Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Organic chemistry and stereoisomers

1,002 views

Published on

These slides are part of a talk to school teachers. They were designed to showcase some of the applications of organic chemistry, the range of natural and synthetic products. I'm not sure how much use it is without my commentary but, as always, it seems a waste to leave it on my hard drive. The second half gave a overview of chirality and stereoisomers as this topic often causes problems with students. This second half owes a lot to an excellent paper by Robert Gawley (J. Chem. Ed. 2005, 82, 1009) and just has prettier papers. This version of the talk includes a section I removed when presenting (due to time) on artificial sweeteners.

Published in: Education
  • Be the first to comment

Organic chemistry and stereoisomers

  1. 1. ORGANICchemistry Massey University Gareth Rowlands 1Wednesday, 18 November 15
  2. 2. relevance stereoisomers ORGANICchemistry 2Wednesday, 18 November 15
  3. 3. !" "#$%r& (Z)-3-hexenal fr&'()* +%$ ,r#'' ©P#w&)_M@-!+.r O 3Wednesday, 18 November 15
  4. 4. ©/&$#-.)!+.'@-!+.r linalool 3,7-dimethylocta-1,6-dien-3-ol '/&)) 0f )!)!&' HO 4Wednesday, 18 November 15
  5. 5. ©T0"#)L%/!"1!$*@-!+.r OH menthol (1R,2S,5R)-2-isopropyl-5-methylcyclohexanol $#'$& #"2 '/&)) 0f /!"$ 5Wednesday, 18 November 15
  6. 6. P P Rh Ph Ph Ph Ph N Et Et isomerisation N Et Et hydrolysis O OH OH addition reduction isomerisation H Natural or man-made? 3000 tons per year +0%,( /&2!+!"&, 2&+0",&'$#"$', #3&r'(#v&, $00$(p#'$& &$+ 6Wednesday, 18 November 15
  7. 7. R C OH O Too many r&#+$!0"' carboxylic acid alcohol R OH alkene C C R4 R1 R2 R3 haloalkane R X 4!2#$!0" r&2%+$!0" '%5$!$%$!0" #22!$!0" &)!/!"#$!0" #22!$!0" &)!/!"#$!0" 7Wednesday, 18 November 15
  8. 8. Fundamental Pr!"+!p)&' R C O O H O H R C O O H O H H H + + C#rb4*)!+ #+!2 P(1p(0r!+ #+!2 O P OO O R1 R2 H H O H H O H H + + O P OO O R1 R2 S%)f0"!+ #+!2 R S O O O H H O H H O H H + + R S O O O 8Wednesday, 18 November 15
  9. 9. Br0/!"#$!0" R1 C C R2H H C C Br H R1 H R2 Br BrR1 H R2 H Ep4!2#$!0"/'%5$!$%$!0" C C O H R1 H R2 R1 C C R2H H HO OHR1 H R2 H D!(*2r4*)#$!0" R1 C C R2H H HO R1 H OH H R2 9Wednesday, 18 November 15
  10. 10. (R)-muscone (R) = 61 ppb & (S) = 223 ppm (R) r!+( /%'.* '/&)) ($>,0)2) ©b#b00"™@-!+.r O 10Wednesday, 18 November 15
  11. 11. O O O O addition reduction ring-cl#ing metathesis no commercial route to pure optical isomer '*"$(&$!+ /%'. !' r#+&/!+ Natural or man-made? Ru Cy3P PCy3Cl Cl Ph 11Wednesday, 18 November 15
  12. 12. O OH O vanillin 1,800 $0"' !'0)#$&2 p&r *&#r >12,000 $0"' +0"'%/&2 p&r *&#r ©(%pp6!&@-!+.r 12Wednesday, 18 November 15
  13. 13. vanillin >10,000 $0"' '*"$(&'!'&2 p&r *&#r Natural or man-made? OH O O O OH addition O OH HO "idation O OH O OH O O OH elimination O OH O 13Wednesday, 18 November 15
  14. 14. haem B r&2 +0)0%r 0f b)002 N N NN CO2HHO2C Fe 14Wednesday, 18 November 15
  15. 15. dye-sensitised solar cells ,r&&" 2*& $0 #50rb '%")!,($ N N NN Zn Ph Ph NC CO2H Ph Ph ©Or,&0"DOT@-!+.r 15Wednesday, 18 November 15
