Desymmetrization phosphate

Miller has reported a minimal kinase for the phosphorylative enantioselective desymmetrization of a meio-inositol derivative. Peptide 132, identihed from a small library, provided the highest selectivity using the meso-tno 130 as substrate. This approach was applied to a hve-step synthesis of D-myoinositol-1-phosphate from readily available myoinositol ... 

Scheme 7.9. Synthesis of oseltamivir phosphate (1) employing an enzymatic monohydrolysis desymmetrization.

The first enzymatic desymmetrizations of prochiral phosphine oxides was recently reported by Kielbasinski et al.88 Thus, the prochiral bis(methoxycarbonylmethyl)-phenylphosphine oxide 93 was subjected to the PLE-mediated hydrolysis in buffer affording the chiral monoacetate (RJ-94 in 72% ee and 92% chemical yield. In turn, the prochiral bis(hydroxymethyl)phenylphosphine oxide 95 was desymmetrized using either lipase-catalyzed acetylation of 95 with vinyl acetate as acyl donor in organic solvent or hydrolysis of 97 in phosphate buffer and solvent affording the chiral monoacetate 96 with up to 79% ee and 76% chemical yield. 

Neri et al89 reported the desymmetrization of A-Boc-serinol 98 by the selective monoacetylation using PPL (porcine pancreas lipase) and vinyl acetate as the acylating agent in organic solvent. The mono acetylated product (R)-99 was obtained after 2 hours with 99% ee and isolated in 69% chemical yield. Traces of the diacetylated product 100 were observed. The cyclization of (R)-99 in basic medium afforded the racemic oxazolidinone 101. The latter was subjected to enzymatic hydrolysis in phosphate buffer affording (R)-... 

Wojtowicz, J.A. and Polak, R.J., 3-Substituted oxetanes, J. Org. Chem. 38 (11), 2061, 1973. Charmantray, R, El Blidi, L., Gefflaut, T., Hecquet, L., Bolte, J., and Lemaire, M., Improved straightforward chemical synthesis of dihydroxyacetone phosphate through enzymatic desymmetrization of... 

The or-analogue 159 has been made by a Pd-catalysed reaction involving an allylic phosphate as reactant, whilst others have also described routes to 159, its hydrogenated analogue, and the enantiomer and diastereoisomers of this, using enzymic desymmetrization to introduce chirality the products were evaluated for their ability to inhibit tumour necrosis factor-a. A chemo-enzymatic approach has also been used to make the cyclopropane-fused analogue 160 and... 

The biocatalytic desymmetrization of various C2-symmetric tertiary phosphine oxides was used for the preparation of P-chiral phosphines. Mikolajczyk et al. [183-185] studied the desymmetrization of bis-functional phosphinates and phosphine oxides. The hydrolysis of prochiral bis(methoxycarbonylmethyl) phenylphosphine oxide 274 was carried out in phosphate buffer in the presence of... 

Fig. 7 (a) Similar equatorially substituted environment about the 4- and 6-hydroxyls of myoinositol derivative 62. (b) P(III) transfer, catalyzed by a tetrazole sidechain and inspired from previous efforts using Pmh sidechains as nucleophilic catalysts for P(V) transfer among several other transformations, (c) Hit Atz-containing peptide 64, derived from a library inspired by 1,3-desymmetrization catalyst 5. (d) Enantioselective preparation of myo-inositol-6-phosphate precursor 65 by means of enantioselective phosphitylation followed by a phosphate-directed P (III) transfer that operates as a kinetic resolution ( 1 65 66 35). (i) Et2NP(OBn)2, 5 mol% peptide 64, 10 A M.S., CHCI3,4°C. (ii) 30% (aq.) H2O2, 0°C, 1 h. 71% yield for 1st pass to yield 85 15 er 74% yield of 65 in second pass as kinetic resolution with peptide 64 [114]... 

Enantioselective copper-catalyzed desymmetrization of meso cyclic allylic bisdiethyl-phosphates has alsobeen conducted with dialkylzinc reagents. Piarulli and Gennari initially showed that the copper(l) complex of a chiral Schiff base catalyzed tlie enantioselective desymmetrization of 4-cyclopentene-l,3-bis(diethylphosphate) with diethyzinc (Equation 20.75). Piarulli, Gennari, and Feringa then improved upon the enantioselectivities... 

The introduction of a phosphate moiety into a polyhydroxy compound by classic chemical methods is tedious since it usually requires a number of protection and deprotection steps. Furthermore, oligophosphate esters as undesired byproducts arising from overphosphorylation are a common problem. Employing enzymes for the regioselective formation of phosphate esters can eliminate many of these disadvantages thus making these syntheses more efficient. Additionally, enantioselective transformations are also possible involving the desymmetrization of prochiral or weso-diols or the resolution of racemates. 

After Hennecke et al. reported chiral sodium phosphate-catalyzed halocyclization via desymmetrization of mci O-haliranium ions formed from l,8-oct-4-ene diols [46a], Denmaric, Huang, and others independently disclosed an enantioselective intramolecular bromocycloetherification reaction with the promotion of the same phosphoric acid, both of which led to exo-cyclized bromofurans 106 as the major products in moderate to good enantioselectivities (Scheme 2.32) [46b,c]. 

In comparison with the asymmetric epoxide-opening reactions described above in Section 9.4, catalytic desymmetrizations of meso-aziridines have relatively limited precedence [151]. Kanai and Shibasaki have disclosed a number of promising results obtained with lanthanide complexes of the chiral phosphinoxide ligand 193 (Scheme 9.24) [152, 153]. These efforts were showcased in the desymmetrization of meso-aziridine 192 with TMSN j to provide azide 194 in 96% yield and 91 % ee. Adduct 194 was subsequently converted into the anti-influenza drug oseltamivir phosphate (Tamiflu, 195) [153]. 

In 2005, Hanson et al. utilized this concept with a phosphate tether in the desymmetrization of C2-symmetric (3S,5S)-l,6-diene-diol (S,S)-24 (Scheme 4.9)... 

Each subunit was constructed by a phosphate-mediated desymmetrization of 24, followed by the aforementioned CM and allylic phosphate displacements. The C1-C14 subunit was envisioned to have the C1-C6 side chain appended via CM to yield advanced intermediate 40 from R,R,Ps)-26. Subsequent regioselective hydrogenation of the C5 - C6 olefin and regioselective Pd(0) -mediated allylic hydride addition (to CIO) would afford a terminal olefin armed for oxidation and subsequent installation of the Cll carbinol center (Scheme 4.15) [7a]. The C15-C30 subunit largely depended on the CM/cuprate approach (Scheme 4.13) and the advanced intermediate 41 would be synthesized from (S,S,Pr)-26 [7bj. 

The synthesis of bicyclic phosphate triester 26 has been accompUshed via a desymmetrization of C2-symmetric diol 24 using a phosphate-tether mediated... 

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