered the intriguing problem of solving the core structure of the sarcodonin class of natural products, establishing that sarcodonins have a benzodioxazine core structure, rather than the recently proposed benzodioxane aminal core structure.

Convergent Synthesis and Structural Confirmation of Phellodonin and Sarcodonin ε

“…Phellodonin ( 1a ) is an alkaloid isolated from the fungus Phellodon niger in 2010 (Figure A) and is part of a growing family of sarcodonin natural products (Figure B) . All of the members of this family were reported to have a striking molecular architecture consisting of a tricyclic benzodioxazine core and an unprecedented N , N -dioxide ring junction (see structure 1 ) .…”

Natural Products with Heteroatom-Rich Ring Systems

“…This structural revision followed the serendipitous synthesis of the benzodioxane aminal 102 , the structure of which was determined by X-ray crystallography and the spectroscopic data of which closely resembled those reported for the sarcodonins . However, the originally proposed benzodioxazine framework was verified in 2013 upon isolation of sarcodonin ε ( 103 ) from Sarcodon scabrosus and X-ray crystallographic analysis of its dimethyl derivative confirming the presence of the benzodioxazine . The biomimetic total synthesis of phellodonin ( 104 ) and sarcodonin ε ( 103 ) by Baran and co-workers in 2013 confirmed unequivocally the N , N -dioxide-containing benzodioxazine framework of the sarcodonin natural product family .…”

“…103 However, the originally proposed benzodioxazine framework was verified in 2013 upon isolation of sarcodonin ε (103) from Sarcodon scabrosus 104 and X-ray crystallographic analysis of its dimethyl derivative confirming the presence of the benzodioxazine. 104 The biomimetic total synthesis of phellodonin ( 104) and sarcodonin ε (103) by Baran and co-workers in 2013 confirmed unequivocally the N,N-dioxide-containing benzodioxazine framework of the sarcodonin natural product family. 105 Sarcodonin (100) exhibited weak cytotoxicity against the KB (ED 50 10.0 μg mL −1 ) and P388 (ED 50 27.0 μg mL −1 ) tumor cell lines.…”

Selected terpenoids from medicinal plants modulate endoplasmic reticulum stress in metabolic disorders

“…Gardenia fructus [30] Natasha Beukes et al [36,37] Triterpenoids [38] Natasha Beukes et al Terpenoids and ER stress and wolfram syndrome 1 (WFS1/wolframin). GRP78 is an ER chaperone and is considered a master UPR regulator.…”

“…This review has selected a few terpenoids that have shown promise as possible treatment options in metabolic diseases. These include: abscisic acid,[18,19] lycopene,[20,21] carotene,[22] cannabidiol (CBD),[23–25] cannabinol (CBN),[26] tetrahydrocannabinol (THC),[27] geraniol,[28] limonene,[29] genipin,[30] linalool,[28,29] menthol,[31] perillyl alcohol,[32] kujigamberol,[33] marrubiin,[34,35] sarcodonin,[36,37] ganoderiol F,[38] artemisinin,[39–41] dehydrocostus lactone,[42–44] farnesol,[28,45] parthenolide[46] and thapsigargin[47] (Table ).…”