Pitkäketjuisten keteenien valmistusreaktiot ja kinetiikka.

Tämän diplomityön tarkoituksena oli tutkia pitkäketjuisten rasvahappokloridien ja alkyyliketeenidimeerien (AKD) valmistusreaktioiden kinetiikkaa. Työn tavoitteena oli saada mittaustuloksia, joiden perusteella voitaisiin kehittää reaktioille kineettinen kineettinen malli ja suorittaa valmistusprosessien alustava optimointi. Teoreettisessa osassa on selvitetty rasvahappokloridien ja alkyyliketeenidimeerien (AKD) eri valmistustapoja. Lisäksi on perehdytty tarkemmin rasvahappokloridien dehydrohalogenointireaktioiden reaktiomekanismeihin ja valmistusprosessin problematiikkaan. Kokeellisessa osassa tutkittiin rasvahappokloridien valmistusta klooraamalla öljyhappoa 30 mol-% fosforitrikloridiylimäärällä lämpötiloissa 45, 50 ja 55OC. Alkyyliketeenidimeerien valmistusta tutkittiin dehydrohalogenoimalla palmitiini- ja öljyhappokloridia 0-30 mol-% trietyyliamiiniylimäärällä inertissä liuottimessa, lämpötiloissa 45 ja 50OC. Reaktiot toteutettiin puolipanosreaktiona, joissa reaktioastiassa olevaan reagenssin ja liuottimen seokseen lisättiin lähtöaine tasaisena massavirtana. Reaktioiden etenemistä seurattiin FT-IR- ja GC-analyysien avulla. Kalorimetrisilla kokeilla tutkittiin öljyhappokloridin dimeroitumisreaktion reaktiolämmön muodostumista ja UV-VIS-analyyseillä seurattiin öljyhappokloridin vanhenemista. Öljyhappokloridin valmistusreaktiolle saatiin hyvä kineettinen malli. Kineettisen mallin puutteena voidaan pitää sitä, ettei kokeissa saatu tietoa mahdollisten sivutuotteiden muodostumisesta. Sovitusohjelmalla saatiin sovitettua estimaatit reaktionopeusvakioille lämpötiloissa 45, 50 ja 55OC. Happokloridien dimeroitumisreaktioiden kineettisen mallin sopivuudelle saatiin suhteellisen hyvä kuva Kuten öljyhappokloridin tapauksessa, myöskään AKD:n valmistusreaktioissa syntynyt sivutuotteita, joten niiden osuutta oletettuun kineettiseen malliin ei tunneta. Sovitusohjelmalla saatiin sovitettua estimaatit reaktionopeusvakioille lämpötiloissa 45 ja 50OC.

Investigations towards the synthesis of isotope labelled analogues of tocopherols and tocotrienols /

Vitamin E is considered as the most effective lipophilic chain breaking antioxidant. a-Tocopherol and its analogues have been studied thoroughly with regards to its biokinetics and bioavailabily. Deuterated tocopherols have been synthesized and utilized in such studies. Tocotrienols are arousing more and more interest because of their high efficiency as antioxidants. However, to date, there is no effective synthetic method reported for deuterated tocotrienols. This thesis is focused on the investigation of the synthetic methods of deuterated tocotrienols and their analogues: 5-trideuteromethyl-a-tocotrienol, 5- trideuteromethyl-p-tocotrienol, tocotrienol acetate, silyl tocotrienol ether, etc. Several synthetic procedures for the preparation of poly-deuterated tocopherols are known. Mainly the deuterium is introduced by use of labelled formaldehyde and deuterated hydrogen chloride under Lewis acid catalysis. However, these methods are not effective in tocotrienols due to exchange of protons for deuterium at other sites under the acidic conditions. We developed several different approaches to generate polydeuterated tocotrienols by using both morpholinomethylation followed by reduction with NaCNBDs as deuterated reducing reagents and transmetalation strategy. The 5-trideuteromethyl-a-tocotrienol was finally obtained in a satisfactory yield of 60%. In addition, this thesis also discussed the study of structural comparison and the chemical property difference of tocopherols and tocotrienols, which provides hints to explain the reactivity difference of them towards oxidation at the C3-C4 positions.Furthermore, the methodology of halogenation and dehydrohalogenation of tocotrienol was explored to prepare a hexaene tocotrienol derivative as a florescent reporter of tocopherol.

Synthetic studies on prostaglandins: "synthesis of a new thia-PGEI analog"

A PGE1 analog, namely (±)-trans-2-(6'-carbomethoxyhexyl)-3- (E-3"-thia-1 "-octene)-4-hydroxycyclopentanone 71, has been prepared for the first time. Towards the synthesis of this compound, several synthetic approaches aimed at the preparation of the required acetylenic and E-halovinylic sulfides as building blocks were investigated. Among all the methods examined, it appeared evident that the best route to ethynyl n.pentyl sulfide 81 is via a double dehydrohalogenation of the corresponding 1,2-dibromoethyl sulfide with sodium amide in liquid ammonia. In addition, the isomerically pure E-2-iodoethenyl n.pentyl sulfide 85 is conveniently prepared in high yield and stereoselectivity by hydrozirconation-iodination of the terminal ethynyl sulfide 81. The classical hydroalumination and hydroboration reactions for the preparation of vinyl halides from alkynes gave only small yields when applied as methods towards the synthesis of 85 . The building block 2-(6'-carbomethoxyhexyl)-4-hydroxy-2- cyclopentenone (±)-1 carrying the upper side-chain of prostaglandin E 1 was prepared by a step-wise synthesis involving transformations of compounds possessing the required carbocyclic framework (see scheme 27). The synthesis proved to be convenient and gave a good overall yield of (±)-1 which was protected as the TH P-derivative 37 or the siloxy derivative 38. With the required building blocks 81 and 37 in hand, the target 1S-thia-PGE1 analog (±)-71 was prepared via the in situ higher cuprate formation-conjugate addition reaction. This method proved to be convenient and stereospecific. The standard cuprate method, involving an organocuprate reagent generated from an isolated vinyl iodide, did not work well in our case and gave a complicated mixture of products. The target compound will be submitted for assessment of bio log ical activity.