Abstract:Divergent and enantiospecific total syntheses of the indolosesquiterpenoids xiamycins A, C, F, H and oridamycin A have been accomplished. The syntheses, which commence from (R)‐carvone, employ a key photoinduced benzannulation sequence to forge the carbazole moiety characteristic of these natural products. Late‐stage diversification from a common intermediate enabled the first syntheses of xiamycins C and F, and an unexpected one‐pot oxidative decarboxylation, which may prove general, led to xiamycin H. All sy… Show more
“…mangrove endophyte (Xu et al 2014 ). Xiamycin and its derivatives were reported as anti-HIV (Meng et al 2015 ), antimicrobial (Christina et al 2013 ) and antifungal against a broad range of fungi (Pfaffenbach et al 2019 ), and antiviral activity (Ding et al 2010 ; Kim et al 2016 ). Fig.…”
The current study reveals the inhibitory potential of novel bioactive compounds of mangrove actinomycetes against nsp10 of SARS-CoV-2. A total of fifty (50) novel bioactive (antibacterial, antitumor, antiviral, antioxidant, and anti-inflammatory) compounds of mangrove actinomycetes from different chemical classes such as alkaloids, dilactones, sesquiterpenes, macrolides, and benzene derivatives are used for interaction analysis against nsp10 of SARS-CoV-2. The six antiviral agents sespenine, xiamycin c, xiamycin d, xiamycin e, xiamycin methyl ester, and xiamycin A (obeyed RO5 rule) are selected based on higher binding energy, low inhibition constant values, and better-docked positions. The effective hydrogen and hydrophobic (alkyl,
–sigma,
–
T shaped and
-alkyl) interaction analysis reveals the four antivirals sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are supposed to be the most auspicious inhibitors against nsp10 of SARS-CoV-2. Quantum chemistry methods such as frontier molecular orbitals and molecular electrostatic potential are used to explain the thermal stability and chemical reactivity of ligands. The toxicity profile shows that selected ligands are safe by absorption, distribution, metabolism, excretion, and toxicity profiling and also effective for inhibition of nsp10 protein of SARS-CoV-2. The molecular dynamic simulation investigation of apo and halo forms of nsp10 done by RMSD of C
atoms of nsp10, all amino acid residues RMSF, count total number of hydrogen bonds and radius of gyration (
R
g
). MD simulations reveal the complexes are stable and increase the structural compactness of nsp10 in the binding pocket. The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity.
Graphical abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s11696-021-01997-x.
“…mangrove endophyte (Xu et al 2014 ). Xiamycin and its derivatives were reported as anti-HIV (Meng et al 2015 ), antimicrobial (Christina et al 2013 ) and antifungal against a broad range of fungi (Pfaffenbach et al 2019 ), and antiviral activity (Ding et al 2010 ; Kim et al 2016 ). Fig.…”
The current study reveals the inhibitory potential of novel bioactive compounds of mangrove actinomycetes against nsp10 of SARS-CoV-2. A total of fifty (50) novel bioactive (antibacterial, antitumor, antiviral, antioxidant, and anti-inflammatory) compounds of mangrove actinomycetes from different chemical classes such as alkaloids, dilactones, sesquiterpenes, macrolides, and benzene derivatives are used for interaction analysis against nsp10 of SARS-CoV-2. The six antiviral agents sespenine, xiamycin c, xiamycin d, xiamycin e, xiamycin methyl ester, and xiamycin A (obeyed RO5 rule) are selected based on higher binding energy, low inhibition constant values, and better-docked positions. The effective hydrogen and hydrophobic (alkyl,
–sigma,
–
T shaped and
-alkyl) interaction analysis reveals the four antivirals sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are supposed to be the most auspicious inhibitors against nsp10 of SARS-CoV-2. Quantum chemistry methods such as frontier molecular orbitals and molecular electrostatic potential are used to explain the thermal stability and chemical reactivity of ligands. The toxicity profile shows that selected ligands are safe by absorption, distribution, metabolism, excretion, and toxicity profiling and also effective for inhibition of nsp10 protein of SARS-CoV-2. The molecular dynamic simulation investigation of apo and halo forms of nsp10 done by RMSD of C
atoms of nsp10, all amino acid residues RMSF, count total number of hydrogen bonds and radius of gyration (
R
g
). MD simulations reveal the complexes are stable and increase the structural compactness of nsp10 in the binding pocket. The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity.
Graphical abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s11696-021-01997-x.
“…However, using trifluoroethanol as a solvent led to full conversion in 4 h and a clean reaction profile (Figure B, see the Supporting Information, p S7 for full details). Fluorinated alcoholic solvents have previously been shown to increase the yields and decrease reaction times of MHAT reactions, , although their role remains somewhat mysterious. These positive effects may arise because these solvents facilitate the formation of dimeric metal complexes , or, in the specific case of the Mukaiyama hydration, because they increase the solubility of oxygen in the reaction mixture. , Alcohol 80 was unstable on silica gel, making it difficult to purify.…”
Detailed herein are our synthesis studies of longiborneol and related natural products. Our overarching goals of utilizing a "camphor first" strategy enabled by skeletal remodeling of carvone, and late-stage diversification using C−H functionalizations, led to divergent syntheses of the target natural products. Our initial approach proposed a lithiate addition to unite two fragments followed by a Conia-ene or Pd-mediated cycloalkylation reaction sequence to install the seven-membered ring emblematic of the longibornane core. This approach was unsuccessful and evolved into a revised plan that employed a Wittig coupling and a radical cyclization to establish the core. A reductive radical cyclization, which was explored first, led to a synthesis of copaborneol, a structural isomer of longiborneol. Alternatively, a metal-hydride hydrogen atom transfer-initiated cyclization was effective for a synthesis of longiborneol. Late-stage C−H functionalization of the longibornane core led to a number of hydroxylated longiborneol congeners. The need for significant optimization of the strategies that were employed as well as the methods for C−H functionalization to implement these strategies highlights the ongoing challenges in applying these powerful reactions. Nevertheless, the reported approach enables functionalization of every natural product-relevant C−H bond in the longibornane skeleton.
“…Sarpong ( Pfaffenbach et al, 2019 ) synthesized indole sesquiterpenoids xiamycins A, C, F, H and oridamycin A. As shown in Figure 1A-IV , aldehyde 17 was prepared from ( R )-carvone (16) after twelve steps as a common late-stage intermediate applied to synthesize several xiamycin congeners.…”
Section: The Total Synthesis Of Terpenoid Enabled By Cobalt-catalyzedmentioning
Transition metal catalysis plays an essential role in the total synthesis of natural products. Cobalt-mediated asymmetric catalysis has successfully been used as a primary or a secondary step in the total synthesis of natural products, especially terpenoids. Terpenoids represent one of the most prominent families among various categories of natural products, attracting immense attention due to their promising physiological activities. This review summarizes the recent advances toward the total synthesis of terpenoids by cobalt-mediated asymmetric catalysis, which may shed some light on their future synthetic efforts toward natural pesticides such as celanguline, azadirachtin, etc.
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