Terpenoids stereochemistry

The possibility of nucleophilic attack on different carbons in the resonance-stabilized carbocation facilitates another modification exploited by nature during terpenoid metabolism. This is a change in double-bond stereochemistry in the allylic system. The interconversions of geranyl diphosphate, linalyl diphosphate, and neryl diphosphate provide neat but satisfying examples of the chemistry of simple allylic carbocations. 

Polyene cyclizations have been of substantial value in the synthesis of polycyclic natural products of the terpene type. These syntheses resemble the processes by which terpenoid and steroidal compounds are assembled in nature. The most dramatic example of biological synthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, the enzyme presumably functions not only to induce the cationic cyclization but also to bind the substrate in a conformation corresponding to the stereochemistry of the polycyclic product.21... 

CoEuparing the different molecular frameworks of natural products with one another poses several problems. The method of choice depends on the intents, which, for an approach to nature as in this book, differ from synthetic strategies (Chanon 1998). First, the drawing of the molecular skeletons is curtailed to the essential, reducing all carbon-carbon bonds to single bonds and disregarding the stereochemistry, except crossed bonds for reasons of clarity. This means that stereochemical series, such as the e r-forms of terpenoids, do not show up. 

P- (1) Indicates above-the-plane stereochemistry in steroids, terpenoids, etc., e.g., 5p-pregnane. 

Stereochemistry often is an integral component to both the chemical structure and the biological function of plant terpenoids. For volatile terpenoids, chiral GC stationary phases (48) provide the enantiomeric separation for quantitative analysis, and, provided an authentic standard of known absolute... 

Independent synthesis of the identified terpenoid is often required to confirm structural assignment (51) and to test the biological and/or pharmacological functions. In addition, biosynthetic studies often require the synthesis of putative precursors for functional characterization of enzymes. Terpenoid stractures challenge chemists in many of the same ways that other natural products do. Their structural diversity (complicated by stereochemistry, carbocyclic skeletons, and often multiple functionalization) provides opportunities for synthetic organic chemists to develop new methodologies for synthesis. Recently, Mai-mone and Baran (52) have reviewed some synthetic challenges terpenoids present and the solutions employed. 

Although the biochemical functions and the stereochemistry of the enzyme active sites are completely established, and many natural and synthetic compounds have been assayed for their inhibitory activity, there is no an unique or preferred structural t5q>e for the highest effectiveness. In this review we have classified the active compounds in phenolics, terpenoids, alkaloids, and other principles. 

The novel heliannane-type sesquiterpenoid (-)-heliannuol E was synthesized in the laboratory of K. Shishido. Interest in the total synthesis of this natural product was not only spurred by its irregular terpenoid structure and significant biological activity but the need to establish the absolute stereochemistry at the C2 and C4 stereocenters. The Sonogashira reaction was utilized to prepare the 3-arylpropargyl alcohol by coupling of a heavily substituted aryl iodide with an unprotected propargyl alcohol in quantitative yield. 

The absolute stereochemistry of mukulol (79) has been determined." The variation in 4,8,13-duvatrienediol content of tobacco leaves has been studied. " Young plants contain the highest concentration. Many terpenoid degradation products of these macrocyclic diterpenoids have been isolated from tobacco leaves. The absolute configurations of some of these, e.g. (80), have been determined. Ovatodiolide (81) and anisomelic acid (82) are two diterpenoid lactones which have been isolated from Anisomeles malabarica (Labiatae). Pukalide (83) is a furanocembranolide which has been obtained from the soft coral Simularia... 

In summary, these important investigations have rationalized the stereochemistry of the 1,3-hydride shift (which transfers a positive centre from C-10 or C-11 at the distal end of FPP to C-1 and so allows initiation of further isomerization or a second cyclization of the Cio or Ci i ring) on the basis of the ring size of the products. This presumably results from fixation of specific conformations of the intermediates on a hypothetical enzyme surface. The larger diversity of structure for sesquiterpenoids than for di- or tri-terpenoids could then reflect the larger conformational flexibility of a Cio or Cii ring (which are often involved in the formation of the former) than of the Ce rings that are usually implicated in the latter. 

A full report of the c.d. of steroidal diol bis-(p-dimethylaminobenzoates) confirms the reliability of theoretical calculations of the coupled Cotton effects of the remote ester groups (exciton chirality method). The c.d. curves show two maxima of opposite signs, separated by some 27 nm, and with intensity inversely proportional to the square of the interchromophore distance. The profile of the observed c.d. curve results from the superimposition of two component curves, each of asymmetric shape.A review of the uses of chiroptical techniques for structural and conformational studies includes examples of the assignment of stereochemistry to steroids and terpenoids, among a wide variety of natural products. The Octant Rule for carbonyl compounds and the rules applicable to other chromophoric systems are discussed critically. 

Terpenoid biosynthesis stereochemistry of the cyclization of allylic pyrophosphates, D.E. Cane, Acc. Chem. Res., 1985, 18, 220. 

The racemic lactone ( )-18 was obtained as a pure and crystalline compound, and its relative stereochemistry had to be determined. I thought, in 1960, XH NMR analysis to be the most appropriate method to solve the problem, because it had already been known to use a vicinal coupling constant for the stereochemical studies of cyclohexane compounds including terpenoids and steroids. Figures 1.13(a) and (b)... 

C]mevalonic acid. This stereochemistry is presumably retained in the C-4 alkylated tryptophane derivative (see also claviceptic acid ) which precedes chanoclavine I (14). When the stereochemistry is reversed to give (14) the 9-H, labelled by [2- C,3/ ,4/ - H]mevalonic acid, is retained. However, in the second reversal (15)—>(16) there is a significant loss of this hydrogen atom. Elemo-clavine is one of the few terpenoids for which it has been proved that only the (3/ )-enantiomer of mevalonic acid is metabolised (see footnote p. 224). 

---