Anwar.Asymmetric synthesis

Anwar.Asymmetric synthesis

• 1.
  Asymmetric synthesis Dr. Shaikh A. R
• 2.
  • Asymmetric catalyticreduction: Asymmetric catalytic reduction is the use of various chiral catalysts to reduce a pro-chiral organic compound to obtain a chiral product. This is one of the several techniques used in chiral synthesis. e.g. H (g) O O 2 OH O RuCl2 [(R)-BINAP] R OMe MeOH R OMe BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl The Noyori asymmetric hydrogenation is a chemical reaction described as an asymmetric reduction of β-keto esters. Example in drug synthesis: Synthesis of Naproxen
• 3.
  Synthesis of Naproxen:
• 4.
  • Asymmetric catalyticoxidation: • Is a technique of oxidising various substrate to give an enantiopure product using a catalyst. • Reactions: • Jacobsen epoxidation of alkenes using manganese- salen complex and NaOCl • Sharpless epoxidation of allyl alcohols using titanium isopropoxide, diethyl tartrate, and t-butyl hydroxyperoxide • Sharpless asymmetric dihydroxylation of alkenes using dihydroquinine or dihydroquinidine ligands on an osmium metal center • Shi epoxidation of alkenes using oxone and a fructose- derived chiral catalyst • Sulfonyloxaziridine enolate oxidation
• 5.
  • Sharpless epoxidation: Example in drug synthesis: Synthesis of Propranolol
• 6.
  • Synthesis ofpropranolol: HO SiCH3 SiCH3 H OH H
• 7.
  • Sharpless epoxidation: Example in drug synthesis: Synthesis of Propranolol
• 8.
  O HO SiCH3 HO SiCH3 ArONa ONa CH3 H3C NH NH 2 H O H3C CH3 OH 4 SCH SiCH3 OH O Tetra-n-butylammonium fluoride SCH3 O Na Bu4NF iprNH2
• 9.
  Synthesis of penicillamin NaOH or Penicillinase - H+ :OH R NH S CH3 CH3 H + O R N OH ..- N: - + NH CH2 CH HS CH3 COOH + O OH OH O CH3 NH ..- CH Decarboxylation H COOH R NH C CH S CH3 H2 O O N CH3 OH H Hydrolysis
• 10.
  Synthesis of penicillamin H OH R N CH2 CH HS CH3 + OH O CH3 NH ..- CH H COOH
• 11.
  Synthesis of Aspartame MeOOC H O COOH N NH2 H H O MeOOC HOOC H C NH C 3 CH COOH NH2 H
• 12.
  Catalytic asymmetric hydrogenation COOH (1)-(R,R)-PNNP-Rh (I) (Cat) NHAC Me COOH (1)-H +. MeOH (z)-2-acetamido-3-phenylacrylic acid H NHAC S-phenylalanine methyl ester (97 %) Or (s)- methyl 2-acetamido-3-phenylpropanoate COOMe MeOOC H NH AC .. O + H .. NH COOH AC H NH2 O O HO COOH - CH3+C CH3 COOH H NH2 :OH Aspartic acid
• 13.
  Synthesis of ethambutol (S,S) OH H Me N N Me H HO COOH NH2 MeS L-Methionine
• 14.
  COOH a. MeOH, ACCl NH2 MeS b. ClCOCOCl (0.5 Aq.), Pyridine, CHCl2 COOMe H SMe N H N MeS O O COOMe Oxalyl diamide
• 15.
  COOH COOH .. NH .. 2 H2N .. NH COOH MeS . .. MeS COOH + NH2 SMe C C C Cl - MeS Cl: Cl Cl O O O O
• 16.
  COOMe COOMe COOMeCOOMe COOMe COOMe Raney Ni, MeOH, H2O NH HN HN NH NH HN MeS Desulfuration Me O O O O Me O O SMe MeS COOMe O Me H SMe N N Me H O COOMe Penultimate Exhaustive reduction LiAlH4, THF COO H O Me H Me N N Me H O COOH Me Ethambutol
• 17.
  Synthesis of Atenolol O O O O N S O O N OH H OH S-Glycidylnosylate O O O N OH H CH2CONH2 2-(4-Hydroxyphenyl)acetamide CH2CONH2 CH2CONH2 O O O O N S Atenolol OH
• 18.
  O O O O N S O O O CH2CONH2 O O O CH S. 2 O N -.O .. O + H..O + CH2CONH2
• 19.
  Synthesis of Atenolol O O O O N S O O O O N O OH H O O OH S-Glycidylnosylate + O N S OH CH2CONH2 CH2CONH2 H3C 2-(4-Hydroxyphenyl)acetamide NH2 Isopropyl amine H3C O N OH H Atenolol CH2CONH2
• 20.
  CH3 + .N .. .+ CH3 CH2 H . . O O- O N OH H CH2CONH2 CH2CONH2