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Organic Chemistry
Table of Contents
Unit 27 Overview: Biomolecules
27.1 Waxes, Fats, and Oils
27.2 Soap
27.3 Phospholipids
27.4 Prostaglandins and Other Eicosanoids
27.5 Terpenoids
27.6 Steroids
27.7 Biosynthesis of Steroids

Terpenoids are fascinating compounds found in plants, playing crucial roles in defense and communication. They're built from simple building blocks like IPP and DMAPP, which combine to form larger molecules through enzymatic reactions.

The biosynthesis of terpenoids involves a series of steps, including phosphorylation and decarboxylation. These processes create diverse structures, from simple monoterpenes like limonene to complex diterpenes like taxadiene, each with unique properties and functions.

Terpenoid Biosynthesis and Reactions

Terpenoid biosynthesis pathway

  • Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) serve as the fundamental building blocks for terpenoids (also known as isoprenoids)
    • IPP and DMAPP are structural isomers that can be interconverted by an isomerase enzyme
    • DMAPP is generated from IPP through the action of this isomerase
  • Prenyltransferase enzymes catalyze the sequential addition of IPP units to DMAPP, generating larger terpenoid precursor molecules
    • Geranyl diphosphate (GPP, C10) is produced by the addition of one IPP unit to DMAPP (monoterpene precursor)
    • Farnesyl diphosphate (FPP, C15) is formed by the addition of two IPP units to DMAPP (sesquiterpene precursor)
    • Geranylgeranyl diphosphate (GGPP, C20) is synthesized by the addition of three IPP units to DMAPP (diterpene precursor)
  • Terpene synthase enzymes convert GPP, FPP, and GGPP into their respective terpene classes: monoterpenes (C10), sesquiterpenes (C15), and diterpenes (C20)
    • These enzymes catalyze a variety of reactions, including cyclization, rearrangements, and other structural modifications to generate the diverse array of terpenoid compounds
    • Examples of terpene synthase products include limonene (monoterpene), farnesene (sesquiterpene), and taxadiene (diterpene)

Mevalonate to isopentenyl diphosphate conversion

  • Mevalonate undergoes phosphorylation by the enzyme mevalonate kinase, yielding mevalonate 5-phosphate
    • This reaction utilizes ATP as the phosphate donor molecule
  • Mevalonate 5-phosphate is further phosphorylated by phosphomevalonate kinase, producing mevalonate 5-diphosphate
    • ATP serves as the phosphate donor in this second phosphorylation step
  • Mevalonate 5-diphosphate undergoes an ATP-dependent decarboxylation reaction catalyzed by diphosphomevalonate decarboxylase, generating isopentenyl diphosphate (IPP)
    • This decarboxylation reaction proceeds through a carbocation intermediate species
    • The loss of carbon dioxide drives the formation of the reactive carbocation

Mechanisms of monoterpenoid cyclization

  • Monoterpene cyclization is initiated by the formation of a carbocation from geranyl diphosphate (GPP)
    • The diphosphate group is eliminated, generating a resonance-stabilized allylic carbocation intermediate
  • The allylic carbocation undergoes a 1,6-cyclization reaction, forming a six-membered ring structure and a new tertiary carbocation
    • This cyclization step is driven by the formation of a more stable tertiary carbocation species
  • The resulting tertiary carbocation can undergo various rearrangements and modifications, depending on the specific monoterpene synthase enzyme involved
    • Hydride shifts and alkyl migrations can occur, leading to the formation of different carbocation intermediates
    • Proton elimination from the carbocation can generate a double bond, yielding the final monoterpene product
  • Examples of monoterpene cyclization products include:
    1. Limonene: formed by a 1,6-cyclization followed by proton elimination (found in citrus fruits)
    2. Menthol: generated by a 1,6-cyclization, hydride shift, and stereospecific reduction of the carbocation (key component of peppermint oil)
    3. $\alpha$-Pinene and $\beta$-pinene: produced by a 1,6-cyclization followed by a Wagner-Meerwein rearrangement and proton elimination (found in pine resin and turpentine)

Terpenoids as Natural Products and Secondary Metabolites

  • Terpenoids are a diverse class of natural products derived from terpenes
  • They are produced through biosynthesis in various organisms, particularly plants
  • Terpenoids function as secondary metabolites, playing important roles in plant defense, communication, and attraction of pollinators
  • The structural diversity of terpenoids arises from various enzymatic modifications, including:
    • Cyclization reactions that form complex ring systems
    • Rearrangement reactions that alter carbon skeletons
    • Oxidation, reduction, and other functional group modifications

Key Terms to Review (54)

