Coibacins A–D, Antileishmanial Marine Cyanobacterial Polyketides with Intriguing Biosynthetic Origins

Catalytic cross-metathesis is a central transformation in chemistry, and yet, corresponding methods for stereoselectively generating acyclic trisubstituted alkenes in either isomeric form do not exist. The key problems are lack of chemoselectivity, namely, the preponderance of side reactions involving only the less hindered starting alkene, ensuing nonproductive processes of homo-metathesis byproducts, and formation of short-lived methylidene complexes. In contrast, in catalytic cross-coupling, another widely used process, substrates are more distinct and homocoupling is less of a problem. Here, we show that through cross-metathesis reactions involving E- or a Z-trisubstituted alkenes, easily prepared from commercially available starting materials by cross-coupling processes, many otherwise desirable and difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to >98% E or 95% Z). Utility is highlighted through concise stereoselective syntheses of biologically active compounds such as indiacen B (anti-fungal) and coibacin D (anti-inflammatory).

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“…Preparation of anti-leishmanial and anti-inflammatory compound coibacin D 42 highlights a series of five catalytic processes (Fig. 5b).…”

Section: Synthesis Of Biologically Active Compoundsmentioning

confidence: 99%

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis

Nguyen

Koh

Mann

et al. 2017

Nature

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“…These neurotoxic compounds are known to either activate (e.g., antillatoxin) or block (e.g., kalkitoxin and jamaicamides) voltage-gated sodium channels [6][7][8]. It is only recently that marine cyanobacteria are known to be an important source of antiprotozoal (e.g., coibacins) and anti-inflammatory (e.g., honaucins) agents [9,10].…”

Section: Introductionmentioning

confidence: 99%

Molecular Targets of Anticancer Agents from Filamentous Marine Cyanobacteria

Tan

Gupta

2014

Handbook of Anticancer Drugs From Marine Origin

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The prokaryotic marine cyanobacteria, especially the filamentous forms, are known to produce a plethora of structurally unique natural products. A majority of these molecules are nitrogen-containing, belonging to the hybrid polyketide-polypeptide structural class. Various activities of clinical significance have been attributed to these molecules, ranging from anticancer, neuromodulating to antiprotozoal properties. Particularly in the area of cancer therapy, a number of potent marine cyanobacterial compounds, including dolastatins 10, 15, and largazole, have been identified as anticancer drug leads and are being further developed synthetically for clinical usage. The high potencies of these compounds are due to their exquisite interactions or interference with cellular pathways, specific macromolecules, or enzymes, such as the JAK-STAT signaling pathway, histone deacetylase, proteasome, protein kinase C, actin and microtubule filaments. This mini review covers more than 90 references and features more than 40 anticancer compounds, consisting of marine cyanobacterial natural products and their synthetic analogues. Biological data of these compounds are discussed based on their molecular targets.

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“…The absolute configuration of the dihydropyran-2-one moiety (C-5) was assigned to be S, based on circular dichroism (CD), while only the trans relative stereochemistry of the cyclopropyl ring was determined by NMR. 1 We embarked on the total synthesis of stereoisomers of coibacin A (1) aiming to establish its absolute configuration. Additionally, we have synthesized the natural isomer of coibacin B (2).…”

Section: Introductionmentioning

confidence: 99%