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Five new alkaloids, hirsutellones A–E, were isolated from the insect pathogenic fungus Hirsutella nivea BCC 2594. Their structures were elucidated by spectroscopic analysis and X-ray crystallography. Hirsutellones displayed significant growth inhibitory activity against Mycobacterium tuberculosis H37Ra.

Azaphilone pigments, monascusones A (1) and B (2), together with two known azaphilones, monascin (3) and FK17-P2b2 (4), were isolated from the CH2Cl2 extract of a yellow mutant of the fungus M. kaoliang grown on rice. Structures of the isolated compounds were elucidated by analyses of spectroscopic data. Monascusone A (1), the major metabolite of M. kaoliang, showed no antimalarial (against Plasmodium falciparum), antitubercular (against Mycobacterium tuberculosis H37Ra), and antifungal (toward Candida albicans) activities. Compound 1 exhibited no cytotoxicity against BC (breast cancer) and KB (human epidermoid carcinoma of cavity) cell lines.

Four new cyclohexadepsipeptides, enniatins L (1), M1 (2), M2 (3), and N (4), have been isolated from an unidentified fungus (BCC 2629), together with the known enniatins B (5), H (6), and I (7), MK1688 (8), and enniatin B4 (9). Compounds 1–4 are the first enniatin analogs with an OH group at the side chain of one of the 2-hydroxycarboxylic acid residues. The structures of 1–4 were elucidated by spectroscopic means and by X-ray crystallography.

A novel 24-membered polyene lactam macrolide, micromonosporin A (=(3E,5E,7Z,15E,17E,19E,21E)-9,11,13-trihydroxy-14,19,24-trimethyl-1-azacyclotetracosa-3,5,7,15,17,19,21-heptaen-2-one; 1) was isolated from the actinomycete, Micromonospora sp. strain TT1-11, which was isolated from a very acidic peat swamp forest.

One-pot reactions between ortho-dihydroxyarenes with 1,2-diols or dithiols in the presence of p-toluenesulfonic acid yielded the corresponding dioxins or dithiins in good to excellent yields.

Aigialone (1) and aigialospirol (2), two structurally unique compounds, were isolated from the mangrove fungus Aigialus parvus BCC 5311. The structure of the new ketene acetal 1 was elucidated by spectral analysis, and its relative stereochemistry was determined by X-ray crystallography. The stereochemistry of aigialospirol (2), elucidated by NMR spectral analysis, suggested that this compound is possibly derived from hypothemycin (3), a metabolite previously isolated from this same fungus.

Two new antimycobacterial dibenzo[b,f]oxepins, bauhinoxepins A (=3,3,5-trimethylbenzo[b]pyrano[g][1]benzoxepin-6,11-diol; 1) and B (=6-methoxy-7-methyl-2-(3-methylbut-2-enyl)dibenzo[b,f]oxepine-1,8-diol; 2), were isolated from the roots of Bauhinia saccocalyx, and their structures were elucidated by analysis of spectroscopic data. Bauhinoxepins A and B exhibited antimycobacterial activities with respective minimum-inhibitory concentrations (MIC) of 6.25 and 12.5 μg/ml. They were inactive (at 20 μg/ml) against the malarial parasite, and also inactive (at 20 μg/ml) towards the Vero, KB, and BC cell lines.

Deprotonation of an oxiranyl β-proton takes place in a stereoselective manner providing the corresponding oxiranyl ‘remote’ anion. The anion is stabilized by chelation between the lithium and the carbonyl moiety of an ester, lactone, imide, or keto-group in the form of a five-membered cyclic intermediate. Certain ester-stabilized oxiranyl anions are stable and can be left in THF solution at −78°C for several hours. The generated anions undergo a stereoselective alkylation reaction to provide products, which could be useful intermediates in the synthesis of bioactive naturally occurring α-methylene bis-γ-butyrolactones.

Two new enniatins H ( 3 ) and I ( 4 ), whose substituents on 2-hydroxycarboxylic acid moieties were different from those of known compounds, were isolated, together with known enniatins B ( 1 ) and B 4 ( 2 ), from the insect pathogenic fungus Verticillium hemipterigenum BCC 1449. Structures of these compounds were elucidated by spectroscopic means. Studies on precursor-directed biosynthesis with strain BCC 1449 led to the production and identification of three analogs, enniatins G ( 5 ), C ( 6 ) and MK1688 ( 7 ), as well as the stereochemical elucidation of 3 and 4 . Enniatins 1 – 7 were evaluated for their antiplasmodial and antimycobacterial activities.