Silyl ether: Silyl ethers are compounds formed by the reaction of alcohols with silyl chlorides, effectively protecting the alcohol group by replacing the hydrogen atom bonded to oxygen with a silyl group. This protection method is widely used in organic synthesis to prevent undesirable reactions at the alcohol site during subsequent chemical reactions.
Isoprene rule: The Isoprene Rule, also known as the Biogenetic Isoprene Rule, is a principle in organic chemistry that explains how natural rubber and various other terpenes are biosynthesized from isoprene units. It suggests that these complex natural products can be conceptualized as being constructed from the joining of several isoprene (C5H8) units in a head-to-tail fashion.
Sigmatropic rearrangement: Sigmatropic rearrangement is a type of pericyclic reaction in organic chemistry where a sigma bond (σ-bond) adjacent to a pi system (π-system) migrates from one position to another, simultaneously affecting the positions of π-electrons. This migration is guided by specific orbital symmetries that allow the reaction to proceed without the need for external reagents.
Sesquiterpenoids: Sesquiterpenoids are a class of terpenes that consist of three isoprene units, resulting in molecules with 15 carbon atoms. They are widely found in plants and some animals, serving various biological functions such as defense mechanisms or signaling molecules.
Mass spectrometry (MS): Mass spectrometry is an analytical technique used in organic chemistry to determine the mass-to-charge ratio of ions. It helps identify the composition of a sample by generating ions and measuring their mass and charge.
Carbonyl: The carbonyl group is a functional group consisting of a carbon atom double-bonded to an oxygen atom. It is a key structural feature in many organic compounds, including aldehydes, ketones, carboxylic acids, and esters, and plays a crucial role in their chemical reactivity and properties.
Carbocation: A carbocation is a positively charged carbon atom that is part of an organic molecule. These reactive intermediates play a crucial role in various organic reactions, including electrophilic additions, nucleophilic substitutions, and elimination reactions.
Rearrangement: Rearrangement refers to the process in organic chemistry where the structure of a molecule is reorganized, often through the formation of a carbocation intermediate, resulting in the generation of a new product with a different arrangement of atoms compared to the original reactant.
Hydride Shift: A hydride shift is a type of rearrangement reaction in organic chemistry where a hydride ion (H-) moves from one carbon atom to an adjacent carbon atom within a molecule. This process is often observed in the context of carbocation intermediates and plays a crucial role in various organic reactions.
Cyclization: Cyclization is the process of forming a cyclic structure from an acyclic precursor molecule. This term is particularly relevant in the context of various organic chemistry reactions and processes, where the formation of rings plays a crucial role in the synthesis of complex molecules and the understanding of biological systems.
Wagner-Meerwein Rearrangement: The Wagner-Meerwein rearrangement is a type of carbocation rearrangement that occurs during certain organic reactions, particularly the SN1 reaction and in the biosynthesis of terpenoids. It involves the migration of a substituent group from one carbon to an adjacent carbocation, resulting in the formation of a more stable carbocation intermediate.
Geranyl Diphosphate: Geranyl diphosphate is a key intermediate in the biosynthesis of many terpenoid compounds, serving as a precursor for the formation of various monoterpenes, sesquiterpenes, and diterpenes. It is an important building block in the diverse array of terpenoid natural products found in living organisms.
Mass Spectrometry: Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of ions to identify and quantify the chemical composition of a sample. It provides detailed information about the molecular structure and fragmentation patterns of compounds, making it a powerful tool in organic chemistry and various other fields.
Isoprene: Isoprene is a simple hydrocarbon molecule that serves as the fundamental building block for a diverse group of organic compounds known as terpenoids, which are prevalent in natural rubber and many essential oils. This versatile molecule is also a key precursor in the synthesis of various diene polymers, including natural and synthetic rubbers.
Geranylgeranyl Diphosphate: Geranylgeranyl diphosphate is a key intermediate in the biosynthesis of various terpenoid compounds, including carotenoids, chlorophyll, and certain plant hormones. It also plays a role in the Friedel-Crafts alkylation and acylation reactions of aromatic rings.
Ether: An ether is a functional group in organic chemistry that consists of an oxygen atom connected to two alkyl or aryl groups. Ethers are widely encountered in various organic compounds, including those found in the contexts of trisubstituted benzenes and terpenoids.
Hydroxyl: The hydroxyl group (–OH) is a functional group consisting of a hydrogen atom bonded to an oxygen atom. It is a key structural feature in many organic compounds and plays a crucial role in various chemical reactions and biological processes.
