Natural Product Chemistry I

Natural Product Chemistry I

Introduction

• Natural Product Chemistry I is a semester course for B.Sc. Chemistry students.

What You will Learn

• The course includes study units and a course guide.
• The course guide describes the materials and how to use them, and provides general guidelines for time allocation per unit.
• Tutor Marked Assignments (TMAs) are in the assignment file.
• Tutorial questions and classes will improve course understanding.
• Students are advised to attend tutorial classes.

Course Aim

• To provide a basic understanding of chemical materials and trends.
• To understand and improve material properties for new material requirements.

Course Objectives

After completing this course, students should be able to:

• Know what natural products are.
• Understand the different types of natural products.
• Give various examples of natural products.
• Describe chemical properties of natural products.
• State the applications of these natural products.

Working Through This Course

• Study each unit carefully, along with recommended textbooks and materials from the National Open University.
• Use the internet for additional information.
• Each unit has a self-assessment exercise.
• Assignments must be submitted for grading.
• Participate in the final examination.
• Devote sufficient time for reading and comprehension.
• Attend tutorial sessions to compare understanding with colleagues.

Course Materials

The materials for this course are:

• The Course Guide
• Study Units
• Self-Assessment Exercises
• Self-Assessment Questions
• Further Readings

Study Units

Module 1: Terpenes

• Unit 1: Biosynthesis of Terpenes
• Unit 2: Classification of Terpenes

Module 2: Steroids

• Unit 1: Nature of Steroids

Module 3: Alkaloids

• Unit 1: Nature of Alkaloids
• Unit 2: Classification of Alkaloids

Presentation Schedule

• Important dates for TMAs and tutorials are in the course materials.
• Submit tutorials and assignments promptly.

Assessment

• Course assessment includes:
  • Self-assessment exercise
  • Tutor Marked Assignment (TMA)
  • Written examination/end of course examination
• Attempt all exercises and assignments.
• Answers should be concise and accurate.
• Consult other materials in addition to the course materials.
• TMAs cover only 30% of the total course marks.

Tutor Marked Assignment (TMA)

• TMA contributes to 30% of the total score.
• Students will be given five (5) TMAs.
• Three (3) must be answered before sitting for the end-of-course examination.
• TMAs will be given and returned by facilitator.
• Assignments are contained in the assignment file to be given to students.
• Students should read and research well before attempting the questions.
• Assignments should be submitted to the facilitator at the stipulated time.
• Contact facilitator for an extension if unable to meet the prescribed deadlin.

Final Examination and Grading

• The end-of-course examination for Natural Product Chemistry 1 accounts for 70% of the total course work.
• The examination will be about 3 hours long.
• The examination questions reflect what was taught during the course materials or in further reading.
• They may be prototype of the self assessment exercises and the TMAs.
• The end-of-course examinations cover all parts of the course.
• Revise course materials, exercises, and assignments prior to the examination.

Course Marking Scheme

The course marking scheme is as follows:

• Assignments 1-5: Best three marks of the five count at 10% each, i.e. 30% of the course marks
• End of Course Examination: 70% of overall course marks
• Total: 100% of the course materials

Facilitators/Tutors and Tutorials

• There are 17 hours of tutorials for this course.
• Students will be informed of their facilitator's name, telephone number, and e-mail address.
• The time, dates, and location of tutorial lessons will be communicated beforehand.
• Tutor Marked Assignments are to be mailed or submitted to the facilitator at least two working days before the scheduled date.
• Duly marked assignments will be returned with comments to improve performance.
• The facilitator will monitor comprehension, progress, and difficulty.
• Attend tutorial lessons at the fixed appointment.
• Ask questions for clarification on difficult topics.
• Active participation during tutorial lessons boosts confidence.

Summary

• Natural Product chemistry provides students insight into the nature and classes of natural products.
• What do natural products represent?
• What are the different type, chemical nature and features of natural products?
• Know different classification of natural products
• Identify the examples of terpenes, steroids and alkaloids.
• Discuss the application of terpenes, steroids and alkaloids.

Module 1: Terpenes - Unit 1: Biosynthesis of Terpenes

Introduction

• In the 19th century, hydrocarbons with the formula C10H16 found in complex plant products were named "terpene".
• Terpenes are found in plant essential oils, the plant fragrance.
• Terpenes are universally present in small amounts in living organisms.
• Terpenes play vital roles in plant physiology and cellular membranes.
• Terpenes variety can be due to ecological factors playing an evolutionary role.

