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The aim of this study is to prepare novel thiophene bicyclo[3.2.1]octadiene derivatives with structure convenient for the introduction of new functional groups. Further on, the study aims at expanding the compound library and at creating preconditions for further biological investigations. The starting substrates were easily obtained by Vilsmeier-Haack’s reaction of bicyclo[3.2.1]octadiene thiophene derivatives From the obtained carbaldehydes, novel methyl-, methoxy- and cyano-substituted styryl thieno-benzobicyclo[3.2.1]octadiene derivatives were formed by Wittig's reaction and subjected to photochemical reactions, in terms of obtaining new annulated structures. As a part of this study, aldol reaction of starting 2-substituted carbaldehyde and acetone was also performed, which produced the thieno-fused benzobicyclo[3.2.1]octadiene compound with an extended conjugation.

To study the effects of the position of the hexatrienyl moiety on the oxazole ring, novel substituted cis/trans-2/4/5-(2-vinylstyryl)oxazoles have been synthesized. These novel compounds were prepared by Wittig reaction from diphosphonium salt of a, a’-o-xylenedibromide, formaldehyde and the corresponding 2-methyl-4-, 4-methyl-2-, 2-pheny-5- and 4-methyl-5-oxazolecarbaldehyde, respectively. Aldehydes were synthesized by several synthetic approaches. By intramolecular photocycloaddition 2-methyl-4-(2-vinylstyryl)oxazole afforded, as major product, fused oxazoline-benzobicyclo[3.2.1]octene with small quantities of 4-(1, 2-dihydronaphthalen-2-yl)-2-methyloxazole, as electrocyclization product. Upon irradiation of 4-methyl-5-(2-vinylstyryl)oxazole endo- and exo-benzobicyclo[2.1.1]hexene products were formed by [2+2] cycloaddition and this was the first instance of the 1, 4-closure to the bicyclo[2.1.1]hexene skeleton in the 2-, 4-, and 5-oxazole-stilbene derivatives studied so far. Derivatives, 2-phenyl-5- and 4-methyl-2-(2-vinylstyryl)oxazole do not react and give only high weight molecular products but are crucial as a comparison in the overall mechanistic study. We have found that depending on the position of the hexatrienyl moiety in the oxazole ring, as well as the position of the methyl/phenyl substituents these new vinylstyryl-2/4/5-oxazole derivatives show diverse photochemical behavior.

Biciklo[3.2.l]-skeleton je zajednička podjedinica mnogih prirodnih struktura kao što su diterpeni i seskviterpeni. Spojevi koji posjeduju ovu podjedinicu kao bazu pokazali su se kao snažni inhibitori dopaminskih i serotoninskih transportera, te imaju važnu ulogu u liječenju bolesti CNS [1]. S druge strane, fotokemijska sinteza omogućila je jednostavan put do velikog broja policikličkih spojeva koji posjeduju benzobiciklo[3.2.1]oktadiensku strukturu [2]. Primjenom još snažnijeg alata u sintezi ovog ključnog funkcionaliziranog supstrata, flow fotokemijski sustav [3] je korišten po prvi put pružajući mogućnost rasta produktivnosti intramolekulske cikloadicije bez uvećanja opreme.Za sve nove potencijalno bioaktivne derivate 1-7 dobivene flow fotokemijom analizirana su preliminarna fizikalno-kemijska svojstva, te se prema in silico modelu za predviđanje aktivnosti pokazalo da benzobiciklo[3.2.1]oktadieni imaju potencijalno dobru CNS aktivnost. Dodatno, spojevi 1, 5 i 7 trebali bi imati dobru sposobnost prodiranja kroz krvno-moždane barijere. Dobiveni fotoprodukti pokazali su i potencijalno dobru inhibicijsku aktivnost na kolinesteraze.

Bicyclo[3.2.l]-skeleton is a common subunit in many natural products such as diterpenes and sesquiterpenes [1a]. Compounds that have this core as a base have been tested and are proved as potent inhibitors of dopamine and serotonin transporters and also play crucial role in treatment of CNS and Alzheimer’s disorders [1b, c]. On the other hand, photochemical synthesis gave a pathway to a whole library of polycyclic compounds that include a vast number of structures with the benzobicyclo[3.2.1]octadiene moiety [2]. To apply an even more powerful tool for this targeted functionalized substrate, continuous flow photochemical system was used for the first time [3] enabling us to scale-up the intramolecular cycloaddition reaction without scaling-up the equipment. For all of the obtained novel potentially bioactive derivatives preliminary physico-chemical properties were also analyzed

