Isoprene rule

The German chemist Otto Wallach (Nobel Prize m chemistry 1910) determined the structures of many terpenes and is credited with setting forth the isoprene rule ter penes are repeating assemblies of isoprene units normally joined head to tail... 

Terpenes are said to have structures that follow the isoprene rule in that they can be viewed as collections of isoprene units... 

Cholesterol was isolated in the eighteenth century, but its structure is so complex that its conect constitution was not determined until 1932 and its stereochemistry not verified until 1955. Steroids are characterized by the tetracyclic ring system shown in Figure 26.9a. As shown in Figure 26.9b, cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C-3, a double bond at C-5, methyl groups at C-10 and C-13, and a C Hiv side chain at C-17. Isoprene units may be discerned in various portions of the cholesterol molecule, but the overall conespondence with the isoprene rule is far- from perfect. Indeed, cholesterol has only 27 carbon atoms, three too few for it to be classed as a tr-iterpene. 

Regardless of Llieu apparent structural differences, all terpenoids are related. According to a formalism called the isoprene rule, they can be thought of as arising from head-to-tail joining of 5-carbon isoprene units (2-methyl-1,3-butadiene). Carbon 1 is the head of the isoprene unit, and carbon 4 is the tail. For example, myreene contains two isoprene units joined head to tail, forming an 8-carbon chain with two 1-carbon branches. a-Pinene similarly contains two isoprene units assembled into a more complex cyclic structure, and humulene contains three isoprene units. See if you can identify the isoprene units in a -pinene and humulene. 

Isoprene rule (Chapter 6 Focus On) An observation to the effect that terpenoids appear to be made up of isoprene (2-methvl-l,3-butadiene) units connected head-to-tail. 

Bloch therefore suggested isoprene units could be condensed first to give squalene and then cholesterol, an extension of Ruzicka s isoprene rule for the biosynthesis of linear and cyclic terpenoids. It was then necessary to show that selectively labeled 14C-acetate could get incorporated into squalene with the correct distribution of 14C and that this squalene could give rise to cholesterol, also with the appropriate position of the 14C label. 

Incorporating partial structures (a) and (b) into the ring and consideration of the isoprene rule leads to the assignment of structure IV as the basic skeleton for compound III. 

Terpenoids are compounds derived from a combination of two or more isoprene units. Isoprene is a five carbon unit, chemically known as 2-methyl-1,3-butadiene. According to the isoprene rule proposed by Leopold Ruzicka, terpenoids arise from head-to-tail joining of isoprene units. Carbon 1 is called the head and carbon 4 is the tail . For example, myrcene is a simple 10-carbon-containing terpenoid formed from the head-to-tail union of two isoprene units as follows. 

The all-tra 5 -squalene (C30H50), discovered in shark liver oil in the 1920s, is a triterpene, but one in which the isoprene rule at violated in one point. Rather than a head-to-tail arrangement of six units of isoprene, there appear to be farnesyl units that have been connected tail to tail. Almost aU steroids are biosynthesized from cholesterol. Cholesterol is biosynthesized from squalene, which is first converted to lanosterol. The conversion of squalene to the steroid skeleton is an oxirane, squalene-2,3-oxide, which is transformed by enzymes into lanosterol, a steroid alcohol naturally found in wool fat. The whole process is highly stereoselective. 

Exercise 30-1 a. Write out all of the possible carbon skeletons for acyclic terpene and sesquiterpene hydrocarbons that follow the isoprene rule. Do not consider doublebond position isomers. 

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