Abstract
Stereoselective synthesis of monoterpene-based 1,2,4- and 1,3,4-oxadiazole derivatives was accomplished starting from α,β-unsaturated carboxylic acids, obtained by the oxidation of (−)-2-carene-3-aldehyde and commercially available (−)-myrtenal. 1,2,4-Oxadiazoles were prepared in two steps via the corresponding O-acylamidoxime intermediates, which then underwent cyclisation induced by tetrabutylammonium fluoride (TBAF) under mild reaction conditions. Stereoselective dihydroxylation in highly stereospecific reactions with the OsO4/NMO (N-methylmorpholine N-oxide) system produced α,β-dihydroxy 1,2,4-oxadiazoles. Pinane-based 1,3,4-oxadiazoles were obtained similarly from acids by coupling with acyl hydrazines followed by POCl3-mediated dehydrative ring closure. In the case of the arane counterpart, the rearrangement of the constrained carane system occurred with the loss of chirality under the same conditions. Stereoselective dihydroxylation with OsO4/NMO produced α,β-dihydroxy 1,3,4-oxadiazoles. The prepared diols were applied as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes. All compounds were screened in vitro for their antiproliferative effects against four malignant human adherent cell lines by means of the MTT assay with the O-acylated amidoxime intermediates exerting remarkable antiproliferative action.
Highlights
In asymmetric synthetic chemistry a growing demand occurs for new chiral ligands and synthons
We recently described the synthesis and transformation of enantiomerically pure pinane- and carane-based 3-amino-1,2-diols, whereas the amino moiety served as a fundamental building block in the synthesis of terpenoid-type nucleoside analogues with remarkable sInotd
We found that the type of the heterocyclic ring system has affected catalytic activities
Summary
In asymmetric synthetic chemistry a growing demand occurs for new chiral ligands and synthons. New strategies are being developed for the synthesis of reliable enantiopure catalysts [1–3]. Incorporation of chirality into ligands by applying optically active monoterpenes as starting materials bears several advantages: the natural chiral origin can determine the stereochemistry of newly forming chiral centers as well the chiral activities of these newly desired chiral catalysts [4,5]. A large variety of chiral amino alcohol and aminodiol-type ligands, derived from monoterpenes, such as α- and β-pinene [6–10], (−)-(S)-perillaldehyde, carene [11–13], and fenchone-camphor [13,14], have been reported as successful chiral catalysts. Monoterpene-based 1,3-heterocycles,2soufc1h1 as 1,3-oxazines or -oxazolidines could be successfully applied as chiral catalysts in a wide range of shteetreeroosceyleclcetsiv, esutrcahnassfo1r,m3-oatxiaoznisne[1s1o,1r7-–o2x1a]z.olidines could be successfully applied as chiral catalysts in a widOenratnhgeeoothfesrtehraenosde,le1c,2ti,v4-eatrnadns1f,o3,r4m-oaxtiaodnisaz[1o1le,1s7h–a2v1]e. Monoterpene-based 1,3-heterocycles,2soufc1h1 as 1,3-oxazines or -oxazolidines could be successfully applied as chiral catalysts in a wide range of shteetreeroosceyleclcetsiv, esutrcahnassfo1r,m3-oatxiaoznisne[1s1o,1r7-–o2x1a]z.olidines could be successfully applied as chiral catalysts in a widOenratnhgeeoothfesrtehraenosde,le1c,2ti,v4-eatrnadns1f,o3,r4m-oaxtiaodnisaz[1o1le,1s7h–a2v1]e. been extensively studied in the past decadOen[2th2e–2o8t]h. eAr hwaindde, r1a,n2,g4e- aonf dbi1o,l3o,g4i-coaxlalydiaacztoivleesphhaavremaalscoopbheoernesexptoesnsseivsseltyhesstuedfiivede-minetmhebepraesdt hdeetceardoear[o2m2–a2t8i]c. rAinwg idsyesrteamngsewofithbiorleomgiacraklalyblaectbivioelopghiacarml pacrooppherotrieess pinocslsuedssintghesspehfiinvoes-mineemkbineraesde ihnehteibroitaorrom[29a]t,icdriaincgylgslyyscteermosl awcyitlhtrarnemsfearraksaebl1e (bDioGlAogTi-c1a)l inphroibpietrotrie[s30i]n,cglulydcinoggenspshyinnothsainsee kkiinnaassee (inGhSiKbi-t3o)r i[n2h9i]b, idtoiarcy[3lg1l]y, cseirrotul iancy(lStrIaRnTs)feirnahsiebi1to(rDG[3A2]T-a1n)dinmhiebtihtoior n[i3n0e], agmlyicnoogpeenptsiydnatsheasienhkiibniatoser a(GctSivKi-t3ie) sin[h3i3b]i.toSro[m31e],dsiirteturpinen(SicIR1T,2) ,i4n-haibnidtor1,[33,24]-oaxnaddmiaeztohlieosn, iinneclaumdiinnogpsetpetriodiads-ebiansheidbictoormapcotiuvnitdiess, h[3a3v]e. aSlosmo eshdowitenrpreemniacrk1a,2b,4le- aanntdipr1o,3li,f4e-roaxtiavdeiaazcotiloens,oinncalduhdeinregntstheuromidan-bcaasnedcercocemllploinuensd[s2,5,h2a6v,3e4–a3ls7o]. showInn rtehme aprrkeasebnlet awnotirpkr,owliefesreattiovuetatcoticorneaotne apdinhaenreen- tahnudmcaarnancaen-bcaesrecdeldl ilihnyedsr[o2x5y,2-6d,e3r4i–v3e7d].1,2,4- and 1,3,4-Ionxtahdeiapzroesleesntaws hoerkte,rwoceyscelticouant atolocgrueaetseopfinparenve-ioaunsdlycaprraenpea-rbeadsemdodnihoytedrrpoexnyi-cd3e-raivmeidno1,-21,,42--daniodl l1i,b3r,4a-royx. aTdhieazsoylnetshaessehsewteerroecystcalircteadnfarloomgureesadofilypraevvaioiluabsllye (p−re)-p(aSr)e-pdemrilolanlodteehrpyedneican3d-a(m−i)n-mo-y1,r2t-edniaoll, alisbrnaartyu.rTahl emsoynnothteerspeesnweesroeusrtcaerste, dthfernomaprpelaydiinlyg athveairlaesbulelt(i−n)g-(tSr)i-dpeenritlallalldigeahnyddseaasncdh(i−ra)-lmcaytratelynsatls, ains tnhaetuernaalnmtioosneolteecrtpiveenaedsdoiutirocneso, fthdeienthayplpzliynicntgotbheenrzeasludlethinygdetr.idWeenatalslolipgalanndnseadstochsicrraelecnattahleysptrsepinartehde ceonmanptoiousnedlescitnivveitardodfiotriotnheoirf adniteitphryollzifienrcattiovebeenffzeactlds eahgyaidnes.t Wfoeuramlsoalipglnaannntehdutmo asncraedehnetrhenetpcreelpl lairneeds bcoymmpeoaunnsdosf tinhevMitrToTf[o3r-(t4h,5e-irdiamnetitphryolltihfeiarzaotilv-2e-yelf)f-e2c,t5s-daigpahinenstylftoeutrrazmoaliluigmnabnrtomhuidmea]nasasdayh.erent cell lines by means of the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