In order to study the influence of heterocyclic nuclei on the photochemical behavior of the conjugated butadiene systems, novel butadiene derivatives E, Z- and E, E-2/3-[4-(2- vinylphenyl)buta-1, 3-dienyl]thiophene as well as E, Z- and E, E-3/4-[4-(2- vinylphenyl)buta-1, 3-dienyl]pyridine have been synthesized. The Wittig reaction was utilized in a two-step reaction course. During the first Wittig reaction the corresponding aldehydes, namely 2/3-thiophenecarboxaldehyde and 3/4- pyridinecarboxaldehyde, reacted with formylmethylene- triphenylphosphorane to give the corresponding acrylaldehydes which reacted with diphosphonium salt of b, b'-o- xylenedibromide in the second Wittig reaction to give new butadiene derivatives. These butadiene derivatives afforded, by photochemical intramolecular cycloaddition, new fused tricyclic as well as tetracyclic derivatives. For the first time a study of efficiency was conducted where the efficiency of intramolecular cycloaddition of these heterocyclic butadiene derivatives was investigated by simultaneous use of ferrioxalate and valerophenone actinometers.

The Diels-Alder reactions were exploited in the preparation of novel long wavelength chlorin photosensitizers for photodynamic therapy. Styryl group and furan carboxamide substituents were used as diene components in [4+2] cycloaddition functionalizations. Pheophorbide a and chlorin e6 were effectively functionalized by cycloaddition reactions using conventional and nonconventional reaction conditions (MW irradiation and extremely high pressure).

Oksazoli spadaju u peteročlane aromatske spojeves dva heteroatoma u jezgri, kisikom i dušikom, koji uvelike utječu na njihova svojstva.Oksazolske strukture se pojavljuju u velikom broju u prirodi prisutnih spojevakoji pokazuju visoku biološku aktivnost. Novi 2-, 4 i 5-(2-vinilstiril)oksazoli sintetizirani su u svrhu istraživanja intramolekulskih reakcija u pobuđenom stanju.Zanjihovu pripravu razvijeni su i korišteni razni sintetski putevi koji su uključivali Wittigovu, Bredereck-Gomperovu te Van Leusenovu reakciju.Položaj stirilne skupine bitno utječe na tijek fotokemijske reakcije i nastajanje različitih produkata.Osvjetljavanjem supstituiranih derivata oksazola, ovisno o supstituentima i njihovim položajima u jezgri, dobiveni su različiti hetero-policiklički spojevi kao što su naftoksazoli, fuzionirani oksazolo-benzobiciklo[3.2.1]heksadienski derivati ili arilni derivati benzokinolina. Svi novi derivati okarakterizirani su modernim spektroskopskim metodama.

Unutar naše grupe napravljena je studija ponašanja raznih butadienskih derivata, gdje je energija potrebna za reakciju dovedena ili fotokemijski ili termičkim putem. Studirani butadienski derivati pokazali su raznoliko ponašanje u pobuđenom stanju pri čemu je izoliran i u potpunosti okarakteriziran veliki broj novih bicikličkih produkata. S obzirom da je biciklo[3.2.1]oktanski kostur prisutan u velikom broju biološki aktivnih spojeva izoliranih iz prirode odlučili smo proširiti dosadašnja istraživanja. Kao jedan od smjerova daljnjeg istraživanja ovog širokog područja odlučili smo se za zamjenu benzenske jezgre heterocikličkom (tiofenskom)jezgrom. U tu svrhu sintetizirani su 2- i 3-[4-(2-vinilfenil)buta-1, 3-dienil]tiofeni. Razvijena su dva zasebna sintetska puta u svrhu povećanja ukupnog iskorištenja. S obzirom na sintezu nastaju dva izomera svakog spoja i to cis, cis- i cis, trans-izomer koji su razdvojeni i okarakterizirani. Također su provedena ispitivanja u pobuđenom stanju koja su dala uvid u ponašanje derivata i omogućila preparativne sinteze novih bicikličkih spojeva.

Fatty hydroxamic acid (FHAs) mixture, composed mainly of oleoyl and linoleyl hydroxamic acid (OHA and LHA respectively), was derived from olive oil triacylglycerides (Scheme). The FHAs mixture was elucidated by means of IR, Raman, MS, one- and two-dimensional homo- and heteronuclear 1H and 13 C-NMR spectroscopy in comparison with corresponding olive oil spectra. The ratio of the OHA and LHA (4:1) was confirmed by MALDI-TOF/TOF mass spectrometry.The results of FHAs cell toxicity on normal fibroblast (BJ) and tumour cell linee (HeLa) revealed that the normal cell line was sensitive to FHAs in whole range of applied concentrations while HeLa tumor cell line was sensitive only at higher FHAs concentrations.The radical scavenging, metal chelating and the antioxidant activity in β- carotene-linoleate assay, as well as the reducing power of FHAs, gave positive results of FHAs activity in these tests. The ADMET predictor parameters revealed that the FHAs in comparison to their corresponding carboxylic precursors (oleic and linoleic acids) are more prominent as leading compound for further research.

