Epoxy Isonitriles, A Unique Class of Antibiotics: Synthesis of Their Metabolites and Biological Investigations

Abstract

Epoxy isonitrile containing natural products often possess specific and potent antibacterial activity against Gram-positive pathogens. This scaffold, however, is extremely labile under acidic and basic conditions, undergoing a Payne rearrangement to produce a stable epoxy ketone metabolite and releasing hydrogen cyanide. We synthesized and performed biological assays with epoxy ketone containing metabolites and identified that the epoxy isonitrile moiety is pertinent for biological activity. Serendipitously, we discovered an α,β-unsaturated epoxy ketone analogue that exhibited moderate activity against Staphylococcus aureus.

Can the isonitrile biosynthesis enzyme ScoE assist with the biosynthesis of isonitrile groups in drug molecules? A computational study

“…[64][65][66] Indeed our calculated triplet spin transition states are >10 kcal mol 1 above those found at the quintet spin state surface (See Electronic Supporting Information, Table S2). Therefore, the reaction mechanism for the iron(IV)-oxo with substrate will start from 5 Re I and take place on a quintet spin surface only leading to products through single-spin-state-reactivity. This contrasts heme systems that typically react on close-lying spin state surfaces through multistate reactivity patterns.…”

Analisis Molekular dan Karakteristik Hidrogen Sianida (HCN)

“…Hidrogen sianida (7; 10; 26; 27; 32; [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] atau biasa disebut formic anammonide, asam hidrosianat, atau asam sianida yang merupakan suatu monobasa dari asam Lewisboron lemah yang dapat digunakan sebagai penyepuhan emas,dan pembuatan pewarna prussian blue (blau), (108) . Asam sianida akan larut dalam air (109; 110) , senyawa ini didalam air akanmembentuk ion CNdan ion H + .Senyawa dengan rumus kimia HCN cairan tak bewarna dan sangat beracun.…”

Medicinal Chemistry of Isocyanides

“…Compound 77 was still active but with a highly reduced potency in comparison to amycomicin, highlighting that the presence of the isocyano group is fundamental for the antibiotic potency of the latter (Figure 25). 140 The indole acryloisonitrile (11), originally named as B371, was isolated from Pseudomonas and displayed a potent antimicrobial and antifungal activity 141 (Table 10). Another indole derivative was then isolated from the actinomycete Nocardia brasiliensis and named brasilidine A (79; Figure 26).…”