Lst leture hirlity This leture enntiomers distereomers / nottion hirlity jetives optil & iologil properties hirl moleules ontining more thn one hirlity enter. retions tht rete stereoisomers 1 Dr. Ky nderg Whih onfigurtion goes in the lnk: or? (_)-2-hloro-3-methylutn-1-ol l / determintion : l,,, tep 1: nk the 4 toms of the in order of deresing tomi numer. tep 2: Build the model oriented EXATLY s shown on the 2-D pge. 2 Dr. Ky nderg Whih onfigurtion goes in the lnk: or? (_)-2-hloro-3-methylutn-1-ol l / determintion : l,,, tep 1: nk the 4 toms of the in order of deresing tomi numer. tep 2: Build the model oriented EXATLY s shown on the 2-D pge. tep 3: old the yellow (lowest tomi #) so tht the other three re fing your fe. 3 Dr. Ky nderg romohlorofluoromethne etion 7.1 Mirror imge F sees in the mirror ()- or ()- F () l l 4 Dr. Ky nderg xns tht rete stereogeni enter 3 3 3 Epoxidtion Epoxidtion 3 2 (peroxyeti id) 3 2 (peroxyeti id) etion 7.9 3 3 2 (peroxyeti id) (_)-1,2-epoxypropne 3 + hirl 3 (_)-1,2-epoxypropne 5 etion 7.9 xns tht rete stereogeni enter 6 1
3 ptilly hirl (_)-1,2-epoxypropne (±)-1,2-epoxypropne 3 2 3 + hirl Epoxidtion (peroxyeti id) mixture ptilly 3 (_)-1,2-epoxypropne 3 ow do we show remi mixture in JME? tik onds imply this is remi mixture. Epoxidtion 3 2 (peroxyeti id) ()-1,2-epoxypropne = ()-1,2-epoxypropne (±)-1,2-epoxypropne etion 7.9 xns tht rete stereogeni enter 7 etion 7.9 8 (_) 50% 3 3 hirl 50% (_) Eletrophili ddition 3 3 3 - + 3 3 etion 7.9 - - 3 9 hirl optilly prohirl 2 omintion hν, Δ etion 7.9 hirl optilly 50% remi mixture 50% 10 ( +_ )- 3 2 3 Alohol to lkyl romide hirl ut remi optilly 2 2 Fumri id hirl optilly intive etion 7.9 ( +_ )- 3 2 3 fumrse hirl ut remi optilly 2 2 2 ()-( )-mli id hirl 11 optilly emi produt mixture? 3 3 2 3 2 Viinl hlohydrin 3 3 3 E-lkene 3 etion 7.13 3 3 - - nti-ddition Doule whmmy 3 12 2
xns tht rete stereoisomers 3 3 2 2 3 Viinl hlohydrin 3 3 3 (2,3) onfigurtion Z-lkene (2,3) onfigurtion etion 7.13 13 xns tht rete stereoisomers 3 3 3 2 2 E-lkene 3 E vs Z lkene 3 3 3 3 Z-lkene 2 3 etion 7.13 3 tereospeifi rxn: nti ddition 2 3 3 14 xns tht rete stereoisomers 3 3 3 2 2 meso E-lkene 3 3 epresenttion 3 Implies the presene of ll onfigurtions (2,3) (2,3) meso 3 3 etion 7.13 3 2 Z-lkene 2 3 enntiomers 3 3 15 xns tht rete stereoisomers E-lkene produt 3 3 2 3 3 etion 7.13 16 xns tht rete stereoisomers Z-lkene produts 3 2 3 3 3 etion 7.13 17 (Z)- 3 rtie 3 A 2 3 3 2 3 I like to keep the onds of the reting sites in the plne of the pper. 2 3 2 (E)- 3 nti-ddition etion 7.13 2 3 3 B 3 2 3 D 2 3 18 3
xns tht rete distereomers tereospeifi rxn: syn ddition 3 2 2 t ydrogention 3 2 dded from ottom fe etion 7.13 3 2 dded from top fe xns tht rete distereomers etion 7.13 M of hydrogention 3 2 t 2 tereo rxn: syn ddition 3 2 3 2 19 tereo rxn: preferene for one stereoisomer 20 1,2-dimethylylohexne We re going to fous on how the ethyl groups orienttions hnge s the retion progresses l 2 pprohes top fe of doule ond Viinl rotte hlohydrin 90 o l l ethyls: ngled down, wedge l l 2, 2 Both pprohes hve the sme proility of ourring, therefore produt mixture will e 50% from eh pproh. ethyls: stright out, wedge ethyls: ngled up, wedge l l l l 2 pprohes ottom fe of doule ond 21 l l prtil rotionmore onds L ethyl: stright wter pprohes from wter pushes ethyl nd methyl L ethyl: ngled up T (proton trnsfer) Viinl hlohydrin L ethyl: ngled down wedge l Doule whmmy ethyl: ngled down wedge lens prtilly reking ond l ethyl: ngled down nti-ddition l l Elvis ethyl: ngled down 22 l l Don t forget understood Viinl hlohydrin l l L ethyl: ngled down, wedge wter pushes ethyl nd methyl Viinl hlohydrin wter pprohes from ethyl: ngled up, wedge l T (proton trnsfer) ethyl: ngled up, wedge ethyls: ngled up, wedge l l 23 L ethyl: flttens, wedge I like to keep the onds of the reting speies in the plne of the pper. Now for the pproh from the ottom fe. l l l 24 4
