Pharmacy

From a temporal point of view, the program can be divided into two phases: the first of these includes the topics listed in sections from A to B, and takes place in the first month of lessons; the second focuses on the topics listed in sections C to D, up to the end of all lessons. A - Introduction: Metabolism forms implemented in living organisms - distinction between primary and secondary metabolism; topics studied by of Biochemistry and Chemistry of Natural Organic Substances; carbon pathway; biosynthetic bricks: C1, C2, C5, C6C3 (C6C2, C6C1), C6C2N, C4N, C5N fragments; origin of biosynthetic bricks. B - Typical construction mechanisms involved in the metabolic pathways and analogies found with respect to the laboratory organic chemistry. Reactions: 1) of alkylation; 2) of transposition; 3) aldol and Claisen type; 4) retro-aldol and retro-Claisen; 5) of carboxylation; 6) of decarboxylation; 7) of transamination; 8) enzymatic REDOX (oxidation through dehydrogenase, oxidase, mono-oxygenase, dioxigenase, amino-oxidase); 9) of oxidation type Bayer-Villiger ; 10) of oxidative coupling of phenols; 11) of glycosylation. C - Classes of natural substances (secondary metabolites) and their biosynthesis. C1 - Acetate pathway. Biosynthesis of fatty acids: saturated (mechanism of action of the fatty acid synthetase enzyme, and classes of compound in which these are incorporated); unsaturated, with double bonds (in position 2.3 and trans configuration, in position 3.4 and cis configuration, unsaturation introduced by desaturase: formation of oleic, linoleic, gamma- and alpha-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid , docosahexanoic acid, ricinoleic acid, vernolic acid); unsaturated, with triple bonds (acetylenic fatty acids, e.g. dehydromatricaria); at branched chain. Biosynthesis of: prostaglandins PGGx, PGHx, PGEx, PGDx, PGFx, PGAx, PGBx, PGCx, PGI2 / 3, x = series 1, 2 and 3; thromboxanes TXAx, TXBx, x = series 1, 2 and 3; leukotrienes LTA4, LTB4, LTC4, LTD4, LTE4. Iterative or non-iterative mechanism of the polichetide synthase enzyme. Biosynthesis of aromatic polyketides: orsellinic acid; floracetofenone; alternariol; 6-methylsalicylic acid; lecanoric acid; anthraquinones; sennosides; anthrones; hypericin; patulin; stilbenes; chalcones; flavonoids; catechins; anthocyanidins; cannabinoids; aflatoxins; tetracyclines; anthracyclines; urushiols; quinolinic (4-hydroxy-2-quinolone) and acridines (1,3-dihydroxy-N-methylacidone) alkaliodes. Biosynthesis of macrolide polyketides: erythromycins; spiramycins; polyenic macrolides (amphotericines); ansa macrolides (ansamycin); linear polyketides; polyether; statins. C2 - Shikimate pathway. Biosynthesis of shikimic, corismic and prephenic acid. Biosynthesis of benzoic acids from 3-dehydroshikimic acid: gallic acid (gallotannins); protocatechic acid; salicylic acid; 4-hydroxybenzoic acid. Biosynthesis of the L-tryptophan, L-phenylalanine, L-tyrosine amino acids. Biosynthesis of catecholamines; melanines; cinnamic acids; lignans, neolignans and lignin; flavonoids, isoflavonoids and stilbenes (naringenin, cyanidin, afzalechine, epicatechin and tannins, genistein, cumestrol, resveratrol); phenylpropanoids (cinnamaldehyde, anethole, eugenol, myristicin); benzoic acids; coumarins (coumarin, umbeliferone, scopolin, dicumarol, psoralen). C3 - Mevalonate pathway. Biosynthesis of mevalonic acid, isopentenyl pyrophosphate and dimethylalyl pyrophosphate. Generation of: emiterpenes (isoprene and 2-methyl-3-buten-2-ol); linear (geranyl, linalyl and neryl pyrophosphate and their direct derivatives) and cyclic (alpha-terpineol, limonene, cineole, car-3-ene, alpha- and beta-pinene, fenchol, fenchone, borneol, camphor and camphene) monoterpenes; iridoids (nepetalactone, valtrate); sesquiterpenes (farnesyl pyrophosphate and its derivatives generated by cyclization of cations of (E,E) and (E,Z) configuration, formed by loss of pyrophosphate anion); diterpenes (geranylgeranyl pyrophosphate and its derivatives, formed through folding enzyme-controlled: taxol, forbol, steviosides, abietic acid, gibberellins); sesterterpenes (geranylfarnesyl pyrophosphate and its derivatives ofiobolin A and scalarin); triterpenes (squalene, its derivatives lanosterol and cycloartenol, generated from the protosterile cation, and its further derivatives lupeol, euphol and alpha and beta amirine, generated from the dammerenyl cation, stereoid structures generated by progressive modification of the lanosterol molecule, steroidal saponins, glycosides cardioactives, phytosterols, stanolesters, ecdysons, bile acids, corticosteroids, estrogens, androgens); tetraterpenes (Z-phytene, lycopene, carotenoids). D - Alkaloids. Classification, based on: a) the family of plants from which they are extracted; b) the amino acid from which they are generated; c) the type of heterocyclic structure present in the molecule. Insights concerning some important examples. Biosynthesis of: nicotine; piperine; atropine and cocaine; ephedrine and mescaline; papaverine and morphine; strychnine, caffeine and theobromine.

