Propose mechanistic pathways for the biosynthesis of the following terpenoids:

Name: Problem 12, Chapter 23: Organic chemistry with biological applications
Uploaded: 2020-06-02T20:10:21-08:00
Duration: 4 min 57 s
Channel: Kevin Zaborsky
Description: Propose mechanistic pathways for the biosynthesis of the following terpenoids:

Propose mechanistic pathways for the biosynthesis of the...

Key Concepts

Isoprenoid Precursors

Terpenoid biosynthesis starts with the formation of universal five-carbon precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). These molecules serve as building blocks for all terpenoids and are generated via two distinct pathways—the mevalonate pathway and the methylerythritol phosphate (MEP) pathway—each utilizing different substrates and enzymes to construct these essential units.

Enzymatic Cyclization Mechanisms

Many terpenoids are formed through enzyme-catalyzed cyclization reactions where linear isoprenoid intermediates are folded into complex cyclic structures. Terpene synthases facilitate these reactions by binding substrates and inducing specific conformations that enable the formation of carbocation intermediates, leading to cyclization, rearrangement, and the eventual production of structurally diverse terpenoid frameworks.

Carbocation Formation and Rearrangement

A key mechanistic feature in terpenoid biosynthesis is the generation of high-energy carbocation intermediates. These reactive species undergo a series of shifts, including hydride and alkyl migrations, which are orchestrated by the enzyme's active site. This stepwise process results in the formation of multiple ring systems and unexpected skeletal rearrangements, contributing to the chemical diversity of terpenoids.

Enzyme Active Site Dynamics

The active sites of enzymes involved in terpenoid biosynthesis play a critical role in stabilizing transient intermediates and directing the course of complex reaction pathways. By precisely orienting the substrate and providing a microenvironment that favors certain reaction trajectories, these enzymes achieve remarkable regio- and stereospecificity during the cyclization and rearrangement processes.

Transcript

00:01 We are given two structures for steroids in parts a and b, and for each part we want to propose a mechanistic pathway for the biosynthesis of each one of these molecules.

00:13 So starting in part a, we can examine the final molecule, and we can rearrange it so that we have a starting material that resembles that final molecule that we are trying to generate.

00:25 But we know that it has to have this diphosphate group since the first step in biosynthesis is for that group to leave.

00:34 And as a result of that group leaving, that will leave behind a carbocadion at that position.

00:43 And the next step in the arrow pushing of this mechanism is that we flow from electron rich areas to electron pore areas.

00:53 So the electrons from this double bond will form a bond here to close this ring, and the other double bond will then shift over here to neutralize that carbocadion.

01:08 And what results is the structure on the far left, where we have formed that double bond to neutralize the carbocadion and close the ring.

01:19 And now going from electron -rich, the electron -rich area of the double bond, we can go to this, which has now become a carbocation.

01:30 After the double bond, the electrons from the double bond previously were removed from that site.

01:36 And after that, we form this bond between those two carbon atoms.

01:43 And now that the electrons have been moved from the double bond in the previous step, the carbocation now...

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