Total synthesis of the putative structure of the novel triquinane based sesquiterpenoid natural product dichomitol

A total synthesis of the recently reported triquinane natural product dichomitol, isolated from the fermentation broth of Dichomitus squalens, has been accomplished from the commercially available 1,5-cyclooctadiene through a series of unambiguous synthetic steps. A complete mismatch between the spectral characteristics of the synthetic product and that of the natural product warrants a revision of the structure of dichomitol.     

Expedient synthesis of villosin and its isomer (E)-labda-8(17),12,14-trien-15(16)-olide

The synthesis of the title compounds has been achieved in concise, highly regiocontrolled fashion from commercially available (+)-sclareolide. In addition, we offer evidence that the structure of a newly reported natural product from Zingiber ottensii is incorrect.     

Synthesis of a proposed structure for the diffusible extracellular factor of Xanthomonas campestris pv. campestris

A proposed structure for the diffusible extracellular factor (DF) of Xanthomonas campestris pv. campestris (Xcc) has been synthesized. Its MS spectrum and biological activity, however, contradict those of the natural product previously reported, suggesting that the structure for DF of Xcc must be reexamined.     

Total synthesis of 5,5′,6,6′-tetrahydroxy-3,3′-biindolyl, the proposed structure of a potent antioxidant found in beetroot (Beta vulgaris)

5,5′,6,6′-Tetrahydroxy-3,3′-biindolyl, the proposed structure of a phenolic antioxidant isolated from the red beetroot (Beta vulgaris), has been synthesised. The spectroscopic data of the synthetic material is not consistent with that reported for the natural product.     

Synthesis of four diastereomers and structural revision of tetradenolide

Four diastereomers of tetradenolide, a cytotoxic α-pyrone isolated from Tetradenia riparia, were synthesized stereoselectively using the Z-selective Horner–Emmons reaction followed by acid catalyzed lactonization. Making comparison of the ¹H and ¹³C NMR spectral data of the four diastereomers with those of the reported value of natural product did not lead to determine the relative stereochemistry of the natural tetradenolide. Thus detailed investigation of the spectral data of the related compounds led us to revise the structure of tetradenolide as deacetylboronolide.     

Xenocladoniamide F,minimal indolotryptoline from the cladoniamide pathway

The isolation and structure elucidation of indolotryptoline alkaloid xenocladoniamide F (8) from a cladoniamide heterologous production system is reported. The structure of 8 is determined by NMR and X-ray crystallography. Relative to the parent cladoniamides, 8 lacks any remnant of an N-methylsuccinimide ring. This pentacyclic alkaloid is the most minimal indolotryptoline natural product yet reported.     

Total synthesis of the proposed structure of `brahol' and the structural revision

Proposed structure of brahol, a natural product, has been disproved by total synthesis of the proposed molecule from myo-inositol. Readily available 1,2;4,5-di-O-isopropylidene-myo-inositol, 3 was converted to 2,5-di-O-acetyl-1,6;3,4-di-O-isopropylidene-allo-inositol by epimerization of the di-triflate of 3. The acetyl group at O-5-position was selectively deprotected by aminolysis or methanolysis enabling the total synthesis of 5-O-methyl-allo-inositol, the proposed structure of brahol in six steps from myo-inositol. A comparison of spectral data of synthetic 5-O-methyl-allo-inositol with that reported for natural brahol revealed that the proposed structure of brahol is incorrect. A detailed structural revision revealed that brahol is nothing but quebrachitol. This study contradicts the first and only report on the natural occurrence of allo-inositol derivative.     

