Poulter reaction

The synthesis of nucleoside diphosphates is best achieved using the Poulter reaction,9 which involves reaction of the tris(tetra-n-butylammonium) salt of pyrophosphate with a nucleoside 5 -tosylate in acetonitrile. A general procedure for the synthesis of nucleoside tosylates of thymidine and 2 -deoxyadenosine is included (Protocol 15), whilst the syntheses of the other tosylates (including ribonucleosides) have been described using related procedures. Simple modification of the protocol, whereby the tetra-n-butylammonium salt of pyrophosphoric acid is replaced by methylene or difluomethylene bis phosphonate, allows the synthesis of hydrolytically stable dNTP analogues.10... 

In the words of Poulter Moore of Stanford Research Institute (quoted in Ref 4, p 197) "A normal shock pulse traveling in an inert medium is continuously doing work on the medium thru which it is traveling, and hence is continuously being attenuated and therefore decelerated. A detonation is a true shock pulse, but one in which the energy lost in attenuation. is being replaced by the energy released by the chemical reaction associated with the detonation pro-... 

Poulter on luminosity) 305-06(Detn of temp by radiation and spectra methods) 384 (Discussion on work done at PicArsn on radiation of pyrotechnic compns) 386 (Effect of radiation from a shock wave in an atmosphere at ordinary pressure is negligible in comparison to an endothermic reaction capable of absorbing thousands of kcal per kg of air at 10000°K) 396 (Discussion on energy loss by radiation from the body of the gas mainly in the form "Bremsstrahlung produced when electrons are deflected by ions) 398, 400, 401 403 (More discussion on radiation) 14) Cook (1958), 97, 150-53, 155 158 15) M.A. Cook et al,... 

Spencer, The Determination of Reaction Rates of Nonideal Explosives from Shaped Charge Penetration Data , Univ of Utah Inst for Study of Rate Processes, TechRept No XLVIl(1955) Contract N7-onr-45107 46) R.J. Eichelberger, JApplPhys 26, 392-402(1955) (Re-examination of the unsteady theory of jet formation by lined cavity charges) 47) Ibid, 27, 63-8 (1956) (Experimental test of the theory of penetration by metallic jets) 48) T.C. Poulter ... 

Poulter, C.D., and Rilhng, H.C. (1978). The prenyl transfer reaction. Enzymatic and mechanistic studies of the l -4 coupling reaction in the terpene biosynthetic pathway. Acc Chem Res 11 307-313. 

Labadie, G.R., Wiswanathan, R., and Poulter, CD. (2007). Farnesyl diphosphate analogues with 6-bioorthogonal azide and alkyne functional groups for protein farnesyl transferase-catalyzed ligation reactions. J Org Chem 72 9291-9297. 

Thulasiram HV, Erickson HK, Poulter CD. Chimeras of two iso-prenoid synthases catalyze all four coupling reactions in isoprenoid biosynthesis. Science 2007 316 73-76. 

The investigations carried out in this area were done primarily to determine the magnitudes of steric and electronic effects on the solvolytic rates and products of reaction in the cyclopropylcarbinyl cation system. The goal of most of these studies was to learn more about the nature of the charge delocalization in the cyclopropylcarbinyl system and of the stereochemistry of the cyclopropylcarbinyl-cyclobutyl and cyclopropyl-carbinyl-allylcarbinyl cation rearrangements. Key papers in these studies were those in 1966 by Schleyer and Van Dine, in 1971 by Majerski and Schleyer and in 1974 by Poulter and Spillner which demonstrated that in the simple cyclopropylcarbinyl system... 

In two important papers Poulter et al. have published their results on the compelling evidence for a stepwise mechanism for the 1 -4 condensation reaction between isopentenyl pyrophosphate and geranyl pyrophosphate to form farnesyl... 

With the preceding reviews of the enzymology of monoterpene cyclization and of model studies relevant to the cyclization process, it is possible to formulate a unified stereochemical scheme for the enzymatic cyclization of geranyl pyrophosphate (Figure 4). The proposal which follows is consistent with the implications of parallel advances in related fields, most notably the contributions of Cane (8,16,24,25,52), Arigoni (67) and Coates (68,69) on the stereochemistry of sesquiterpene and diterpene cyclizations, and of Poulter and Rilling (29,70) on the stepwise, ionic mechanism of prenyl transferase, a reaction type of which several monoterpene, sesquiterpene and diterpene cyclizations are, in a sense, the intramolecular equivalents. 

