25. Condensation Chemistry

Lawsone, found in the extract of henna, reacts with amino acid residues to give the characteristic color associated with henna tattoos. Suggest a mechanism for the reaction shown.

The following covalent inhibitor blocks function in a protease found in the porcine epidemic diarrhea virus by reacting with a cysteine amino acid residue (shown below) in the active site. Draw the expected complex that forms between the inhibitor and the enzyme active site (J. Med. Chem. 2017, 60, 3212–3216.) [Assume the presence of active site bases if you need them.]

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Write equations showing the expected products of the following enamine alkylation and acylation reactions. Then give the final products expected after hydrolysis of the iminium salts.

(d) piperidine enamine of cyclopentanone + methyl vinyl ketone

What reagents should be used to prepare the following compounds?

b.

Show how the following products might be synthesized from suitable Michael donors and acceptors.

(c)

Show how an acetoacetic ester synthesis might be used to form a δ-diketone such as heptane-2,6-dione.

Show how cyclohexanone might be converted to the following δ-diketone (Hint: Stork).

The following reaction was used in the synthesis of aculeatin A, a natural product that is active against KB cell lines. Although it only worked under acidic conditions, a mechanism can be drawn where the reaction might proceed under basic conditions. Suggest this mechanism (J. Org. Chem. 2014, 79, 1498–1504). [The most acidic proton is indicated . . . and number your carbons!]

Show how the following products might be synthesized from suitable Michael donors and acceptors.

(a)

Show how the following products might be synthesized from suitable Michael donors and acceptors.

(d)

Show reaction sequences (not detailed mechanisms) that explain these transformations:

(b)

Show how the following products might be synthesized from suitable Michael donors and acceptors.

(b)