Synthesis and structural revision of naturally occurring ayapin derivatives

The synthesis of three highly oxygenated naturally occurring coumarins, 8-methoxy-6,7-methylenedioxycoumarin, 5-methoxy-6,7-methylenedioxycoumarin and 5,8-dimethoxy-6,7-methylenedioxycoumarin is described for the first time, together with a new method for the preparation of ayapin (6,7-methylenedioxycoumarin). Comparison of the spectroscopic data of the synthetic tetraoxygenated coumarin 5,8-dimethoxy-6,7-methylenedioxycoumarin with literature reports resulted in the structural revision of several natural coumarins. Two coumarins, both identified as 5,8-dimethoxy-6,7-methylenedioxycoumarin must have other structures, while the structure of another coumarin, described as the isomeric 7,8-dimethoxy-5,6-methylenedioxycoumarin has to be revised to 5,8-dimethoxy-6,7-methylenedioxycoumarin.     

Synthesis and structural revision of eurypamides isolated from the Palauan sponge Microciona eurypa

Eurypamides A and B, 1 and 2, were successfully synthesized by employing Tl(NO₃)₃ (TTN) oxidation of the corresponding halogenated phenols, 9, 16, and 26. This investigation revealed that the dihydroxyarginine residue of 1 should be revised to possess (2S,3R,4S)-configuration. In addition, the synthesis of 2 provided a pure sample, which was previously characterized in a mixture.     

A radical mediated first total synthesis from ‘diacetone glucose’ and determination of the absolute stereochemistry of xylobovide

The first total synthesis by an intramolecular radical cyclisation protocol on a carbohydrate derived 5-hexynyl system, and determination of the absolute stereochemistry of xylobovide are reported.     

Synthesis and structural revision of calafianin, a member of the spiroisoxazole family isolated from the marine sponge, Aplysina gerardogreeni

Calafianin 1 was successfully synthesized by employing a spiroisoxazoline compound, which was produced by electrochemical oxidation of the oximino-phenol derivative 7 followed by reduction. This investigation revealed a structural revision of 1, the trans-relationship of two oxygen atoms between the epoxide and the isoxazoline.     

Synthesis of melampolides and cis,cis-germacranolides as natural herbicide models

The comparative study between the theoretical molecular properties of the starting materials and the yields in the transformation of melampolides to cis,cis-germacranolides using SeO₂/t-BuOOH (TBHP) as oxidant allows to establish a feasible relationship with their values of dipolar moment. Conditions for this transformation are optimized and some mechanistic considerations are made based in this finding. Cluster analysis of the phytotoxic activity of the melampolides and cis,cis-germacranolides obtained shows that the activity is greatly influenced by the spatial shape of the backbone, prevailing upon other factors such as the presence of reactive functional groups.     

Synthesis of the fungal natural product (−)-xylariamide A

The first synthesis of the fungal natural product (−)-xylariamide A 1 is reported. N,O-Bis(trimethylsilyl)acetamide induced coupling of d-tyrosine with (E)-but-2-enedioic acid 2,5-dioxo-pyrrolidin-1-yl ester methyl ester 5 produced the dechloro natural product 6, which was subsequently monochlorinated using oxone and KCl to yield synthetic 1. (−)-Xylariamide A 1, (+)-xylariamide A 2 and (−)-dechloroxylariamide A 6 displayed no cytotoxic or antimicrobial activity.     