Synthesis, structural revision, and biological activities of 4′-chloroaurone, a metabolite of marine brown alga Spatoglossum variabile

4′-Chloroaurone (1a), the only aurone reported from a marine source, Spatoglossum variabile was synthesized from 2-hydroxyacetophenone along with six structural analogs. The products obtained were Z-isomers and these were converted into E-isomers by photoisomerization. The E and Z isomers of aurones showed distinct proton and carbon chemical shifts. However, the spectroscopic data of either Z-4′-chloroaurone (1a) or its E-isomer (2a) did not match with those reported for the natural product and thus requires revision of the structure assigned. The proton NMR spectroscopic data reported for the natural product matches with those reported for a known isocoumarin (5). The synthesized E and Z aurones were evaluated for their antioxidant and antibacterial activities. The aurone, Z-2-[(3,4-dihydroxyphenyl)methylene]benzo[b]furan-3-one exhibited significant antioxidant activity. Interestingly, Z-aurones are active against Gram-positive and Gram-negative bacteria, whereas the corresponding E-aurones were inactive.     

Total synthesis and structure revision of petrobactin

The total synthesis and the revised structural assignment of petrobactin, a siderophore isolated from the marine bacterium Marinobacter hydrocarbonoclasticus, is reported. The key step in the synthesis involved condensation of N¹-(2,3-dibenzoyloxybenzoyl)-N⁴-benzylspermidine with 1,3-di-(p-nitrophenyl)-2-tert-butyl citrate. Proton NMR spectra of the synthesized product compared with those reported for the natural product revealed that the compound did not contain 2,3-dihydroxybenzoyl moieties as published; instead, the splitting pattern suggested 3,4-dihydroxybenzoyl fragments. The 3,4-dihydroxybenzoyl analogue was accessed via a similar route; the proton and carbon-13 NMR spectra of this compound were consistent with those reported for natural petrobactin.     

Structure elucidation and stereoselective total synthesis of pavettamine, the causal agent of gousiekte

The structure elucidation of a novel natural product pavettamine (1), the causal agent of the plant toxicosis gousiekte, is reported. The structure was defined by analysis of NMR and MS data and the relative configuration followed from the ¹³C NMR data of the acetonide derivative. The absolute stereochemistry was established by total synthesis from (2S)-malic acid using chiral sulfoxide methodology as (2S,4R,8R,10S)-1,11-diamino-6-aza-undecane-2,4,8,10-tetraol.     

New pentacyclic cyclol-type naphthohydroquinone from the roots of Pentas bussei

The novel naphthohydroquinone, methyl 5,10-dihydroxy-7-methoxy-1,1,3a-trimethyl-1a,2,3,3a,10c,10d-hexahydro-1H-4-oxacyclobuta[cd]indeno[5,6-a]naphthalene-9-carboxylate 2, was isolated from the hexane extract of dried roots of Pentas bussei. Its structure elucidation was done by detailed spectroscopic methods. It is the first cyclol moiety containing naphthohydroquinone to be reported, and a novel natural product from P. bussei.     

Synthesis of 1,7-dimethoxy-2-hydroxyxanthone,a natural product with potential activity on erectile dysfunction

The natural product,1,7-dimethoxy-2-hydroxyxanthone(1),isolated from Securidaca inappendiculate Hassk,has a potential in the treatment of erectile dysfunction due to its significant relaxation activity on rabbit Corpus cavernosum.However,the isolation of compound 1 is problematic because of its high similarity in structure to its analogs.In this paper,the first synthesis of 1 was reported featuring two key reactions:a copper-catalyzed coupling reaction and an intramolecular cyclization.     

Enantioselective total synthesis of a natural hydrocarbazolone alkaloid,identification of its stereochemistry,and revision of its spectroscopic data

The natural hydrocarbazolone alkaloid (1R,2R,3R)-3-hydroxy-1,2-dimethyl-1,2,3,9-tetrahydro-4H-carbazol-4-one has been synthesized in a catalytic and enantioselective manner. A key hydrocarbazole derivative was constructed by the holmium-catalyzed Diels-Alder reaction of (silyloxyvinyl)indole as the diene. Total synthesis of the natural product clarified the ambiguity in the spectroscopic data reported for natural products.     

