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The development of new and effective antimicrobial agents with novel chemical skeletons and working mechanisms is highly desirable due to the increased number of resistant microbes. Different new compounds based upon a 3D-spiro chromanone scaffold such as Mannich bases 2 and 3 in addition to azo dye 4 were synthesized. Besides, the condensation reactions of the hydrazide-spiro chromanone 8 with different ketonic reagents led to the synthesis of pyrazoles (9 & 10) and anils (11 & 13). Moreover, the methoxyl substituted spiro chromanone 14 was condensed with different hydrazines and hydrazides to give the corresponding hydrazones 15–18 in up to 85% yields. The condensation of the hydrazone 18 with salicylaldehyde yielded coumarinyl spiro chromanone 19 in an excellent yield, whereas its reaction with benzaldehyde followed by hydrazine afforded aminopyrazole derivative 21 in 82% yield. The antimicrobial evaluation suggested that hydrazide 8 has a substantial activity against different microbes (S. aureus: D = 22 mm, MIC = 1.64 μM; E. coli: D = 19 mm, MIC = 1.64 μM; C. albicans: D = 20 mm, MIC = 6.57 μM). Moreover, promising antimicrobial activities were observed for azo dye 4 (D = 13–19 mm, MIC = 5.95–11.89 μM), hydrazone 17 (D = 17–23 mm, MIC = 1.88–3.75 μM), and aminopyrazole 21 (D = 14–19 mm, MIC = 2.24–8.98 μM). The molecular docking revealed that compounds 4, 8, 17, and 21 had good to high binding affinities with different microbial targets such as penicillin-binding proteins (−7.4 to −9.9 kcal), DNA gyrase (−7.8 to −9.0 kcal), lanosterol 14-alpha demethylase (−8.2 to −11.2 kcal), and exo-beta-1,3-glucanase (−8.2 to −11.9 kcal). The QSAR analysis ascertained a good correlation between the antimicrobial activity of 3D-spiro chromanone derivatives and their structural and/or physicochemical parameters.

New compounds were synthesized by the reaction of 3-acetyl-5- methoxy-2-methylbenzofuran (1) with cyanoacetylhydrazine which afforded the hydrazide hydrazone derivative 2. Compound 2 underwent a series of heterocyclization reactions to give the new pyrazole, isoxazole, cyclopentanothiophene, thiazole, triazole, 2H-chromene and pyridone derivatives (3-13). The elemental and spectral data (IR, 1H NMR and MS) characterized their structures. Screening for some selected compounds was carried for their potential antioxidant activities using ABTS. Among the tested samples compounds 9, 11, 5 and 10 exhibited promising activity.

The photooxygenation of imperatorin (1a) afforded the corresponding allylic hydroperoxides 2a and 3a in very good yields. Similarly, the photooxygenation of alloimperatorin derivatives 1c, d gave the allylic hydroperoxides 2c, d and 3c, d in quantitative yields. On the other hand, on photooxygenation of alloimperatorin (1b) exclusively the dienone hydroperoxide 4b was obtained. When the reaction time was prolonged, the bis(hydroperoxide) 5b was also formed by successive photooxygenation of 4b.

The epoxidation of allylic hydroperoxides 2a–h by dimethyldioxirane afforded the epoxy hydroperoxides 3a–h in very good yields. On the other hand, only the substrates 2a, b and 2d–f can be converted into the corresponding epoxy hydroperoxides by peroxy acids in reasonable to good yields. The peroxy acid and dimethyldioxirane epoxidations of allylic hydroperoxides proceed, in contrast to those of the allylic alcohols, in low but opposite diastereoselectivity. The configuration of diastereomeric epoxy hydroperoxides were determined by NMR-NOE experiments and chemical correlation.

The aerial parts of Francoeuria crispa gave, in addition to known sesquiterpene lactones, two new ones. From the polar parts a large amount of two diterpene glycosides derived from ent-kauren-19-oic acid were obtained.

