Synthesis of Neoechinulin A and Derivatives

Abstract

Neoechinulin A isolated from Eurotium rubrum showed cytoprotection activity against peroxynitrite generated from SIN-1 [3-(4-morpholinyl)sydnonimine hydrochloride] in PC12 cells. As we are interested in this biological activity, we synthesized neoechinulin A and its derivatives. In this article, we fully report the isolation of natural neoechinulin A and B, a total synthesis of (-)-neoechinulin A, and determination of the absolute configuration of natural neoechinulin A. In addition, we describe herein syntheses of neoechinulin A derivatives, including a biotinylated neoechinulin A derivative, which will be useful for identification of the binding proteins of neoechinulin A.

Solid-Phase Total Synthesis of Dehydrotryptophan-Bearing Cyclic Peptides Tunicyclin B, Sclerotide A, CDA3a, and CDA4a using a Protected β-Hydroxytryptophan Building Block

“…16. The synthesis of (-)-neoechinulin A by Kuramochi et al 41 A similar dehydration was described by Liu and coworkers in 2019. The dehydration of a functionalized -hydroxytryptophan 1.38 species was used to generate the corresponding dehydrotryptophan compound 1.39 as a key intermediate in the synthesis of speradine C (Scheme 1.17).…”

“…Janthinocin A can be dehydrated to give Janthinocin C under acidic conditions as demonstrated by Johnson et al 40 In 2008, Kuramochi and coworkers demonstrated that a -hydroxytryptophan dipeptide 1.35 could be used in the synthesis of Z-dehydrotryptophan-containing cyclic dipeptide neoechinulin A a potent antioxidant and radical scavenger. 41 They found that a diastereomeric mixture of a -hydroxytryptophan-containing dipeptide 1.35 could be converted to the corresponding Z-dehydrotryptophan-containing dipeptide upon exposure to acid 1.36 (Scheme 1.16). 41 The dehydration was found to take place more slowly than removal of the acid-labile indole protecting group.…”

“…41 They found that a diastereomeric mixture of a -hydroxytryptophan-containing dipeptide 1.35 could be converted to the corresponding Z-dehydrotryptophan-containing dipeptide upon exposure to acid 1.36 (Scheme 1.16). 41 The dehydration was found to take place more slowly than removal of the acid-labile indole protecting group. Nevertheless, the deprotected indole intermediate 1.…”

“…Kuramochi and coworkers postulated that the reaction likely proceeds via initial direct elimination of water from the -hydroxytryptophan dipeptide intermediate generating a stabilized indolic cation followed by stereoselective elimination to exclusively generate the thermodynamically favored Z-enamide. 41 Scheme 1. 16.…”

Synthesis and Antiviral Activities of Neoechinulin B and Its Derivatives

“…Therefore, natural products serve as excellent sources for discovering antiviral agents. 1 We have previously reported that neoechinulin B ( 1a ), isolated from Eurotium rubrum Hiji025, 2 exhibited antiviral effects against hepatitis C virus (HCV). 3 Mechanistic studies revealed that this compound disrupted the formation of double-membrane vesicles (DMVs), which are the sites of viral RNA replication, by inhibiting the liver X receptor (LXR)-regulated gene induction required for DMV formation.…”