Objectives

After completing this unit, students should be able to:

• Define terpenes and terpenoids.
• Understand the history behind terpenes.
• Describe the biosynthesis of terpenes.
• State the form in terpenes occur naturally.

Definition of Terpenes and Terpenoids

• "Terpene" is derived from the word "turpentine".
• Terpenes are molecules whose structure is based on units of isoprene (methylbuta-1,3-diene).
• Hemiterpene, with 5 carbon atoms is called isoprene.
• When terpenes are modified chemically, the resulting compounds are called terpenoids.
• Also know as Isoprenoids, terpenoids are a subclass of the prenyllipids, and are the oldest group of small molecular products synthesized by plants.
• Terpenoids can be described as modified terpenes, where methyl groups are moved or removed, or oxygen atoms are added.

History of Terpenes

• Terpenes history spans various civilizations.
• Found in essential oils, they were used in Ancient Egypt for religious aims.
• Camphor was introduced in Europe from the East by the Arabs around the 11th century.
• Obtaining plant essential oils by fatty extraction was known by the early Middle Ages.
• In the 12th century, Arnaud de Villanos described distillation of oils from rosemary and sage.
• He made an "oleum mirabile" from oils of turpentine and rosemary.
• Analyses of oils of turpentine were made in 1818 by JJ Houston de la Billardière.
• Dumas proposed in 1866 the name "terpene", derived from turpentine, instead of camphor for crystalline oxygenated substances extracted from essential oils.
• In 1887, Wallach O, proposed that one isoprenic unit of 5 carbon atoms (C5H8) is present in the molecule of terpenes.
• The structure of camphor was established by Bredt in 1893
• The structure of pinene was established by Wagner in 1894
• The structure of citral was established by Tiemann in 1895.
• β-Carotene was isolated in 1837 by Wackenrodder from carrots.
• Its correct molecular form was determined in 1907 by Willstätter.
• Since 1945 there has been an extensive explosion in natural product chemistry due to the advent of chromatographic and spectroscopic techniques.
• The discovery of the isoprene unit is the basis of the concept of the "isoprenic rule" edicted in 1953 by Ruzicka completed by Lynen.
• Mevalonic acid was shown in 1956 to be a biosynthetic precursor of cholesterol.
• An increasing number of terpenoids are described in the plant kingdom and many have important biological activities.
• Sesquiterpenes and diterpenes have antibiotic properties.
• Some sesquiterpenes and diterpenes are insect and plant hormones, respectively.

Biosynthesis of Terpenes

• Terpenoids originate through the condensation of the universal phosphorylated derivative of hemiterpene.
• Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) give geranyl pyrophosphate (GPP).
• In higher plants, IPP is derived from the classic mevalonic acid pathway in the cytosol.
• It is also derived from the methylerythritol phosphate pathway in plastids.
• The cytosolic pool of IPP serves as a precursor of sesquiterpenes, triterpenes, sterols and polyterpenes.
• The plastid pool of IPP provides the precursors of mono-, di- and tetraterpenes.

There are two metabolic pathways of creating terpenoids:

• Mevalonic acid pathway
• MEP/DOXP pathway.

Mevalonic acid pathway

• Many organisms manufacture terpenoids through the HMG-CoA reductase pathway which also produces cholesterol.
• The reactions take place in the cytosol.
• The pathway was discovered in the 1950s.

MEP/DOXP pathway

• Also known as non-mevalonate pathway or mevalonic acid-independent pathway.
• Takes place in the plastids of plants and apicomplexan protozoa, as well as in many bacteria.
• It was discovered in the late 1980s.
• Pyruvate and glyceraldehyde 3-phosphate are converted by DOXP synthase (Dxs) to 1-deoxy-D-xylulose 5-phosphate.
• DOXP reductase (Dxr, IspC) converts to 2-C-methyl-D-erythritol 4-phosphate (MEP).
• The subsequent three reaction steps catalyzed by 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase (YgbP, IspD), 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (YchB, IspE), and 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (YgbB, IspF) mediate the formation of 2-C-methyl-D-erythritol 2,4-cyclopyrophosphate (MECPP).
• MECPP is converted to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) by HMB-PP synthase (GcpE, IspG).
• HMB-PP is converted to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH).
• IPP and DMAPP are the end-products in either pathway, and are the precursors of isoprene, monoterpenoids (10-carbon), diterpenoids (20-carbon), carotenoids (40-carbon), chlorophylls, and plastoquinone-9 (45-carbon).
• Synthesis of all higher terpenoids proceeds via formation of geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP).虽然两种途径，MVA和MEP，在大多数生物体中是相互排斥的，但在植物和少数细菌物种中已经报道了它们之间的相互作用。

Organism Pathways

• Bacteria use either MVA or MEP.
• Archaea use MVA.
• Green algae use MEP.
• Plants use both MVA and MEP.
• Animals use MVA.
• Fungi use MVA.

