An important class of molecules comprised of both natural and designed products is the iminosugars. — Organic Chemistry Chemistry Question
Synthesis of Antiviral Drugs
An important class of molecules comprised of both natural and designed products is the iminosugars. While not true carbohydrates, they are able to mimic sugars, acting as inhibitors of many enzymes. Due to this ability, they have been shown to have significant activity as antivirals, as well as in treatments of some genetic disorders such as Gaucher’s disease. Inspired by the significant activity, a number of synthetic organic chemists have pursued these targets. Consider two syntheses of the glucose mimic, DNJ.
Draw structures of the missing intermediates along their route, A–D:
[VISUAL]
Model Answer
[VISUAL] Organic structures of intermediates A, B, C, and D are shown in the original solution.
Draw the missing intermediates in the synthesis, J–P.
[VISUAL]
Model Answer
[VISUAL] Organic structures of intermediates J, K, L, M, N, O, and P are shown in the original solution.
The triflate group (Tf) transforms a hydroxyl group into a better leaving group. Rank the following groups in terms of leaving group ability from best (1) to worst (5).
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Model Answer
3 5 2 1 4
Although it occurs in a single flask, the transformation of Q to DNJ can be considered to occur in 3 distinct steps. Suggest structures for the two intermediates Q' and Q" that arise as the reaction proceeds:
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Model Answer
Intermediate Q':
O
OH
NH 2
HO
HO
OH
Intermediate Q'':
N H
OH
OH
HO
OH
Rather than the organic solvents required for the two syntheses of DNJ, the synthesis of this furanose-mimicking iminosugar employs only water as the solvent– a fact which makes the synthesis cheaper and greener. Draw the missing structures for the intermediates, X and Y, that can be isolated as individual compounds and for the transitive intermediate, Z.
Hint: In this case, the tungsten catalyst selectively provides the (S, S) epoxide of the remaining olefin.
[VISUAL]
Model Answer
[VISUAL] Organic structures of intermediates X, Y, and transitive intermediate Z are shown in the original solution.