Primena taktičke kombinacije organokatalitičke aldolizacije i reduktivnog aminovanja na sintezu polihidroksilovanih alkaloida značajnih za medicinu
organocatalytic aldol addition/reductive amination in synthesis of medicinally important polyhydroxylated alkaloids
Докторанд
Marjanović Trajković, JasnaМентор
Saičić, Radomir N.Чланови комисије
Ferjančić, ZoranaBihelović, Filip
Matović, Radomir
Метаподаци
Приказ свих података о дисертацијиСажетак
Ispitana je dvostruka asimetrična indukcija u aldolnim reakcijama između dioksanona i
hiralnih acikličnih α-supstituisanih aldehida katalizovanih prolinom, i tom prilikom je
utvrđeno da je stereohemijski ishod ove reakcije kontrolisan reagensom, sa dobrim
stepenom dijastereoselektivnosti. Sa cikličnim aldehidima stereokontrola nije
zadovoljavajuća.
Takođe, kombinacijom organokatalizovane aldolizacije i reduktivnog aminovanja,
sintetisano je šest biološki aktivnih jedinjenja: (+)-2-epi-hiacintacin A2, (–)-3-epihiacintacin
A1, 1-deoksi-galaktonodžirimicin (DGJ), 2,5-dideoksi-2,5-imino-D-altritol
(DIA), (–)-4-epi-fagomin i (+)-aza-galaktofagomin. Pored ovih iminošećera, istim
pristupom sintetisano je još tri molekula - pipekolinska kiselina, 3-hidroksipipekolinska
kiselina i 4-deoksifagomin - koji predstavljaju sintetički značajne intermedijere za
dobijanje drugih biološki aktivnih jedinjenja. U svim sintezama kao ključna reakcija
korišćena je asimetrična aldolna adicija 2,2-dimetil-1,3-d...ioksan-5-ona (dioksanona) na
odgovarajući aldehid katalizovana prolinom i praćena reduktivnim aminovanjem.
Formirana su dva nova stereocentra primenom principa katalitičke asimetrične sinteze i
jedan dijastereoselektivnim reduktivnim aminovanjem.
Double asymmetric induction was investigated in proline-catalyzed aldol additions
between dioxanone and chiral α-substituted aldehydes, and it was found that, with
acyclic aldehydes, the stereochemical outcome of this reaction was controlled by a
reagent, with a good level of diastereoselectivity. Stereocontrol with cyclic aldehydes is
not satisfactory.
Six biologically active compounds as well as some significantly useful intermediates
were synthesized by a combination of organocatalytic aldol addition and reductive
amination: (+)-2-epi-hyacinthacine A2, (–)-3-epi-hyacinthacine A1, 1-deoxygalactonojirimycin
(DGJ), 2,5-dideoxy-2,5-imino-D-altritol (DIA), (–)-4-epi-fagomine and (+)-
aza-galacto-fagomine. In addition to these iminosugars, three other molecules -
pipecolic acid, 3-hydroxypipecolic acid and 4-deoxyfagomine - are synthesized by
applying this tactical combination on the same way, and they are significant
intermediates in synthesis of other biologically active compounds. Prol...ine-catalyzed
asymmetric aldol addition of 2,2-dimethyl-1,3-dioxan-5-one (dioxanone) to the
corresponding aldehyde, followed by reductive amination, was used as the key
transformation in all syntheses. Two new stereocentres were formed in these reactions
using the principle of catalytic asymmetric synthesis and one by diastereoselective
reductive amination.