Zur Kenntnis der Triterpene. 190. Mitteilung. Eine stereochemische Interpretation der biogenetischen Isoprenregel bei den Triterpenen

Abstract

The biogenetic isoprene rule in its application to the triterpenes is discussed from a stereochemical standpoint. On the basis of a well defined system of arbitrary assumptions a scheme has been developed leading from squalene to the formulae of the basic representatives of all known cyclic triterpene groups ‐ i.e. euphol, tirucallol, lupeol, taraxasterol, germanicol, β‐amyrin, taraxerol, friedelin, α‐amyrin, lanosterol ‐ in their full structural and configurational detail. This result is considered to support the squalene hypothesis of the biogenesis of cyclic triterpenes.

Enzymatic cyclization of all‐trans pentaprenyl and hexaprenyl methyl ethers by a cell‐free system from the protozoon Tetrahymena pyriformis

“…According to Ruzicka's biogenetic isoprene rule, the scalarane stereochemistry of ether (2) is the expected one, since it derives from the cyclization of an allchair folded pentaprenyl ether, i.e. from a conformation similar to the folding adopted for squalene cyclization into tetrahymanol [25]. Concerning the stereochemistry of the cyclization products of hexaprenyl methyl ether (3), a striking problem appears.…”

The biosynthesis of polyisoprenoids

“…In 1955, not long after squalene was established as a precursor of cholesterol, Ruzicka and his colleagues published a paper 53 which might be termed the apotheosis of the isoprene rule. Essentially, the cyclizations of squalene were pictured as reactions of an electron-deficient centre with the available electrons of a double bond.…”

“…A series of four I ,2-shifts is then possible, two hydrogen atoms and two methyl groups migrating; and finally the positive charge is lost as a proton from C-9, leaving lanosterol. This cyclization of squalene to lanosterol is represented ( after Eschenmoser et al 53 ) …”

Contiguous Stereogenic Quaternary Carbons: A Daunting Challenge in Natural Products Synthesis

“…Stimulated by the initial insight of Stork and Burgstahler (2) and Eschenmoser et al (3) and the seminal systematic investigations of the Johnson school (4), biomimetic cascade cyclizations of acyclic precursors is now a deep-rooted synthesis strategy. We will look at two biomimetic total syntheses, from the laboratories of Corey and Heathcock, in which cascade cyclizations were used to forge contiguous quaternary carbon stereocenters.…”

“…Alkylation of 38 with allylic bromide 39 provides the thio-Claisen rearrangement substrate 40. At 90°C in dimethylformamide (DMF), this N,S-ketene acetal undergoes [3,3]-sigmatropic rearrangement to produce thiolactam 41 as a single diastereomer (26). However, because of the steric destabilization associated with joining two qua- ternary carbons, product 41 is only slightly favored (36:64) in the apparent thermodynamic equilibrium set up between 40 and 41 under these conditions (27).…”