Total synthesis and biological evaluation of atrop-O-benzyl-desmethylabyssomicin C

Matović, Radomir; Bihelovic, Filip; Gruden, Maja; Saičić, Radomir N.

doi:10.1039/c4ob01436g

Cited by 15 publications

(23 citation statements)

References 17 publications

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“…Though concise and relatively high yielding, this synthetic approach has since been paralleled or superseded by alternate strategies; 53 notably Bihelovic and Saicic's approach, which avoids epoxide ring opening of the tetronate in the hope of higher tolerance in the generation of analogues for SAR studies. [54][55][56] Scheme 4: Convergent synthesis of atrop-abyssomicin (24) via connection of spirotetronate intermediate 25 with aldehyde 26 over 6 steps to give 27, which is subjected to ring closing metathesis, oxidation and final deprotection to give 24.…”

Section: Abyssomicin C: a Promising Antibacterial For Tuberculosismentioning

confidence: 99%

A twist of nature – the significance of atropisomers in biological systems

2015

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. (2015). A twist of nature-the significance of atropisomers in biological systems. Natural Product Reports: a journal of current development in bioorganic chemistry, 32 (11), 1562-1583. A twist of nature-the significance of atropisomers in biological systems AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized. AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized.

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Section: Abyssomicin C: a Promising Antibacterial For Tuberculosismentioning

confidence: 99%

A twist of nature – the significance of atropisomers in biological systems

2015

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Section: Structural Classification and Bioactivitymentioning

confidence: 99%

“…Presently, thirty-two natural abyssomicins have been identified, and numerous derivatives were synthesized [ 27 , 28 , 29 , 30 , 31 , 34 , 35 , 39 , 40 , 41 , 42 , 49 , 50 , 51 , 52 ]. Out of all the abyssomicins screened for antimicrobial activity, only four natural abyssomicins (abyssomicin 2, C, J and atrop-abyssomicin C) [ 27 , 28 , 29 , 30 , 35 ] and nine synthetic derivatives were active ( Table 1 and Table 2 ) [ 24 , 31 , 39 , 40 , 41 , 42 , 51 ]. Active abyssomicins against Gram-positive bacteria, including Micrococcus luteus , Bacillus thuringiensis , Enterococcus faecalis , MRSA, and vancomycin-resistant S. aureus (VRSA) strains are abyssomicin C and its atropoisomer, 4 atrop-abyssomicin C derivatives (Benzyl ether derivative, Chloro derivative, and two diastereoisomeric methoxymethyl (MOM) ethers derivatives), atrop-O-benzyl-desmethylabyssomicin C, oxidized derivative of abyssomicin I, acetyl abyssomicin C, 3-dithiolane atrop -abyssomicin C, and dithiolane abyssomicin C, and abyssomicin 2 ( Table 1 ) [ 30 , 31 , 32 , 33 , 34 , 37 , 42 , 51 , 57 ].…”

Section: Structural Classification and Bioactivitymentioning

confidence: 99%

“…The antibacterial activity of abyssomicins has been explored through biosynthetic evaluation, total synthesis, and pharmacological studies. Elegant synthetic routes have given access to new chemistries and the synthesis of several naturally occurring abyssomicins, as well as various novel analogues [ 12 , 26 , 31 , 32 , 33 , 34 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

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Review on Abyssomicins: Inhibitors of the Chorismate Pathway and Folate Biosynthesis

et al. 2018

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Antifolates targeting folate biosynthesis within the shikimate-chorismate-folate metabolic pathway are ideal and selective antimicrobials, since higher eukaryotes lack this pathway and rely on an exogenous source of folate. Resistance to the available antifolates, inhibiting the folate pathway, underlines the need for novel antibiotic scaffolds and molecular targets. While para-aminobenzoic acid synthesis within the chorismate pathway constitutes a novel molecular target for antifolates, abyssomicins are its first known natural inhibitors. This review describes the abyssomicin family, a novel spirotetronate polyketide Class I antimicrobial. It summarizes synthetic and biological studies, structural, biosynthetic, and biological properties of the abyssomicin family members. This paper aims to explain their molecular target, mechanism of action, structure–activity relationship, and to explore their biological and pharmacological potential. Thirty-two natural abyssomicins and numerous synthetic analogues have been reported. The biological activity of abyssomicins includes their antimicrobial activity against Gram-positive bacteria and mycobacteria, antitumor properties, latent human immunodeficiency virus (HIV) reactivator, anti-HIV and HIV replication inducer properties. Their antimalarial properties have not been explored yet. Future analoging programs using the structure–activity relationship data and synthetic approaches may provide a novel abyssomicin structure that is active and devoid of cytotoxicity. Abyssomicin J and atrop-o-benzyl-desmethylabyssomicin C constitute promising candidates for such programs.

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“…[598], shikimic acids and pinitol [599], carbasugars [600], madangamine D ( a later step forms a macrocyclic amine via RCM) [601], the kaurene core [602], various securinega alkaloids [603], a labyssomicin C derivative (e.g. 228 in a moderately diastereoselective RCM using a substrate featuring diastereotopic vinyl groups) [604], the crotogoudin ring system [605], tetrahydrocannabinol derivatives (e.g. 229) [606], diaminocyclohexenes [607], maeocrystal V (an earlier step in the synthesis employs enantioselective rhodium carbene-mediated C-H activation) [608], tamiflu (e.g.…”

Section: )mentioning

confidence: 99%

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

Herndon

2016

Coordination Chemistry Reviews

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Total synthesis and biological evaluation of atrop-O-benzyl-desmethylabyssomicin C

Cited by 15 publications

References 17 publications

A twist of nature – the significance of atropisomers in biological systems

A twist of nature – the significance of atropisomers in biological systems

Review on Abyssomicins: Inhibitors of the Chorismate Pathway and Folate Biosynthesis

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

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