Robinson hypothesis

Whereas squalene has 30 carbons, cholesterol has only 27 carbons, and other steroids have even fewer carbons. Therefore degradation must accompany (or follow) cyclization. Robinson was the first to propose a manner in which squalene might cyclize to provide the tetracyclic ring system of the steroids. This was followed by an alternate hypothesis by Bloch and Woodward. The two proposals suggest different labelling patterns in tetracyclic products. For example, if one thinks about cholesterol as the product, the two proposals suggest that the black methyl groups would have to be lost. These are different for the two proposals. Experiments eventually disproved the Robinson hypothesis and supported the Bloch-Woodward hypothesis. For an eariy experiment see Woodward,... 

L-tryptophan is compulsory, the biosynthetic machinery displays wide latitude in its ability to condense a second auxiliary amino acid—L-alanine in the case of (+)-ll,ll -dideoxyverticillin A (1)—to afford a tryptophan-derived diketopiperazine intermediate 13. Mirroring Woodward and Robinson s biogenetic hypothesis for the calycanthaceous alkaloids, single-electron oxidation of the electron-rich tryptophan residue would likely initiate an oxidative dimerization of the diketopiperazine precursor with concomitant cyclization to yield the octacyclic intermediate 17. Subsequent A-methylation of the amides would then yield an unembellished skeletal core of the dimeric epipolythiodiketopiperazine alkaloids. The first step en route... 

He suggested that the ionic formulas, like the nonionic formulas, "represent formulations of extremes" and that no bond across the ring is required. Using the hypothesis of the motions of valence electrons, as developed by Stark and Kossel, Arndt suggested the possibility of intermediate valence states (Zwitterstufen) as well.32 Independently, Robinson proposed possible electronic shifts in pyrones and similar systems, but he did not state the idea of a definite "intermediate state" of the molecule between the ionic and uncharged formulas.33... 

Robinson (J. C. S., 113, 639 125, 827) has put forward the hypothesis that the fundamental reactions involved are, in succession, a rearrangement to an unsaturated hydrazine, an isomeric change of the o-benzidine type, and finally the elimination of ammonia from the resulting diamine ... 

ADDITION TO CHAPTER XXVIII An oxidation theory of the biogenesis of thebaine was briefly advanced by Robinson in 1948 and reference was made to the formation of bis-nor-laudano sine alkaloids such as oxyacanthine as affording some help in regard to the nuclear oxidations required for the above hypothesis . Robinson added, The formation of such diphenyl ethers is clearly an oxidative process it can of course be imitated in the laboratory in various ways on much simpler substances [5]. This discussion of the problem pre-dates the more elaborate theory outlined by Schop f. 

Although Robinson s pyrrolidine formula (XV) for strychnine serves admirably as a working hypothesis for the interpretation of the various reactions, several pieces of experimental evidence appear to be incompatible with attachment of the carbon end of the ethanamine chain at C4. At 100° bromine in hydrobromic acid attacks the ethenoid linkage of 2,3-dioxonucidine, but it has been reported (126) that bromine in water at 5° substitutes for one hydrogen atom. (It has been stated, without experimental confirmation, that the same holds true for 2,3-dioxodihydronucidine.) This has been interpreted by Leuchs as a bromination alpha to the ketone, which of necessity requires the location of a hydrogen at C4 (strychnine numbering) in 2,3-dioxonucidine and its dihydro derivative. Such an argument precludes the attachment of the ethanamine chain to C4 in strychnine. 

For a decade, a rival theory due to Slater (1955, 1959) provided considerable motivation for more detailed experimental as well as theoretical investigations. This, very interesting and elegant theory, which is discussed in more detail by Robinson and Holbrook (1972) and Nikitin (1974), as well as in chapter 8, is more akin to a dynamical than a statistical theory. Because the Slater theory treats the vibrations classically, it also requires the use of fewer oscillators to fit the experiment (sec fig. 1.1). Its flawed fundamental hypothesis that the molecule s modes were strictly harmonic, thereby preventing energy flow among them, and its failure to account quantitatively for the experimentally measured rates led to its being quickly overshadowed by the successes of the RRKM/QET theory. 

In 1917, Robert Robinson (1886-1975) published a one-pot synthesis of tropinone, a precursor of some tropane alkaloids, from addition of relatively simple molecules in aqueous solution. This synthesis made the tropane alkaloids much more accessible. Robinson came to suspect that the reaction he employed suggested the actual natural biosynthetic pathway for tropane syntheses. Nearly a century later, many chemists feel that Robinson s hypothesis was correct. 

This assumption is akin to the hypothesis of localised hydrolysis invoked by Robinson and Harned to explain the reversal of the order of activity coefficients of alkali metal hydroxides, fluorides, acetates and formates in water. 

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