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Α. Asymmetric Synthesis [ 8 h]

  Ιmportance of chirality in Nature and in the development of bioactive molecules

  Importance of asymmetric synthesis

  Chiral elements

  Diastereomers and meso-compounds

  Analytical techniques for the determination of the optical purity

  Strategy in asymmetric synthesis

  Classical and kinetic resolution of enantiomers

  Chiral substrates – starting materials (Chiral Pool)

  Chiral reagents

  Chiral auxiliary groups

  Catalytic asymmetric synthesis with chiral organometallic complexes

  Applications to asymmetric reactions of epoxidation, dihydroxylation, aminohydroxylation, hydrogenation of various functional groups, 

  sulfoxidation,

  Catalytic asymmetric synthesis with simple and biphasic organocatalysts,

  Applications to asymmetric reactions of epoxidation, sulfoxidation, reduction of various functional groups, alkylation, conjugate addition,

   Diels Alder and other cycloadditions, heteroatom introduction (οxidations), Henry/ Aza-Henry/ Mannich/ and aldol reactions,

   Examples from the syntheses of swainsonine, fluoxetine, efavirenz, (-)-frontalin, (-)-podorhizon, Indinavir, esomeprazole, naproxen,

    sugars, unnatural α-amino acids, β-amino acids, pregabalin and γ-amino acids, duloxetine, propranolol, damascene,metolachlor,

  Factors affecting the choice of strategy in asymmetric synthesis of a chiral drug in industrial scale

  Case-study: Development of the industrial asymmetric synthesis of Aliskiren

Β. Τopics of contemporary advanced Organic Synthesis with applications to the Pharmaceutical Industry  [6 h]

  Cycloaddition reactions in the synthesis of a variety of compounds

  Metal-mediated reactions

  Multicomponent reactions (MCR)  in the synthesis of a variety of compounds

  Activation of C-H bonds for C-C and C-heteroatom bond formation

C. Selected case-studies of organic synthesis of approved drugs

Selection from the following [6 h]:

·              Darunavir (2^nd generation inhibitor of the HIV-1 protease – Treatment of HIV )

·              Aliskiren ( Renin inhibitor – Treatment of hypertension)

·              Sitagliptin (Dipeptyl-peptidase-4 inhibitor – Antidiabetic drug)

·              Montelucast (Leucotriene receptor antagonist – Treatment of asthma/allergy)

·              Sorafenib (Kinase inhibitor – Treatment of primary kidney cancer)

·              MK4965 (Non-nucleoside reverse transcriptase   inhibitor -  Treatment of HIV-1)

·              Tamiflu (Neuraminidase inhibitor – Treatment of influenza)

·              Alogliptin [Dipeptidyl-peptidae-4 selective inhibitor 4 (DPP4) – Treatment of

               diabetes type 2]

·              Bazedoxifen [Selecrive regulator of estrogen receptors (SERMs) – Treatment of

               postmenopausal osteoporosis]

·              Bilastine [Histamine H1 receptor (HRH1) antagonist  - Treatment of allergic

               rhinoconjunctivitis and οf urticaria] 

·              Zucapsaicin (Vanilloid receptor type 1 selective agonist – Treatment of muscle

               and joints pain)

·              Dronedarone (Μultiple channels blocker – Αntiarrhythmic  drug)

·              Icotinib [Selective inhibitor of tyrosine kinase of epidermal growth factor  

               (EGFR-TKI)   -  2^nd or 3^rd line drug for advanced or metastatic  stage of non-small cell lung cancer (NSCLC) ]