The biosynthesis of brevetoxin B is thought to involve a compound with several alkenes. Here are some important steps in the process:
Step 1: Ten of the compound’s fourteen alkenes are selectively epoxidized by oxygenase enzymes. Amazingly, this occurs with control of stereochemistry.
Step 2: The resulting poly-epoxidized intermediate undergoes a ring-opening cascade reaction to form brevetoxin B through the arrow-pushing mechanism shown below.
During this cascade, what happens to stereochemistry at each of the reacting epoxide carbons? (Hint: Don’t be intimidated by the size of the molecule and think SN2).
a. In some cases, the stereochemistry is inverted, but in other cases, stereochemistry is retained. It depends if the carbon of the epoxide undergoing attack is tertiary or not.
b. All of the epoxide opening reactions occur with retention of stereochemistry at the carbon of the epoxide being attacked.
c. I don’t know, this molecule is way too big!
d. All of the epoxide opening reactions occur with inversion of stereochemistry at the carbon of the epoxide being attacked.
The correct answer and explanation is:
The correct answer is:
d. All of the epoxide opening reactions occur with inversion of stereochemistry at the carbon of the epoxide being attacked.
Explanation:
Brevetoxin B biosynthesis involves a fascinating series of selective epoxidations followed by a ring-opening cascade reaction. Understanding the stereochemical outcomes of the epoxide opening steps is crucial, and the key to this is recognizing the mechanism involved.
Step 1: Epoxidation
The first step in the biosynthesis selectively introduces multiple epoxides into the precursor molecule. These epoxides are highly reactive due to the significant ring strain and the presence of an electrophilic carbon susceptible to nucleophilic attack.
Step 2: Epoxide Ring-Opening Cascade
The poly-epoxidized intermediate undergoes a series of nucleophilic attacks to form the polycyclic brevetoxin B skeleton. These attacks occur via an SN2 (bimolecular nucleophilic substitution) mechanism, which is characterized by a backside attack of the nucleophile and an inversion of configuration at the carbon being attacked.
- SN2 Mechanism and Stereochemistry:
- Epoxides open through an SN2-like process because the carbon-oxygen bond is highly polarized.
- A nucleophile (such as an internal oxygen or another functional group) attacks the least hindered carbon of the epoxide.
- The attack occurs from the opposite side of the leaving oxygen, leading to inversion of stereochemistry.
- Consistent Inversion Throughout the Cascade:
- Since each epoxide opening follows SN2-type reactivity, each step results in stereochemical inversion at the reacting carbon.
- This inversion is critical for forming the correct three-dimensional shape of brevetoxin B.
Thus, all of the epoxide-opening reactions occur with inversion of stereochemistry at the carbon being attacked, making answer (d) the correct choice.
Now, I’ll generate an image to illustrate the concept.
I’ve generated an illustration showing the brevetoxin B biosynthesis process, including the selective epoxidation and the ring-opening cascade with stereochemical inversion at each epoxide carbon. Let me know if you’d like any modifications or further explanations!
