Practice Exam 3-A – ANSWER KEY

Chemistry 27: Practice Exam 3-A

Instructions: Please verify that your exam has 9 pages (including this one). Complete your
answers for the following questions neatly, legibly, and concisely in the space provided below. If
you provide multiple answers for the same question, place a box around the answer that you would
like graded. Otherwise, your first answer (and nothing else) will be graded. For your convenience,
scratch paper is attached at the back of the exam packet. You may remove the scratch paper, but
work on these pages will NOT be graded! Be sure to manage your time wisely (83 minutes).

Collaboration is not allowed on the exam. All answers submitted for evaluation must be exclusively
the results of your own efforts. The use of molecular models is allowed but not necessary; no other
exam aids, including calculators, will be allowed or required. On this exam, you may abbreviate
iminium formation and hydrolysis, as well as transaldimination, by the conventions shown in
lecture.

This course endorses and promotes Harvard College’s expectations around academic integrity.
Below is the text of the Honor Code for your review; all work for this course, including exams,
should abide by these standards.

The Harvard College Honor Code

Members of the Harvard College community commit themselves to producing academic work of
integrity – that is, work that adheres to the scholarly and intellectual standards of accurate
attribution of sources, appropriate collection and use of data, and transparent acknowledgement of
the contribution of others to their ideas, discoveries, interpretations, and conclusions. Cheating on
exams or problem sets, plagiarizing or misrepresenting the ideas or language of someone else as
one’s own, falsifying data, or any other instance of academic dishonesty violates the standards of
our community, as well as the standards of the wider world of learning and affairs.

I affirm my awareness of the standards of the Harvard College Honor Code.

Signature:_______________________________________________________________

Print Name: ____________________________________________________________

HUID: __________________________________________________________________

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 Practice Exam 3-A – ANSWER KEY

Chemistry 27: Practice Exam 3-A

HUID: ____________________________________________

Question Point Value Score

1 10 _________
2 17 _________
3 23 _________
4 22 _________
5 28 _________

Total 100

Please circle your TF and section time below:

Amanda Amanda Beverly Beverly Conor

1:00 pm 8:30 am 8:30 am 7:00 pm 1:00 pm

Conor Eileen Eileen Lydia

2:30 pm 4:00 pm 7:00 pm 1:00 pm

Lydia Nathaniel Nathaniel Mac

2:30 pm 1:00 pm 4:00 pm 7:30 pm

Matt Matt Mike Mike

8:30 am 10:00 am 4:00 pm 11:30 am

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Question 1. (10 points) 3-oxodecabonyl-ACP and S-adenosyl methionine are used by bacteria to form
the product below. The product serves as a small molecule communication signal between bacteria to
coordinate population growth. Propose a curved-arrow mechanism for this reaction. Be sure to account
for the identity and formation of all co-products.

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Question 2. (17 points) Draw the curved-arrow mechanism for the reaction shown below, which is
performed by an FAD-dependent monooxygenase. You may use whatever co-substrate you see
fit.

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Question 3. (23 points) The transformation shown below is catalyzed by a PLP-dependent

enzyme. Provided a curved-arrow mechanism for this transformation.

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Question 4. (22 points total) Human oxidosqualene cyclase catalyzes the conversion of
oxidosqualene to lanesterol. The Arabidopsis thaliana plant has thirteen different oxidosqualene
cyclases. The products from two of these cyclases are shown below.

4-a. (10 points) Starting from oxidosqualene, provide a mechanism for the formation of arabidiol. A
suggestive conformation of oxidosqualene has been provided for you. While you do not have to
show carbocation intermediates in the cyclization cascade, you must show all carbocation
intermediates in any carbocation shift or termination steps.

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4-b. (12 points) The mechanisms for forming arabidiol and thalianol proceed through a common
carbocation intermediate. Starting from the common intermediate, provide a curved-arrow
mechanism for the formation of thalianol. Clearly indicate the stereochemistry and depict each
carbocation intermediate as an individual step.

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Question 5. (28 points) Romidepsin, shown below, is biosynthesized by a PKS/NRPS hybrid

assembly line. The romidepsin assembly line includes a unique tailoring domain, the
aminotransferate (AmT) domain. A general example of the reaction catalyzed by the AmT domain
is provided below.

5-a. (15 points) Based on the structure of romidepsin, fill in the assembly line table below. The
structures of some potentially useful starting materials have been provided for you. Note: There
may be more spaces for modules in the table than are necessary.

Starting
Module AT KS KR DH ER ACP C A PCP E AmT TE
Material
0 Cys A PCP AmT
1 MalCoA AT KS KR DH ACP
2 MalCoA AT KS KR ACP
3 Val C A PCP E
4 Cys C A PCP E
5 2,3-DHThr C A PCP
6 Val C A PCP TE

5-b. (4 points) Fill in the answers on the lines below:

The function of the TE domain is: _______macrolactonization_________

The number of molecules of ATP used in the assembly line is: ______5_______

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5-c. (9 points) Your assembly line table in part a should include at least one KS domain. Select
the earliest KS domain in your table, and draw a mechanism for the step or steps catalyzed by the
KS domain. Since the protein that catalyzes the formation of romidepsin is a hybrid PKS/NRPS
assembly line enzyme, both the ACP and PCP domains have been provided below.

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Scratch Paper

No work on this page will be graded