Synthesis and noncovalent DNA-binding properties of thiazole derivatives related to leinamycin

A series of compounds related to the macrocyclic portion of the DNA-damaging antitumor agent leinamycin were prepared as tools to characterize noncovalent DNA binding by this natural product. Acyclic (Z,E)-dienes were assembled via a Sonogashira coupling followed by partial hydrogenation. A Stille coupling was used in the cyclization step leading to a macrocyclic thiazole-diene analogue. Results obtained using the synthetic analogues reported here indicate that the extended π-system on the `left-hand side' of leinamycin is required for noncovalent association of the natural product with duplex DNA.     

Synthesis of (+)-agelasine C. A structural revision

An efficient synthesis of (+)-agelasine C has been achieved from ent-halimic acid. The structure and absolute configuration of the natural product (−)-agelasine C was established and a structure for epi-agelasine C, is proposed.     

Synthesis of (+)-pechueloic acid and (+)-aciphyllene. Revision of the structure of (+)-aciphyllene

1αH,7αH,10αH-Guaia-4,11-dien-3-one and its 1βH,10βH diastereomer, easily obtained from (+)-dihydrocarvone, are good starting materials for the synthesis of natural guaiane derivatives. Allylic oxidation of the 1αH,10αH isomer gave as main product its 13-hydroxy derivative and a small amount of (+)-7β-hydroxy-1αH,10αH-guaia-4,11-dien-3-one, whereas the 1βH,10βH diastereomer afforded selectively the (−)-7α-hydroxy-1βH,10βH enantiomer in excellent yield. From the 13-hydroxy derivative (+)-pechueloic acid and (+)-methyl pechueloate were synthesized. Deoxygenation at C₃ of the 1βH,10βH guaiadienone afforded a guaiadiene with the reported structure for aciphyllene but its spectral data did not agree with those reported for the natural diene. The structure of natural (+)-aciphyllene has been corrected to 1αH,7αH,10αH-guaia-4,11-diene obtained by deoxygenation of the 1αH,10αH guaiadienone.     

Enantioselective synthesis of possible diastereomers of heptadeca-1-ene-4,6-diyne-3,8,9,10-tetrol; putative structure of a conjugated diyne natural product isolated from Hydrocotyle leucocephala

Enantioselective synthesis of possible diastereomers of heptadeca-1-ene-4,6-diyne-3,8,9,10-tetrol, a structure proposed for the natural product isolated from Hydrocotyle leucocephala is accomplished. The reported spectral data of the natural product did not match those of any of the isomers that were synthesized and established that the structure proposed for the natural product is not correct and requires revision.     

The isolation and synthesis of 3-chloro-4-hydroxyphenylacetamide produced by a plant-associated microfungus of the genus Xylaria

Chemical investigations of the fermentation broth from the microfungus Xylaria sp. have afforded the new natural product 3-chloro-4-hydroxyphenylacetamide 1 and the previously reported fungal metabolite 3-chloro-4-hydroxyphenylacetic acid 2. This letter reports the isolation and full spectroscopic characterisation of compounds 1 and 2 by NMR, UV, IR and MS data. The crystal structure and one-pot synthesis of 3-chloro-4-hydroxyphenylacetamide are also reported.     

Enantioselective total synthesis of polyoxygenated cyclohexanoids: (+)-streptol, ent-RKTS-33 and putative ‘(+)-parasitenone’. Identity of parasitenone with (+)-epoxydon

Short, simple and enantioselective syntheses of the natural product (+)-streptol, the non-peptide apoptosis inhibitor ent-RKTS-33 and the putative structure of ‘parasitenone’ have been accomplished from the readily available chiral building block. ‘Parasitenone’ has been shown to be identical with the known natural product epoxydon.     

Radical carboxyarylation approach to lignans. Total synthesis of (-)-arctigenin, (-)-matairesinol, and related natural products

[reaction: see text] Total syntheses of seven biologically important lignan natural products, including (-)-arctigenin, (-)-matairesinol, and (-)-alpha-conidendrin, by way of a highly stereoselective domino radical sequence is presented. The reported stereochemistry of the natural product 7-hydroxyarctigenin is shown to be erroneous; a diastereoisomeric structure is assigned to the natural product.