Epoxidation of imperatorin (1a) by dimethyldioxirane (DMD) affords the natural product prangenin (2a) in excellent yield. Similarly, alloimperatorin (1b) and its methyl and acetate derivatives 1b–d are epoxidized with DMD to give the corresponding epoxides 2b–d in quantitative yields. Furthermore, the reaction of the imperatorin allylic hydroperoxide 1e with DMD, and for comparison with m-chloroperbenzoic acid (CPBA), yields the diastereomeric epoxy hydroperoxides (R*,S*)- and (R*,R*)-2e in low but of opposite diastereoselectivity. Thus, for DMD the (R*,S*)/(R*,R*-2e ratio is 56:44 and for CPBA 40:60.

When irradiated at 360 nm, furocoumarins with a hydroperoxide group in a side chain efficiently give rise to a type of DNA damage that can best be explained by a photo-induced generation of hydroxyl radicals from the excited photosensitizers. The observed DNA damage profiles, i.e. the ratios of single-strand breaks, sites of base loss (AP sites) and base modifications sensitive to formamidopyrimidine--DNA glycosylase (FPG protein) and endonuclease III, are similar to the DNA damage profile produced by hydroxyl radicals generated by ionizing radiation or by xanthine and xanthine oxidase in the presence of Fe(III)--EDTA. No such damage is observed with the corresponding furocoumarin alcohols or in the absence of near-UV radiation. The damage caused by the photo-excited hydroperoxides is not influenced by superoxide dismutase (SOD) or catalase or by D2O as solvent. The presence of t-butanol, however, reduces both the formation of single-strand breaks and of base modifications sensitive to FPG protein. The cytotoxicity caused by one of the hydroperoxides in L5178Y mouse lymphoma cells is found to be dependent on the near-UV irradiation and to be much higher than that of the corresponding alcohol. Therefore the new type of photo-induced damage occurs inside cells. Intercalating photosensitizers with an attached hydroperoxide group might represent a novel and versatile class of DNA damaging agents, e.g. for phototherapy.

Reichardia tingitana var. orientalis afforded, in addition to lupeol, taraxasterol, and the corresponding acetates, three sesquiterpene lactones of the guaianolide type including a new glucoside. The structures were elucidated by spectral methods.

Artemisia monosperma afforded four flavonoids, two acetylenes, eight p -hydroxyacetophenone derivatives and three p -coumaric acid derivatives, two of them being new. The structures were elucidated by spectral methods. The flavonoids present are naringenin 7-methyl ether, eriodictyol 7-methyl ether, quercetin 3,7-dimethyl ether and quercetin 7,3′-dimethyl ether.

When β-keto-ester1 a was reacted with dimethyl acetylenedicarboxylate ring expansion occurred to give substituted cyclooctadienones.Michael reactions of the title compounds1 with unsaturated ketones gave adducts, some of which underwent further cyclization reactions. A new route to α-tetralone ring system10 via cyclization of the intermediateMichael adduct9 is described.

A reinvestigation of the aerial parts of Pyrethrum santolinoides afforded, in addition to known compounds, four new sesquiterpene lactones, three germacranolides and an eudesmanolide. The structures were elucidated by high field 1H NMR techniques.

DoubleMannich reaction of the title compound1 with morpholine acetate in ethanol gave the symmetrical bis-base2, whereas such reaction in acetic acid afforded the vinyl-ketonic base3. Reactions of3 with morpholine, piperidine, thiophenol and dimethyl phosphite were investigated.Mannich reaction of2 with primary amines gave di-basically substituted γ-piperidones6a-b. Compound1 reacts with ethylenediamine and formaldehyde to give the diazatricyclic system7.

Achillea fragrantissima afforded, in addition to several known glaucolides, five new compounds whose structures were elucidated by high field 1 H NMR spectroscopy.

Photochemical behavior of imperatorin was investigated including photolysis and sigmatropic effects in different solvents and photodimerization. The structures of the photoproducts obtained were determined by chemical and spectral methods.

When β-keto-ester1 a was reacted with dimethyl acetylenedicarboxylate ring expansion occurred to give substituted cyclooctadienones.Michael reactions of the title compounds1 with unsaturated ketones gave adducts, some of which underwent further cyclization reactions. A new route to α-tetralone ring system10 via cyclization of the intermediateMichael adduct9 is described.