  16. 16. paclitaxel !'0)#$&2 fr0/ p#+!7+ *&w $r&& T80)™ %'&2 $0 $r&#$ +#"+&r ©J&r/&* B0#r2@F)!+.r O AcO H OH OBz OH O O OH Ph BzHN AcO O AcO 16Wednesday, 18 November 15
  17. 17. semi-synthesis 0"& fr#,/&"$ /#"-/#2& ©Er!+ H%"$@-!+.r Natural or man-made? O AcO H OPG OBz OH AcO O AcO HO O AcO H OPG OBz OH O O OH Ph BzHN AcO O AcO N PGO O O amid! formatio" 17Wednesday, 18 November 15
  18. 18. avermectin B1a #"$!-p#r#'!$!+ ("&/#$02&' #"2 #r$(r0p02') ©S+0$ N&)'0"@-!+.r O O O H O H O H O HO H O OH H O O O OHO 18Wednesday, 18 November 15
  19. 19. Br0/!"#$!0" R4 C R1 C R3 R2 + Br2 additio! Br BrR4 R2 R1 R3 H*2r0,&"#$!0" R4 C R1 C R3 R2 + H2 additio! H R4 R1 H R3 R2 Basic r&#+$!0"' hydrogenation 0"& 0f $(& /1$ !/p0r$#"$ !"2%'$r!#) r&#+$!0"' 19Wednesday, 18 November 15
  20. 20. ivermectin B1a semi-synthesis %'&2 !" $(& 7,($ #,#!"'$ r!v&r b)!"2"&'' ©W!.!C0//0"' Natural or man-made? O O O H O H O H O HO H O OH H O O O OHO 20Wednesday, 18 November 15
  21. 21. Brincidofovir $r&#$/&"$ f0r '/#))p4 #"2 %'&2 #,#!"'$ &b0)# ©NIAID@F)!+.r Synthetic N N NH2 O O OH P OO HO O { 2&)!v&r* {w#r(&#2 21Wednesday, 18 November 15
  22. 22. Substitutions '#/& #' 2!'p)#+&/&"$ 0f (#)!2&' &$+ N N H NHCOPh O OCPh3 O substitution N N NH2 O OH Ph3CO substitution TsO P O OEt OEt N N NH2 O O Ph3CO P O OEt OEt pseudo halide Basic r&#+$!0"' 22Wednesday, 18 November 15
  23. 23. pyrethrin "#$%r#) !"'&+$!+!2& f0%"2 !" +(r*'#"$(&/%/ +!"&r#r!!f0)!%/ O O O ©M%'$#", J0&@-!+.r 23Wednesday, 18 November 15
  24. 24. Cl Cl O O CN O Synthetic ©A/b&rBr00.&@-!+.r cypermethrin '*"$(&$!+ !"'&+$!+!2& f0%"2 !" R#!2™ 24Wednesday, 18 November 15
  25. 25. ISOMERS 25Wednesday, 18 November 15
  26. 26. Constitutional !'0/&r' C4H8O O O HO bp = 66°C bp = 80°C (b%$$&r'+$0+( & #+&$0"&) bp = 121°C 26Wednesday, 18 November 15
  27. 27. O OH HO HO HO OH O HO HOHO HO O HO HO O OH O HO HO O OH OHO HO O OH O HO HO O OHO HOOH OH O HO Stereoisomers 2!#'$&r&0/&r' starch p0)*/&r 0fα-,)%+1& 27Wednesday, 18 November 15
  28. 28. cellulose p0)*/&r 0fβ-,)%+1& ©K%/#r#v&)@-!+.r Stereoisomers 2!#'$&r&0/&r' O HO HO HO OH OH O HO HO HO OH O HO HO O OH O HO HO O OH O HO HO O OH O HO HO O OH O HO HO O OH OH 28Wednesday, 18 November 15
  29. 29. Stereoisomers 2!#'$&r&0/&r' cis and trans isomers #)$&r' '(#p& #"2 p0)#r!$* trans E cis Z 29Wednesday, 18 November 15
  30. 30. Stereoisomers oleic acid /p = 13°C (0)!v& 0!)) OH O 2!#'$&r&0/&r' 30Wednesday, 18 November 15
  31. 31. Stereoisomers elaidic acid /p = 45°C OH O 2!#'$&r&0/&r' 31Wednesday, 18 November 15
  32. 32. OH O (not a) Stereoisomers stearic acid /p = 63°C (f0%"2 !" b%$$&r) 2!#'$&r&0/&r' 32Wednesday, 18 November 15
  33. 33. Stereoisomers "#"0/0$0r Me(ax) Me(ax) (3R,3'R)-(P,P)-trans stable Me(eq) Me(eq) (3R,3'R)-(M,M)-trans unstable (3R,3'R)-(M,M)-cis unstable Me(eq) Me(eq) (3R,3'R)-(P,P)-cis stable Me(ax) Me(ax) ≥ 280 nm ≥ 380 nm ≥ 280 nm ≥ 380 nm 20°C60°C direction of rotation alkene isomerisation 33Wednesday, 18 November 15