Synthesis and chemical structure of natural rubber adduct with SO2 and study of the thermal stability

Natural rubber (NR, cis-1,4-polyisoprene) was reacted in solution with SO₂ at room temperature in different solvents (tetrahydrofuran, CHCl₃, CH₂Cl₂ and tetralin). The reaction product consisted of an adduct between NR and SO₂. The chemical structure of the adduct was studied by FT-IR spectroscopy, by thermogravimetry coupled with FT-IR (TGA-FT-IR), by differential thermal analysis (DTA) and by derivative thermogravimetry (DTG). The maximum SO₂ uptake from NR was 21% as determined by TGA. The TGA of the NR-SO₂ shows that the adduct decomposes in two steps initially releasing SO₂ at lower temperature and then decomposing at higher temperature like common NR. It is proposed that the chemical structure of the NR-SO₂ adduct consists of SO₂ molecules added to the double bonds of the isoprene units forming a sulfone derivative with three-membered rings known as thiirane-1,1-dioxide. On heating the thiirane ring decomposes releasing SO₂ in an extrusion reaction giving back the NR macromolecule.The possible potential applications of the NR-SO₂ adduct which is cheap and easy to prepare are outlined.     

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, stereochemistry confirmation and biological activity evaluation of a constituent from Isodon excisus

A synthesis and stereochemistry confirmation of a constituent recently isolated from the whole plant Isodon excisus is reported. An enantioselective catalytic boron-mediated reduction of an α-bromoketone was utilized in the key synthetic transformation. The methodology described herein was also used for the synthesis of the natural product's enantiomer and several derivatives. In addition, the compounds were evaluated for inhibitory activity in a caspase induction assay. The natural product was found to be devoid of activity, but several derivatives had moderate inhibitory activity (EC₅₀<1 μM).     

Total synthesis and structure revision of deacetylravidomycin M

Total synthesis of the unnatural enantiomer of deacetylravidomycin M was accomplished. The key steps include, (1) aryl C-glycosidation of the azido-bearing fucosyl acetate 2 by using catalytic Sc(OTf)₃, (2) the [2+2] cycloaddition reaction of alkoxybenzyne bearing an azido sugar to ketene silyl acetal, and (3) the ring expansion reaction of alkoxybenzocyclobutenone. The synthesis revealed that the natural product is not the proposed amine, but the corresponding N-oxide.     

Synthesis and elucidation of absolute stereochemistry of salaprinol, another thiosugar sulfonium sulfate from the ayurvedic traditional medicine Salacia prinoides

Synthesis and elucidation of absolute stereochemistry of salaprinol (3) isolated from the root and stems of Salacia prinoides, which has been used for the treatment of diabetes in India, Sri Lanka, and Southeast Asia countries, is described. Compound 3 and its 2′-epimer, epi-salaprinol (epi-3) were synthesized via the coupling reaction of a cyclic sulfate, 2-O-benzylglycerol 1,3-cyclic sulfate (5), with a thiosugar, 1,4-dideoxy-1,4-epithio-d-arabinitol (6), as the key reaction, and S configuration of the asymmetric center in the side chain of 3 was elucidated by the X-ray crystallographic analysis.     

Synthesis and assignment of the absolute stereochemistry of (+)-hemifistularin 3

The first total synthesis of the marine natural product (+)-hemifistularin 3 in enantiomerically pure form was accomplished by using the amide forming reaction of (+)-spiroisoxazoline ester with the (+)-octopamine derivative. The stereodivergent strategy employed in this effort enabled the assignment of the absolute configurations at the three stereogenic centers in (+)-hemifistularin 3.     

Preparation of optically pure cross-conjugated cyclopentadienones

The synthesis of optically pure cross-conjugated cyclopentadienones is readily achieved in two steps via a one-pot alkylcuprate addition/aldol condensation/dehydration sequence using racemic or enantioenriched endo-3a,4,7,7a-tetrahydro-1H-4,7-methano-inden-1-ones followed by microwave-mediated Lewis acid-catalysed retro Diels-Alder reaction. An alternative route involving a modified Baylis-Hillman protocol followed by conjugate addition with alkylcuprates and a retro Diels-Alder reaction was also investigated.     

