Allenes, phosphorylated

The second chapter Synthesis and Biological Activity of 2,5-Dihydro-1,2-Oxaphosphole-2-Oxide Derivatives deals with the recent synthetic methods, particularly those using phosphorylated allenes as the starting materials, of these compounds which show interesting biological properties. 

The unique combination of double bonds in the molecules of those compounds, each with different reactivity along with the easy preparation, makes phosphorylated allenes useful substrates for the synthesis of different cyclic and noncyclic organophosphorus compounds. Recent investigations increase the scope of application of phosphorylated allenes as precursors in organic syntheses. Most of them are accompanied by the formation of five- or six-membered phosphorus heterocycles, which in many cases demonstrate certain biological activity. 

All the synthetic protocols described above have limitations to some extent and the yields of the products were modest. In some cases the formation of 1,2-alkadi-enephosphonate derivatives is essential for obtaining the final cyclic products. This is the reason why many authors have used the higher reactivity of 1,2-alkadi-enephosphonates, discovered by Mark [42] in 1962 for the preparation of 2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives. Since then, the oxaphospholic cyclization of 1,2-alkadienephosphonate system of double bonds has become the easiest method for the synthesis of these compounds. The special structure of phosphorylated allenes is responsible for their special properties, which has attracted the attention of chemists for a long time [43 16],... 

Phosphorylated allenes have been widely used as building blocks for the synthesis of five- and six-membered phosphorus heterocycles [48-52],... 

Figure 10.7 (a) In HAD enzymes Asp mediates phosphoryl group transfer to a variety of acceptors, including H20 (b) the catalytic scaffold around the essential Mg2+ion. (From Allen and Dunaway-Mariano, 2004. Copyright 2004, with permission from Elsevier.)... 

Allen, K.N. and Dunaway-Mariano, D. (2004) Phosphoryl group transfer evolution of a catalytic scaffold, TIBS, 29, 495-503. 

Less common addition reactions such as the bromination of trifhioromethyl-substi-tuted butatrienes [30] or the reaction of tetrafluoroallene with boron trifluoride have also been reported [283]. Especially the interaction of phosphorylated allenes with electrophiles was summarized in a review by Alabugin and Brel [8], whereas Smadja [284] published a more general overview about the electrophilic addition to allenic derivatives. 

Phosphorylated allenes 195 (R1 = H or Me) are a source of secondary ( )-allylamines. The allenes are treated with an amine R2NH2 (R2 = t-Bu or 4-MeCgH4 and the products, which exist as equilibrium mixtures of enamines 196 and imines 197, are olefinated by successive reaction with methyllithium and an aldehyde R3CHO (R = i-Bu, 4-MeCgH4, PhCH2CH2 etc). Reduction with sodium borohydride finally yields the... 

Ketenes easily add water,alcohols, amines and thiols to give derivatives of phosphorylated carboxylic acids ( -7). Phosphorylated ketenes undergo reactions of cyclo"aadition to vinyl ethers,diazomethane,styrene, cyclopentadiene, etc. From phosphorylated ketenes other phosphorylated cumulenes can be obtained,for example allenes,isocyanates,ketenimines... 

Allenes bearing a phosphoryl group and a suitable 5-hydroxyalkyl side chain at Cl undergo 6-exo ring closure upon treatment with base to afford 4-phosphoryl 3,6-dihydropyrans 230 (Equation 105) <2004JOC6867>. Similarly, a silver promoted cyclization of the allene 231 provides the 3,6-dihydropyran 232 in moderate yield (Equation 106) <2004JA15978>. 

Allen CA, Hakansson G, Allen JF (1995) Redox conditions specify the proteins synthesized by isolated chloroplasts and mitochondria. Redox Report 1 119-123 Allen JF (1992) Protein phosphorylation in regulation of photosynthesis. Biochim BiophysActa... 

The mechanism by which reversible phosphorylation occurs is a central part in our understanding of the overall regulation process. It is currently described by the interplay of a continuously active phosphatase and a light-activated kinase (Allen et al., 1981). The activation of the latter enzyme can be produced in experimental conditions where the intersystem electron carriers are in a reduced state. Indirect evidence have favored kinase activation by the reduced plastoquinones (Allen et al., 1981)... 

Allen, J.F., Bennett,J., Steinback, K.E. and Amtzen, C.J. 1981. Chloroplast protein phosphorylation couples plastoquinone redox changes to distribution of excitation energy between the two photosystems. Nature (Lond) 291.25-29. 

Horton, P., Allen, J.F., Black, M.T. and Bennett, J. 1981. Regulation of phosphorylation of chloroplast membrane polypeptides by the redox state of the plastoquinones. FEBS Lett., 125.193-196. 

