Stereospecificity losses

The Corey-Winter olefin synthesis is based on the stereospecific loss of carbon dioxide or carbon disulfide from the carbenes formed by treatment with bivalent organophosphorus compounds of thionocarbonates or trithiocarbonates [218-220]. 

Papaverine.—The biosynthesis of the simple benzylisoquinoline papaverine (89) is known to proceed via nor-reticuline (48) and tetrahydropapaverine (88).71 Dehydrogenation of the latter affords papaverine, and examination of the stereochemistry of the processes involved has led to the conclusion72 that loss of the proton at C-3 [in nor-reticuline (48)] is stereospecific (loss of the pro-S hydrogen atom) but removal of the C-4 proton is essentially non-stereospecific. These observations are perhaps best explained if enzyme-catalysed oxidation of (88) occurs to give (90), subsequent non-stereospecific imine-enamine isomerization occurring without enzyme participation to give (91). A further amine to imine oxidation then occurs to give papaverine (89).72... 

The stereochemistry of the alkene product in Wittig reactions is thought to be influenced by the reversibility of formation of the isomeric threo and erythro oxaphosphetanes (or betaines) which undergo stereospecific loss of triphenyl-phosphine oxide to give the trans (E) and cis (Z) alkenes, respectively (Scheme 4). Factors that enhance the reversibility of this initial step favour the threo intermediate and hence the (E) alkene. Stabilized phosphoranes give a predominance of the (E) alkene while non-stabilized phosphoranes give the (Z) alkene. In general, stabilized phosphoranes react readily with aldehydes (see Protocol 4) while non-stabilized phosphoranes will react with aldehydes, hemiacetals (see Protocol 5) and ketones.2,3... 

Many steroid alcohols are readily converted into olefins by thionyl chloride or phosphorus oxychloride in pyridine. It has been amply demonstrated that the reaction involves stereospecific loss of an a i -coplanar proton, even if this results in formation of the less stable of the possible olefins. The reaction is thought to proceed through intermediate chloro-sulphite or dichlorophosphate esters, which suffer base-catalysed removal of a fraws-vicinal proton. 

Deuterioandrost-4-ene-3,17-dione (311) afforded the 4,6-dienone (313), with retention of deuterium, on treatment with chloranil, revealing stereospecific loss... 

The facts on the oxidation of the C32 aldehyde are remarkably similar to those seen for the aro-matase catalyzed reaction. The formate moiety that is expelled contains one dioxygen-derived oxygen atom and incorporates one oxygen and one hydrogen atom from the aldehyde precursor There is also a stereospecific loss of the syn 15a... 

Battersby et al. used (13S)- and (13R )-labeled scoulerine (58b) to study the biosynthesis of rhoeadine. Both of them were incorporated by living P. rhoeas plants into rhoeadine. This alkaloid, isolated from plants fed with (7J 5)-labeled scoulerine, had lost 79% of the tritium present in the precursor, whereas the (/37 )-labeled scoulerine afforded rhoeadine which retained 74% of the original tritium. Bearing in mind the configurational purity of the precursors, these values prove that a stereospecific loss of the pro-5-hydrogen occurs from C-13 of scoulerine at some stage of its transformation into rhoeadine. It seems likely from structural considerations... 

The biosynthesis of phytoene proceeds without reduction of prephytoene. The phytoene molecule therefore contains a central double bond. Phytoene synthases from different organisms either form cis- or trans-phytoene. Formation of cis-phytoene requires the stereospecific loss of the Hb in the postulated intermediate I, whereas removal of yields irans-phytoene (Fig. 95). 

A third and most significant study involves tracer experiments with Papaver rhoeas L. Both 135- and 13/ -tritium labeled scoulerines were incorporated into rhoeadine, but the rhoeadine isolated from plants fed with 135-labeled scoulerine had lost 19% of the tritium present in the precursor, whereas the 13/ -Iabeled scoulerine afforded rhoeadine which had retained 74% of the original tritium. A stereospecific loss of the pro-5 hydrogen must, therefore, have occurred from the C-13 of scoulerine at some specific stage of its biotransformation into rhoeadine. It seems likely that scoulerine is converted first into stylopine which is oxidized to 42. A-Methylation and rearrangement then provide the correct skeleton from which rhoeadine can arise... 

On the basis of the above hypothesis, cadaverine 6.26) assumed importance as a normal precursor for piperidine alkaloids, and it has been shown that its incorporation into A -methylpelletierine 6.19) involves stereospecific loss of one of the C-1 protons [the pro-S)-hydrogen atom] [17] this is accommodated within the model sequence. Decarboxylation of the lysine is also stereospecific (for the L, or S, isomer), but curiously the results indicate apparently that protonation of 6.25) in plants proceeds with opposite stereochemistry to that observed in micro-organisms [18]. 

Cinnamic acid (48) is synthesized universally in higher plants and widely in fungi from (25)-phenylalanine by phenylalanine ammonium lyase. This process is a trans elimination of the elements of ammonia, with stereospecific loss of the 3-pro S) proton of phenylalanine (46). Phenylpyruvic acid (49) (shown in its enol form) is the normal biogenetic precursor of phenylalanine, and is in equilibrium with it by means of the action of aminotransferases and amino acid oxidases (see Fig. 11). To distinguish between the participation of cinnamic acid (48) and phenylpyruvic acid (49) and to clarify the mechanism involved in the proton losses, (2R,35)-[3- H]-, (2S,3R)-[3- H], and (25)-[f/- C]phenylalanines were administered to the cultures. The incorporations resulted in the removal of 57% and 76%, respectively, of the labeled hydrogen. 

These results Indicate that there is a stereospecific loss of the hydrogen from the 5-side of C-6 in scoulerine in the conversion to chelidonlne). 

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