D. PAVIA

1. D. PAVIA NATURAL PRODUCTS CHEMISTRY CHEM 425a/552 THE GOLD PROBLEM To answer this problem, you need to give a structure for each compound that is represented by a letter in a circle. This problem amounts to a structure proof of compound A (what is it ?). CH3NO2 H2 / Pd-BaSO4 G F E Rosenmund NaOEt / EtOH C11H13NO5 C10H12O4 C10H11O4Cl 1) Zn/HOAc 2) Na/Hg SOCl2 D CrO3 / H2SO4 B A Jones C10H12O5 xs CH3I NaOH C11H17NO3 derivative 1) SOCl2 an acid mp 240oC decomp. 1)NaOH/D C D mp 242oC Tannins 2) H3O+ (note 7) 2) NH3 from oak galls or tea leaves C7H6O5 C7H7NO4

2. PART TWO 1) Postulate a reasonable biosynthetic sequence that the plant might use to synthesize compound A. 2) Mechanisms are not required, but you should have a step-by-step sequence of intermediates. At each step, place the identity of the coenzyme or enzyme that could bring about the desired transformation. 3) Here are some of the coenzymes and intermediates you could choose from: any amino acids or a-ketoacids formaldehyde or acetaldehyde NAD+/NADH CoenzymeA (CoASH) ATP oxygen/hydroxylase combination Acetyl Coenzyme A SAM (SAdM) pteridines FAD/FADH2 thiamine (B1) pyridoxyl-5’-phosphate (B6) 4) How could you prove (by experiment) that your sequence of steps is correct?

3. NOTES 1. You will have to look up the structure of tannins. They are found in “oak galls”, big knobby (gnarly) growths that grow on oak trees due to insect damage, and in tea leaves. When they are hydrolyzed you get compound C and glucose. 2. You will have to look up compounds C and D in tables of unknowns and derivatives. 3. If you don’t know the Rosenmund Reduction you will have to look it up. 4. The step F to G is like an aldol condensation, the nitro compound has acidic hydrogens. The NO2 group stabilizes the negative charge by resonance. The anion is a good nucleophile. 5. The reagents given in G to A are really strong reducing reagents. They are not subtle. We would probably use LiAlH4 today. 6. You should also be able to give me the actual name for compound A. HINT: It’s in your lecture notes! 7. In some reference books, compound D is listed with mp 189o, but as mp 242o in others!

4. 8. Derivatives Old-time chemists (those who worked before spectroscopy was invented) used derivatives to identify compounds. A derivative is a second compound made from the first one in order to allow a confirmation of its identity. For instance, a common way of identifying an acid would be to convert it to an amide using SOCl2 followed by NH3. The original compound’s identity would be confirmed if the melting point of the amide had the expected value (one already reported in the literature) for the amide derivative of that compound. Most textbooks of “qualitative organic analysis” have tables of derivatives listed in the back of the book organized by the starting functional group. A table of acids, for instance, would list a series of carboxylic acids by increasing boiling point and then by melting point. In a column opposite each acid in the table the melting points of commonly used derivatives would be listed: for acids the melting points of the corresponding amides and anilides (a derivative made with aniline instead of ammonia) are given. Useful derivatives are usually solid compounds because solids are easier to purify (crystallization) and melting points are easier to determine than boiling points. Over the years chemists developed suitable derivatives for every major functional group and they became standardized. Therefore, when you look in the tables only certain derivatives (the standard ones) are listed. Most chemists would know what these standard derivatives are.

5. EXAMPLE: Suppose you had a ketone with a boiling point from 231-234o C. A portion of what you will see in the tables of unknowns follows: semicarbazone 2,4-dinitrophenyl- hydrazone ketones bp mp 2-undecanone 231 12 12263 4-chloroacetophenone 232 12 204236 4-phenyl-2-butanone 235 - 142127 There are three possible ketones in this range to consider. But if you make the 2,4-dinitrophenylhydrazone derivative and the melting point is 236o, you know immediately that you have 4-chloroacetophenone. If you wanted additional confirmation you could also make the semicarbazone (204o). There are a number of books in the organic lab (under or on the melting point stands) that have tables of unknowns. The most complete book is: Zvi Rappoport, CRC Handbook for Tables for Organic Compound Identi- fication, CRC Press. Also useful are the book by Shiner, Fuson and Curtin and the 354-355 lab book by the Organic “Three Musketeers” P,L and K.