o:17557
Primena taktičke kombinacije organokatalitičke aldolizacije i reduktivnog aminovanja na sintezu polihidroksilovanih alkaloida značajnih za medicinu
doktorska disertacija
organocatalytic aldol addition/reductive amination in synthesis of medicinally important polyhydroxylated alkaloids : doctoral dissertation
sr
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-dioksan-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. Proline-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.
Prirodno-matematičke nauke - Organska hemija / Life sciences - Organic chemistry
Datum odbrane: 02.03.2018.
aldolna reakcija / aza-galaktofagomin / aza-šećeri / 1-deoksigalaktonodžirimicin/ enantioselektivna sinteza / Fabry-jeva bolest / fagomin /iminošećeri / Krabbe-ova bolest / organokataliza / pipekolinska kiselina / poremećajiskladištenja glikolipida / prirodni proizvodi / reduktivno aminovanje / totalna sinteza /
aldol addition / aza-galacto-fagomine / aza-sugars / 1-deoxygalactonojirimycin/ enantioselective synthesis / Fabry’s disease / fagomine / glycolipid storagedisorders / iminosugars / Krabbe’s disease / natural products / organocatalysis /pipecolic acid / reductive amination / total synthesis
yes
50004495
91552101
5734
91552100
50004495
2018-04-23T10:23:28.053Z
45
no
46
mentor
Jasna, 1988-
Marjanović Trajković
2018
63
mentor
Radomir N
Saičić
2018
63
mentor
Zorana, 1970-
Ferjančić
2018
63
član komisije
Filip, 1981-
Bihelović
2018
63
član komisije
Radomir
Matović
2018
184 lista
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http://phaidrabg.bg.ac.rs/o:17557
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yes
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aldolna reakcija / aza-galaktofagomin / aza-šećeri / 1-deoksigalaktonodžirimicin/ enantioselektivna sinteza / Fabry-jeva bolest / fagomin /iminošećeri / Krabbe-ova bolest / organokataliza / pipekolinska kiselina / poremećajiskladištenja glikolipida / prirodni proizvodi / reduktivno aminovanje / totalna sinteza /
aldol addition / aza-galacto-fagomine / aza-sugars / 1-deoxygalactonojirimycin/ enantioselective synthesis / Fabry’s disease / fagomine / glycolipid storagedisorders / iminosugars / Krabbe’s disease / natural products / organocatalysis /pipecolic acid / reductive amination / total synthesis
1738
11A19
2018