Construction of the suitably substituted geranic acid for making the furan ring has been effected too. For example, Poulter et al. have prepared the substituted geranate 865 by reaction of 4-methyl-3-pentenylcopper with the acetylenic ester 866. The ester 865 then underwent cyclization in the presence of acid to the lactone 867, related to scobinolide (161), and the action of acid on the lactol produced from 867 with diisobutylaluminum hydride gave perillene (849). The lactone 867 has also been prepared by a slightly different method the C9 alcohol 868 was made (in poor yield) from isobutenol and prenyl chloride with butyllithium. The extra carbon atom was introduced by the action of sodium cyanide on the epoxide of 868, and hydrolysis of the cyano group followed by dehydration yielded the lactone 867. The dimethylthioacetal of 867 has been used to synthesize perillene (849). This thioacetal was made from the suitably substituted ketene thioacetal 869 and dimethylsulfonium methylide. Thus the ketene thioacetal 870 (readily prepared from acetone, carbon disulfide, and sodium amylate, followed by methylation °) can be prenylated with lithium... 

The early steps in the ergot alkaloid biosynthetic pathway are outlined in Fig. 1. The first determinant and rate-limiting step is the prenylation of tryptophan to 4-(y,y-dimethylallyl)tryptophan (DMAT), catalyzed by dimethy-lallyl-diphosphate L-tryptophan dimethylallyltransferase (DMAT synthase EC 2.5.1.34) (Heinstein et al., 1971 Gebler and Poulter, 1992). The prenyl group for the DMAT synthase reaction is provided in the form of dimethylallyl diphosphate (DMAPP), which is derived from mevalonic acid. After the formation of DMAT, the free amino group of this intermediate is N-methylated with a methyl group donated by S-adenosylmethionine (AdoMet). The N-methylated DMAT is then converted into chanoclavine I by closure of the... 

Further information about the carbonium ion intermediates in these systems comes from studies in which ammonium analogs of the carbonium ion are used as inhibitors. Poulter and co-workers 41, 42) have shown that in these reactions the ammonium analog is a very weak inhibitor, but in the presence of pyrophosphate ion, binding becomes dramatically stronger. In a molecule in which the pyrophosphate is covalently attached to form an internal ion pair, an extremely powerful inhibitor is generated. 

Poulter has reviewed the evidence supporting an ionization-condensation-elimination mechanism (Vol. 8, p. 24) in the prenyl-transfer reaction. 

Nerolidyl pyrophosphate does not serve as a precursor for squalene (Poulter and Rilling, 1981). The condensation requires NADPH in yeasts and, if this reductant is not present, famesyl pyrophosphate (8) accumulates. During the course of the reaction, two pyrophosphate groups are released, one hydrogen lost and one hydrogen replaced by a hydrogen from NADPH. One (15 )-hydrogen atom is removed from famesyl pyrophosphate. 

The first reaction involves a prenyl transfer step in which C(10 of one of the allylic substrates (the donor) is bonded to the C(2)-C(3) double bonds of the other (the receptor) to produce a cyclopropylcarbinyl diphosphate with a CV-2-3 structure (Poulter, 1990). In this manner, famesyl pyrophosphate (8) yields presqualene pyrophosphate (9). Only (/ )-presqualene pyrophosphate has been found in nature. 

In the second reaction, the latter compound rearranges to a T-1 stmcture with a saturated linkage between the two original famesyl residues in a series of steps that involve loss of inorganic pyrophosphate and incorporation of hydride from NADPH to yield squalene (4) (Poulter, 1990). 

The mechanism probably resembles that for prenylation of dimethylallyl pyrophosphate, geranyl pyrophosphate, and famesyl pyrophosphate to yield mono-, sesqui-, and diter-penes, respectively (Harrison, 1985). Mechanisms in which an X-group is involved, followed by a trans elimination and similar reactions, appear to be ruled out (Harrison, 1985 Poulter, 1990 Poulter et al, 1979). 

To rationalize these data, Floss et al. proposed the mechanism shown in Scheme 55 wherein a direct electrophilic aromatic substitution reaction from an enzyme-bound DMAPP ion pair species alkylates C-4 of the tryptophan nucleus [82]. The minor product, where partial loss of stereochemical integrity is sacrificed, was envisioned to occur via rotation around the C-l/C-2 bond of the allylic carbocation species as shown in Scheme 55. Poulter et al. subsequently published a mechanistic study on DMAT synthase that is fully consistent with this interpretation [84]. 

Rawal applied the Poulter procedure in the total synthesis of pederin, an example that also highlights the power of the Curtius rearrangement for installation of an acyclic hemiaminal. Saponification of a-methoxyester 81 and DPPA-mediated acyl azide formation led to rearranged iV-acyl hemiaminal 82, a strategy pioneered by Roush and Matron in their approach to the structurally closely related mycalamide and onnamide systems. In the Rawal example, the reaction occurred smoothly in the presence of a free neopentyl alcohol group at Cl3. 

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