Previous publications on the photochemistry of different heteroaryl substituted hexatrienes showed interesting intramolecular cycloaddition reactions and the formation of bicyclo[3.2.1] octadienes as unsaturated structural analogues of the bicyclo[3.2.1]octane skeleton which is found in numerous biologically important active natural products. The photochemical behaviour of mono- and dichloro-substituted butadiene derivatives was studied at low concentrations. These compounds display diverse photochemical behaviour. The α-chloro derivatives photocyclize to give six-membered ring photoproducts. p-Chloro substituted butadienes undergo intramolecular [2 + 2] cycloaddition followed by formation of benzobicyclic structures. The steric hindrance of chlorine(s) in a-position(s) cause a greater deviation from planarity, relative to p-substitution, and shift conformer equilibria and affects the reaction pathways and yields.

Jedna od kompleksnijih grana organske kemije je heterociklička kemija. Oksazoli su skupina spojeva koji spadaju u skupinu peteročlanih aromatskih spojeva a imaju dva heteroatoma u jezgri, kisik i dušik. Vrlo su interesantni jer se pojavljuju u velikom broju u prirodi prisutnih spojeva koji pokazuju visoku biološku aktivnost. Novi, do sada neopisani 4 i 5-(2-vinilstiril)oksazoli sintetizirani su u svrhu istraživanja njihovih intramolekulskih reakcija u pobuđenom stanju. Spojevi su priređeni nizom reakcija. Da bi dobili 5-(2-vinilstiril)oksazol u zadovoljavajućoj količini razvijena su dva različita sintetska puta. Dobiveni izomeri osvjetljavani su u fotokemijskom reaktoru u cilju sinteze novih policikličkih spojeva te studije utjecaja položaja heteroatoma na intramolekulske reakcije cikloadicije i ciklizacije. Svi novi heterociklički derivati okarakteriztirani su modernim spektroskopskim metodama.

Područje , * apsorpcije jednostavnih alkena nalazi se na 

U cilju priprave novih policikličkih struktura fotokemijskom metodologijom, priređeni su supstituirani butadienski derivati 1-4 te je istražena fotokemija ovih novih sustava s produljenom konjugacijom. Naši prijašnji rezultati [1, 2] na fotokemiji nesupstituiranih (R = H) i supstituiranih butadiena 1 i 3 (R = CH3) pokazali su zanimljivu i različitu fotokemiju i fotofiziku ovih spojeva relativno slične strukture. Uvođenje klora kao supstituenta u nesupstituirani spoj (1- 4) mijenja tok fotoreakcije što je posljedica značajnih steričkih i elektronskih utjecaja na fotokemijska svojstva molekule. Razumijevanje ključnih efekata supstituenata u fotokemijskim reakcijama ovih novih butadienskih derivata i objašnjenje reakcijskih mehanizama u nastajanju fotoprodukata, čini sintezu ovih sustava pogodnom za usmjeravanje fotoreakcije ka raznim interesantnim strukturama za daljnje transformacije i funkcionalizaciju. [1] I. Škorić, M. Šmehil, Ž. Marinić, K. Molčanov, B. Kojić- Prodić, M. Šindler-Kulyk, J. Photochem. Photobiol. A 207 (2009) 190-196. [2] I. Škorić, I. Kikaš, M. Kovács, L. Fodor, Ž. Marinić, K. Molčanov, B. Kojić-Prodić and O. Horváth, J. Org. Chem. 76 (2011) 8641-8657.

Oksazolski prsten, peteročlana aromatska struktura s kisikom i dušikom, pojavljuje se u velikom broju u prirodi prisutnih spojeva [1, 2] i nizu struktura supstituiranih u položajima 2, 4 i 5 kao i raznim fuzioniranim spojevima koji su zanimljivi zbog visoke biološke aktivnosti [3]. Također su građevni elementi spojeva koji se koriste kao scintilatori, laserska bojila, agensi za izbjeljivanje, u fotografiji i kao aditivi u sredstvima za podmazivanje [4]. Pregledom literature, na naše iznenađenje, ustanovili smo da 5-stiril-oksazoli i njihovi 5-heterociklički analozi nisu opisani. Takvi konjugirani oksazolski sustavi dobri su supstrati za daljnje fotokemijske reakcije koje vode ka novim poli-heterociklički spojevima.U nastavku istraživanja fotokemijskih intramolekularnih reakcija nezasićenih heterocikličkih sustava s dva ili više heteroatoma[5, 6] u ovom radu sintetizirani su 5-stiril-oksazol i novi konjugirani heterociklički 5-oksazolski derivati (2-4) iz odgovarajućih konjugiranih aldehida reakcijom s Van Leusenovim reagensom (TosMIC). Svi novi spojevi okarakterizirani su modernim spektroskopskim metodama.