Introductory description

N/A

Module web page

Module aims

Outline syllabus

This is an indicative module outline only to give an indication of the sort of topics that may be covered. Actual sessions held may differ.

This module will be concerned with the design and execution of synthetic approaches to complex
target organic molecules, with reference to absolute and relative stereocontrol, disconnections
and use of protecting groups when appropriate. The selection of examples has been made with a
view to including many diverse examples of target structures, several of which are
pharmaceutically significant, and a broad range of synthetic chemistry reactions (which will have
been taught in previous years).

Syllabus
A compulsory set of lectures and workshops will be used to disseminate the material in the
following areas:

1. Introduction to strategy, disconnections, retrosynthesis, protecting groups and extreme targets
   which may include palytoxin, Vitamin B12, Brevitoxin, azadirachtin, vancomycin.
2. Early classics of total synthesis in organic chemistry, which may include colchicine, morphine,
   strychnine, thienamycin, penicillin, lepadiformine A and epi-stemoamide..
3. Lessons learnt from the synthesis of small important organic molecules which may include
   hirsutene, periplanone B, complex alkaloids and epothilones.
4. Molecules with a high degree of functionality, which may include avermectin, erythromycin,
   Amphotericin B and Deoxyerthyrionlide B.
5. Construction of highly complex structures which may include ginkolide B, calicheamycin, taxol, ingenol.
6. The use of cycloadditions in complex molecule synthesis, which may include FR182877,
   estrone, platensimycin, progesterone, daphniphylline alkaloids, abyssomicin C and incargranine A.
7. Enantioselective strategies which may include biotin a-arylpropionic acids, menthol, zaragozic
   acid, statins, Jorunnamycin A.
8. Peptide synthesis with emphasis on peptide bond formation, coupling reagents, orthogonal
   protecting groups and solid phase synthesis. Relevant examples may include some natural
   peptides (e.g. oxytocin, vasopressin and angiotensin; vancomycin and cyclosporins) and peptide-
   based drugs (e.g. angiotensin and protease inhibitors, synthetic peptide hormones, enfuvirtide
   and eptifibatide).
9. Carbohydrate synthesis, with emphasis on glycosidic bond formation (including
   stereoelectronic effects that influence the selectivity at the anomeric position) and the use of
   protecting groups.
10. Strategies for the synthesis of oligosaccharides. Relevant examples may include acarbose,
    heparins and carbohydrate-based vaccines.

These classes will involve introductory lecture/seminars, and problem classes (workshops). Academics will be available to respond to questions via email and students may book a time to discuss any queries.

Learning outcomes

By the end of the module, students should be able to:

• Be aware of subject knowledge to an appropriate level.
• demonstrate a contextual understanding of contemporary synthetic methods.
• have gained an ability to interpret and evaluate contemporary research work.

Indicative reading list

Because this is a research module the recommended texts are likely to be recently published
research articles and thus may change over the years.

Additional texts that are recommended for reading in association with the notes.
Books
Classics in Total Synthesis; K. C. Nicolaou and E. J. Sorensen, Wiley-VCH 1996. Classics in Total
Synthesis II, K. C. Nicolaou and E. J. Sorensen, VCH 2003.

Molecules that changed the world, K. C. Nicolaou and T. Montagnon, Wiley-VCH, 2008.

S. Warren and P. Wyatt, Organic Synthesis: The Disconnection Approach, Wiley, 2nd Edn 2008 and
the associated workbook, 2nd Edition 2009.

‘General Aspects of the Glycosidic Bond Formation’, A. V. Demchenko, from ‘Handbook of
Chemical Glycosylation: Advances in Stereoselectivity and Therapeutic Relevance’, Wiley, 2008.

The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates, Stephen D. Roughley and Allan M. Jordan, J. Med. Chem. 2011, 54, 3451–3479.

In addition, other annual reviews of progress frequently appear in review journals. For more
detailed reviews of particular areas, students can search the web of knowledge or Scifinder
Scholar for comprehensive literature surveys.

Research element

e.g. essay, dissertation, individual or group research, research skills activity, etc.

International

e.g. includes mobility opportunities, explores concepts and ideas in a global context, fosters a global mindset and awareness of diversity, etc.

Subject specific skills

Problem solving
Independence and initiative
Information literacy and research skills

Transferable skills

Problem solving
Independence and initiative
Information literacy and research skills