  34. 34. Nanomotor to /0v& 0b9&+$' rotor controls direction anchor 34Wednesday, 18 November 15
  35. 35. Nanomotor to /0v& 0b9&+$' x 8 real time 35Wednesday, 18 November 15
  36. 36. CHIRALITY 36Wednesday, 18 November 15
  37. 37. Chirality !" 1 2!/&"'!0" #+(!r#) +(!r#) J. C(&/. E2. 2005, 82, 1009 1 Dimension allows only translation (no rotation) 37Wednesday, 18 November 15
  38. 38. Chirality !" 1 2!/&"'!0" #+(!r#) +(!r#) J. C(&/. E2. 2005, 82, 1009 1 Dimension allows only translation (no rotation) external mirror point internal mirror point 38Wednesday, 18 November 15
  39. 39. Chirality !" 2 2!/&"'!0"' J. C(&/. E2. 2005, 82, 1009 2 Dimensions allows translation & rotation (in plane) #+(!r#) external mirror line internal mirror lines 39Wednesday, 18 November 15
  40. 40. Chirality !" 2 2!/&"'!0"' J. C(&/. E2. 2005, 82, 1009 2 Dimensions allows translation & rotation (in plane) #+(!r#) external mirror line internal mirror lines +(!r#) 40Wednesday, 18 November 15
  41. 41. Chirality !" 2 2!/&"'!0"' Tetris™ :p)#!"' $(& !/p0r$#"+& 0f +(!r#)!$* #+(!r#) +(!r#) 41Wednesday, 18 November 15
  42. 42. Chirality !" 2 2!/&"'!0"' Tetris™ :p)#!"' $(& !/p0r$#"+& 0f +(!r#)!$* #+(!r#) +(!r#) internal mirror lines 42Wednesday, 18 November 15
  43. 43. Chirality !" 2 2!/&"'!0"' Tetris™ #+(!r#) + #+(!r#) = "0 pr0b)&/ #+(!r#) #+(!r#) 43Wednesday, 18 November 15
  44. 44. Chirality !" 2 2!/&"'!0"' Tetris™ #+(!r#) + +(!r#) = "0 pr0b)&/ #+(!r#) +(!r#) 44Wednesday, 18 November 15
  45. 45. Chirality !" 2 2!/&"'!0"' Tetris™ +(!r#) + +(!r#) = pr0b)&/ 45Wednesday, 18 November 15
  46. 46. Chirality !" 2 2!/&"'!0"' Tetris™ +(!r#) + +(!r#) = "&&2 +0rr&+$ p!&+& 46Wednesday, 18 November 15
  47. 47. Chirality !" 3 2!/&"'!0"' #+(!r#) +(!r#) 47Wednesday, 18 November 15
  48. 48. Chirality !" 3 2!/&"'!0"' #+(!r#) +(!r#) external mirror plane internal mirror plane 48Wednesday, 18 November 15
  49. 49. Chirality !" 3 2!/&"'!0"' #+(!r#) +(!r#) tetrahedral atoms (+#rb0", p(1p(0r%' &$+) 49Wednesday, 18 November 15
  50. 50. CHIRAL 50Wednesday, 18 November 15
  51. 51. CHIRAL 51Wednesday, 18 November 15
  52. 52. p(0$0,r#p(: W!))! R0)f&' CHIRAL 52Wednesday, 18 November 15
  53. 53. Why is chirality !/p0r$#"$? 53Wednesday, 18 November 15
  54. 54. Why is chirality !/p0r$#"$? ©C)1&_$0_(0/&@-!+.r 54Wednesday, 18 November 15
  55. 55. Why is chirality !/p0r$#"$? ©C)1&_$0_(0/&@-!+.r O O H3N H O O NH3H L-alanine 1.5 ; 'w&&$&r $(#" '%+r1& D-alanine b!$$&r 55Wednesday, 18 November 15
  56. 56. Why is chirality !/p0r$#"$? ©/#r7'75 & &'-2&-w&@-!+.r (R)-carvone '/&)) 0f 'p&#r/!"$ (S)-carvone '/&)) 0f +#r#w#* O H O H 56Wednesday, 18 November 15
  57. 57. O O H3N H O O NH3H Why is chirality !/p0r$#"$? ©NIAID@-!+.r L-alanine (%/#"' D-alanine b#+$&r!#) +&)) w#)) 57Wednesday, 18 November 15
  58. 58. Why is chirality !/p0r$#"$? (S,S)-ethambutol $%b&r+%)1$#$!+ (R,R)-ethambutol +#%'&' b)!"2"&'' HO NH H N HO OH HN H N OH 58Wednesday, 18 November 15
