Isariotins E and F, Spirocyclic and Bicyclic Hemiacetals from the Entomopathogenic Fungus <i>Isaria tenuipes</i> BCC 12625

Natural products play an important role as a source not only of potential therapeutic drugs but also of starting materials for semisynthetic new medicines. The epoxyquinoid family, composed by cyclohexane epoxides and related structures, exhibit these characteristics without doubt.Since 2004, significant efforts have been devoted to the stereocontrolled synthesis of these molecules with different and interesting strategies. More than 50 works on this field have been published during this period of time. In addition, many of these polyoxygenated cyclohexenoids exhibit diverse and impressive bioactive shapes. This review aims to analyze the recent advances in the enantioselective processes that have been performed for the total syntheses of these target molecules. It includes a wide range of methodologies for the introduction of chirality either enzymatic or chemical ones. This summarizes microbial preparation of starting materials, lipase kinetic resolutions, use of compounds from the chiral pool, use of chiral auxiliaries and asymmetric catalysis. In a special section, syntheses of scyphostatin are also included.

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“…6) isolated from entomophatic fungi-afflicting insects [164]. 6) isolated from entomophatic fungi-afflicting insects [164].…”

Section: Perspectivesmentioning

confidence: 99%

Enantioselective Synthesis of Natural Epoxyquinoids

Pandolfi

Schapiro²,

Heguaburu³

et al. 2013

COS

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“…Corallolide B (8) is a naturally occurring diterpene isolated from the Caribbean gorgonian octocoral Pseudopterogorgia bipinnata collected near Providencia Island, Colombia, and reported to inhibit the growth of Mtb by 95% at 128 μg/mL in in vitro anti-TB assays [40]. The new spirocyclic and bicyclic hemiacetal, isariotin F (9), was isolated from the entomopathogenic fungus Isaria tenuipes BCC 12625 and displayed anti-TB activity against Mtb H 37 Ra with an MIC value of 60.4 μM [41]. Erythrophloin C (10) and suberosol B (11), two constituents from the roots of Beilschmiedia erythrophloia, exhibited anti-TB activity against Mtb H 37 Rv, showing MIC values of 50 and 28.9 μg/mL, respectively [42].…”

Section: Newly Reported Anti-tb Natural Products From 2009 To Presentmentioning

confidence: 99%

“…Recently, there has been a great deal of research pertaining to the modification of PA-824 [71][72][73][74][75]. It is believed that the stereochemistry of these molecules is also important as in the case of OPC-67683 (41). Analogue 42 bearing a chiral center of S-configuration has an excellent MIC of 0.8 1.6 μg/mL for H 37 Rv and shows nearly 60-times greater potency than its Rconfiguration analogue 43 [72].…”

Section: Some Cases Showing the Importance Of Stereochemistry In Semimentioning

confidence: 99%

Stereochemistry at the Forefront in the Design and Discovery of Novel Anti-tuberculosis Agents

Huang

Kozikowski³

2011

CTMC

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Today, 75% of new drugs introduced to the market are single enantiomers and new techniques in asymmetric synthesis and chiral separation expedites chiral drug discovery and development worldwide. The enantiomers of a chiral drug present unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of chiral drugs determines their pharmacokinetic, pharmacodynamic, and toxicological actions. Thus, it is imperative that only the pure and therapeutically active isomer be prepared and marketed. Tuberculosis (TB), a highly contagious and airborne disease that is caused by infection with Mycobacterium tuberculosis (Mtb), currently represents one of the most threatening health problems globally. The emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), as well as HIV co-infection along with a lengthy treatment regimen, highlights an urgent need for the development of new anti-TB agents. Currently, new chiral anti-TB agents are being developed from some well-known anti-TB agents, high throughput screening (HTS) hits, and natural products. This review will focus on the reported chiral anti-TB agents together with the clinical importance of their chirality and stereochemistry.

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“…[1] In a search for bioactive secondary metabolites of entomopathic fungi-afflicting insects, Bunyapaiboonsri et al reported isolating two novel compounds, isariotin E (3) and F (2) along with the known bicycle TK-57-164A (1), a compound previously described as an agricultural bactericide. [2,3] Isariotin F (2) exhibited activity against the malaria parasite Plasmodium falciparum K1, three cancer cell lines (KB, BC, NCI-H187), and nonmalignant (Vero) cells (IC 50 = 5.1, 15.8, 2.4, 1.6, and 2.9 mm, respectively). Furthermore Bunyapaiboonsri et al speculated that isariotin E (3) might serve as the biosynthetic progenitor of 1 and 2 (Scheme 1).…”

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confidence: 99%

“…Benefiting from Bunyapaiboonsris insight, [2] we suspected that the [3.3.1]-bicyclic nonane core found in compound 1 might arise via the intermediacy of an enol formed by the diastereoselective conjugate addition of methoxide to compound 3 (Scheme 1). An observation of a similar epoxide directed conjugate addition reported by Ogita and co-workers for scyphostatin supported this notion.…”

mentioning

confidence: 99%