Nopporn Thasana

Bacillus subtilis SSE4 produces subtulene A, a new lipopeptide antibiotic possessing an unusual C15 unsaturated β-amino acid

Subtulene A, a new cyclic lipopeptide, was isolated from the culture broth of Bacillus subtilis SSE4. This antibiotic compound contained the seven common α‐amino acids, l‐Asn‐1, d‐Tyr‐2, d‐Asn‐3, l‐Gln‐4, l‐Pro‐5, d‐Asn‐6, l‐Ser‐7 and the unique β‐amino acid‐8 present in the iturin family. 1D and 2D NMR, as well as MS analyses, identified the β‐amino acid as 3‐amino‐13‐methyltetradec‐8‐enoic acid, an Iso C15 long chain β‐amino acid. B. subtilis SSE4 was also found to produce iturin A. B. subtilis SSE4 culture filtrate exhibited both antifungal and antibacterial activities.

Synthesis of aryl α-keto esters via the rearrangement of aryl cyanohydrin carbonate esters

A facile synthesis of aryl α-keto esters is reported involving the rearrangement of aryl cyanohydrin carbonate esters induced by the α-carbanion to the nitrile group generated by LDA. However, under similar conditions, an o-benzyloxycyanohydrin carbonate ester rearranged via a domino reaction leading to 2-phenylbenzofuran-3-carboxylic acid.

Synthesis and biological activities of azalamellarins.

The synthesis of azalamellarins, a new series of lactam analogues of biologically active lamellarins, was achieved using Cu(I)-mediated and microwave-assisted C-N(amide) bond formation. Seventeen azalamellarins, including N-allylazalamellarins and N-propylazalamellarins chi-D, L-N, and J-dehydro J, were synthesized and evaluated for their cytotoxicity against the cancer cell lines HuCCA-1, A-549, HepG2, and MOLT-3. The results showed that certain azalamellarins exhibited good activities in the micromolar IC(50) value range (IC(50)=the drug concentration that causes 50 % of cell-growth inhibition after 72 h of continuous exposure to the test molecule), comparable to their parent lamellarin analogue.

Lycophlegmariols A–D: Cytotoxic serratene triterpenoids from the club moss Lycopodium phlegmaria L.

Lycopodium serratene triterpenoids, along with an abietane-type diterpene were isolated from the methanol extract of club moss Lycopodium phlegmaria L. The structures of these hitherto unknown lycopodium terpenoids were elucidated on the basis of spectroscopic analysis. Pentacyclic triterpenoids, 21β-hydroxy-serrat-14-en-3α-ol (1) and 21β-hydroxy-serrat-14-en-3α-yl acetate (2) were isolated together with four serratene triterpeneoids established as 21β,29-dihydroxyserrat-14-en-3α-yl dihydrocaffeate (lycophlegmariol A, 5), 21β,24,29-trihydroxyserrat-14-en-3β-yl dihydrocaffeate (lycophlegmariol B, 6), 21α,24-dihydroxyserrat-14-en-3β-yl 4-hydroxycinnamate (lycophlegmariol C, 7), and 14β,21α,29-trihydroxyserratan-3β-yl dihydrocaffeate (lycophlegmariol D, 8) as well as a known lycophlegmarin (9). An abietane-type diterpene, 8,11,13-abietatriene-3β,12-dihydroxy-7-one (margocilin, 10), was isolated for the first time from a Lycopodium plant. Lycophlegmariol B (6), D (8) and compound 1 showed inhibitory effects against MOLT-3 acute lymphoblastic leukemia (T-lymphoblast) with IC(50) of 14.7, 3.0 and 2.9 μM, respectively.

The application of the Baker-Venkataraman rearrangement to the synthesis of benz[b]indeno[2,1-e]pyran-10,11-dione

Abstract A tetracyclic benzocyclopentabenzopyran-4-one was synthesized via a domino reaction involving an initial aroyl transfer as in the Baker–Venkataraman rearrangement. The derived 1,3 diketone underwent the intramolecular acylation followed by cyclization to give the product.

Stereocontrolled synthesis of an indole moiety of sespendole and stereochemical assignment of the side chain.

Two possible diastereomers of the indole moiety of sespendole were synthesized from 3-hydroxy-4-nitrobenzaldehyde in a highly stereoselective manner. Comparison of (1)H and (13)C NMR spectra of the two synthetic materials with those sespendole leads us to propose that the relative stereochemistry of the epoxyalcohol is syn.

Synthesis of unsymmetrical benzil licoagrodione.

A synthesis of unsymmetrical 1,2-diarylethane-1,2-dione is reported involving the intramolecular cyclization of anionic benzylic ester of the aryl benzyl ether followed by oxidation employing dioxirane. With the use of microwave irradiation, licoagrodione was prepared from Claisen rearrangement of the corresponding allyl phenyl ether 1,2-diketone readily available from the Lindlars reduction of the corresponding alkyne derivative. Subsequent removal of protecting groups then furnished the desired product.

THE FIRST SYNTHESIS OF WRIGHTIADIONE

The first synthesis of tetracyclic isoflavone wrightiadione 1 was achieved through the benzylic oxidation of the key intermediate isoflavone 2 which in turn could be obtained by condensation of 2-indanone with methyl salicylate and LDA.