  59. 59. What is the problem with +(!r#) /0)&+%)&'? Identical 'p&+$r1+0p!+#))* 59Wednesday, 18 November 15
  60. 60. What is the problem with +(!r#) /0)&+%)&'? Identical p(*'!+#))* 60Wednesday, 18 November 15
  61. 61. Only separable if add +(!r#)!$* 61Wednesday, 18 November 15
  62. 62. N H H O N3 CO2CH3 O OH Cl N H H O N3 H3CO2C O OH Cl OH OCH3 N H H CO2CH3 O O Cl CH3O O N3 N H H H3CO2C O O Cl OCH3 O N3 Only separable if add +(!r#)!$* towards Norvasc™ (6&r$&"'!0" 62Wednesday, 18 November 15
  63. 63. N H O HN N H O NH HO2C OBzBzO CO2 N H O NH2 precipitate HO2C OBzBzO CO2H Only separable if add +(!r#)!$* towards ropivacaine™ )0+#) #"#&'$(&$!+ 63Wednesday, 18 November 15
  64. 64. epothilones #"$!-+#r+!"0,&" O O OH O S N OH O 64Wednesday, 18 November 15
  65. 65. Start from a chiral molecule +(!r#) p00) O O HO (–)-pantolacton! O O O O O OH O S N OH O 65Wednesday, 18 November 15
  66. 66. Temporary addition of chirality +(!r#) #<!)!#r* NHO O O Cl OTBS ( )3 amid! formatio" O O O N OTBS ( )3 su#titutio" O O O N OTBS ( )3 O OTBS ( )3 O O OH O S N OH O 66Wednesday, 18 November 15
  67. 67. External control +(!r#) r&#,&"$ BnO OTES O B O O CO2iPr CO2iPr BnO OTES OH O O OH O S N OH O 67Wednesday, 18 November 15
  68. 68. chiral product chiral catalyst substrate (achiral) chiral catalyst chiral catalyst substrate (achiral) chiral product External control +(!r#) +#$#)*'!' 68Wednesday, 18 November 15
  69. 69. ©J#+.#)1@-!+.r (R)-fluoxetine (Prozac™) &p4!2#$!0" (4!2#$!0"/#22!$!0") O NH•HCl CF3 69Wednesday, 18 November 15
  70. 70. Hydrogenation (reduction) +(!r#) +#$#)*'!' Ph O Me2N SM : catalyst 10,000 : 1 H2 96% 97.5%ee Ph Me2N H OH Ar2 P P Ar2 Ru Cl Cl N H2 H2 N iPr H OMe OMe Ar = 3,5-Me2C6H3 70Wednesday, 18 November 15
  71. 71. Ph OH Ti(OiPr)4 (+)-DIPT TBHP 89% >98%ee Ph OH O Ph NHMe O CF3 O OH TBHP iPrO2C CO2iPr OH OH (+)-DIPT Epoxidation (oxidation/addition) +(!r#) +#$#)*'!' 71Wednesday, 18 November 15
  72. 72. Solvaldi™ '0f1b=!r Hepatitis C treatment $10.28 b!))!0" (US) !" 2014 O HO F N O NH O OP NH O O O O 72Wednesday, 18 November 15
  73. 73. Theend 73Wednesday, 18 November 15
  74. 74. The directors cut 74Wednesday, 18 November 15
  75. 75. Chemistry title !" "#$%r& cyanidin-3,5-O-diglucoside r&2 +0)0%r f0%"2 !" )&#v&' #"2 w!"& ©90("2&,r&&@-!+.r O O O OH O OHO HO OH OH HO OH OH HO OH OH 75Wednesday, 18 November 15
  76. 76. O O OH OH O HO HO OH OH HO OH Chemistry title !" "#$%r& cyanidin-3-O-glucoside b)%& +0)0%r f0%"2 !" b)#+.+%rr#"$ ©R!+(#r2 S$&bb!",@-!+.r 76Wednesday, 18 November 15
  77. 77. Chemistry title "#$%r#) 0r /#"-/#2& ©NIAID@F)!+.r linezolid (Zyvox) '*"$(&$!+ #"$!b!0$!+ f0r 2r%, r&'!'$#"$ b#+$&r!# ON O N H O N O F 77Wednesday, 18 November 15
  78. 78. Chemistry title b#'!+ r&#+$!0"' Substitutions '#/& #' 2!'p)#+&/&"$ 0f (#)!2&' &$+ Cl O NH4OH substitution Cl OH NH2 O Cl condensation Cl OH N Ar N H N O F O O Ph substitution N N O F O O Ph OH N Ar esterification substitution ON O N N O F Ar 78Wednesday, 18 November 15