Synthesis of cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans

Substituted cis-3,4-diarylpiperidines and cis-3,4-diaryltetrahydropyrans are synthesized in modest overall yields starting from 4-aryl-1,2,5,6-tetrahydropyridines and 4-aryl-1,2,5,6-tetrahydropyrans via the following sequence: (1) pinacol-type ring contraction having the combination of m-chloroperoxybenzoic acid and boron trifluoride etherate, (2) Grignard addition with arylmagnesium bromide reagents and followed by boron trifluoride etherate-mediated intramolecular ring-expanded rearrangement, and (3) hydrogenation with hydrogen on 10% palladium-activated carbon. A facile synthesis of 3,4-diarylpyridines was also described by base-induced aromatization.     

Tri-component reaction of 2-alkyl-4,5-dichloropyridazin-3(2H)-ones: synthesis of 5-cyano-5-(pyrimidin-2-yl)-2,7-dialkyl-5H-dipyridazino-[4,5-b:4,5-e]-4H-thiopyran-1,6-dione and 2-(4-cyanophenoxy) pyrimidine

Reaction of 2-alkyl-4,5-dichloropyridazin-3(2H)-ones with p-cyanophenol and 2-mercaptopyrimidine in the presence of base gave 2,4,5-trisubstituted-pyridazin-3(2H)-ones 4-9, 2-(4-cyanophenoxy)pyrimidine (10) and 5-cyano-5-(pyrimidin-2-yl)-2,7-dialkyl-5H-dipyridazino[4,5-b:4,5-e]-4H-thiopyran-1,6-diones 11 as a novel heterocycle.     

Brominated polyunsaturated lipids and their stereochemistry from the Chinese marine sponge Xestospongia testudinaria

Chemical examination of the Chinese marine sponge Xestospongia testudinaria led to the isolation of 39 new brominated polyunsaturated compounds, which were designated with the trivial names xestospongienes A-Z and Z₁-Z₁₃. The structures of these compounds were elucidated by analyzing extensive spectroscopic (IR, MS, 1D, and 2D NMR) data and the results from CD spectral assignment, chemical conversion, and Mosher reaction.     

Revised structure of tetrapetalone A and its absolute stereochemistry

The chemical structure of tetrapetalone A (1), a novel lipoxygenase inhibitor from Streptomyces sp., was revised by using the ¹H-¹⁵N HMBC technique. Furthermore, the absolute stereochemistry of all the asymmetric carbons in 1 was determined based on the detailed NOE data of 1 and its derivative.     

A re-investigation of resveratrol synthesis by Perkins reaction. Application to the synthesis of aryl cinnamic acids

A re-investigation of resveratrol synthesis by Perkins reaction allowed to improve this method and to determine the configuration of the intermediates. The results were applied to the synthesis of several aryl cinnamic acids for biological evaluation.     

Synthesis of fluorinated imines and carbodiimides from azides via aza-Wittig reaction

The Staudinger reaction of fluoroalkylazides were studied. A series of N-fluoroalkylimines were synthesized via aza-Wittig reaction of N-fluoroalkyliminophosphoranes. The N,N′-difluoroalkylated carbodiimide was also synthesized via the reaction of N-fluoroalkyliminophosphoranes with carbon dioxide or carbon disulfide.     

Synthesis and characterization of tetramethylene-syn-sesterbicyclo[2.2.2]octene

The synthesis of syn-sesterbicyclo[2.2.2]octene (7) bilaterally grafted by an exocyclic s-cis-butadiene moiety is achieved from 1,8,9,10-tetrachloro-11,11-dimethoxy-endo-tricyclo[6.2.1.0^2,7]undeca-3,5,9-triene (8) employing repetitive Diels-Alder cycloadditions between 1,3-cyclohexadiene, generated from p-benzoquinone, and diethyl fumarate or maleic anhydride as the exocyclic butadienyl equivalent, followed by subsequent transformation to the conjugated diene moieties. In comparison with the corresponding sesquibicyclo[2.2.2]octene 6, the ¹H NMR demonstrates the anisotropic shielding effect operating within the three parallel laticyclic double bonds. However, the UV absorption of 7 shows less effect by the increase of laticyclic conjugated ethylene units.