Squarrosine A and Pyrrolhuperzine A, New Lycopodium Alkaloids from Thai and Philippine Huperzia squarrosa.

Two new Lycopodium alkaloids, squarrosine A (1) and pyrrolhuperzine A (2), were isolated from the Thai and Philippine plant Huperzia squarrosa. (R)-2-Piperidineacetic acid (5) was a known alkaloid, but has now been isolated for the first time from a natural source. Their structures were elucidated using extensive spectroscopic analyses and, for pyrrolhuperzine A (2), confirmation by chemical transformation. The new compounds exhibited moderate acetylcholinesterase inhibitory activities.

Streptanoate, a new anticancer butanoate from Streptomyces sp. DC3.

Infectious diseases are still a global problem because of the steady increase in the number of microorganisms resistant to current antimicrobial agents as well as the occurrence of new emerging infectious microorganisms.1 Improvements in antimicrobial agents have been driven by concerns on safety and efficacy in terms of improved pharmacodynamics, which includes better adsorption, distribution and activity against a wide range of microorganisms, and less serious side effects. The general mechanisms of action of antimicrobial agents are inhibition of cell wall and cytoplasmic membrane synthesis, disruption of cell membrane permeability, inhibition of protein synthesis, inhibition of nucleic acid synthesis and inhibition of electron transport systems.2 Cancer is a leading cause of death in the world. Although there are effective drugs for the treatment of some cancers, these drugs often have significant side effects (that is, hair loss, anemia, immune suppression), and target cells can develop resistance. There is, therefore, a need for novel, effective and low-toxicity anticancer agents to be developed. There are a few scientific reports describing the isolation of antimicrobial compounds from various sources in Thailand. We set out to identify new bioactive compound(s) from Streptomyces sp. isolated from soil collected in Bangkok, Thailand. A new strain, Streptomyces sp. DC3, was isolated and found to produce a novel bioactive compound designated as streptanoate (1) (Figure 1). Streptomyces sp. DC3 was isolated from a soil sample collected from Bangkok, Thailand by spreading on actinomyces isolation agar from Difco, Becton, Dickinson and Company, Franklin Lakes, NJ, USA consisting of 0.01% asparagine, 0.05% dipotassium phosphate, 0.0001% ferrous sulfate, 0.01% magnesium sulfate, 0.2% sodium caseinate, 0.4% sodium propionate and 1.5% agar and incubated at 28 °C for 7-14 days. Gram-staining and 16S ribosomal RNA gene amplification were performed and followed by DNA sequencing. The colony morphology of Streptomyces DC3 on mannitol soya agar consisting of 2% soya flour, 2% mannitol and 1.5% agar showed round, dry and gray-green-white spores. The reverse side colony colouration is yellow-brown. Spore chain and spore morphology was determined by observation of a fully matured culture under microscope. Streptomyces DC3 is a gram-positive high GC content organism and appeared as long, rod-shaped filamentous. The spore-bearing aerial hyphae were in a simple category called flexibilis, which is a bit curled. The spores are round-shaped with smooth surface. PCR amplification of the 16S rRNA gene with the universal primers of BT3369 (5′-GGCGTGCTTAACACATGCAAGTC-3′) and BT3370 (5′-TACCTTGTTACGACTTCGTCCCAA-3′) resulted in a 1512-bp product.3 The 16S rRNA gene sequence showed high similarity to members of Streptomyces. Based on morphological characteristics and 16S rRNA gene sequence analysis, the bacterium was identified and designated as Streptomyces sp. DC3. An isolated colony of DC3 was used to inoculate eight flasks (1000ml in size) each containing 200ml of mannitol soya broth consisting of 2% soya flour and 2% mannitol; the flasks were then incubated at 28 °C with 180 r.p.m. shaking for 25 days. The cell-free supernatant was harvested by centrifugation at 7000 r.p.m. for 20min and extracted with either: hexane, dichloromethane, n-butanol or ethylacetate at a ratio of 1:1 (v/v). The crude organic solvent extracts were tested for antimicrobial activity against various microorganisms via a disk diffusion assay as previously described.4 The n-butanol crude extract (76.9mg) exhibited the highest inhibition against a number of gram-positive bacteria and yeasts (Table 1). Anticancer activity was also assessed using MTT and XTT assays to determine cell viability.5,6 The assays were performed using the cancer cell lines: HuCCA-1 (human cholangiocarcinoma) (Siriraj Hostpital, Thailand), A549 (human lung cancer, non-small cell) (ATCC, Manassas, VA, USA; CCL-185), Hela (human cervical carcinoma) (Chulabhorn Research Institute), Molt-3 (T-lymphoblast, acute lymphoblastic leukemia) (ATCC; CRL-1552), T47-D (hormonedependent breast cancer) (ATCC; HTB-133), HepG2 (hepatocarcinoma) (ATCC; HB-8065), MDA-MB-231 (hormone-independent breast cancer) (M.D. Anderson Cancer center, USA), HL-60 (acute promyelotic leukemia) (ATCC; CCL-240), S102 (human liver cancer)