Monoterpenes: Monoterpenes are a class of terpenes, which are a large and diverse group of organic compounds found in many plants. Monoterpenes are the simplest terpenes, consisting of two isoprene units and having the molecular formula C10H16. They are commonly found in essential oils and contribute to the distinctive aromas and flavors of many plants.
Diterpenes: Diterpenes are a class of organic compounds that belong to the terpenoid family. They are characterized by the presence of four isoprene units, resulting in a 20-carbon skeleton structure. Diterpenes are found in a variety of natural sources, including plants, fungi, and some marine organisms, and they exhibit a wide range of biological activities and applications.
Camphor: Camphor is a naturally occurring organic compound that is extracted from the wood of the camphor laurel tree. It is a waxy, flammable substance with a distinct, pungent odor and is widely used in various industries, including medicine, cosmetics, and as a food additive.
Isoprene Rule: The isoprene rule is a fundamental principle in organic chemistry that describes the structure and biosynthesis of terpenoid compounds. It states that terpenoids are constructed from isoprene units, which are five-carbon molecules with a specific arrangement of carbon-carbon double bonds.
Plant Defense: Plant defense refers to the various mechanisms and strategies employed by plants to protect themselves from herbivores, pathogens, and other environmental stresses. These defense mechanisms are crucial for the survival and fitness of plants in their natural habitats.
Isomerase: Isomerase is an enzyme that catalyzes the conversion of one isomer of a compound into another isomer. These enzymes play a crucial role in the metabolism of terpenoids, a class of organic compounds found in plants and animals.
$\beta$-pinene: $\beta$-pinene is a naturally occurring bicyclic monoterpene found in the essential oils of various plants. It is an important compound in the context of terpenoids, a diverse class of organic compounds that serve crucial roles in plant metabolism and defense mechanisms.
Natural Products: Natural products are chemical compounds that are produced by living organisms, such as plants, animals, and microorganisms. These compounds are often used in various applications, including medicine, agriculture, and industry, due to their unique properties and potential benefits.
Terpenoids: Terpenoids, also known as isoprenoids, are a diverse class of organic compounds derived from the combination of several isoprene units. They are found in a wide variety of plants and are responsible for many of the characteristic aromas and flavors associated with various herbs, spices, and essential oils.
Cyclic Structure: A cyclic structure is a molecular arrangement in which atoms are connected in a closed loop, forming a ring. This structural feature is commonly observed in organic compounds and plays a crucial role in the context of terpenoids, a class of natural products.
Prenyltransferase: Prenyltransferases are a class of enzymes that catalyze the addition of prenyl groups, such as isopentenyl pyrophosphate (IPP) or dimethylallyl pyrophosphate (DMAPP), to various acceptor molecules. These enzymes play a crucial role in the biosynthesis of terpenoids, an important class of natural products.
Gas Chromatography: Gas chromatography (GC) is an analytical technique used to separate, identify, and quantify individual components in a complex mixture of gases or volatile liquid samples. It relies on the partitioning of analytes between a stationary phase and a mobile phase to achieve separation and detection.
Isoprene Unit: The isoprene unit is a fundamental building block of terpenoid compounds, which are a diverse class of organic molecules found in nature. It consists of a five-carbon skeleton with a double bond, and serves as the repeating structural motif for the synthesis of larger and more complex terpenoid structures.
Farnesyl Diphosphate: Farnesyl diphosphate is a key intermediate in the biosynthesis of various terpenoid compounds, including steroids. It is an essential precursor molecule that serves as the starting point for the production of a wide range of biologically important molecules.
Taxadiene: Taxadiene is a key intermediate in the biosynthesis of the important anticancer compound paclitaxel (Taxol®) in the Pacific yew tree. It is a tetracyclic diterpene that serves as a precursor for the formation of the complex taxane ring system found in paclitaxel and related taxanes.
Secondary Metabolites: Secondary metabolites are organic compounds produced by plants, fungi, and some bacteria that are not directly involved in the organism's growth, development, or reproduction. Unlike primary metabolites, which are essential for survival, secondary metabolites are often specialized compounds that serve ecological functions such as defense, signaling, and competition.
Biosynthesis: Biosynthesis is the process by which living organisms, such as plants and animals, produce complex chemical compounds from simpler precursor molecules. It is a crucial aspect of biological chemistry that underlies the formation of essential biomolecules, including prostaglandins, terpenoids, and steroids.
Phosphomevalonate Kinase: Phosphomevalonate kinase is an enzyme that plays a crucial role in the mevalonate pathway, which is the primary biosynthetic route for the production of terpenoids, a diverse class of organic compounds found in many living organisms.
Allylic Carbocation: An allylic carbocation is a positively charged carbon atom that is adjacent to a carbon-carbon double bond. These reactive intermediates are important in many organic reactions, particularly those involving terpenoids.
