Synthesis of Antibiotics

     Antibiotics are agents that are used to kill microorganisms or inhibit their growth. They can either occur naturally or can be synthetically produced. Extremely common today are semi-synthetic modifications of natural compounds. These chemical, biosynthetic antibacterial compounds are classified according to their biological effect on microorganisms. Bactericidal agents kill bacteria altogether while bacteriostatic agents slow down or stall bacterial growth. One specific semisynthetic antibiotic is what is known as Erythromycin.

     Erythromycin is what is considered a macrolide antibiotic. Macrolide antibiotics slow the growth of and often kill sensitive bacteria by reducing the production of important proteins needed by the bacteria to survive. This drug is notorious for being similar to penicillin in what it is used for and how it is synthesized. Often it is used as a substitute for people who are allergic to penicillin being that penicillin is such a common allergy. It is commonly used to treat respiratory tract infections, acne, Gonorrhea, Chlamydia, and other STDs. It is also applied to the eyes of newborn babies in order to prevent ophthalmia neonatorum. Erythromycin works by improving gastric emptying as well as its symptoms, though oral use of this drug is generally for short term use rather than long term.

     The chemical structure of Erythromycin, C38H69NO12, is extremely complicated and elaborate. Its synthesis published by Robert B. Woodward in 1981, the drug consists of a 14-membered lactone ring along with ten asymmetric centers and two sugars, L-cladinose and D-desosamine. The compound’s complexity makes it extremely hard to produce synthetically therefore it is produced by the bacterium Saccharopolyspora erythraea. Synthesis of this drug includes an intricate series of reactions. Reactions include hydrolysis and stereospecific aldolization. Oxidations and reductions are also involved in the synthesis by the pure enone’s conversion to desired dithiadecalin product. This product is further converted to ketone as well as an aldehyde. Overall, the synthesis contains roughly 50 steps split into 4 parts.

     Erythromycin comes in 4 forms: Erythromycin A, B, C and D. Erythromycin A is known for being the most antibacterial, with B, C and D following respectively. As discussed previously, this drug is considered to inhabit bacteriostatic activity, otherwise it inhibits growth of bacteria rather than stopping it or killing in completely. Its bacteriostatic capability is most displayed at high concentrations by interfering with aminoacyl translocation. This process objects to the functionality of important proteins, which is overall how antimicrobial action is put in place. One should be aware of the side effects erythromycin may cause, for example, abdominal pain, nausea, diarrhea, and vomiting.

     Zithromax is a semi-synthetic antibiotic, an example of the subclass, azalides and slightly differs in structure from the classical macrolides. It is used to treat and prevent infection within an area thought to be caused by bacteria. Like all other antibiotics, zithromax has an active ingredient, which in this case is azithromycin, a subclass of macrolide antibiotics. Azithromycin is derived from erythromycin but differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring and is has improved activity through its glycosylated side chains. In this form, it has a molecular formula of C38H72N2O12. However, when Azithromycin is a dihydrate, which means it contains two molecules of water or its elements, it has a molecular formula of C38H72N2O12*2H2O. Also, Azithromycin contains inactive ingredients such as pregelatinized starch, lactose, sucrose, sodium phosphate, hydroxypropyl cellulose, or xanthan gum that all supplement the active ingredient.

 

     Azithromycin binds to 50s ribosomes and interferes with protein synthesis but does not affect nucleic acid synthesis. It binds to the 23S rRNA of the bacterial 50S ribosomal subunit, which includes the activities such as catalyzation of  peptide bond formation, prevention of premature polypeptide hydrolysis, provision of a binding site for the G-protein factors, assistance of protein folding after synthesis. blocking of protein synthesis by inhibiting the transpeptidation or translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit. Azithromycin was the target of an enantioselective synthesis, which is a chemical reaction where one or more new elements of chirality,a molecule that has a non-superposable mirror image, are formed in a substrate molecule and which produces the stereoisomeric products in unequal amounts are formed in a substrate molecule and produces the stereoisomeric products in unequal amounts. Also, all the stereogenic quaternary carbon centers were enhanced by the desymmetrization of 2-substituted glycerols using a chiral imine/CuCl catalyst, otherwise known as copper (I) chloride.

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     Synthesis of antibiotics such as erythromycin and azithromycin shows how the chemical structure and formula can be modified in order to change its function and its effect on the body accordingly. Although erythromycin was created first, scientists and doctors were able to enhance its molecular formula in order to enhance the process and activity in which it deals with an infected area. Also, these synthetic drugs offset and affect series of reactions such as hydrolysis, which can either interfere or not affect other processes. Overall, the synthesis of such antibiotics require much difficulty due to the fact that many factors such as the complexity of the compound or different incorporated ingredients that change the orientation of each function and process.

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