Structurally unique isocoumarin glucosides, named halorosellins A (1) and B (2), were isolated from the EtOAc extract of a broth of the marine fungus Halorosellinia oceanica. Other new minor metabolites including 4,8-dihydroxy-6-methoxy-4,5-dimethyl-3-methyleneisochroman-1-one (3), 3-acetyl-7-hydroxy-5-methoxy-3,4-dimethyl-3H-isobenzofuran-1-one (4) and an ophiobolane sesterterpene, 17-dehydroxyhalorosellinic acid (5), were also isolated. Structures of these compounds were elucidated by analyses of spectroscopic data. Compound 4 exhibited mild antimycobacterial activity (MIC value of 200 µg mL−1).

Precursor-directed biosynthesis of beauvericin analogs, cyclohexadepsipeptide antibiotics, was investigated using the insect pathogenic fungus Paecilomyces tenuipes BCC 1614. Feeding l -isoleucine or d -alloisoleucine in liquid medium led to the enhanced production of beauvericin A and beauvericin B together with beauvericin and a missing analog, beauvericin C. Feeding experiments with d -isoleucine or l -alloisoleucine resulted in the production of diastereomers of beauvericins A, B and C, named allobeauvericins A, B and C, respectively.

Aigialomycins A-E (2-6), new 14-membered resorcylic macrolides, were isolated together with a known hypothemycin (1) from the mangrove fungus, Aigialus parvus BCC 5311. Structures of these compounds, including absolute configuration, were elucidated by spectroscopic methods, chemical conversions, and X-ray crystallographic analysis. Hypothemycin and aigialomycin D (5) exhibited in vitro antimalarial activity with IC(50) values of 2.2 and 6.6 microg/mL, respectively, while other analogues were inactive. Cytotoxicities of these compounds were also evaluated.

The C-4 sulfated isoflavonoid, torvanol A (1), and the steroidal glycoside, torvoside H (3), together with the known glycoside, torvoside A (2), were isolated from a MeOH extract of Solanum torvum fruits. Upon enzymatic hydrolysis with beta-glucosidase, torvoside A (2) and torvoside H (3) yielded the corresponding acetal derivatives 4 and 5, respectively. Torvanol A (1), torvoside H (3) and compound 5 exhibited antiviral activity (herpes simplex virus type 1) with IC(50) values of 9.6, 23.2 and 17.4 microg/ml, respectively. Compounds 1-5 showed no cytotoxicity (at 50 microg/ml) against BC, KB and Vero cell lines.

1-Aryl-4,6-diamino-1,2-dihydro-1,3,5-triazines bearing diverse substituents at C2 and on the aromatic ring have been synthesized in good yield from an acid-catalyzed reaction between corresponding arylbiguanide and carbonyl compound in the presence of triethyl orthoacetate as a water scavenger.

Nucleophilic additions of lithium keto and ester enolates and mono- and bifunctional Grignard reagents to artemisitene provided C-16-derived artemisinin monomers, dimers, trimers, and tetramers whose antimalarial and cytotoxic activities have been evaluated.

Three known compounds, 2-hexylidene-3-methylsuccinic acid (1), cytochalasin Q (2), and 5-carboxymellein (3), together with two new derivatives, 2-hexylidene-3-methylsuccinic acid 4-methyl ester (4) and an ophiobolane sesterterpene named halorosellinic acid (5), were isolated from culture broth of the marine fungus Halorosellinia oceanica BCC 5149. Compounds 1-3 exhibited moderate cytotoxicity against KB and BC-1 cell lines with IC(50) values of 1-13 microg/mL, while compounds 2, 3, 5, and 6 showed antimalarial activity with respective IC(50) values of 17, 4, 13, and 19 microg/mL. Halorosellinic acid (5) possessed only weak antimycobacterial activity with the minimum inhibitory concentration of 200 microg/mL.

Phomoxanthones A (1) and B (2), two novel xanthone dimers, were isolated from the endophytic fungus Phomopsis sp. BCC 1323. Structures of 1 and 2 were elucidated by spectroscopic methods. These compounds exhibited significant in vitro antimalarial and antitubercular activities and cytotoxicity.

Both forms of the enantiomerically pure methylenolactocin, nephrosterinic and protolichesterinic acid have been synthesized via tandem aldol–lactonization reactions from corresponding optically active itaconate–anthracene adducts.

Bioassay-guided fractionation of the extracts from the insect pathogenic fungus Cordyceps nipponica BCC 1389 led to the isolation of N-hydroxy- and N-methoxy-2-pyridones, cordypyridones A-D (1-4). Structures of these compounds, including absolute configuration, were determined by spectroscopic methods, chemical conversions and single-crystal X-ray diffraction analyses. Codypyridones A and B, atropisomers of each other, exhibited potent in vitro antimalarial activity with IC(50) values of 0.066 and 0.037 microg/mL, respectively, while their cytotoxicity was much weaker.