Hsieh-Wilson LC, Benfenati F, Snyder GL, Allen PB, Nairn AC, Greengard P (2003) Phosphorylation of spinophilin modulates its interaction with actin filaments. J Biol Chem 278 1186 1194. 

McAvoy T, Allen PB, Obaishi H, Nakanishi H, Takai Y, Greengard P, Nairn AC, Hemmings HC, Jr (1999) Regulation of neurabin I interaction with protein phosphatase 1 by phosphorylation. Biochemistry 38 12943-12949. 

Snyder GL, Allen PB, Fienberg AA, Valle CG, Huganir RL, Nairn AC, Greengard P (2000) Regulation of phosphorylation of the GluRl AMPA receptor in the neostriatum by dopamine and psychostimulants in vivo. J Neurosci 20 4480 1488. 

Allen, J.F. 1991. Protein phosphorylation in regulation of photosynthesis. Biochim. Biophys. Acta 1098, 275-335. 

A convenient synthesis of new 2-substituted-2-(diethyl phosphono)-3-is-opropenyl-2H-azirines (363) starting from phosphorylated allenes (364) has been developed (Figure 61a). 

Allen and Eiler discovered that whereas the polymerized acid had four primary phosphoric dissociations per tetranucleotide unit, after action of the crystalline enzyme one secondary phosphoric dissociation per tetranucleotide unit made its appearance (in addition to the four primary dissociations). They decided that this behavior is compatible with Levene s open-chain formula (VII) for the tetranucleotide provided that, in the polymer, the secondary hydroxyl of one phosphoryl group per tetranucleotide unit is involved in the polymerization. They also pointed out that it could be interpreted as the opening of the cyclic structure proposed by Takahashi (VIII). 

A new perspective was opened up recently when Denmark demonstrated diat with chirally modified phosphoryl-activated allenes an asymmetric induction could be effected. From easily generated allenyl phosphoramidates containing an optically active amino alcohol, the diastereomeric adducts (37) and (39) could be obtained by addition of dlyl alcohol. When the separated adducts were employed in the carb-anionic Claisen rearrangement, a remarkable asymmetric induction (90 10) could be achieved with preferential formation of the diastereomers (38) or (40) respectively, whereas in a thermal reaction no stereoselection was observed (Scheme 63). Another example of an asymmetric induction in Claisen rearrangements is reported by Welch. ... 

N. Bowling, X. Huang, G.E. Sandusky, R.L. Fouts, K. Mintze, M. Esterman, P.D. Allen, R Maddi, E. McCall, C.J. Vlahos, Protein kinase C-a and -e modulate connexin-43 phosphorylation in human heart, J Mol Cell Cardiol 33, 789-798 (2001). 

FIGURE 10.8 The phosphoglucomutase reaction proceeds via two phosphoryl transfer reactions. (Adaptedfrom Allen Dunaway-Mariano,... 

In the same way, phosphoryl-substituted carbenes reacted selectively with one double bond of an allene to give cyclopropane 1 no yield was reported. ... 

An equally compelling piece of evidence that protein phosphorylation is controlled by the redox state ofplastoquinone pool was provided by Horton, Allen, Black and Bennett " using potentiometric titration of both fluorescence and LHC II phosphorylation, as shown in Fig. 7 (B). Details on the use of redox titration ofPS-II fluorescence-yield changes to monitor the redox-state changes of the plastoquinone pool in PS II will be discussed in Chapter 17. The data points for fluorescence as well as for phosphorylation, as measured by the level of radioactive P-labeled LHC II, fit the Nernst equation [see footnote on p. 92] with an (at pH 7.8) of 0 mV and an n-value of 2, reflecting a two-electron change for the electron carrier involved, presumably PQ. Thus crucial links are established between the redox state of plastoquinone, the activation of kinase for LHC II phosphorylation and changes in chlorophyll fluorescence. 

Fig. 7. (A) Time course of phosphorylation of LHC II during the state 1-to-state 2 (left) and state 2-to-state 1 (right) transitions in pea chloroplasts. (B) Redox titration of P incorporation into LHC II and ATP-induced fluorescence decrease. (A) adapted from Telfer, Allen, Barber and Bennett (1983) Thylakoidprotein phosphorylation during state 1-state 2 transitions in osmotically shocked pea chloroplasts. Biochim Biophys Acta. 722 176-181 (B) from Horton, Allen, Black and Bennett (1981) Regulation of phosphorylation of chloroplast membrane polypeptides by the redox state of plastoquinone. FEBS Lett 125 194.

---