As a prerequisite, the student must possess notions and skills acquired by attending the Organic Chemistry course, and in particular, adequate knowledge: a) of the specific reactive properties possessed by the various types of organic substances, conferred on them by the presence of particular functional groups in the relevant structure; b) the mechanisms involved in the main types of polar and radical reactions.

Dewick, P. M.: Chimica, biosintesi e bioattività delle sostanze naturali, Piccin Nuova Libraria SpA, Padova, 2012. ISBN: 882992234X. alternatively, Hanson, J. R.: Natural products, the secondary metabolites, Royal Society of Chemistry, Cambridge, 2003. ISBN 0-85404-490-6.

The lessons are carried out by always associating the theoretical contents with the use of writing on the blackboard of the mechanisms involved in the analyzed biosynthesis process. For this reason, the first part of the course provides a systematic mechanistic analysis of those reactions governed by enzymes which, from time to time connected to each other in different succession, will be able to justify their belonging to the particular biosynthetic pathway in which are reported. A further rationalization of the topics addressed during the lessons is then obtained by associating the biosynthesis of each particular class of natural substances analyzed with one of the three well-known biosynthetic pathways of acetate, shickimate and mevalonate. As a stimulus to encourage active participation in the lesson, students are frequently invited to propose the single biosynthetic step, comprensive of the related mechanism, which can correctly interpret a particular reactive step deliberately proposed as missing by the teacher.

Mandatory attendance

The assessment of the degree of preparation of the student is carried out by requesting the discussion on the blackboard of the biosynthetic steps that govern the formation of a natural substance randomly selected among those discussed during the lessons. The draw is made four days before the scheduled exam date. During the presentation, the student will also be invited to explain the mechanistic characteristics with which some of the steps presented are carried out, and other in-depth questions rationally connected to the biosynthesis object of the exam.

The lessons are carried out by always associating the theoretical contents with the use of writing on the blackboard of the mechanisms involved in the analyzed biosynthesis process. For this reason, the first part of the course provides a systematic mechanistic analysis of those reactions governed by enzymes which, from time to time connected to each other in different succession, will be able to justify their belonging to the particular biosynthetic pathway in which are reported. A further rationalization of the topics addressed during the lessons is then obtained by associating the biosynthesis of each particular class of natural substances analyzed with one of the three well-known biosynthetic pathways of acetate, shickimate and mevalonate. As a stimulus to encourage active participation in the lesson, students are frequently invited to propose the single biosynthetic step, comprensive of the related mechanism, which can correctly interpret a particular reactive step deliberately proposed as missing by the teacher.