Racemosol and demethylracemosol, together with their possible biogenetic precursors, preracemosol A and preracemosol B, were isolated from the roots of Bauhinia malabarica Roxb. While only racemosol and demethylracemosol exhibited cytotoxicity against KB and BC cell lines, all four compounds exhibited moderate antimalarial activity.

Department of Chemistry, Faculty of Science,Mahidol University, Bangkok 10400, Thailand;and National Center for Genetic Engineering andBiotechnology (BIOTEC), National Science andTechnology Development Agency (NSTDA), 73/1,Rama VI Rd., Rajdhevee, Bangkok 10400, Thailandprasat@biotec.or.th.Received March 23, 2000

Cordyanhydrides A and B, two new alkenoic acids bearing two and three maleic anhydride moieties in the linear acid chain, were isolated and identified from a culture broth of the insect pathogenic fungus Cordyceps pseudomilitaris BCC 1620.

Treatment of dimethyl 1,3-butadiene-2,3-dicarboxylate with Fe 2 (CO) 9 provided the corresponding tricarbonyl(η 4 -dimethyl 1,3-butadiene-2,3-dicarboxylato-O)iron, [Fe(C 8 H 10 O 4 )(CO) 3 ], (II), as the main product and the novel μ-[(1,2-η,κO 3 :3,4-η,κO 2 )-dimethyl 1,3-butadiene-2,3-dicarboxylato]bis(tricarbonyliron), [Fe 2 (C 8 H 10 O 4 )(CO) 6 ], (III). In the crystal structure of (II), the electron-deficient butadiene complexes with one Fe(CO) 3 group, whereas in (III), the butadiene adopts an unusual conformation and forms a complex with two Fe(CO) 3 groups. In (III), each Fe atom possesses a trigonal bipyramidal geometry, with one olefinic bond and two carbonyl ligands occupying the basal positions, and the keto oxygen of the ester and the other carbonyl ligand occupying apical positions.

Six bioactive naphthoquinone derivatives, erythrostominone, deoxyerythrostominone, 4-O-methyl erythrostominone, epierythrostominol, deoxyerythrostominol and 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa-1,3-dienyl)-1,4-naphthoquinone, were isolated from the insect pathogenic fungus Cordyceps unilateralis BCC1869. While the latter is synthetically known, both it and 4-O-methyl erythrostominone are products of fungus strain C. unilateralis BCC1869.

The syntheses of α-methylene γ-butyrolactones and α-methylene bis-γ-butyrolactones are made simple through the use of the versatile dimethyl itaconate - anthracene adduct, 1 .

[reaction: see text] An unusually bridged epidithiodiketopiperazine, pretrichodermamide A (3), was isolated from the fungus Trichoderma sp. BCC 5926. During the extensive effort to crystallize 3 for X-ray crystallographic analysis, conversion of this compound to trichodermamide A with coproduction of S(8) occurred.

Directed by substituent R1, the α-allyl-γ-butyrolactone 9 either undergoes cyclisation to give the alcoholic cyclopentenone 12 or 1,2-acyl migration to give 13, when subjected to treatment with LDA in THF/TMEDA. An effective strategy to nullify this directive influence, and dictate cyclisation, is exemplified in a model synthesis of spiro[4,5]dec-2-ene-1,6-dione 19 by a one-pot tandem cyclisation — elimination process starting from 16.

Two known spirodihydrobenzofuran terpenes (1 and 2) were isolated from a mycelium extract of the fungus Stachybotrys nephrospora BCC 3900. Compound 1 (Mer-NF5003F or stachybotrydial) exhibited potent antiviral activity (the IC50 value of 4.32 microg/mL) comparable to the standard drug, acyclovir, while compound 2 was inactive against the HSV-1 virus. Both 1 and 2 possessed antiplasmodial activity (IC50 values of 0.85 and 0.15 microg/mL for 1 and 2, respectively), and were not toxic towards the Vero cell line. A regiospecific conversion of the dialdehyde 1 to the lactone 2 proceeded simply under acidic conditions.

Bisalkylthioarenes can be prepared efficiently from reactions between dihydroxyarenes and thiols under acidic conditions.

Various derivatives of artemisinin covalently linked to iron chelators were synthesized, and their antimalarial activities were evaluated. Although results show no indication that the presence of an iron chelator in the vicinity of artemisinin potentiates its action, the linked compounds prepared still retain comparable activities to that of artemisinin.

Several terpenes, including the novel diterpene peroxide (5) with potent activity against Plasmodium falciparum, have been isolated from Amomum krervanh (“cardamom”).