1,6-Cyclization: 1,6-Cyclization is a key reaction in the biosynthesis of terpenoids, a diverse class of natural products. It involves the formation of a six-membered ring structure from a linear precursor through the intramolecular cyclization of a carbon-carbon double bond and a nucleophilic functional group, often an alcohol or an ether.
Farnesene: Farnesene is a class of naturally occurring organic compounds classified as sesquiterpenes, which are a type of terpene. Terpenes are a large and diverse group of organic compounds found in many plants and some insects, and they play important roles in various biological processes.
Terpenes: Terpenes are a large and diverse class of organic compounds found in plants, fungi, and some insects. They are characterized by their distinctive aroma and are often responsible for the fragrance and flavor of various natural products.
Limonene: Limonene is a naturally occurring organic compound that is classified as a terpene. It is the primary constituent of the oil extracted from citrus fruit rinds and is responsible for the distinct citrus aroma and flavor.
Diphosphomevalonate Decarboxylase: Diphosphomevalonate decarboxylase is an enzyme involved in the terpenoid biosynthesis pathway. It catalyzes the decarboxylation and dehydration of 5-diphosphomevalonate to isopentenyl diphosphate, a crucial step in the production of various terpenoid compounds.
Alkyl Migration: Alkyl migration is a rearrangement reaction in organic chemistry where an alkyl group (a hydrocarbon chain) shifts its position within a molecule. This process is particularly important in the context of terpenoid compounds, which are a class of naturally occurring organic chemicals.
Mevalonic Acid Pathway: The mevalonic acid pathway, also known as the isoprenoid biosynthesis pathway, is a metabolic pathway that produces isoprene units, which are the building blocks for the synthesis of various terpenoid compounds, including cholesterol, steroid hormones, and other important biomolecules.
Terpene Synthase: Terpene synthase is a family of enzymes responsible for the biosynthesis of terpenes, a diverse class of organic compounds found in plants and other organisms. These enzymes catalyze the cyclization and rearrangement of linear prenyl diphosphate substrates, leading to the formation of a wide variety of terpene structures.
$\alpha$-pinene: $\alpha$-pinene is a bicyclic monoterpene hydrocarbon that is a major constituent of the essential oils of many plants, particularly coniferous trees. It is known for its distinctive pine-like aroma and is widely used in the fragrance and flavor industries.
Isopentenyl Diphosphate: Isopentenyl diphosphate (IPP) is a key intermediate in the biosynthesis of terpenoids, a large and diverse class of organic compounds found in many living organisms. It serves as the fundamental building block for the synthesis of various terpene molecules, which play crucial roles in diverse biological processes.
Sesquiterpenes: Sesquiterpenes are a class of organic compounds that are composed of three isoprene units, resulting in a total of 15 carbon atoms. They are part of the larger group of terpenoids, which are a diverse family of natural products found in plants and some animals.
Menthol: Menthol is a naturally occurring organic compound found in various mint plants, such as peppermint and spearmint. It is known for its distinctive minty aroma and cooling sensation, making it a widely used ingredient in various products, including personal care items, pharmaceuticals, and food flavorings.
Head-to-Tail Condensation: Head-to-tail condensation is a fundamental process in the biosynthesis of terpenoids, where two molecules are joined together in a specific orientation to form a larger molecule. This process is crucial for the formation of the characteristic carbon skeletons found in various terpenoid compounds.
Insect Pheromones: Insect pheromones are chemical signals released by insects to communicate with members of the same species. These volatile organic compounds play a crucial role in various aspects of insect behavior and ecology, including mating, aggregation, alarm, and trail-marking.
Dimethylallyl Diphosphate: Dimethylallyl diphosphate (DMAPP) is a key intermediate in the biosynthesis of terpenoids, a diverse class of organic compounds found in plants and other organisms. It serves as a building block for the synthesis of various terpene-based molecules, including those involved in plant metabolism and defense mechanisms.
MEP Pathway: The MEP (Methylerythritol Phosphate) pathway, also known as the non-mevalonate pathway, is an alternative metabolic route for the biosynthesis of isoprenoids, a diverse class of organic compounds that includes terpenoids. This pathway is found in many bacteria, plants, and some protists, and serves as an important source of essential biomolecules such as carotenoids, chlorophyll, and certain hormones.
Mevalonate Kinase: Mevalonate kinase is a key enzyme involved in the mevalonate pathway, which is a crucial metabolic pathway responsible for the biosynthesis of various terpenoid compounds, including cholesterol, steroid hormones, and other important biomolecules.
Isoprenoids: Isoprenoids are a diverse class of organic compounds derived from the five-carbon building block isoprene. They are a fundamental part of the terpenoid family and play crucial roles in various biological processes within living organisms.