Ethynylbenzenoid metabolites of Antrodia camphorata: synthesis and inhibition of TNF expression

Abstract

An improved synthesis of the anti-inflammatory natural product antrocamphin A (2), involving a key Castro-Stephens reaction, is presented, along with the first total synthesis of its congener antrocamphin B (3). Approaches towards the more complex co-metabolite antrodioxolanone (4) were unsuccessful, but a samarium diiodide-mediated pinacol coupling of antrocamphin B did provide the chiral epimers (51). Antrocamphin A (2) inhibits Tumour Necrosis Factor (TNF) reporter gene expression, but its development as an anti-inflammatory agent may be limited by cytotoxicity.

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

“…Two isomers, 3,4,5-trimethoxytoluene ( 44 ) and 2,4,6-trimethoxytoluene ( 44d ), were commercially available. 2,3,4-Trimethoxybenzaldehyde ( 47 ) was reduced to 2,3,4-trimethoxytoluene ( 44a ) using PdCl 2 and Et 3 SiH [41] (Scheme 4), while the other three isomers were synthesised according to reported procedures [42–44]. Comparison of all six isomers to the two natural products (Table 7) resulted in their identification as 3,4,5-trimethoxytoluene ( 44 ) and 2,4,5-trimethoxytoluene ( 45 ).…”

The atopic dermatitis-like lesion and the associated MRSA infection and barrier dysfunction can be alleviated by 2,4-dimethoxy-6-methylbenzene-1,3-diol from Antrodia camphorata

“…The previous work [28] suggests the anti-inflammatory effect of A. camphorata against the production of nitric oxide, IL-1β, COX-2, and TNF-α in the lipopolysaccharide-activated macrophages. Some benzenoids isolated from A. camphorata have attracted attention due to the anti-inflammatory activity in T cells and macrophages [29,30]. The keratinocytes of AD patients indicate a propensity to produce cytokines and chemokines [31], both of which can be employed as the clinical markers.…”

Total Synthesis of (−)‐Perezoperezone through an Intermolecular [5+2] Homodimerization of Hydroxy p‐Quinone

“…Our synthesis commenced with a stereospecific construction of perezone monomer 18 . Toluene 13 was prepared in 90 % yield starting from commercially available 3, 5‐dimethoxytoluene 12 via a known three‐step sequence . With ample amounts of toluene 13 in hand, mono‐lithiation of 13 followed by trapping of the intermediate with trimethyl borate and acid work‐up yielded the sterically hindered boronic acid 14 .…”