Summarized Classification of Terpenes

A rational classification of the terpenes has been established based upon the number of isoprene (or isopentane) units incorporated in the basic molecular skeleton:

• Monoterpenes: 2 Isoprene units, 10 Carbon atoms
• Sesquiterpenes: 3 Isoprene units, 15 Carbon atoms
• Diterpenes: 4 Isoprene units, 20 Carbon atoms
• Sesterpenes: 5 Isoprene units, 25 Carbon atoms
• Triterpenes: 6 Isoprene units, 30 Carbon atoms
• Carotenoids: 8 Isoprene units, 40 Carbon atoms
• Rubber: >100 Isoprene units, >500 Carbon atoms
• Mono-, sesqui-, di-, and sesterpenes contain the isoprene units linked in a head to tail fashion.
• The triterpenes and carotenoids (tetraterpenes) contain two C15 and C20 units respectively linked head to head.
• Many terpenes are hydrocarbons, but oxygen-containing compounds include alcohols, aldehydes or ketones.
• These derivatives are called terpenoids.
• Mono- and sesquiterpenes are chief constituents of essential oils.
• Other terpenes are constituents of balsams, resins, waxes, and rubber.

Importance of Terpenes

• Terpenoids are naturally-occurring organic chemicals derived from five-carbon isoprene units assembled and modified in thousands of ways.
• Most are multicyclic structures differing not only in functional groups but also in their basic carbon skeletons that can be found in all classes of living things and are the largest group of natural products.
• Oleoresin is a roughly equal mixture of turpentine (85% C10-monoterpenes and 15% C15-sesquiterpenes) and resin (C20-diterpene).
• It acts in many conifer species to seal wounds and is toxic to both invading insects and their pathogenic. A number of inducible terpenoid defensive compounds (phytoalexins) from angiosperm species are well.
• These include both sesquiterpenoid and diterpenoid types.
• Isoprenoid units are also found within the framework of other natural molecules.
• Indole alkaloids, several quinones (vitamin K), alcohols (vitamin E, vitamin A formed from β-carotene), phenols, isoprenoid alcohols (also known as terpenols or polyprenols) also contain terpenoid fragments.
• The origin of the ubiquitous isoprene unit and its conversion into various compounds has been extensively studied.
• Terpenes are produced primarily by a wide variety of plants, which emit terpene from their osmeterium. They are the major components of resin, and of turpentine produced from resin; and terpenes are major biosynthetic building blocks.
• Terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers.
• Essential oils are used widely as natural flavor additives for food, as fragrances in perfumery, and in traditional and alternative medicines such as aromatherapy.
• Synthetic variations and derivatives of natural terpenes and terpenoids greatly expand the variety of aromas used in perfumery and flavors used in food additives.
• The aroma and flavor of hops, highly desirable in some beers, comes from terpenes.
• Plant terpenoids are used extensively for their aromatic qualities.
• They play a role in traditional herbal remedies and are under investigation for antibacterial, antineoplastic, and other pharmaceutical functions, and they contribute to the scent of eucalyptus, the flavors of cinnamon, cloves, and ginger, and the color of yellow flowers Known terpenoids include citral, menthol, camphor, salvinorin A, and the cannabinoids found in cannabis.

Conclusion

• The terpenoids, or isoprenoids, are a varied class of naturally-occurring chemicals derived from isoprene units assembled and modified.
• These lipids can be found in all classes of living things, and are the largest group of natural products.

Summary

• Terpenoids may be defined as a group of molecules whose structure is based on a various but definite number of isoprene units.
• The name 'terpene' was proposed by Dumas in 1866.
• Terpenes can be synthesized from two pathway; mevalonic acid pathway and the non-mevalonate pathway.
• Terpenes are a class of organic compounds, produced primarily by a wide variety of plants and some animals like insects