3 (2_,3_)- 3-penten-2-ol E/Z Enntiomers & / 3 3 4 2 3 di di di 1 etion 7.12 5 3 esolution of enntiomers eprtion of remi mixture into its enntiomeri omponents esolution of enntiomers 3 2 3 N 2 2 3 etion 7.14 3 3 3 3 N 2 3 3 N 2 3 enntiomers 3 25 26 etion 7.12 Mximum # of stereoisomers = When stereogeni enters re equivlently sustituted (possile ugrs meso forms), the # is less thn 3 holi 3 id 3 etion 7.12 ldohexose (sugr) llose (2,3,4,5)- (2,3,4,5)- (2,3,4,5)- (2,3,4,5)- (2,3,4,5)- ltrose (2,3,4,5)- (2,3,4,5)- (2,3,4,5)- et. gluose totl. 27 2,3,4,5,6-penthydroxyhexnl holi id (ile) # of hirlity enters? ow mny enntiomers of holi id re there? ow mny distereomers? of holi id re there? # of stereoisomers? Any possiility of meso-forms? 28 The mrine orgnism new highly potent nlogue utilizes hirl enzymes of ryosttin 1 to tlyze only one of the stereoisomers yosttin 1 yosttin synthesis 19 steps nd 2% yield Bugul neritin, orl-like ritter lled ryozon tht is the soure of the promising ner drug ryosttin. The urrent reipe lls for 14 tons of hrvested Bugul to produe out hlf n oune of ryosttin. ientists hve sueeded t mking ext replis of ryosttin from hemils tht n e ought in ny l tlog, ut their proesses n tke up to 70 expensive steps, ompred to the 10 to 15 used to mke most ommerilly vile drugs. 14 ws produed in >3% yield nd only 17 steps http://nsw.org/users/ktwong/mooherld/ryosttin.html http://www.li.nsu.edu:2075/gi-in/rtile.gi/jst/2002/124/i46/html/j027509+.html 29 http://www.li.nsu.edu:2075/gi-in/rtile.gi/jst/2002/124/i46/html/j027509+.html+.html 30 5
yosttin synthesis symmetri enter is synonymous with hirl enter Dniel omins: New syntheti methodologies, strtegies for symmetri synthesis, direted metlltion retions, stereoseletive redutions, tlyti symmetri synthesis, new hirl uxiliries, nd the totl synthesis of nturl produts nd iologilly tive ompounds. http://www.nsu.edu/hemistry/fultyges/dl.reserh.html http://www.li.nsu.edu:2075/gi-in/rtile.gi/jst/2002/124/i46/html/j027509+.html 31 Dniel L. omins, jn. Joseph, o ong, im. Al-wr, hristopher J. Foti, Yue-mei Zhng, Xinghi hen, Donld. LMunyon nd Mri Guerr-Weltzien, "Asymmetri ynthesis nd yntheti Utility of 2,3- Dihydro-4-pyridones," ure nd Applied hem., 1997, 69, 477. Dn omins work Dniel L. omins, resh M. Thkker, Mtthew F. Bevsky, nd Mohmmed M. Bdwi, "hirl Auxiliry Medited itet-pengler etions: Asymmetri yntheses of (-)-Ludnosine, (+)-Gluine nd (-)-Xylopinine," Tetrhedron 1997, 53, 16327. Dniel L. omins, Xinghi hen nd Lwrene A. Morgn, "Enntiopure N - Ayldihydropyridones s yntheti Intermedites: Asymmetri ynthesis of (-)-eptiine nd (-)-Tylophorine," J. rg. hem., 1997, 62, 7435. Jeffrey T. Kuethe nd Dniel L. omins, "Asymmetri Totl ynthesis of (+)-nnistivine," J. rg. hem., 2004, 69, 5219.. http://www.nsu.edu/hemistry/fultyges/dl.pulitions.html 32 tereogeni enters other thn ron i: four tetrhedrlly distriuted sustituents i & etion 7.16 sp 3 hyridized toms with 3 different sustituents nd lone pir 33 tereogeni enters other thn ron N N very fst No resolution euse of immedite remiztion due to rpid inversion (smll energy rrier) etion 7.16 N 34 tereogeni enters other thn ron etion 7.16 sp 3 hyridized toms with 3 different sustituents nd lone pir tereogeni enters other thn ron etion 7.16 + sp 3 hyridized toms with + 3 different sustituents nd lone pir slow ine the inversion is slow, enntiomers n e resolved (seprted) (lrger energy rrier for inversion from to.) 35 3 2 2 2 Inversion from to does not our redily euse of the lrge energy rrier of inversion. 3 36 (_)-utyl methyl sulfoxide 6