  79. 79. ©.#!b#r#87@-!+.r Accidents will happen #r$!7+!#) 'w&&$"&r' O O HO HO HO HO O OH OH OHOH NH S O O O N H S O Na O O sucrose '%,#r saccharin (300-400;) cyclamate (30-50;) 79Wednesday, 18 November 15
  80. 80. Saccharin was accidentally discovered in 1879 when Constantin Fahlberg spilt some on his hand before touching his mouth. All values refer to how many times sweeter than sucrose a molecule is. Walters, D. E. The Rational Discovery of Sweeteners. In Sweeteners/Discovery, Molecular Design, and Chemoreception; ACS Symposium Series 450; American Chemical Society: Washington, DC, 1990; pp 1-2 80Wednesday, 18 November 15
  81. 81. Accidents will happen #r$!7+!#) 'w&&$"&r' aspartame (200;) sucralose (320-1000;) O O H N O NH3 O O Ph O HO Cl OH OH O O OH OHCl Cl 81Wednesday, 18 November 15
  82. 82. Aspartame discovered in 1965 when James Schlatter licked his fingers to try an pick up some weigh paper. He was making peptides to assess their anti-ulcer efficacy. Sucralose was discovered in 1976 when a scientist (Phadnis) thought his colleague has asked him to taste the molecule (he actually told him to test the compound). Walters, D. E. The Rational Discovery of Sweeteners. In Sweeteners/Discovery, Molecular Design, and Chemoreception; ACS Symposium Series 450; American Chemical Society: Washington, DC, 1990; pp 1-2 82Wednesday, 18 November 15
  83. 83. Accidents will happen #r$!7+!#) 'w&&$"&r' N H S O Na O O N H S O NH4 O O N H S OH O O N S O Na O O N H S O Na O O N H S O Na O O sweet 50% sweetness sour flavourless sweet aftertaste salty or bitter 83Wednesday, 18 November 15
  84. 84. Cyclamate discovered in 1937 during research aimed towards anti-fever treatments. Graduate student Michael Sveda put his cigarette on the lab bench and when he came to smoke it found it was very sweet. Walters, D. E. The Rational Discovery of Sweeteners. In Sweeteners/Discovery, Molecular Design, and Chemoreception; ACS Symposium Series 450; American Chemical Society: Washington, DC, 1990; pp 1-2 Small changes in structure can have a profound impact on taste. J. Org. Chem. 1944, 9, 89 84Wednesday, 18 November 15
  85. 85. ©.#!b#r#87@-!+.r Accidents will happen #r$!7+!#) 'w&&$"&r' aspartame (200;) neotame (11,000;) O O H N O NH3 O O Ph O O H N O NH2 O O Ph 85Wednesday, 18 November 15
  86. 86. Apparently hydrophobic groups increase the sweetner potency while blocking the nitrogen slows degradation both during storage and in the body. Polanski, J. et al. Molecular Design and the Development of New Sweeteners. In Optimising Sweet Taste in Foods; Spillane, W. J., Ed.; CRC Press: Boca Raton; 2006; pp. 307-326. C&EN. 2014, 92, 11 H2N H NN CO2 NC O O Lugduname sweetest sweetener 220,000 - 300,000 x sucrose not approved for consumption yet 86Wednesday, 18 November 15
  87. 87. Stereoisomers The Visual Cascade N H rhodopsin N rhodopsin H ligh! 2!#'$&r&0/&r' 87Wednesday, 18 November 15
  88. 88. N rhodopsin H N H rhodopsin O OH O R O OH O isomerisatio! hydrolysi" reductio! esterificatio!isomerisatio! hydrolysi" #idatio! condensatio! 88Wednesday, 18 November 15

×