Two new pimarane diterpenes, diaportheins A (1) and B (2), were isolated from a culture broth of the fungus Diaporthe sp. BCC 6140. Diaporthein B (2) strongly inhibited the growth of Mycobacterium tuberculosis with the MIC value of 3.1 microg/mL, while diaporthein A (1) showed only mild activity (MIC value of 200 microg/mL).

Spiro[4.4]non- and spiro[4.5]dec-2-ene-1,6-diones [2; n = 0 and 1] were prepared in moderate to high enantiomeric purities via asymmetric allylation of enamines 6 and ketal derivatives 7 and 8 formed from keto-esters 5, followed by a carbanionic cyclization process.

A new cyclohexadepsipeptide, named hirsutellide A (1), was isolated from a cell extract of the entomopathogenic fungus Hirsutella kobayasii BCC 1660. The structure of 1 was elucidated by analyses of spectroscopic data, and its absolute stereochemistry was addressed by the use of Marfey's method. Hirsutellide A (1) exhibited antimycobacterial and antimalarial activities, but was inactive toward the Vero cell line (at 50 microg/mL).

Stereospecific deprotonation of the epoxy proton at the beta-position of the alpha,beta-epoxy esters 5 and 6 yielded oxiranyl "remote" anions 7 and 8, which could then be used for alkylation. The anions 7 and 8 underwent a consecutive aldol lactonization to give, respectively, epoxy lactones 11 and 13 with high stereoselectivity. Generation of the remote anions as well as their stereoselective reactions served as a new synthetic route to the naturally occurring alpha-methylenebis-gamma-butyrolactones, 1.

Bioassay-guided fractionation of the cell extract of the insect pathogenic fungus Aschersonia tubulata BCC 1785 led to the isolation of dustanin (1), 3 beta,15 alpha,22-trihydroxyhopane (3), 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-diene-3 beta-ol (6), together with the new 3 beta-acetoxy-15 alpha,22-dihydroxyhopane (4). Chemical structures of these compounds were elucidated by spectral analyses as well as chemical transformation. Compounds 1 and 4 exhibited antimycobacterial activity with the minimum inhibitory concentration (MIC) of 12.5 micrograms/ml.

Title synthesis consists of the tertiary amine catalysed regiospecific ring opening of 2-chloro-3-chloromethyloxirane (1,3-dichloropropene oxide) with alkanethiols.

Spiro[4.4]non- and spiro[4.5]dec-2-ene-1,6-diones [2; n = 0 and 1] were prepared in moderate to high enantiomeric purities via asymmetric allylation of enamines 6 and ketal derivatives 7 and 8 formed from keto-esters 5, followed by a carbanionic cyclization process.

Treatment of chalcone-epoxide 1 with lithium tetramethylpiperidide gives two anions: enolate 3 and the remote anion 4 which upon formation, 4 adds to unreacted starting material 1 to yield the diastereoisomeric products 5 and 6.

The syntheses of α-methylene γ-butyrolactones and α-methylene bis-γ-butyrolactones are made simple through the use of the versatile dimethyl itaconate - anthracene adduct, 1 .

Cordyanhydrides A and B, two new alkenoic acids bearing two and three maleic anhydride moieties in the linear acid chain, were isolated and identified from a culture broth of the insect pathogenic fungus Cordyceps pseudomilitaris BCC 1620.

Three known compounds, 2-hexylidene-3-methylsuccinic acid (1), cytochalasin Q (2), and 5-carboxymellein (3), together with two new derivatives, 2-hexylidene-3-methylsuccinic acid 4-methyl ester (4) and an ophiobolane sesterterpene named halorosellinic acid (5), were isolated from culture broth of the marine fungus Halorosellinia oceanica BCC 5149. Compounds 1-3 exhibited moderate cytotoxicity against KB and BC-1 cell lines with IC(50) values of 1-13 microg/mL, while compounds 2, 3, 5, and 6 showed antimalarial activity with respective IC(50) values of 17, 4, 13, and 19 microg/mL. Halorosellinic acid (5) possessed only weak antimycobacterial activity with the minimum inhibitory concentration of 200 microg/mL.

Bioassay-guided fractionation of the extracts from the insect pathogenic fungus Cordyceps nipponica BCC 1389 led to the isolation of N-hydroxy- and N-methoxy-2-pyridones, cordypyridones A-D (1-4). Structures of these compounds, including absolute configuration, were determined by spectroscopic methods, chemical conversions and single-crystal X-ray diffraction analyses. Codypyridones A and B, atropisomers of each other, exhibited potent in vitro antimalarial activity with IC(50) values of 0.066 and 0.037 microg/mL, respectively, while their cytotoxicity was much weaker.